Κυριακή 10 Ιανουαρίου 2021

Comparison of universal screening in major lynch-associated tumors: a systematic review of literature

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Abstract

Lynch syndrome (LS) is associated with an increased lifetime risk of several cancers including colorectal (CRC), endometrial (EC), ovarian (OC), urinary (UT) and sebaceous tumors (ST). The benefit for universal screening in CRC and EC is well known. However, this benefit in other major lynch-associated tumors is unclear. We performed a systematic review of all published articles in the MEDLINE database between 2005 to 2017 to identify studies performing universal screening for LS in unselected CRC, EC, OC, UT and ST. All cases with MSI-H (instability in two or more markers) or missing one or more proteins on IHC testing were considered screening positive. Cases with MLH1 promoter hypermethylation or BRAF mutation positive were considered to have somatic mutations. A total of 3788 articles were identified in MEDLINE yielding 129 study arms from 113 studies. The overall pooled yield of universal LS screening and germline mismatch gene mutation was significantly dif ferent across the major LS-associated tumors (Mann Whitney test, p < 0.001). The pooled screening yield was highest in ST [52.5% (355/676), 95% CI 48.74–56.26%] followed by EC [22.65% (1142/5041), 95% CI 21.54–23.86%], CRC [11.9% (5649/47,545), 95% CI 11.61–12.19%], OC [11.29% (320/2833), 95% CI 10.13–12.47%] and UT [11.2% (31/276), 95% CI 7.48–14.92%]. ST also had the highest pooled germline positivity for mismatch repair gene mutation [18.8%, 33/176, 95%CI 13.03–24.57], followed by EC [2.6% (97/3765), 95% CI 2.09–3.11], CRC [1.8% (682/37,220), 95% CI 1.66–1.94%], UT [1.8%(3/164), 95% CI − 0.24–3.83%] and OC [0.83%(25/2983), 95% CI 0.48–1.12%]. LS screening in EC yielded significantly higher somatic mutations compared to CRC [pooled percentage 16.94% [(538/3176), 95%CI 15.60–18.20%] vs. 5.23% [(1639/26,152), 95% CI 4.93–5.47%], Mann Whitney test, p < 0.0001. Universal LS testing should be routinely performed in OC, UT and STs in addition to C RC and EC. Our findings also support consideration for IHC and somatic mutation testing before germline testing in EC due to higher prevalence of somatic mutations as well as germline testing in all patients with ST. Our results have implications for future design of LS screening programs and further studies are needed to assess the cost effectiveness and burden on genetic counselling services with expanded universal testing for LS.

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ACE-2-interacting Domain of SARS-CoV-2 (AIDS) Peptide Suppresses Inflammation to Reduce Fever and Protect Lungs and Heart in Mice: Implications for COVID-19 Therapy

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Abstract

COVID-19 is an infectious respiratory illness caused by the virus strain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and until now, there is no effective therapy against COVID-19. Since SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) for entering into host cells, to target COVID-19 from therapeutic angle, we engineered a hexapeptide corresponding to the ACE2-interacting domain of SARS-CoV-2 (AIDS) that inhibits the association between receptor-binding domain-containing spike S1 and ACE-2. Accordingly, wild type (wt), but not mutated (m), AIDS peptide inhibited SARS-CoV-2 spike S1-induced activation of NF-κB and expression of IL-6 in human lungs cells. Interestingly, intranasal intoxication of C57/BL6 mice with recombinant SARS-CoV-2 spike S1 led to fever, increase in IL-6 in lungs, infiltration of neutrophils into the lungs, arrhythmias, and impairment in locomotor activities, mimicking some of the important symptoms of COVID-19. Howe ver, intranasal treatment with wtAIDS, but not mAIDS, peptide reduced fever, protected lungs, improved heart function, and enhanced locomotor activities in SARS-CoV-2 spike S1-intoxicated mice. Therefore, selective targeting of ACE2-to-SARS-CoV-2 interaction by wtAIDS may be beneficial for COVID-19.

