Lessons learnt during the first 100 days of COVID-19 pandemic in India Rajesh Bhatia, Priya Abraham Indian Journal of Medical Research 2020 151(5):387-391

Contact lens use at the time of SARS-CoV-2 pandemic for healthcare workers Raghav Bhargava Indian Journal of Medical Research 2020 151(5):392-394

Impact of COVID-19 pandemic on health system & Sustainable Development Goal 3 Sonalini Khetrapal, Rajesh Bhatia Indian Journal of Medical Research 2020 151(5):395-399

Clinical management of COVID-19 George M Varghese, Rebecca John, Abi Manesh, Rajiv Karthik, OC Abraham Indian Journal of Medical Research 2020 151(5):401-410 The novel coronavirus disease 2019 (COVID-19) with its early origin from Wuhan city in China has evolved into a global pandemic. Maximal precautionary measures and resources have been put forward by most nations in war footing to mitigate transmission and decrease fatality rates. This article was aimed to review the evidence on clinical management and to deal with the identification of high-risk groups, warning signs, appropriate investigations, proper sample collection for confirmation, general and specific treatment measures, strategies as well as infection control in the healthcare settings. Advanced age, cardiovascular disease, diabetes, hypertension and cancer have been found to be the risk factors for severe disease. Fever lasting for >five days with tachypnoea, tachycardia or hypotension are indications for urgent attention and hospitalization in a patient with suspected COVID-19. At present, reverse transcription-polymerase chain reaction (RT-PCR) from the upper respiratory tract samples is the diagnostic test of choice. While many drugs have shown in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are insufficient clinical data to promote or dissuade their usage. Among the currently available drugs, hydroxychloroquine and lopinavir/ritonavir may be considered for patients with severe COVID-19 infection, awaiting further clinical trials. Stringent droplet and contact precautions will protect healthcare workers against most clinical exposures to COVID-19.

COVID-19 pandemic from an ophthalmology point of view Parul Chawla Gupta, M Praveen Kumar, Jagat Ram Indian Journal of Medical Research 2020 151(5):411-418 Coronavirus disease 2019 (COVID-19) is caused by a highly contagious RNA virus termed as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Ophthalmologists are at high-risk due to their proximity and short working distance at the time of slit-lamp examination. Eye care professionals can be caught unaware because conjunctivitis may be one of the first signs of COVID-19 at presentation, even precluding the emergence of additional symptoms such as dry cough and anosmia. Breath and eye shields as well as N95 masks, should be worn while examining patients with fever, breathlessness, or any history of international travel or travel from any hotspot besides maintaining hand hygiene. All elective surgeries need to be deferred. Adults or children with sudden-onset painful or painless visual loss, or sudden-onset squint, or sudden-onset floaters or severe lid oedema need a referral for urgent care. Patients should be told to discontinue contact lens wear if they have any symptoms of COVID-19. Cornea retrieval should be avoided in confirmed cases and suspects, and long-term preservation medium for storage of corneas should be encouraged. Retinal screening is unnecessary for coronavirus patients taking chloroquine or hydroxychloroquine as the probability of toxic damage to the retina is less due to short-duration of drug therapy. Tele-ophthalmology and artificial intelligence should be preferred for increasing doctor-patient interaction.

National sero-surveillance to monitor the trend of SARS-CoV-2 infection transmission in India: Protocol for community-based surveillance Muthusamy Santhosh Kumar, Tarun Bhatnagar, Ponnaiah Manickam, V Saravana Kumar, Kiran Rade, Naman Shah, Shashi Kant, Giridhara R Babu, Sanjay Zodpey, CP Girish Kumar, Jeromie Wesley Vivian Thangaraj, Pranab Chatterjee, Suman Kanungo, Ravindra Mohan Pandey, Manoj Murhekar, Sujeet K Singh, Swarup Sarkar, JP Muliyi, Raman R Gangakhedkar, D.C.S Reddy Indian Journal of Medical Research 2020 151(5):419-423 Conducting population-based serosurveillance for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) will estimate and monitor the trend of infection in the adult general population, determine the socio-demographic risk factors and delineate the geographical spread of the infection. For this purpose, a serial cross-sectional survey would be conducted with a sample size of 24,000 distributed equally across four strata of districts categorized on the basis of the incidence of reported cases of COVID-19. Sixty districts will be included in the survey. Simultaneously, the survey will be done in 10 high-burden hotspot cities. ELISA-based antibody tests would be used. Data collection will be done using a mobile-based application. Prevalence from the group of districts in each of the four strata will be pooled to estimate the population prevalence of COVID-19 infection, and similarly for the hotspot cities, after adjusting for demographic characteristics and antibody test performance. The total number of reported cases in the districts and hotspot cities will be adjusted using this seroprevalence to estimate the expected number of infected individuals in the area. Such serosurveys repeated at regular intervals can also guide containment measures in respective areas. State-specific context of disease burden, priorities and resources should guide the use of multifarious surveillance options for the current COVID-19 epidemic.

Laboratory surveillance for SARS-CoV-2 in India: Performance of testing & descriptive epidemiology of detected COVID-19, January 22 - April 30, 2020 ICMR COVID Study Group, COVID Epidemiology & Data Management Team, COVID Laboratory Team, VRDLN Team Indian Journal of Medical Research 2020 151(5):424-437 Background & objectives: India has been reporting the cases of coronavirus disease 2019 (COVID-19) since January 30, 2020. The Indian Council of Medical Research (ICMR) formulated and established laboratory surveillance for COVID-19. In this study, an analysis of the surveillance data was done to describe the testing performance and descriptive epidemiology of COVID-19 cases by time, place and person. Methods: The data were extracted from January 22 to April 30, 2020. The frequencies of testing performance were described over time and by place. We described cases by time (epidemic curve by date of specimen collection; seven-day moving average), place (area map) and person (attack rate by age, sex and contact status), and trends were represented along with public health measures and events. Results: Between January 22 and April 30, 2020, a total of 1,021,518 individuals were tested for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Testing increased from about 250 individuals per day in the beginning of March to 50,000 specimens per day by the end of April 2020. Overall, 40,184 (3.9%) tests were reported positive. The proportion of positive cases was highest among symptomatic and asymptomatic contacts, 2-3-fold higher than among those with severe acute respiratory infection, or those with an international travel history or healthcare workers. The attack rate (per million) by age was highest among those aged 50-69 yr (63.3) and was lowest among those under 10 yr (6.1). The attack rate was higher among males (41.6) than females (24.3). The secondary attack rate was 6.0 per cent. Overall, 99.0 per cent of 736 districts reported testing and 71.1 per cent reported COVID-19 cases. Interpretation & conclusions: The coverage and frequency of ICMR's laboratory surveillance for SARS-CoV-2 improved over time. COVID-19 was reported from most parts of India, and the attack rate was more among men and the elderly and common among close contacts. Analysis of the data indicates that for further insight, additional surveillance tools and strategies at the national and sub-national levels are needed.

A cluster of SARS-CoV-2 infection among Italian tourists visiting India, March 2020 Jeromie Wesley Vivian Thangaraj, Manoj Murhekar, Yatin Mehta, Sushila Kataria, Megha Brijwal, Nitesh Gupta, Aashish Choudhary, Bharati Malhotra, Madhavi Vyas, Himanshu Sharma, Naveen Yadav, Tarun Bhatnagar, Nivedita Gupta, Lalit Dar, Raman R Gangakhedkar, Balram Bhargava Indian Journal of Medical Research 2020 151(5):438-443 Background & objectives: A cluster of SARS-CoV-2 infection occurred among Italian tourists visiting India. We report here the epidemiological, clinical, radiological and laboratory findings of the first cluster of SARS-CoV-2 infection among the tourists. Methods: Information was collected on demographic details, travel and exposure history, comorbidities, timelines of events, date of symptom onset and duration of hospitalization from the 16 Italian tourists and an Indian with laboratory-confirmed SARS-CoV-2 infection. The clinical, laboratory, radiologic and treatment data was abstracted from their medical records and all tourists were followed up till their recovery or discharge or death. Throat and deep nasal swab specimens were collected on days 3, 8, 15, 18, 23 and 25 to evaluate viral clearance. Results: A group of 23 Italian tourists reached New Delhi, India, on February 21, 2020 and along with three Indians visited several tourist places in Rajasthan. By March 3, 2020, 17 of the 26 (attack rate: 65.4%) had become positive for SARS-CoV-2 infection. Of these 17 patients, nine were symptomatic, while eight did not show any symptoms. Of the nine who developed symptoms, six were mild, one was severe and two were critically ill. The median duration between the day of confirmation for COVID-19 and RT-PCR negativity was 18 days (range: 12-23 days). Two patients died with a case fatality of 11.8 per cent. Interpretation & conclusions: This study reconfirms higher rates of transmission among close contacts and therefore, public health measures such as physical distancing, personal hygiene and infection control measures are necessary to prevent transmission.

Development of indigenous IgG ELISA for the detection of anti-SARS-CoV-2 IgG Gajanan Sapkal, Anita Shete-Aich, Rajlaxmi Jain, Pragya D Yadav, Prasad Sarkale, Rajen Lakra, Srikant Baradkar, Gururaj Rao Deshpande, Deepak Mali, Bipin N Tilekar, Triparna Majumdar, Himanshu Kaushal, Yogesh Gurav, Nivedita Gupta, Sreelekshmy Mohandas, Ketki Deshpande, Ojas Kaduskar, Malvika Salve, Savita Patil, Shivshankar Gaikwad, AP Sugunan, M Ashok, Sidhartha Giri, Jayanthi Shastri, Priya Abraham, Raman R Gangakhedkar, COVID Support Team Indian Journal of Medical Research 2020 151(5):444-449 Background & objectives: Since the beginning of the year 2020, the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted humankind adversely in almost all spheres of life. The virus belongs to the genus Betacoronavirus of the family Coronaviridae. SARS-CoV-2 causes the disease known as coronavirus disease 2019 (COVID-19) with mild-to-severe respiratory illness. The currently available diagnostic tools for the diagnosis of COVID-19 are mainly based on molecular assays. Real-time reverse transcription-polymerase chain reaction is the only diagnostic method currently recommended by the World Health Organization for COVID-19. With the rapid spread of SARS-CoV-2, it is necessary to utilize other tests, which would determine the burden of the disease as well as the spread of the outbreak. Considering the need for the development of such a screening test, an attempt was made to develop and evaluate an IgG-based ELISA for COVID-19. Methods: A total of 513 blood samples (131 positive, 382 negative for SARS-CoV-2) were collected and tested by microneutralization test (MNT). Antigen stock of SARS-CoV-2 was prepared by propagating the virus in Vero CCL-81 cells. An IgG capture ELISA was developed for serological detection of anti-SARS-CoV-2 IgG in serum samples. The end point cut-off values were determined by using receiver operating characteristic (ROC) curve. Inter-assay variability was determined. Results: The developed ELISA was found to be 92.37 per cent sensitive, 97.9 per cent specific, robust and reproducible. The positive and negative predictive values were 94.44 and 98.14 per cent, respectively. Interpretation & conclusions: This indigenously developed IgG ELISA was found to be sensitive and specific for the detection of anti-SARS-CoV-2 IgG in human serum samples. This assay may be used for determining seroprevalence of SARS-CoV-2 in a population exposed to the virus.

