Κυριακή 4 Σεπτεμβρίου 2022

Outcomes of Partial Oral Antibiotic Treatment for Complicated S. aureus Bacteremia in People Who Inject Drugs

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Abstract
Background
Staphylococcus aureus represents the leading cause of complicated bloodstream infections among persons who inject drugs (PWID). Standard of care (SOC) intravenous (IV) antibiotics result in high rates of treatment success, but are not feasible for some PWID. Transition to oral antibiotics may represent an alternative treatment option.
Methods
We evaluated all adult patients with a history of injection d rug use hospitalized from 1/2016 through 12/2021 with complicated S. aureus bloodstream infections, including infective endocarditis, epidural abscess, vertebral osteomyelitis, and septic arthritis. Patients were compared by antibiotic treatment (SOC IV antibiotics, incomplete IV therapy, or transition from initial IV to partial oral) using the primary composite endpoint of death or readmission due to microbiologic failure within 90 days of discharge.
Results
Patients who received oral antibiotics after an incomplete IV antibiotic course were significantly less likely to experience microbiologic failure or death than patients discharged without oral antibiotics (p < 0.001). There was no significant difference in microbiologic failure rates when comparing patients who were discharged on partial oral antibiotics after receiving at least 10 days of IV antibiotics to SOC regimens (P > 0.9).
Conclusion
Discharge of P WID with partially treated complicated S. aureus bacteremias without oral antibiotics results in high rates of morbidity and should be avoided. For PWID hospitalized with complicated S. aureus bacteremias who have received at least 10 days of effective IV antibiotic therapy after clearance of bacteremia, transition to oral antibiotics with outpatient support represents a potential alternative if the patient does not desire SOC IV antibiotic therapy.
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Deformation of implant retaining screws—Study with stereoscopic microscopy and microCT

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Abstract

Background

The prosthetic screw fixes the prostheses to the implants. Upon osteointegration, the untightening of the prosthetic screw is the most common problem in oral rehabilitation with implants.

Objective

To study the deformation of the implant retaining hexagonal screw head.

Methods

This investigation used two methods for evaluating the screw head's area of deformation (mm2): a stereoscopic microscopy and micro computed tomography (microCT). For stereoscopic microscopy, 16 titanium alloy (T) and 16 titanium gold-plated alloy (G) screws of the Zimmer Biomet™ brand were used, divided into eight groups: group 0 (control group), groups T1 and G1 (screws tightened 10 times to 20 Ncm), the groups T2 and G2 (screws tightened 20 times to 20 Ncm) and the groups T3 and G3 (screws tightened 10 times to 30 Ncm). In the study with microCT, one screw was randomly chosen from each of the groups described above to perform the scanning by microCT.

Results

When comparing the type of screw material using stereoscopic microscopy, no statistically significant differences were found (p > 0.05). Contrarily, different number of successive grips and different torque value showed statistically significant differences in the head section of the retaining screws (p < 0.05). The observation by microCT showed the torque applied is crucial to the head deformation in titanium screws. In gold-plated screws the successive tightening appears to be pivotal.

Conclusion

Titanium and gold screws tend to behave similarly. By increasing the tightening cycles and the torque values of protocols greater levels of deformations can be expected. In general, microCT data showed better results for gold-plated titanium alloy.

Clinical Significance

To control severe screw head deformation and the impossibility of untightening the implant's restoration, clinicians should avoid extreme torque values and prevent surpassing 10 tightening cycles.
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Body Dysmorphic Disorder in Adult Patients With an Orofacial Cleft: An Unseen Psychological Burden

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Body Dysmorphic Disorder in Adult Patients With an Orofacial Cleft: An Unseen Psychological Burden

Adults with orofacial clefts are at a higher risk of developing conditions associated with appearance. In this study, we examine the role that orofacial clefts have on the incidence on Body Dysmorphic Disorder in a US cohort.


Objectives

Facial dysmorphic disorder (FDD), a variant of body dysmorphic disorder, occurs when individuals are preoccupied with perceived defects in their facial appearance. Cleft lip and/or palate (CL/P) requires many clinical interventions and has significant psychological impacts on a patient's perception of appearance. This study identified psychological burdens related to living as an adult with CL/P and characterizes the degree of FDD symptoms in an adult craniofacial population.

Methods

This was a prospective, single-center, cross-sectional case–control study using semi-structured interviews and symptom assessments at a university-based craniofacial center. Patients without CL/P undergoing non-cosmetic facial surgery were recruited as controls (n = 20). Patients with an orofacial cleft (n = 30) were recruited from medical and dental providers at the University of North Carolina. Body Dysmorphic Disorder-Yale Brown Obsessive Compulsive Scale (BBD-YBOCS) scores were collected from a control population and patients with CL/P to assess FDD severity.

Results

Demographic factors such age, biological sex, and ethnicity had no significant impact on FDD symptom scores. Patient with CL/P were more likely to have significant FDD symptoms (BDD-YBOCS greater than 16) than patients without CL/P (OR 10.5, CI95 2.7–41.1), and had a mean difference in FDD symptoms scores of 10.04 (p < 0.0001; CI95 5.5–14.6). Patients with CL/P seen by a mental health provider in the past 3 months had 3-fold lower overall FDD symptom scores (OR 0.081; CI95 0.0085–0.77).