Graphical Abstract

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Prevalence and predictors of small intestinal bacterial overgrowth in systemic sclerosis: a systematic review and meta-analysis

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Abstract

The reported prevalence of small intestinal bacterial overgrowth (SIBO) among patients with systemic sclerosis (SSc) is highly variable. We conducted this systematic review and meta-analysis to estimate the prevalence and identify predictors of SIBO in SSc by summarizing all of the available data. A comprehensive literature search of the PubMed, Cochrane Library, and EMBASE databases from inception to July 2020 was conducted for studies correlating SIBO with SSc. Studies were screened, and relevant data were extracted and analyzed. The pooled prevalence of SIBO among SSc patients and the odds ratio (OR) of SIBO among SSc patients compared with healthy controls were calculated. Furthermore, predictors of SIBO in SSc were evaluated. Fourteen studies containing 700 SSc patients and 217 healthy controls met the inclusion criteria. The pooled prevalence of SIBO in SSc was 34% (95% CI 27–42%). The OR of SIBO in SSc patients was 12.51 (95% CI 6.51–24.03) compared wi th the healthy controls. Subgroup analyses showed that the prevalence of SIBO in SSc was higher in studies using the lactulose hydrogen breath test (LHBT) for diagnosis (56%, 95% CI 46–67%) compared with those that used the glucose hydrogen breath test (GHBT) (27%, 95%CI 20–35%) and a jejunal aspirated culture (JAC) (35%, 95%CI 25–51%). The prevalence of SIBO in SSc was higher in studies conducted in Western countries (38%, 95% CI 31–47%) than those conducted in Asian countries (15%, 95%CI 10–23%), and the prevalence of SIBO in the SSc population defined by ACR-EULAR 2013 (50%, 95% CI 0.21–0.79) was higher than the prevalence defined by ACR 1980 (30%, 95% CI 0.17–0.42) or other criteria (32%, 95% CI 0.16–0.48) Moreover, the risk of diarrhea was higher in SSc patients with SIBO than those without SIBO (OR 8.82, 95% CI 4.09–19, P < 0.00001); gender, SSc subset, digital ulcer, and pulmonary fibrosis do not seem to be associated with SIBO in SSc. Antibiotic therapy seems to be effective with SIBO in SSc patients. Approximately one-third of SSc patients tested positive for SIBO with a significantly increased risk over the controls. The prevalence of SIBO in SSc varied according to the SIBO diagnostic test performed, geographic area, and SSc diagnostic criteria. The presence of diarrhea may be a predictor of SIBO in SSc. Antibiotic treatment can lead to eradication of SIBO and gastrointestinal symptomatic improvement in SSc patients.

Key Points
• The pooled prevalence of SIBO in SSc patients was 34%, which varied according to the SIBO diagnostic test performed, geographic area and SSc diagnostic criteria.
• The risk of SIBO in SSc was increased by nearly thirteenfold compared to the healthy controls.
• Diarrhoea, but not gender, SSc subset, digital ulcer and pulmonary fibrosis, was associated with SIBO in SSc patients.
• For SSc patients with SIBO, antibiotic treatment can lead to eradication of SIBO and gastrointestinal symptomatic improvement.
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The association of the progression of knee osteoarthritis with high-sensitivity CRP in community-dwelling people—the Yakumo study

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Abstract

Objective

We aimed to investigate the relationship between high-sensitivity CRP (hs-CRP) levels and the knee osteoarthritis (KOA) status and whether high hs-CRP levels predict the progression of clinical KOA in community-dwelling people.

Methods

We enrolled 247 subjects (male, n = 99; female, n = 148) who participated in the "Yakumo study" at least twice from 2003 to 2008. The KOA was evaluated by knee X-ray using the knee osteoarthritis computer-aided diagnosis (KOACAD) measurement system to obtain the mJSW, the size of the osteophyte area (OPA), and femorotibial angle (FTA). The pain intensity of the knee joint was measured using a visual analog scale (VAS, 0–100). First, we performed a multiple regression analysis to assess the relationship between the initial hs-CRP and mJSW, OPA, FTA, and VAS. Second, we examined the correlated coefficients between the amount of change hs-CRP and radiographic progressions and VAS changes. Third, we divided into two groups. Group H elevated hs-CRP levels (> 0.1 mg/dl). We picked up the subject matched to Group H according to BMI, age, sex, and medial mJSW at baseline in a 1:1 ratio; these participants were classified as the control group (Group L). The Mann-Whitney U test was used to compare the demographic data between the two groups. P values of < 0.05 were considered to indicate statistical significance.