Analysis of RNA sequences of 3636 SARS-CoV-2 collected from 55 countries reveals selective sweep of one virus type Nidhan K Biswas, Partha P Majumder Indian Journal of Medical Research 2020 151(5):450-458 Background & objectives: SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) is evolving with the progression of the pandemic. This study was aimed to investigate the diversity and evolution of the coronavirus SARS-CoV-2 with progression of the pandemic over time and to identify similarities and differences of viral diversity and evolution across geographical regions (countries). Methods: Publicly available data on type definitions based on whole-genome sequences of the SARS-CoV-2 sampled during December and March 2020 from 3636 infected patients spread over 55 countries were collected. Phylodynamic analyses were performed and the temporal and spatial evolution of the virus was examined. Results: It was found that (i) temporal variation in frequencies of types of the coronavirus was significant; ancestral viruses of type O were replaced by evolved viruses belonging to type A2a; (ii) spatial variation was not significant; with the spread of SARS-CoV-2, the dominant virus was the A2a type virus in every geographical region; (iii) within a geographical region, there was significant micro-level variation in the frequencies of the different viral types, and (iv) the evolved coronavirus of type A2a swept rapidly across all continents. Interpretation & conclusions: SARS-CoV-2 belonging to the A2a type possesses a non-synomymous variant (D614G) that possibly eases the entry of the virus into the lung cells of the host. This may be the reason why the A2a type has an advantage to infect and survive and as a result has rapidly swept all geographical regions. Therefore, large-scale sequencing of coronavirus genomes and, as required, of host genomes should be undertaken in India to identify regional and ethnic variation in viral composition and its interaction with host genomes. Further, careful collection of clinical and immunological data of the host can provide deep learning in relation to infection and transmission of the types of coronavirus genomes.

Ticagrelor versus clopidogrel in patients with ST-elevation myocardial infarction: postdischarge mild bleeding and its clinical impacts No abstract available