Conclusions

Adults with CL/P would benefit from treatment for cleft-specific needs and psychological support as they face unique stressors related to their appearance, including an increase in FDD-associated symptoms. This study emphasizes the importance of recognizing psychological symptoms and providing ongoing multidisciplinary care to adults with CL/P.

Level of Evidence

3; Individual case–control study Laryngoscope, 2022
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Computer Simulation of the Electrical Stimulation of the Human Vestibular System: Effects of the Reactive Component of Impedance on Voltage Waveform and Nerve Selectivity

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AbstractThe vestibular system is responsible for our sense of balance and spatial orientation. Recent studies have shown the possibility of partially restoring the function of this system using vestibular implants. Electrical modeling is a valuable tool in assisting the development of these implants by analyzing stimulation effects. However, previous modeling approaches of the vestibular system assumed quasi-static conditions. In this work, an extended modeling approach is presented that considers the reactive component of impedance and the electrode-tissue interface and their effects are investigated in a 3D human vestibular computer model. The Fourier finite element method was employed considering the frequency-dependent electrical properties of the different tissues. The electrode-tissu...
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Intra‐pulpal connective tissue formation and the advanced carious lesion: Is chondrogenesis and heterotopic ossification a response to pulpal inflammation?

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Abstract

Aims

a) To investigate both the formation of dense connective tissue within the dental pulp, and its association with pulpal inflammation in teeth with advanced carious lesions; and b) to investigate in vitro whether inflammation affects the expression of markers related to chondrogenesis/ osteogenesis in pulp cells.

Materials and methods

Radiology and Histology: Forty-six teeth with advanced carious lesions were radiographically investigated for intra-pulpal radiodense structures. Specimens were processed for histology and stained with haemotoxylin/eosin and proteoglycan-specific stains. The intrapulpal connective tissue was scored as pulp stones or ectopic connective tissue. Cell culture: pulpal cells from human third molars (n=5) were cultured in chondrogenic medium +/- TLR2/4 agonists. Expression of the genes IL6, TLR2/4, SOX9, COL1A1, COL2A1, TGFB1, RUNX2 and ALPL was assessed by qPCR. Proteoglycan content within cultures was assessed spectrophotometrically.

Results

Radio-dense structures were discovered in about half of all pulps. They were associated with ectopic connective tissue (χ2=8.932, P=0.004, OR=6.80, 95% CI: [1.84, 25.19]), and with pulp stones (χ2=12.274, df=1, P<0.001, OR=22.167, 95% CI: [2.57, 200.00]). The morphology of the ectopic tissue resembled cartilage and was associated with inflammatory infiltration of the pulp (χ2=10.148, P=0.002, OR=17.77, 95% CI: [2.05, 154.21]). After continuous stimulation of cultured cells with TLR2/4 agonists, the expression of two inflammatory markers increased: IL6 at days 7 (P=0.020) and 14 (P=0.008); TLR2 at days 7 (P=0.023) and 14 (P=0.009). Similarly, expression of chondrogenic markers decreased: SOX9 at day 14 (P=0.035) and TGFB1 at day 7 (P=0.004), and the osteogenic marker COL1A1 at day 7 (P=0.007). Proteoglycan content did not differ between unstimulated and stimulated cells.

Conclusions

Ectopic connective tissue resembling cartilage can form in teeth affected by advanced carious lesions. This tissue type is radiographically visible and is associated with inflammatory infiltration of the pulp. Although TLR2/4 agonists led to an inflammatory response in cell culture of pulp cells, the effect on the expression of osteogenic/chondrogenic markers was limited, suggesting that immune cells are needed for connective tissue formation in vivo.
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Key mutations on spike protein altering ACE2 receptor utilization and potentially expanding host range of emerging SARS‐CoV‐2 variants

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Abstract

Increasing evidence supports inter-species transmission of SARS-CoV-2 variants from human to domestic or wild animals during the ongoing COVID-19 pandemic, which is posing great challenges to epidemic control. Clarifying the host range of emerging SARS-CoV-2 variants will provide instructive information for the containment of viral spillover. The spike protein (S) of SARS-CoV-2 is the key determinant of receptor utilization, and therefore amino acid mutations on S will probably alter viral host range. Here, in order to evaluate the impact of S mutations, we constructed 20 Hela cell lines stably expressing ACE2 orthologs from different animals, and prepared 27 pseudotyped SARS-CoV-2 carrying different spike mutants, among which 20 bear single mutation and the other 7 were cloned from emerging SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Lambda (B.1.429) and Mu (B.1.621). Using pseudoviral reporter assa y, we identified that the substitutions of T478I and N501Y enabled the pseudovirus to utilize chicken ACE2, indicating potential infectivity to avian species. Furthermore, the S mutants of real SARS-CoV-2 variants comprising N501Y showed significantly acquired abilities to infect cells expressing mouse ACE2, indicating a critical role of N501Y in expanding SARS-CoV-2 host range. In addition, A262S and T478I significantly enhanced the utilization of various mammals ACE2. In summary, our results indicated that T478I and N501Y substitutions were two S mutations important for receptor adaption of SARS-CoV-2, potentially contributing to the spillover of the virus to many other animal hosts. Therefore, more attention should be paid to SARS-CoV-2 variants with these two mutations.