Results

The initial hs-CRP was a significant explanatory factor for mJSW and VAS change in multiple regression analysis. The change of VAS value negatively correlated with the change of hs-CRP. Besides, the change of hs-CRP did not correlate with the radiographical change. Among these subjects, 55 had elevated hs-CRP levels (> 0.1 mg/dl) (Group H). Among the 192 subjects whose hs-CRP levels were ≤ 0.1 mg/dl, 55 subjects were matched to patients in Group H according to the age, sex, BMI, and average minimum joint space width (mJSW) at baseline and were used as a control group (Group L). The narrowing of the medial mJSW and the amount of change in OPA in group H were significantly greater than group L. The amount of change in FTA and VAS scores did not differ between the two groups.

Conclusion

Hs-CRP levels would be significantly associated with the progression of knee osteoarthritis.

Key Points
• We investigated the relationship between hs-CRP levels and the progression and the pain of osteoarthritis knee.
• We used a KOACAD system, which can measure the medial and lateral joint space narrowing, osteophyte, and femoral-tibia angle from plain radiographs automatically.
• Hs-CRP levels were significantly associated with the progression of knee osteoarthritis.
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Standardized framework to report on the role of sleeping position in sleep apnea patients

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Abstract

Purpose

Sleep apnea is a multifactorial illness which can be differentiated in various physiological phenotypes as a result of both anatomical and non-anatomical contributors (e.g., low respiratory arousal threshold, high loop gain). In addition, the frequency and duration of apneas, in the majority of patients with OSA, are influenced by sleeping position. Differences in characteristics between non-positional patients (NPP) and positional patients (PP) suggest another crucial phenotype distinction, a clinical phenotype focusing on the role of sleeping position on sleep apnea. Since this clinical phenotype distinction has therapeutic implications, further research is necessary to better understand the pathophysiology behind this phenotypic trait and to improve management of PP. Therefore, we suggest a standardized framework that emphasizes the role of sleeping position when reporting clinical and research data on sleep apnea.

Methods

We identified 5 key topics whereby a standardized framework to report on the role of sleeping position would be of added value: (1) sleep study data, (2) anatomical, morphological and physiological factors, (3) drug-induced sleep endoscopy (DISE) findings, (4) sleep apnea management, and (5) effectiveness versus efficacy of positional therapy in sleep apnea management. We performed a literature search to identify evidence to describe and support the rationale behind these 5 main recommendations.

Results

In this paper, we present the rationale behind this construct and present specific recommendations such as reporting sleep study indices (disease severity) and sleep time spent in various sleeping positions. The same is suggested for DISE findings and effect of treatment. Sleep study indices (disease severity), anatomical, morphological, and physiological factors in sleep apnea patients should be reported separately for PP and NPP.

Conclusion

Applying these suggestions in future research will improve patient care, assist in better understanding of this dominant phenotype, and will enhance accurate comparisons across studies and future investigations.

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Πέμπτη 7 Ιανουαρίου 2021

Closure of Gastrointestinal Fistulas and Leaks with the Over-the-Scope Clip: Case-Series Analysis

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Abstract

Over-the-scope clip (OTSC) is widely used in clinics for the treatment of iatrogenic perforations and fistulas and for hemostasis. The aim of this study was to retrospectively evaluate cases applied with the over-the-scope clip for gastrointestinal fistula or leakage. The study included patients on whom over-the-scope clip was performed because of leakage or fistula in the gastroenterology surgery endoscopy unit between June 2016 and January 2020. The cases were evaluated in terms of age, gender, diagnosis, localization of the defect, additional disease, size of the defect, procedure success, clinical success, number of clips, time of over-the-scope-clip application after the first procedure and duration of follow-up. In 9 patients, 11 over-the-scope clips were used. The procedure was performed in the upper gastrointestinal tract in 5 (55.56%) cases and in the lower gastrointestinal tract in 4 (44.44%) cases. Technical success was achieved in all 11 procedures pe rformed in 9 cases. Long-term clinical success was achieved in 8 of 9 cases. The over-the-scope clip is an endoscopic method that can be used safely in the treatment of gastrointestinal fistulas and leakage of < 1 cm with a low possibility of morbidity and a high success rate.

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Trans-pulmonary closure of an aorto-pulmonary window in a patient of tetralogy of Fallot: a case report

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Abstract

We present a case of tetralogy of Fallot (TOF) accompanied by a type II aorto-pulmonary window with severe pulmonary arterial hypertension in a pediatric patient. A successful repair of tetralogy of Fallot with trans-pulmonary patch closure of aorto-pulmonary window was done.

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