Scoring balloon predilation before bioresorbable vascular scaffold implantation in patients with in-stent restenosis: the RIBS VI ‘scoring’ study Background Currently drug-eluting stents (DESs) and drug-eluting balloons are recommended in patients with in-stent restenosis (ISR). However, the efficacy of bioresorbable vascular scaffolds (BVS) after scoring balloon (SCB) predilation in these patients is unknown. Methods RIBS VI (NCT02672878) and RIBS VI ‘Scoring’ (NCT03069066) are prospective multicentre studies assessing the value of BVS in patients with ISR. Inclusion and exclusion criteria were identical in both studies. Results of conventional BVS implantation (112 patients) were compared with those obtained with systematic SCB therapy before BVS (108 patients). Angiographic follow-up was scheduled for all patients. Results On late angiography (93% of eligible patients) the in-segment minimal lumen diameter (primary end-point) (1.88 ± 0.5 vs. 1.90 ± 0.4 mm, P = 0.81), % diameter stenosis (28 ± 17 vs. 29 ± 15%), late lumen loss (0.23 ± 0.4 vs. 0.22 ± 0.4 mm) and binary restenosis rate (8.5 vs. 9.3%) were similar in the conventional BVS and SCB + BVS groups, respectively. At 1-year follow-up (100% of patients) target lesion revascularization (TLR) requirement (9.8 vs. 11.1%) was similar with the two strategies. Freedom from cardiac death, myocardial infarction and TLR was 88% and 87%, respectively. Results remained unchanged after adjusting for potential baseline confounders and were consistent in 10 prespecified subgroups. Conclusion This study suggests that results of conventional BVS implantation in patients with ISR are not improved by systematic predilation with SCB. ClinicalTrials.gov ID: NCT02672878 (RIBS VI) and NCT03069066 (RIBS VI ‘Scoring’). * Fernando Alfonso and Javier Cuesta contributed equally to the writing of this article. Received 23 March 2020 Accepted 4 April 2020 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.coronary-artery.com. Correspondence to Fernando Alfonso, MD, Departamento de Cardiología, Hospital Universitario de La Princesa, Instituto Investigación Sanitaria, Instituto Princesa (IIS-IP), CIBER-CV, Universidad Autónoma de Madrid, c/ Diego de León 62, Madrid 28006, Madrid, Spain, E-mail: falf@hotmail.com Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Effect of intervention timing on one-year mortality in elderly non–ST-segment elevation myocardial infarction patients Background The best timing for early invasive therapy in non–ST-segment elevation myocardial infarction (NSTEMI) patients remains controversial. We sought to determine the optimal timing of early catheterization in order to improve long-term outcomes in elderly (>65  years old) patients with NSTEMI. Methods Using data from the CRUSADE registry linked to Medicare claims, we evaluated the association of early catheterization within the first 24  h or earlier time cut-points of NSTEMI presentation with long-term mortality among older Medicare beneficiaries. Results Of 15  575 NSTEMI patients from 398 CRUSADE hospitals (2003–2006), 3880 (24.9%) received early (≤12  h) catheterization. Compared with those undergoing later catheterization, patients treated early were younger and had less comorbid illness. Relative to those treated later, patients receiving early catheterization had similar 1-year all-cause mortality (11.8% vs 11.9%, P  =  0.90). Using on- vs off-hour presentation as an instrumental variable, balancing potential measured and unmeasured confounders, early and later catheterization patients had nonsignificant differences in 1-year mortality (+5.6% [−11.5%, +22.7%]). Similar results were observed in clinically relevant subgroups, such as age (< or ≥75  years), gender, diabetes status, Global Registry of Acute Coronary Events score (< or ≥140), presence of heart failure, and sensitivity analyses of alternative definitions of early catheterization (≤6 and ≤24  h). Conclusions Among older NSTEMI patients, we found that <24  h or earlier (neither <6 nor 12  h) of catheterization timing were not significantly associated with differences in long-term mortality. * Ben He and Eric D. Peterson contributed equally to the writing of this article. Received 5 March 2020 Accepted 24 May 2020 Correspondence to Ben He, MD, PhD, Department of Cardiology, Shanghai Chest Hospital, West Huai Hai Road, No. 241, Shanghai, China, Tel: +86 21 22200000; fax: +86 21 22200001; e-mail: heben241@126.com Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Safety and efficacy of intracoronary thrombolytic therapy via a new infusion catheter in patients with ST-segment elevation myocardial infarction with large thrombus burden: a pilot study Background A large intracoronary thrombus burden is associated with adverse clinical results. The optimal management of this scenario remains unknown. We aimed to determine the efficacy and safety of a new rapid infusion catheter combined with low-dose intracoronary thrombolysis in patients with ST-segment elevation myocardial infarction (STEMI) with a large thrombus burden. Methods and results This pilot study included 22 patients with STEMI with a large thrombus burden. A large thrombus burden was defined as a definite thrombus with the largest dimension of at least two vessel diameters [thrombolysis in myocardial infarction (TIMI) thrombus grades 4 and 5]. All patients received primary percutaneous coronary intervention guided by the presence of recurrent chest pain or clinical myocardial ischemia evidences. All patients regained myocardial perfusion immediately after the infusion catheter crossed the thrombus. Local fibrinolysis with low-dose recombinant human prourokinase was administered continuously via the infusion catheter for 30 min. Repeat coronary angiography revealed marked thrombus resolution, with an improvement in TIMI flow from 0.14 ± 0.35 at baseline to 2.82 ± 0.40. Only one patient with postlysis thrombus grades 4–5 was observed. No major bleeding events were observed. Conclusions In patients with STEMI presenting with a large thrombus burden, all patients regained myocardial perfusion immediately after the infusion catheter crossed over the thrombus, and low doses of intracoronary thrombolysis could significantly reduce the thrombus burden and improve the coronary flow without major bleeding. * Tao Chen and Qi Wang contributed equally to the writing of this article. Received 22 April 2020 Accepted 25 May 2020 Correspondence to Jun Guo, MD, Department of Cardiovascular, Chinese PLA General Hospital, Beijing 100853, China, Tel: +86 18511296301; fax: +86 010 6818 4552; e-mail: junguodoc@163.com Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Likelihood of myocardial infarction, revascularization and death following catheterization laboratory activation in patients with vs. without both chest pain and ST elevation Background Emergent cardiac catheterization laboratory activation (CCLA) for patients with suspected ST-elevation myocardial infarction (STEMI) is employed to expedite acute revascularization (AR). The incidence of false-positive CCLA, in which AR is not performed, remains high. The combination of chest pain (CP) and electrocardiographic ST elevation (STE) are the hallmarks of STEMI. However, CCLA is sometimes initiated for patients lacking this combination. The study objective was to quantify the difference in likelihood of AR and mortality in patients with vs. without both CP and STE. Methods Retrospective analysis of 1621 consecutive patients for whom CCLA was initiated in a six-hospital network. We assessed the likelihood of acute myocardial infarction (AMI), presence of a culprit lesion (CL), performance of AR, and hospital mortality among patients with both CP and STE (+CP/+STE) compared with patients lacking one or both [non(CP/STE)]. Results 87.0% of patients presented with CP, 82.4% with STE, and 73.7% with both. Among +CP/+STE patients, AMI was confirmed in 90.4%, a CL in 88.9%, and AR performed in 83.1%. The corresponding values among non(CP/STE) patients were 35.8, 31.9, and 28.1%, respectively (P < 0.0001 for each). Nevertheless, mortality among non(CP/STE) patients was three-fold higher than in +CP/+STE patients (13.3% vs. 4.5%; P < 0.0001), with non-coronary deaths 24-fold more likely. Conclusion Patients lacking the combination of CP and STE have a markedly lower likelihood of AMI and AR than +CP/+STE patients, but significantly higher mortality. Protocols aimed at rapid, focused evaluation of non(CP/STE) patients prior to CCLA are needed. Received 20 April 2020 Accepted 26 May 2020 Correspondence to Peter Puleo, MD, St. Luke’s University Hospital, 801 Ostrum St. PPH2, Bethlehem, PA 18015, USA, Tel: +484 375 5836; fax: +484 526 4010; e-mail: ppuleo@ptd.net This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CC-BY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Elevated troponin levels in patients with atrial tachyarrhythmias Objective Data regarding the significance of elevated troponin in the setting of atrial tachyarrhythmia remain inconclusive. In the present study, we aimed to explore the discriminative ability of troponin for obstructive coronary artery disease (CAD) among patients with atrial tachyarrhythmias. Methods We retrospectively identified patients with atrial tachyarrhythmias and elevated serum troponin levels, who underwent invasive coronary angiography during the same admission. The prevalence of obstructive CAD among these patients was compared to that of historically matched patients who underwent coronary angiography due to suspected non-ST elevation myocardial infarction and had no arrhythmias. Results Overall 318 patients with suspected non-ST elevation myocardial infarction were analyzed (n = 159 with atrial tachyarrhythmias and n = 159 without arrhythmias). Obstructive CAD was detected in 39% of patients with an arrhythmia compared to 85.5% in the control group (P < 0.001). A multivariable analysis demonstrated that parameters associated with obstructive CAD among patient with atrial tachyarrhythmias and elevated troponin were diabetes mellitus [odds ratio (OR) 2.7, 95% confidence interval (CI) 1.23–5.91, P = 0.013], prior ischemic heart disease (OR 4.48, 95% CI 1.93–10.4, P < 0.001) and troponin level (OR 3.18 for every 1000 ng/L increment, 95% CI 1.85–5.48, P < 0.001). Conclusions Elevated troponin is not a reliable indicator for the presence of underlying obstructive CAD among patients who present with atrial tachyarrhythmias. Risk stratification of these patients should rely on the degree of troponin elevation, and the presence of diabetes mellitus and prior ischemic heart disease. * Dr. Zach Rozenbauma and Dr. Orly Sapir contributed equally to the writing of this article. Received 4 September 2019 Accepted 3 January 2020 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.coronary-artery.com. Correspondence to Zach Rozenbaum, MD, Department of Cardiology, Tel Aviv Medical Center, 6 Weizman Street, Tel Aviv, Israel, Tel: +972 3 6973395; fax: +972 3 6962334; e-mail: zachroze@gmail.com Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Temporal trends in management and outcome of patients with acute coronary syndrome according to admission low-density lipoprotein cholesterol levels Background The importance of differences in baseline low-density lipoprotein cholesterol (LDL-C) levels and pretreatment with statins on the temporal improvement in outcome of acute coronary syndrome (ACS) patients has not been studied yet. Methods Patients were divided into two groups according to baseline LDL-C levels: LDL-C <130 mg/dl and LDL-C ≥130 mg/dl. Baseline characteristics, clinical data and outcomes were compared for each LDL-C group between patients enrolled in early (2000–2006), mid (2008–2010) and recent (2013–2016) surveys. Results The study population was comprised of 8343 patients. Patients with LDL-C <130 mg/dl were older and were more commonly pretreated with aspirin and statins compared to patients with LDL-C ≥130 mg/dl. Patients included in recent surveys were more frequently selected for an invasive strategy with coronary angiography and subsequent revascularization, and were more commonly treated with guideline-based medical therapy. For patients with a LDL-C ≥130 mg/dl, the temporal improvements in therapy were associated with lower 1-year mortality rates (7.2, 4.4 and 3.5% for patients in early, mid and late surveys, respectively, P = 0.006). That temporal improvement in outcomes existed only in statin-naïve patients. For patients with LDL-C <130 mg/dl, temporal improvement in treatment was not accompanied by a reduction in 30 day or 1-year mortality rates. Conclusion Treatment of ACS patients has improved over the past decades regardless of LDL-C levels. This improvement was accompanied by lower mortality rates in ACS patients with LDL-C ≥130 mg/dl, but not in patients with LDL-C <130 mg/dl. Received 19 November 2019 Accepted 28 December 2019 Correspondence to Mony Shuvy, MD, Heart Institute, Hadassah-Hebrew University Medical Centre, Jerusalem, Israel, Tel: +972 2 6776564; fax: +972 2 6411028; e-mail: monysh@gmail.com Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Mediation analysis for the relationship between dyslipidemia and coronary artery disease via hypersensitive C-reactive protein in a case-control study Background The pathological basis of coronary artery disease (CAD) is atherosclerosis which is associated with inflammation and dyslipidemia. However, the involvement of hypersensitive C-reactive protein (hs-CRP) in lipid metabolism and how it affects the pathogenesis of CAD is uncertain. Objective To explore whether the relationship between dyslipidemia and CAD is partly mediated by hs-CRP levels. Methods Three hundred fifteen pairs of randomly sexand age-matched CAD and non-CAD subjects collected from Zhongda Hospital Affiliated to Southeast University were involved in the final analysis. We gathered information about each subjects clinical history as well as their results of detected hs-CRP and lipid levels. Linear regression analysis was used to determine the association between dyslipidemia and hs-CRP levels in which univariate and multivariate logistic regression analyzes were performed to determine the relationship between hs-CRP levels and CAD as well as dyslipidemia and CAD. Mediation analysis was used to evaluate whether hs-CRP levels act as a mediator of the relationship between dyslipidemia and CAD. Results Dyslipidemia and hs-CRP levels were significantly associated with an increased risk of CAD, with β = 0.594 (P = 0.001) and β = 0.016 (P = 0.024), respectively, and there was a correlation between dyslipidemia and hs-CRP levels (β = 3.273, P = 0.004). Mediation analysis results revealed that the correlation between dyslipidemia and CAD was 8.27% mediated by hs-CRP levels with a direct effect of 0.621 and an indirect effect of 0.056. Conclusion Hs-CRP levels played a partial mediation role in the association between dyslipidemia and CAD. Received 19 November 2019 Accepted 19 April 2020 Correspondence to Li-na Wang, PhD, Key Laboratory of Environmental Medicine Engineering, Ministry of Education, Department of Epidemiology & Biostatistics, School of Public Health, Southeast University, 87 Ding Jiaqiao Rd., Nanjing 210009, China, Tel: +86 25 832 72569; fax: +86 25 832 24322; e-mail: lnwang@seu.edu.cn Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Concomitant acute myocardial infarction and stress cardiomyopathy No abstract available

Regional variations in cardiovascular risk factors and access to care among US veterans with cardiovascular disease Background It remains unclear whether cardiovascular risk factors and access to healthcare for veterans with cardiovascular disease (CVD) vary among US regions. This study sought to determine the extent of regional variations in cardiovascular risk factors and access to medical care in a cohort of veterans with CVD in the USA. Methods The 2016 Centers for Disease Control Behavioral Risk Factor Surveillance Survey was utilized to identify a cohort of veteran patients with CVD. Participants were classified based on four US regions: (1) Northeast, (2) Midwest, (3) South, and (4) West. We compared demographic data, medical history, and access to care for veterans of each US region. The outcomes of interest included financial barriers to medical care and annual medical checkup. Results Among the 13 835 veterans, 18.3% were from the Northeast, while 23.5, 37.1, and 21.1% were from the Midwest, South, and West, respectively. Veterans of each region differed significantly with respect to demographic characteristics, prior medical history, and access to care. Rates of financial barriers to medical care were similar across the four regions (7.3 vs. 7.1 vs. 8.0 vs. 6.9%, P = 0.203). Veterans from the West had the lowest rates of medical checkup within the past year (91.7 vs. 89.5 vs. 91.4 vs. 86.6%). On multivariate analysis, the Midwest [odds ratio (OR) 0.69; 95% CI, 0.53–0.89] and West (OR 0.53; 95% CI 0.41–0.68) regions were independently associated with lower rates of medical checkup within the past year compared to the Northeast. Conclusions In this observational study involving US veterans with CVD, cardiovascular risk factors and frequency of annual medical checkup differed amongst each US region. Further large-scale studies examining the prevalence of impaired access to care and quality of care in US veterans with CVD are warranted. Received 27 December 2019 Accepted 6 April 2020 Correspondence to Puja B. Parikh, MD, MPH, FACC, FAHA, FSCAI, Department of Medicine, Division of Cardiology, Health Sciences Center, T16-080, Stony Brook, NY 11794-8160, USA, Tel: +631 444 1066; fax +631 444 1054; e-mail: puja.parikh@stonybrookmedicine.edu Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Cerebral musings on environmental humanities, human transgression, and healthcare preparedness: Looking beyond the “streetlight effect” of the COVID-19 pandemic Bhaskara P Shelley Archives of Medicine and Health Sciences 2020 8(1):1-8

Bedside clinical teaching: Arresting the decline Robert Pickles Archives of Medicine and Health Sciences 2020 8(1):9-10