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Robotic lateral oropharyngectomy following diagnostic tonsillectomy is oncologically safe in patients with human papillomavirus‐related squamous cell cancer: Long‐term results

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Abstract

Introduction

To report the long-term oncological and functional outcomes of en bloc TORS lateral oropharyngectomy to address the close/involved margin following diagnostic tonsillectomy in HPV-related SCC of unknown primary.

Material and methods

A single tertiary center observational cohort over a 4-year period. Primary outcome measures were disease-specific survival (DSS), overall survival (OS), and PSS NOD (Performance Status Scale-Normalcy of Diet) scores.

Results

TORS specimens did not evidence residual carcinoma in 93% of patients. Of 14 patients, 50% received surgery alone (median follow-up 57 months; range 46–96), the remainder surgery and adjuvant therapy (median follow-up of 58 months; range 51–69) with 100% DSS, OS and no deterioration of PSS NOD scores.

Conclusions

Long-term oncological outcomes confirm TORS lateral oropharyngectomy alone is an oncologically safe treatment. Due consideration of this approach is warranted to mitigate against the morbidity of adjuvant radiotherapy treatment in this group of patients.
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Should Linezolid Replace Clindamycin as the Adjunctive Antimicrobial of Choice in Group A Streptococcal Necrotizing Soft Tissue Infection and Toxic Shock Syndrome? A Focused Debate

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Abstract
Group A Streptococcus (GAS) necrotizing soft tissue infections and toxic shock syndrome remain high-mortality conditions. In vitro and animal model data, as well as multiple observational studies, suggest adjunctive clindamycin (i.e., given with a beta-lactam) reduces invasive GAS infection mortality by inhibiting exotoxin production. Unfortunately, clindamycin resistance in GAS has been rapidly increasing in the United States (US) since the mid-2010s, though the clinical significance of this remains unclear. Linezolid is a promising alternative adjunctive agent to which US GAS isolates remain near-universally susceptible, with a similar mechanism of action and similar in vitro evidence of GAS virulence factor attenuation. However, the clinical data supporting linezolid's value in severe GAS infections are far more limited. Here, the authors review the data and reasoning behind a general preference for clindamycin or linezolid in a focused, pro-con debate format.
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Estimating Waning of Vaccine Effectiveness: a Simulation Study

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Abstract
Background
Developing accurate and reliable methods to estimate vaccine protection is a key goal in immunology and public health. While several statistical methods have been proposed, their potential inaccuracy in capturing fast intra-seasonal waning of vaccine-induced protection needs to be rigorously investigated.
Methods
To compare statistical methods for vaccine effectiveness (VE) estimation, we generated simulated data using a multiscale agent-base d model of an epidemic with an acute viral infection and differing extents of VE waning. We apply a previously proposed framework for VE measures based on the observational data richness to assess changes of vaccine-induced protection over time.
Results
While VE measures based on hard-to-collect information (e.g. the exact timing of exposures) were accurate, usually VE studies rely on time-to-infection data and the Cox proportional hazard model. We found that its extension utilizing scaled Schoenfeld residuals, previously proposed for capturing VE waning, was unreliable in capturing both the degree of waning and its functional form and identified the mathematical factors contributing to this unreliability. We showed that partitioning time and including a time-vaccine interaction term in the Cox model significantly improved estimation of VE waning, even in the case of dramatic, rapid waning. We also proposed how to optimize the partitioning scheme.
Conclusions
While appropriate for rejecting the null hypothesis of no waning, scaled Schoenfeld residuals are unreliable for estimating the degree of waning. We propose a Cox-model-based method with a time-vaccine interaction term and further optimization of partitioning time. These findings may guide future analysis of VE waning data.
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Native and activated antithrombin inhibits TMPRSS2 activity and SARS‐CoV‐2 infection

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Abstract

Host cell proteases such as TMPRSS2 are critical determinants of SARS-CoV-2 tropism and pathogenesis. Here, we show that antithrombin (AT), an endogenous serine protease inhibitor regulating coagulation, is a broad-spectrum inhibitor of coronavirus infection. Molecular docking and enzyme activity assays demonstrate that AT binds and inhibits TMPRSS2, a serine protease that primes the Spike proteins of coronaviruses for subsequent fusion. Consequently, AT blocks entry driven by the Spikes of SARS-CoV, MERS-CoV, hCoV-229E, SARS-CoV-2 and its variants of concern including Omicron, and suppresses lung cell infection with genuine SARS-CoV-2. Thus, AT is an endogenous inhibitor of SARS-CoV-2 that may be involved in COVID-19 pathogenesis. We further demonstrate that activation of AT by anticoagulants, such as heparin or fondaparinux, increases the anti-TMPRSS2 and anti-SARS-CoV-2 activity of AT, suggesting that repurposing of native and activated AT for COVID-19 tr eatment should be explored.

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