Computed tomography evaluation of sinonasal masses with histopathological correlation Musaib Ahmad Dar, Suhail Rafiq, Farzana Manzoor, Irshad Mohideen Archives of Medicine and Health Sciences 2020 8(1):11-14 Background and Aim: A variety of nonneoplastic and neoplastic conditions involving the nasal cavity (NC), paranasal sinuses (PNSs), and nasopharynx are commonly encountered in clinical practice. Etiological factors for the development of sinonasal masses are human papillomavirus 6 and 11, allergens, air pollution, and industrial carcinogens, tobacco, alcohol, and occupational exposure to heavy metal particles. The aim was to explicate and corroborate the CT radiological features of sinonasal masses of benign versus sinister differential diagnosis. Materials and Methods: A total of 50 cases of sinonasal masses were included in this study. Written informed consent from the patients was obtained. Detailed clinical history and local and general examinations were done according to the pro forma attached with a special reference to the nose, PNSs, and oral cavity. These cases were subjected to after routine hematological and biochemical evaluation, nasal endoscopy, X-ray PNSs/computed tomography scan, fine-needle aspiration cytology, and, whenever required, biopsy. Results: On radiological assessment, of 50 patients, 45 patients were declared benign, while as 5 patients were diagnosed as having primary or secondary malignancy involving sino-NCs. Based on bone erosions along with internal hyperdense contents and enhancement pattern, there was some amount of discordance among radiological and histopathological diagnosis. One case which was diagnosed as malignancy (likely metastasis) was found to have invasive fungal sinusitis. Among the three radiologically diagnosed inverted papillomas (based on focal hyperostosis, subtle calcification, and cerebriform enhancement on postcontrast study), only 1 case correlated histopathologically. The rest were hemangioma and schwannoma (very rare). Radiological esthesioneuroblastoma, hemangioma, angiofibroma, and rhinolith correlated well with histopathology. Conclusion: Imaging plays an important role in the evaluation of sinonasal masses. Benign lesions are diagnosed very accurately. The distinction between sinonasal and invasive fungal sinusitis is still debatable, and hence, histopathological correlation is necessary. The presence of significant cervical lymphadenopathy can serve as a surrogate marker of malignancy.

Comparative utility of bone marrow aspiration and trephine biopsy in evaluation of hematological disorders Lekshmi Vijayamohanan, Sarita Asotra, Kavita Kumari, Pooja Murgai, Digvijay Dattal Archives of Medicine and Health Sciences 2020 8(1):15-19 Background: Bone marrow examination is a useful investigative tool to diagnose several hematological and nonhematological disorders. While the aspiration provides excellent cytological detail, the biopsy provides information regarding the spatial relationships of cells, marrow architecture, and valuable information when aspirate is nondiagnostic. We conducted this study to compare the diagnostic usefulness and comparison between aspirate and trephine biopsies in the evaluation of hematological disorders. Aim: The aim was to assess the relative efficacy of bone marrow aspiration and trephine biopsy and the overall diagnostic utility of this procedure in the diagnosis of hematological and nonhematological disorders. Materials and Methods: This is a retrospective study of 6-month duration at a tertiary care hospital in Himachal Pradesh. Patients were aged from 1 to 85 years. A total of 169 cases were studied, in whom bone marrow aspiration and trephine biopsy were performed, with special stains used where required. Results: A specific pathology was found in 89 cases(52.66%), rest being a normal or unsatisfactory study. Trephine biopsy was fundamental in the diagnosis in 69 cases(48.93%). Nearly 21.05% of the aspirates indicating a normal study further revealed a specific pathology on trephine biopsy and 38.88% of the unsatisfactory aspirates revealed definite pathology on biopsy. We noted that 8.87% of cases were diagnosed by trephine biopsy alone, with 89.94% concordance between trephine biopsy and aspiration. Conclusion: Bone marrow aspirate cytology and trephine biopsy are useful adjuncts to each other and should be used to supplement each other in arriving at a definite diagnosis, and they remain as a key diagnostic tool in hematological disorders.

Clinicohistopathologic study of lichenoid interface dermatitis Aparna Muralidhar, Suguna Belur Venugopal, AS Nandini Archives of Medicine and Health Sciences 2020 8(1):20-25 Background: Interface dermatitis (IFD)/lichenoid tissue reactions are among the most frequently presenting disorders in dermatology, which in common have a constellation of histopathological features but varied clinical presentation. Aim: Clinicopathologic correlation and determination of histomorphologic changes associated with various lichenoid IFD of the skin. Materials and Methods: This was a prospective study with purposive sampling of patients reporting to the outpatient department of dermatology, venerology, and leprosy of our hospital from January 2017 to July 2018. Skin biopsies of 150 patients of either sex diagnosed provisionally as one of the lichenoid IFD on clinical grounds were studied. Clinicohistopathologic correlation was done. Results: We encountered 58 cases of classic lichen planus, seven variants of lichen planus (hypertrophic lichen planus, ashy dermatosis, lichen planus pigmentosus, actinic lichen planus, lichen planopilaris, lichen nitidus, and lichen striatus), and 16 cases of lichenoid eruptions. About 82.6% of the cases were concordant histopathologically. The peak incidence was in 20–40 years of age with an equal predilection for males and females. A majority of the lesions were multiple, pruritic, papules, and plaques involving the limbs. Histopathologically, the most consistent findings were basal cell vacuolar degeneration followed by melanin incontinence. Conclusion: Lichenoid IFDs are exclusive clinicopathological entities with several variants. Subtle features noted on histopathology help in differentiating these lesions. Understanding and interpreting these subtle changes aids in better clinical management of the patient.

The effect of strength training of the calf muscle pump on cardiovascular parameters Andrew Lalchhuanawma, Divya Sanghi Archives of Medicine and Health Sciences 2020 8(1):26-30 Background: The heart pump allows blood to flow where the network of arteries, capillaries, and veins throughout the body regulates the rate of circulation of the blood. Parameters that determine the fitness level of the cardiovascular system include heart rate (HR), blood pressure (BP), VO2 max, fatigue, etc., The calf muscle pump is the most important of the lower limb, as it is the most efficient and has the largest capacitance. It has been suggested that increased leg strength, independent of cardiovascular training, may augment an aerobic endurance performance. Aim: The aim of this study is to determine the effect of strength training of gastrocnemius and soleus muscles on cardiovascular parameters. Materials and Methods: An experimental study carried out at MRIIRS Institution for 1 year. Forty-five recreational players aged between 20 and 30 years were selected after obtaining informed consent. Participants were divided equally into three groups by a convenient chit method. They were assessed for cardiovascular parameters of HR, BP, VO2 max, fatigue, and FI at baseline and after 8 weeks training program. Group A participated in gastrocnemius and soleus; Group B participated in gastrocnemius, and Group C participated in the soleus muscle training program. Results: Paired t-test for pre–post training shows a significant difference P < 0.05 for all the groups. ANOVA used between groups pre–post training were found to be significant for HR and systolic BP (SBP), and nonsignificant for diastolic BP (DBP) and VO2 max. Kruskal–Wallis test used between groups before and after training was found to be significant for fatigue and fitness index (FI). Jonckheere-trend test Post hoc analysis showed that Group A performed better than Group C and B. Wilcoxon signed-rank test for fatigue and FI showed a significant difference for all the groups. Conclusion: Eight weeks of leg muscle training on cardiovascular parameters have an effect on cardiovascular parameters of HR, SBP, FI, and fatigue. The results showed no significant effects on DBP and VO2 max.

Morphometric variations in sigmoid notch and condyle of the mandible: A retrospective forensic digital analysis in North Indian population Varsha Kanjani, Prashant Kalyani, Neha Patwa, Vaibhav Sharma Archives of Medicine and Health Sciences 2020 8(1):31-34 Introduction: The peculiarity of anatomical structures such as mandible, frontal sinus, sella turcica, nasal septum, and styloid process present in human skull and their variations leads to the revolution in forensic anthropology. The digitization in radiology enables a health professional to store the previous antemortem records and thereby compare it with postmortem records in case of mass disasters. Aim: The present retrospective analysis was conducted to evaluate the morphological variations in the sigmoid notch and condyles of the mandible and also to determine its peculiarity in establishing individual's identity. Materials and Methods: The study included 1200 panoramic radiographs of individuals in the age range of 10–60 years among population of Jodhpur, Rajasthan. The radiographs were taken using PLANMECA machine and enrolled radiographs were outlined using tracing tool installed in the software. The morphological variations of sigmoid notch and condyle in the panoramic radiographs were analyzed bilaterally for both males and females using Statistical Package for the Social Sciences (SPSS) software version 21.0. Results: The sloping shape of the sigmoid notch was most commonly found (43%), followed by wide (37.66%) and round shape (19.25%). The most common shape of condyle observed was round (46.12%), followed by angled (29.29%), convex (21.95%), and flat shape (2.62%). The distribution of sigmoid notch and condylar shape variations among right and left sides was not statistically significant. Conclusion: In forensic anthropology, the morphological variations among sigmoid notch and condyle of mandible using single panoramic radiographic view can be used as an adjuvant for personal identification.

Expression of human epidermal growth factor receptor 2/neu in breast carcinoma: Experience from a tertiary care center in Tamil Nadu, India Syed Ahmed Hussain, S Prakashiny, Naseem Noorunnisa, R Revathi Shree, Senthil N Ganesh Archives of Medicine and Health Sciences 2020 8(1):35-40 Background and Aim: Women diagnosed with the foremost common cancer are the breast carcinoma. Human epidermal growth factor receptor 2 (HER2)/neu status has become an important part of immunohistochemical evaluation of breast carcinoma. Hence, the main aim of our study was to correlate the HER2/neu expression in breast carcinoma patients with certain clinicopathological parameters to ensure the better prognosis of the disease. Materials and Methods: The present study included 56 breast carcinoma patients. The surgically dissected breast carcinoma specimens were subjected to immunohistochemistry staining and were evaluated for certain clinicopathological prognostic parameters that included tumor size, Nottingham modification of the Scarff Bloom-Richardson (NSBR) grading, necrosis, lymph vascular invasion, fibrosis, stromal reaction, and lymph node metastasis. Statistical analysis by the Chi-square and Student's t-test was performed. Results: Most patients belonged to the postmenopausal age group (62.5%). Only 19 (33.9%) out of 56 patients showed positive for HER2/neu expression with maximum HER2/neu expression noted in the 40–60 years' (44.83%) age group. A greater proportion of cases (66.07%) had tumor size ranging from 2 to 5 cm with a majority of HER2/neu-positive (40.5%) cases among them. Majority of patients (96.24%) were of infiltrating ductal carcinoma. With respect to NSBR grading, 50% patients in Grade 3 showed positive HER2/neu expression (P = 0.048). It was also observed that 17 patients showed positive HER2/neu expression at the varying stages of lymph node metastasis (P = 0.022). Conclusion: The evaluation of HER2/neu expression indicates it to be a stronger prediction of poor prognosis due to its association with prognostic parameters.

Total antioxidant/oxidant status in chronic periodontitis patients with type II diabetes following nonsurgical periodontal therapy Ruby Ramya Vincent, Devapriya Appukuttan, Aruna Balasundaram, Vanaja Krishna Naik, Dhayanand John Victor Archives of Medicine and Health Sciences 2020 8(1):41-46 Background: Diabetes and periodontitis are chronic inflammatory diseases characterized by a dysregulated inflammatory response involving oxidative stress (OS). Nonsurgical periodontal therapy (NSPT) eliminates bacterial load followed by reduction in inflammatory burden due to reduced levels of proinflammatory mediators. Aim: The study aimed to evaluate the effect of NSPT on the OS biomarkers in the gingival crevicular fluid (GCF) of generalized chronic periodontitis (GCP) patients with Type II diabetes mellitus (DM). Materials and Methods: Eighty participants were allotted into Group I, systemically healthy with GCP (n = 20); Group II, GCP with Type II DM (n = 20); Group III, Type II DM without chronic periodontitis (CP) (n = 20); and Group IV, periodontally and systemically healthy controls (n = 20). Plaque index, gingival index (GI), probing pocket depth (PPD), and clinical attachment loss (CAL) were recorded. GCF was evaluated for total antioxidant capacity (TAOC), total oxidant status (TOS), and OS index (OSI). Patients in group I and II received NSPT. Results: Groups I, II, and III at baseline demonstrated significantly lower GCF TAOC and higher TOS and OSI when compared to Group IV (P < 0.001). GI in Group I at baseline negatively correlated with TAOC, whereas PPD and OSI were positively correlated (P < 0.05). Following NSPT, significant improvements were observed in the clinical parameters and in the TAOC levels in both group I and II patients (P < 0.001). In diabetics with GCP following NSPT, it was observed that OSI positively correlated (r = 0.46, P < 0.05) with CAL. In group I and II patients, TOS and OSI reduced significantly from baseline (P < 0.001). Conclusions: Based on the study results, we infer that NSPT can positively modulate the levels of OS biomarkers by restoring the oxidative imbalance. Further, the study underscores the role of periodontal therapy in decreasing oxidative burden in diabetics with periodontal disease.

Arbitrarily primed polymerase chain reaction-based identification of dystrophic onychomycosis Sandeep Kaur, Anu Gupta, Prabhjot Kaur Gill Archives of Medicine and Health Sciences 2020 8(1):47-52 Background and Objective: Onychomycosis is a fungal infection of the nails; when caused by dermatophytes, it is called as Tinea unguium. The aim was to explicate the utility of arbitrarily primed polymerase chain reaction (AP-PCR) to augment the early and accurate clinical diagnosis of dystrophic onychomycosis. Materials and Methods: The collected nail samples were divided into three portions. The first portion was explored for direct microscopic examination, the second portion was used for culturing of the nail samples on sabouraud dextrose agar media, and the third portion was used for DNA extraction followed by AP-PCR identification of dermatophytes. Results: All 48 samples with dystrophic onychomycosis were diagnosed by three methods, namely, 20% Potassium hydroxide microscopy, culture growth, and AP-PCR. With all the methods, Trichophyton rubrum was found as major causative agents for dermatophyte nail infection (60%), followed by Trichophyton mentagrophytes (23% cases). AP-PCR is a convenient method to achieve a higher dermatophyte identification rate with lesser time and shows complete concordance with conventional culture for two Trichophyton species. Conclusion: AP-PCR is a rapid, specific, and sensitive procedure for the diagnosis of nail fungal infection.

99mTc-MIP-1404 SPECT/CT for Assessment of Whole-Body Tumor Burden and Treatment Response in Patients With Biochemical Recurrence of Prostate Cancer Objective This study aims to investigate the value of 99mTc-MIP-1404 SPECT/CT for assessment of whole-body tumor burden and treatment response in patients with biochemical recurrence of prostate cancer who undergo androgen deprivation therapy (ADT) or external beam radiation therapy (EBRT). Methods A total of 125 patients with biochemical recurrence of prostate cancer underwent 99mTc-MIP-1404 SPECT/CT. All 364 prostate-specific membrane antigen (PSMA)–positive lesions in the field of view were assessed quantitatively to calculate PSMA-derived metabolic tumor parameters, including whole-body PSMA tumor volume and whole-body total lesion PSMA. These metrics were correlated with serum prostate-specific antigen (PSA) levels and Gleason scores. In a subset of 50 patients who underwent 99mTc-MIP-1404 SPECT/CT before the initiation of ADT or EBRT, TL-PSMA and SUVmax were compared with radiographic response assessment by CT based on RECIST 1.1 and to biochemical response (BR) determined by changes in serum PSA levels. Results Serum PSA levels correlated with SUVmax, whole-body PSMA tumor volume, and whole-body total lesion PSMA in patients with 1 and in those with more than 1 PSMA-positive lesion (P < 0.05). The correlations were significant for both well-differentiated (Gleason score ≤7) and poorly differentiated tumors (Gleason score ≥8) (P < 0.05). The agreement between TL-PSMA derived from SPECT and BR in patients who underwent 99mTc-MIP-1404 SPECT/CT before and after initiation of ADT was 80% (95% confidence interval [CI], 0.43–0.91; Cohen κ = 0.68; P < 0.05); in these patients, the agreement between TL-PSMA and CT was 60% (95% CI, 0.20–0.72; Cohen κ = 0.46; P < 0.05) and the agreement between BR and CT was 52% (0.07–0.61; Cohen κ = 0.34; P < 0.05). Comparable results were found for patients who underwent SPECT/CT before and after initiation of EBRT, with the strongest agreement between TL-PSMA and BR (80%; 95% CI, 0.38–0.93; Cohen κ = 0.66; P < 0.05) compared with the agreement between TL-PSMA and CT (60%; 95% CI, 0.13–0.69; Cohen κ = 0.69; P < 0.05) and between BR and CT (48%; 95% CI, 0–0.54; Cohen κ = 0.26; P = 0.11). Discordant findings between SPECT and CT were most likely due to limitations in the assessment of small lymph node metastases and bone involvement, which were detectable on SPECT but not on CT. Conclusions The results of our study show that 99mTc-MIP-1404 SPECT/CT is a promising method for the evaluation of treatment response in patients with biochemical recurrence of prostate cancer who undergo either ADT or EBRT. TL-PSMA for assessment of treatment response has the strongest correlation with serum PSA levels, superior to SUVmax-based evaluation and response assessment based on CT data and RECIST 1.1. Received for publication January 17, 2020; revision accepted April 4, 2020. Conflicts of interest and sources of funding: none declared. Correspondence to: Christian Schmidkonz, MD, Clinic of Nuclear Medicine, University of Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany. E-mail: christian.schmidkonz@uk-erlangen.de. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Rare Case of Testicular Sarcoidosis Detected on FDG PET/CT in a Patient With PUO Genitourinary sarcoidosis is an uncommon entity, and testicular sarcoidosis is even rarer. We present a case of 66-year-old man who presented to our hospital as PUO (pyrexia of unknown origin) and later diagnosed as testicular sarcoidosis with the help of FDG PET/CT. Received for publication January 12, 2020; revision accepted April 10, 2020. Conflicts of interest and sources of funding: none declared. Correspondence to: Girish Kumar Parida, MD, Department of Nuclear Medicine and PET/CT, Tata Main Hospital, Jamshedpur 831001, India. E-mail: grissh135@gmail.com. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Lenograstim-Induced Nodal Extramedullary Hematopoiesis: A Challenging Diagnosis in Lymphoma Evaluation With: 18: F-FDG PET/CT We report the case of a 23-year-old man with nodal EMH (extramedullary hematopoiesis) occurring during treatment for a stage IIA “gray-zone” lymphoma. Although it is often related to myeloproliferative bone marrow disease, benign etiologies such as lenograstim treatment after chemotherapy can also induce EMH and be responsible for false-positive 18F-FDG PET/CT examinations. In this respect, GLUT overexpression in hematopoietic lineages and macrophages of the inflammatory environment are responsible for increased 18F-FDG uptake. Histopathologic confirmation of new hypermetabolic lesions on follow-up PET/CT may be required when the new lesions do not conform with the treatment responses in the preexisting lesions. Received for publication January 30, 2020; revision accepted April 8, 2020. Conflicts of interest and sources of funding: none declared. Correspondence to: Benjamin Leroy-Freschini, MD, Department of Nuclear Medicine and Molecular Imaging, ICANS, 17, Rue Albert Calmette, BP 23025, 67033 Strasbourg Cedex, France. E-mail: b.leroy-freschini@icans.eu. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Pitfalls in the Detection of Insulinomas With Glucagon-Like Peptide-1 Receptor Imaging Purpose Physiological pancreaticoduodenal uptake of radiolabeled exendin-4 in Brunner glands of the proximal duodenum is the most common pitfall for false interpretation of glucagon-like peptide-1 receptor (GLP-1R) imaging. The aim of this study was to analyze the pancreaticoduodenal uptake in GLP-1R PET/CT and SPECT/CT images and to identify additional potential reading pitfalls in patients with suspected insulinoma. Methods A post hoc analysis of a prospective study, including 52 consecutive patients, was performed. All patients underwent 1 68Ga-exendin-4 PET/CT and 2 111In-exendin-4 SPECT/CT scans (4 and 72 hours postinjection) in a randomized crossover order. Three board-certified nuclear medicine physicians read all scans independently. They were unaware of other results. Reference standard was surgery with histopathological confirmation of an insulinoma/nesidioblastosis and normalization of blood glucose levels after surgery. Results There were no false-positive readings. However, there were a number of false-negative PET/CT and SPECT/CT readings, respectively: (1) due to false interpretation of uptake in the pancreaticoduodenal region (falsely interpreted as physiological uptake in Brunner glands instead of an insulinoma in 0.6% vs 9.0%), (2) due to ectopic insulinoma (0% vs 2.6%), (3) due to small insulinoma (1.9% vs 5.1%), (4) due to insulinoma overlap with kidneys (1.9% vs 4.5%), and (5) due to nesidioblastosis (0.6% and 1.9%). Pitfalls were identified in all GLP-1R PET/CT and SPECT/CT scans. Conclusions Peripancreatic uptake, small size of an insulinoma, insulinoma overlap with kidneys, and presence of nesidioblastosis are potential pitfalls in GLP-1R imaging, which can lead to false reading results. Received for publication February 27, 2020; revision accepted April 19, 2020. Conflicts of interest and sources of funding: The study was supported by the Swiss National Science Foundation (grant 320030-152938) and the Desirée and Niels Yde’s Foundation (grant 389-12), which had no role in study design, data collection, analysis, interpretation, or writing of the report. No conflict of interest for all authors. The study was approved by the regional scientific ethics committee, and all procedures performed in studies involving human participants were in accordance with the ethical standards of the regional scientific ethics committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. Correspondence to: Damian Wild, MD, PhD, Clinic of Radiology and Nuclear Medicine, University Hospital Basel, Petersgraben 4, 4053 Basel, Switzerland. E-mail: damian.wild@usb.ch. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Superior Vena Cava Syndrome Induced Collateral Circulation on 99mTc–Macroaggregated Albumin Lung Perfusion Scintigraphy Perfusion lung scintigraphy using SPECT/CT is one mainstay in diagnosing pulmonary embolism. Although typically almost all tracer will be accumulated in the lung capillaries, occasionally abnormal uptake can be detected. As superior vena cava syndrome leads to aberrant blood flow, tracer injected to an arm vein might partly circumvent the pulmonary capillary bed and accumulate in well-perfused anatomical structures. In this case, next to the commonly described liver enhancement, more prominent pseudo-uptake of various thoracic vertebrae was observable. However, a time-related FDG PET/CT demonstrated only the hepatic pseudo-uptake. Taken together, careful assessment of superior vena cava syndrome patient studies is highly recommended. Received for publication January 21, 2020; revision accepted April 19, 2020. Conflicts of interest and sources of funding: none declared. Correspondence to: David Kersting, MD, MSc, Department of Nuclear Medicine, University Hospital Essen, D-45147 Essen, Germany. E-mail: david.kersting@uk-essen.de. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

10-Year Clinical Experience With 18F-Choline PET/CT: An Italian Multicenter Retrospective Assessment of 3343 Patients Purpose The primary aim of this multicenter retrospective analysis is to examine the role of 18F-choline PET/CT as a diagnostic tool for staging and restaging prostate cancer (PCa) in a large population in the light of 10 years of clinical experience. A secondary aim of the study is to produce data on the predictors of a positive 18F-choline PET/CT result in the setting of PCa primaries and biochemical recurrences. Materials and Methods This multicenter retrospective cohort study is based on data collected by 9 Italian nuclear medicine departments. Between October 2008 and September 2019, 3343 men underwent 18F-choline PET/CT scans before receiving definitive treatments for a primary PCa or biochemical recurrence. Inclusion criteria were (1) histologically proven PCa (on surgical specimens or prostate biopsies from patients not treated surgically) and (2) availability of clinical and pathological data, including serum prostate specific antigen (PSA) level at the time of PET/CT scanning. Results 18F-choline PET/CT was performed in 545 cases (16.4%) for cancer staging and in 2798 (83.6%) for restaging purposes, and the result was positive in 540 (99.1%) for the former and 1993 (71.2%) for the latter. A positive PET/CT result was always associated with a high Gleason score (>7) and high PSA levels (P < 0.01). The percentage of patients with a PSA threshold less than 1.0 ng/mL for performing PET/CT was higher in the years 2014 to 2019 (n = 341, 25% of cases) than during the previous period (n = 148, 16%; in 2008–2013). When used for staging purposes, receiver operating characteristic analysis showed that PSA levels of 9.2, 16.4, and 16.6 ng/mL were the optimal cutoffs for distinguishing between positive and negative PET/CT findings for local disease, lymph node involvement, and metastasis, respectively. In the restaging setting, a PSA level of 1.27 ng/mL was the optimal cutoff for distinguishing between a positive and negative PET/CT scan. Conclusions 18F-choline PET/CT can help identify early recurrences, even in the case of low PSA levels (<1 ng/mL). Our data suggest that important improvements have been made in the interpretation of 18F-choline images and in patient selection in the last 5 years. Received for publication March 10, 2020; revision accepted April 19, 2020. Conflicts of interest and sources of funding: none declared. Ethical statement: all patients gave their informed consent to 18F-choline PET/CT examination. Correspondence to: Laura Evangelista, MD, PhD, Nuclear Medicine, Department of Medicine–DIMED, University of Padua, Via Giustiani, 2 35128 Padua, Italy. E-mail: laura.evangelista@unipd.it. Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.nuclearmed.com). Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

PET/CT-Guided Tissue Sampling in Patients With a Failed or Inconclusive CT-Guided Procedure: Outcomes and Contributing Factors Background CT-guided tissue sampling is a very effective tool. However, false-negative results are obtained when regions such as necrotic core or surrounding reactive fibrosis and inflammation are sampled. PET/CT-guided sampling can circumvent these limitations. Purpose The aim of this study was to analyze the effectiveness of PET/CT-guided sampling in patients with at least 1 instance of failed or inconclusive CT-guided procedure and factors determining the accurate sampling and complications. Methods One hundred eleven patients were prospectively included. After feasibility analysis in a diagnostic 18F-FDG PET/CT, sampling was performed in 106 patients (45 women, 61 men; mean age, 48.09 ± 15.42 years; biopsy in 80 and fine-needle aspiration cytology [FNAC] in 26 patients), using robotic arm and a lower IV injection dose of 74 to 111 MBq (2–3 mCi) 18F-FDG. In all patients, final check scans revealed needle at the target site. Using planned needle path as reference, deviations in first check scan were measured. Patient (n = 30) and respiratory motion (n = 57) were also recorded. Results Accurate lesion targeting was achieved in 81 cases (63 positive lesions, 12 confounding lesions, and 7 inadequate samples). Lesion was missed in 5 instances, and blood/necrotic tissue sampled in 19. Overall 18F-FDG–avid lesions were accurately targeted in 77.36% of patients (86.25% [biopsy] + 50% [FNAC]). Significant variables affecting targeting were needle gauge, deviation from intended entry point, procedure duration, procedure type, and patient movement. Using binomial regression, the significant parameters were procedure type (biopsy vs FNAC; odds ratio [OR], 5.916; P = 0.002), patient movement (OR, 0.275; P = 0.023), and procedure duration (OR, 1.195; P = 0.011). Overall complication rate was 21.70%, with 4.71% major complications. It was dependent on target depth (mean depth, 69.74 ± 20.29 mm [complications] vs 47.18 ± 22.60 mm; P < 0.001). Positive correlation was seen between the target depth and distance of needle from the intended target (Spearman ρ = 0.307; P = 0.001). In 28 procedures, the physician was asked to wear a pocket dosimeter, who received a mean dose of 2.52 (SD, 3.10) μSv. Conclusions PET/CT-guided sampling should be considered where CT-guided biopsy has failed or is inconclusive. The outcome is impacted by needle gauge and patient movement, and complication rate is dependent on target depth. Received for publication November 22, 2019; revision accepted April 19, 2020. The study was performed done in All India Institute of Medical Sciences, New Delhi, India. Conflicts of interest and sources of funding: none declared. Rakesh Kumar and Anshul Sharma contributed equally to this work. Correspondence to: Anshul Sharma, MD, Department of Nuclear Medicine, All India Institute of Medical Sciences, Sri Aurobindo Marg, Ansari Nagar, Ansari Nagar East, New Delhi, India 110029. E-mail: anshul.aiims@gmail.com. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional committee (approval no. IESC/T-137/01.04.2011) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent (with translation in patients’ native language) was taken from every patient. This consent form and its translation were approved by the institutional ethical committee before the initiation of the study. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

A Case of Localized Malignant Peritoneal Mesothelioma With Lung Cancer Detected by 18F-FDG PET/CT A 62-year-old woman was referred for cough and lower abdominal pain. 18F-FDG PET/CT showed strong uptake not only in the left lung mass and hilar and mediastinal lymph nodes, but also a huge lower abdominal mass. All lesions were initially thought to be multiple metastases because bronchial biopsy of the lung mass showed poorly differentiated adenocarcinoma. However, the abdominal mass was found to be malignant peritoneal mesothelioma after surgical resection. It was difficult to diagnose this case correctly before resection because localized malignant peritoneal mesothelioma is rare. Received for publication February 5, 2020; revision accepted April 18, 2020. Conflicts of interest and sources of funding: none declared. Correspondence to: Shotaro Kobayashi Shimizu, MD, 2-10-39 Shibata, Kita-Ku, Osaka 530-0012, Japan. E-mail: shotaro.kb.shimizu@gmail.com. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Prominent Bone Marrow Metastases Without Concurrent Intra-Chest Metastasis in a Case of Cardiac Angiosarcoma Primary cardiac angiosarcoma is rare and often advances by dissemination. Lungs are the most common metastatic sites, especially when the tumor originates in the right side of the heart. Bone metastases from cardiac angiosarcoma very rarely occur without concurrent pulmonary metastases. We report a case of cardiac angiosarcoma having prominent bone metastases without concurrent pulmonary lesions, as demonstrated by FDG PET/CT scan. Conflicts of interest and sources of funding: none declared. Received for publication February 28, 2020; revision accepted April 18, 2020. Correspondence to: Xiaohong Ou, MD, Department of Nuclear Medicine, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu 610041, Sichuan, People’s Republic of China. E-mail: Xuqinmao@126.com. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Widespread Skin Infiltration of Leukemia Cutis on 18F-FDG PET/CT A 67-year-old man experienced multiple cutaneous nodules for 3 weeks. His initial skin biopsy only showed local inflammation. However, after a 2-week anti-inflammation therapy, the skin manifestations were not improved while the leukocyte count gradually increased. FDG PET/CT revealed widespread cutaneous and subcutaneous hypermetabolic lesions in many parts of the body, and heterogeneously increased uptakes in the bone marrow. Bone marrow biopsy and second skin biopsy were performed. Pathological examination from both specimen demonstrated acute monocytic leukemia. Received for publication February 25, 2020; revision accepted April 22, 2020. Conflicts of interest and sources of funding: none declared. Correspondence to: Weibing Miao, MD, PhD, Department of Nuclear Medicine, First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Rd, Fuzhou, 350005, Fujian, China. E-mail: miaoweibing@126.com. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Hearing Preservation Outcomes With Standard Length Electrodes in Adult Cochlear Implantation and the Uptake of Electroacoustic Stimulation Background: Cochlear implantation with preservation of residual low-frequency hearing enables patients to utilize acoustic and electrical stimulation. It is widely accepted that preservation of residual low-frequency hearing is beneficial in both background noise and for music appreciation. The extent to which patients may benefit is not fully understood, but the importance of these concepts is reflected in electrode design developments and also refinement of surgical technique. Greater understanding is needed around factors that may affect hearing preservation. This study reports experience in adults using standard length cochlear implant arrays. Objective: The study reviews hearing preservation outcomes using the HEARRING GROUP method for factors such as gender, electrode type, insertion depth, laterality, preoperative hearing level, and time between surgery and audiogram. Furthermore, the study reviews rates of electroacoustic stimulation use in those with postoperative functional residual low-frequency hearing. Methodology: Retrospective case series. Inclusion criteria: preoperative ≤ 85 dB HL at 250 Hz and aged ≥ 18 years. The hearing preservation percentages were calculated using the HEARRING group formula S=[1 − ((PTApost − PTApre)/(PTAmax − PTApre))*100]%. . Preservation of > 75% was considered complete, 25 to 75% partial, and 1 to 25% minimal. Standardized operative technique with facial recess approach, posterior tympanotomy, and minimally traumatic round window insertion was performed for each implant. Results: Fifty-three implantations in 52 patients met the inclusion criteria. The mean age at implantation was 55.5 years. The average time since the last audiogram was 10 months. The mean average total pre and postoperative pure-tone averages were 92.4 dB, 99.2 dB, respectively, using minimum reporting standards for adult cochlear Implant (CI). Thirty percent demonstrated complete hearing preservation, 35.8% partial hearing preservation, and 20.8% minimal hearing preservation. Overall, mean hearing preservation was 52.9%. Sex, age at implantation, insertion depth, lateral versus perimodiolar electrode, and preoperative hearing level did not statistically significantly affect rates of hearing preservation in our study. There was a statistically significant deterioration in hearing preservation outcomes difference at 3 months compared with 12 months postoperatively. Only two patients within our study out of 17 with functional postoperative hearing went on to use electroacoustic stimulation. Conclusion: Hearing preservation varies between patients and postoperative outcomes are difficult to predict. This study adds to existing literature in terms of likelihood of hearing preservation following cochlear implantation. In turn, this improves our ability to counsel patients as to the chances of preserving residual low-frequency hearing postoperatively and their ability to use electroacoustic stimulation. Address correspondence and reprint requests to Laura Harrison, F.R.C.S., B.M.B.S., B.Medsci., UCL Ear Institute, 332 Gray's Inn Road, London WC1X 8DA, UK; E-mail: lauraharrison707@gmail.com The authors disclose no conflicts of interest. Copyright © 2020 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

A Structural Analysis of Tympanic Compartments of the Middle Ear in Patients With Down's Syndrome: A Temporal Bone Study Hypothesis: There may be findings peculiar to the temporal bones of children with Down's syndrome (DS). The purpose of this study is to investigate the temporal bone histopathology of the children with DS. Background: Otitis media with effusion is a highly prevalent condition with DS. Knowledge of the volume of the tympanic compartments and the area of the tympanic isthmus might be important to find out the pathogenesis of highly prevalent otitis media with effusion in those patients. Methods: We compared the volume of the epitympanum, mesotympanum, and the areas of the tympanic isthmus and tympanic orifice of eustachian tube in temporal bones from patients with DS. We also investigated the eustachian tube histopathologically. Results: The mean volume of the epitympanum and the mesotympanum was significantly smaller in the DS group than the control group. We found no significant difference in the mean diameter of the protympanic opening and tympanic orifice between the two groups. The mean narrowest area of the aerated and bony tympanic isthmus also was not significantly different between the two groups. An immature development of eustachian tube and cartilage was seen. We found mesenchyme remaining at the epitympanum and/or mesotympanum in all specimens in the DS group, and in five specimens in the control group. Conclusion: In the presence of the small middle ear, poorly developed eustachian tube, and tensor muscle, a vicious circle occurs, making otitis media with effusion difficult to resolve. Address correspondence and reprint requests to Sebahattin Cureoglu, M.D., Ph.D., Department of Otolaryngology—Head and Neck Surgery, University of Minnesota, Lions Research Building, Room 210, Mayo Mail Code 2873, 2001 6th Street SE, Minneapolis, MN 55455; E-mail: cureo003@umn.edu This project was funded by the International Hearing Foundation; the 5 M Lions International; and the Starkey Foundation. The authors disclose no conflicts of interest. Copyright © 2020 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Insertion Depth for Optimized Positioning of Precurved Cochlear Implant Electrodes Hypothesis: Generic guidelines for insertion depth of precurved electrodes are suboptimal for many individuals. Background: Insertion depths that are too shallow result in decreased cochlear coverage, and ones that are too deep lift electrodes away from the modiolus and degrade the electro-neural interface. Guidelines for insertion depth are generically applied to all individuals using insertion depth markers on the array that can be referenced against anatomical landmarks. Methods: To normalize our measurements, we determined the optimal position and insertion vector where a precurved array best fits the cochlea for each patient in an IRB-approved, N = 131 subject CT database. The distances from the most basal electrode on an optimally placed array to anatomical landmarks, including the round window (RW) and facial recess (FR), was measured for all patients. Results: The standard deviations of the distance from the most basal electrode to the FR and RW are 0.65 mm and 0.26 mm, respectively. Owing to the high variability in FR distance, using the FR as a landmark to determine insertion depth results in >0.5 mm difference with ideal depth in 44% of cases. Alignment of either of the two most proximal RW markers with the RW would result in over-insertion failures for >80% of cases, whereas the use of the third, most medial marker would result in under-insertion in only 19% of cases. Conclusions: Normalized measurements using the optimized insertion vector show low variance in distance from the basal electrode position to the RW, thereby suggesting it as a better landmark for determining insertion depth than the FR. Address correspondence and reprint requests to Rueben A. Banalagay, 2301 Vanderbilt Pl., VU Station B #351679, Nashville, TN 37235; E-mail: rueben.a.banalagay@vanderbilt.edu The content is solely the responsibility of the authors and does not necessarily represent the official views of this institute. R.F.L. is a consultant with Advanced Bionics, Johnson&Johnson, Ototronix, and Medel. This research was supported in part by grants R01DC014037, R01DC008408, and R01DC014462 from the National Institute on Deafness and Other Communication Disorders. IRB approval number 090155. The authors disclose no conflicts of interest. Supplemental digital content is available in the text. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://journals.lww.com/otology-neurotology). Copyright © 2020 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Potential Ototopical Antiseptics for the Treatment of Active Chronic Otitis Media: An In-Vitro Evaluation Objectives: Primary: to compare, in vitro, the antimicrobial activity of different antiseptic agents versus quinolone drops, against the common organisms of chronic otitis media. Secondary: to examine the possible role of pH on the antimicrobial activity of the antiseptic solutions. Methods: Three antiseptic powders (boric acid; iodine; and a 1:1 combination of these two) and four solutions (2% boric acid; 2% acetic acid; 3.25% aluminum acetate; and 5% povidone iodine) were tested against five bacteria and two fungi common in chronic otitis media, using both agar plates and the modified broth dilution method. These results were compared with the antimicrobial activity of quinolone drops. The potential role of pH of solutions was tested by reducing the acidity of the agents and repeating the broth dilution. Results: Of the powders, iodine, and iodine/boric acid combined, are very effective against all organisms. Boric acid powder showed moderate effectiveness against all organisms. All solutions performed poorly on the agar plates. 5% povidone iodine has good effectivity when tested with the broth dilution method. 3.25% aluminum acetate had the best activity against Pseudomonas aeruginosa. Conclusion: Boric acid powder and 5% povidone iodine solution show promise for clinical use. Boric acid powder has proven clinical effectiveness. 5% povidone iodine requires further clinical research. Although very effective in vitro, iodine powder is toxic to tissues and cannot be recommended for clinical use. The pH of solutions does not seem to play a significant role in their antimicrobial activity in vitro. Address correspondence and reprint requests to Andries Francois van Straten, F.C.O.R.L. (SA), Faculty of Medicine and Health Sciences, Room 5054, Clinical Building, Building 91, Francie van Zijl Drive, Tygerberg, 7505 Cape Town, South Africa; E-mail: vanstraten.andre@gmail.com Address for reprints: Same as for correspondence. The authors disclose no conflicts of interest. Copyright © 2020 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Current Management of CPAP After Otologic and Neurotologic Surgery Background: Obstructive sleep apnea is a highly prevalent disorder often treated with continuous positive airway pressure (CPAP). CPAP transmits high pressures through the Eustachian tube, and has significant implications for patients undergoing surgery of the middle ear, inner ear, and lateral skull base. In such patients, nothing is known regarding the likelihood of surgical complications with CPAP use, or medical complications with its cessation. No consensus or guidelines exist for postoperative management of this vitally important but potentially hazardous therapy. Objective: To gain an understanding of the current state of practice with regards to postoperative CPAP management in patients undergoing middle ear, stapes, cochlear implant, and lateral skull base surgeries. Methods: An electronic survey was sent to all members of the American Neurotology Society via email. Results: The survey was completed by 54 neurotologists. Duration of postoperative CPAP limitation had similar distribution for surgery of the middle ear, stapes, and skull base: fewer surgeons recommend immediate use, with more advising ≤1 week and ≥2 week abstinence. For cochlear implantation, immediate use is most commonly advocated. The rationale for restricting postoperative CPAP use varied by surgery type. Subgroup analysis showed no variations by region; however, surgeons with >15 years of experience tend to advocate for earlier return to CPAP than those with less experience. Conclusion: Current neurotology practice varies widely concerning CPAP management after otologic and neurotologic surgeries, both with regard to duration of CPAP abstinence and in rationale for its limitation. Address correspondence and reprint requests to Nathan D. Cass, M.D., University of Michigan Medical School, Ann Arbor, MI 48109; E-mail: ncass@med.umich.edu No sources of funding were received for this study. S.C.B. received research funding from Oticon Medical and Cochlear Corporation, honorarium from Acclarent. The authors disclose no conflicts of interest. Supplemental digital content is available in the text. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://journals.lww.com/otology-neurotology). Copyright © 2020 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Quality of Otology and Neurotology Research in Otolaryngology Journals Objective: To identify trends in the quality of otology studies published in general otolaryngology journals over a 20-year period. Study Design: Retrospective analysis. Methods: Otologic and neurotologic papers from 1997, 2007, and 2017 were identified in the three general otolaryngology journals with the highest Eigenfactor scores: the Laryngoscope, European Archives of Otorhinolaryngology, and Otolaryngology–Head and Neck Surgery. The studies were reviewed and assigned level of evidence (LoE) based on standards set by the Centres for Evidence Based Medicine (CEBM). One-way analysis of variance were calculated with a 95% bootstrap sensitivity analysis performed. Results: A total of 786 otology articles were reviewed for level of evidence, of which 557 (70.8%) were original, clinical research, eligible for LoE assignation. Total publications increased for each year in all three journals. Both the absolute number and proportion of high evidence studies (level of evidence 1 and 2) increased with respect to time in all three journals. Lower evidence studies (level of evidence 3, 4, or 5) made up 66.8% of total publications in 2017. There was a reduction in average level of evidence (towards higher quality evidence) by 0.431 units from 1997 to 2017 (Diff = –0.431 between 1997 and 2017, p < 0.001). There was no significant difference in rate of change of level of evidence between 1997 and 2007 and 2007 and 2017 (0.033, p = 0.864). Conclusion: Over a 20-year period the number of total publications increased with time. The majority of otology publications in 2017 were lower evidence studies, though significant increases in the number and proportion of high evidence studies in general otolaryngology journals were observed throughout the study period. Address correspondence and reprint requests to Daniel H. Coelho, M.D., Otolaryngology–Head & Neck Surgery, Virginia Commonwealth University School of Medicine, PO Box 980146, Richmond, VA 23298-0146; E-mail: daniel.coelho@vcuhealth.org Funding: Statistical analysis was supported by the Biostatistics Consulting Laboratory, which is partially supported by Award No. UL1TR002649 from the National Institutes of Health's National Center for Advancing Translational Science. Financial Disclosures: None. The authors disclose no conflicts of interest. Copyright © 2020 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

The National Landscape of Acute Mastoiditis: Analysis of the Nationwide Readmissions Database Objective: To determine risk factors for readmission, prolonged length of stay, and discharge to a rehabilitation facility in patients with acute mastoiditis. Trends in treatment and complication rates were also examined. Study Design: Retrospective cohort study. Setting: Nationwide Readmissions Database (2013, 2014). Patients: Pediatric and adult patients in the Nationwide Readmissions Database with a primary diagnosis of acute mastoiditis. Interventions: Medical treatment, surgical intervention. Outcome Measures: Rates of and risk factors for readmission, prolonged length of stay, and discharge to a rehabilitation facility. Procedure and complication rates were also examined. Results: Four thousand two hundred ninety-five pediatric and adult admissions for acute mastoiditis were analyzed. The overall rates of readmission, prolonged length of stay, and discharge to a rehabilitation facility were 17.0, 10.4, and 10.2%, respectively. Children 4 to 17 years of age had the highest rates of intracranial complications, and children ≤3 years were most likely to undergo operative intervention. Any procedure was performed in 31.2% of cases, and undergoing myringotomy or mastoidectomy was associated with lower rates of readmission but higher rates of prolonged length of stay. Those with intracranial complications and subperiosteal abscesses had the highest surgical intervention rates. Conclusions: Readmission, prolonged length of stay, and discharge to a rehabilitation facility are common in patients with acute mastoiditis with various sociodemographic and disease-related risk factors. While once a primarily surgical disease, a minority of patients in our cohort underwent procedures. Undergoing a surgical procedure was protective against readmission but a risk factor for prolonged length of stay. Address correspondence and reprint requests to Zachary G. Schwam, M.D., Mount Sinai Department of Otolaryngology—Head and Neck Surgery, 1 Gustave L. Levy Place, Box 1189, New York, NY 10029; E-mail: zachary.schwam@mountsinai.org G.B.W. is on the surgical advisory board for Oticon and Med-El. He consults for Med-El, cochlear, and Advanced Bionics. M.K.C. has received travel grants from Med-El, Cochlear, Stryker, educational research grants from Advanced Bionics, and has done clinical research with Advanced Bionics, Cochlear, and Otonomy. The abstract for this manuscript was selected as a poster presentation at the 2019 American Otological Society Meeting in Austin, Texas, May 3 to 5, 2019. The authors disclose no conflicts of interest. Supplemental digital content is available in the text. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://journals.lww.com/otology-neurotology). Copyright © 2020 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

A Position Paper on Systematic and Meta-Analysis Reviews No abstract available

Association of Speech Recognition Thresholds With Brain Volumes and White Matter Microstructure: The Rotterdam Study Objectives: Brain volumetric declines may underlie the association between hearing loss and dementia. While much is known about the peripheral auditory function and brain volumetric declines, poorer central auditory speech processing may also be associated with decreases in brain volumes. Methods: Central auditory speech processing, measured by the speech recognition threshold (SRT) from the Digits-in-Noise task, and neuroimaging assessments (structural magnetic resonance imaging [MRI] and fractional anisotropy and mean diffusivity from diffusion tensor imaging), were assessed cross-sectionally in 2,368 Rotterdam Study participants aged 51.8 to 97.8 years. SRTs were defined continuously and categorically by degrees of auditory performance (normal, insufficient, and poor). Brain volumes from structural MRI were assessed on a global and lobar level, as well as for specific dementia-related structures (hippocampus, entorhinal cortex, parahippocampal gyrus). Multivariable linear regression models adjusted by age, age-squared, sex, educational level, alcohol consumption, intracranial volume (MRI only), cardiovascular risk factors (hypertension, diabetes, obesity, current smoking), and pure-tone average were used to determine associations between SRT and brain structure. Results: Poorer central auditory speech processing was associated with larger parietal lobe volume (difference in mL per dB increase= 0.24, 95% CI: 0.05, 0.42), but not with diffusion tensor imaging measures. Degrees of auditory performance were not associated with brain volumes and white matter microstructure. Conclusions: Central auditory speech processing in the presence of both vascular burden and pure-tone average may not be related to brain volumes and white matter microstructure. Longitudinal follow-up is needed to explore these relationships thoroughly. Address correspondence and reprint requests to André Goedegebure, Ph.D., Department of Otorhinolaryngology, Head and Neck Surgery, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands; E-mail: a.goedegebure@erasmusmc.nl N.M.A. wrote the manuscript and analyzed the data. All authors discussed the results and implications and commented on the manuscript at all stages, and they were responsible for the study design. The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University, Rotterdam, The Netherlands; the Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Netherlands Genomics Initiative; the Ministry of Education, Culture, and Science; the Ministry of Health, Welfare, and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. Hearing-related research within the Rotterdam Study is partly funded by The Heinsius Houbolt Foundation. Separately, N.M.A. is supported by the Intramural Research Program at the National Institute on Aging, Baltimore, Maryland (N.M.A. received funding). F.R.L., A.G., and P.H.C. report funding by Cochlear Ltd. The authors disclose no conflicts of interest. Supplemental digital content is available in the text. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://journals.lww.com/otology-neurotology). Copyright © 2020 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Effect of Vestibular Schwannoma Size and Nerve of Origin on Posterior External Auditory Canal Sensation: A Prospective Observational Study Objective: Posterior external auditory canal (EAC) hypesthesia (Hitselberger's sign) has been previously described to occur in all vestibular schwannomas (1966) but has not been studied since. We hypothesized that sensory loss may be related to tumor size and sought to determine if this clinical sign could predict preoperative characteristics of vestibular schwannomas, intraoperative findings, and/or surgical outcomes. Study Design: Prospective observational study. Setting: Tertiary referral center. Patients: Twenty-five consecutive patients who underwent surgery for vestibular schwannoma. Intervention: Patients were tested for the presence of EAC hypesthesia or anesthesia. Main Outcome Measures: Preoperative, intraoperative, and postoperative findings were recorded, including facial nerve function, hearing function, tumor size, tumor nerve of origin, and extent of resection. Results: Twelve patients (48%) demonstrated either posterior EAC hypesthesia (11 patients) or anesthesia (1 patient). Sensory loss was a significant predictor of size (tumor maximal diameter) (p = 0.004). Median tumor diameter was 1.7 cm in the cohort with intact sensation versus 2.9 cm in the cohort with sensory loss. Patients with sensory loss were also significantly more likely to be associated with a superior vestibular nerve origin tumor (p = 0.01). Preoperative sensory loss did not significantly predict postoperative facial outcome (p = 0.10). Conclusion: Neurological exam findings may be overlooked in the workup of brain tumors. Posterior EAC hypesthesia is a predictor of tumor size and superior vestibular nerve origin. These findings may have implications for patient selection, particularly with the middle cranial fossa approach. Furthermore, given this relationship with tumor size, this clinical biomarker should be studied as a potential predictor of tumor growth. Address correspondence and reprint requests to Gautam U. Mehta, M.D., Division of Neurosurgery, House Institute, 2100 West 3rd Street, Ste 111, Los Angeles, CA 90057; E-mail: gmehta39@gmail.com The authors disclose no conflicts of interest. Copyright © 2020 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company