Notes

Three psychophysical metrics associated with hearing temporal integration in macaques.
Aortic stenosis (AS) remains one of the most common valvular heart diseases, with enormous impact on patient survival. Over the past years, transcatheter aortic valve implantation (TAVI) has become a reality worldwide, offering a less invasive method to treat AS. Apart from the classical indications for aortic valve disease, recent studies tried to address unanswered questions for TAVI - asymptomatic severe AS, bicuspid aortic valves and moderate AS in patients with heart failure. This review discusses the rationale of those possible indications, pitfalls and current evidence in the medical literature.
Treatment of patients with inflammatory bowel diseases (IBD; Crohn's disease (CD), ulcerative colitis (UC) who have a prior history of cancer pose a unique challenge. The impact of Vedolizumab (VDZ) on the risk of new or recurrent cancers in patients with a previous malignancy is unknown.

This was a retrospective study of patients with IBD with a history of current or prior cancer who were subsequently initiated on VDZ, tumor necrosis factor α antagonists (anti-TNF), or had no immunosuppressive therapy after the index cancer diagnosis. The occurrence of a new primary cancer or recurrent cancer was ascertained on follow-up. Multivariable Cox-proportional hazard models were used to determine the independent effect of post-cancer treatment on new/recurrent cancer.

The study included 96 patients exposed to VDZ after a prior diagnosis of cancer who were compared to 184 and 183 patients exposed to anti-TNF or no immunosuppressive therapy, respectively. The most common primary cancer were solid tumors (50%). Over a median of 6.2 person-years of follow-up, 18 patients on VDZ developed new (7) or recurrent (11) cancer corresponding to a rate of 22 per 1000 person-years after cancer diagnosis. In a multivariable Cox-model, after adjusting for confounders, there was no increase in the risk of new or recurrent cancer with VDZ (HR 1.38 95% CI 0.38 - 1.36) or anti-TNF therapy (HR 1.03, 95% CI 0.65 - 1.64), when compared to no IS.

Neither Vedolizumab nor TNF-antagonists were associated with increased risk of new or recurrent cancers in patients with prior malignancy.
Neither Vedolizumab nor TNF-antagonists were associated with increased risk of new or recurrent cancers in patients with prior malignancy.
50% to 80% Crohn's disease (CD) and 10% to 30% ulcerative colitis (UC) patients require surgery over their lifetime. Biologic therapies may alter this natural history, but data on the effect of biologics on surgery rates in this patient population are mixed. We sought to investigate the influence of biologics on surgery prevalence in CD and UC.

We used a commercial database (Explorys Inc, Cleveland, OH), which includes electronic health record data from 26 major integrated US healthcare systems. We identified all patients who were diagnosed with CD or UC that were treated with any biologics between 2015 and 2020. The primary outcome was to examine the association between biologics therapy and the prevalence of bowel resection. Also, we identified the factors associated with surgery in IBD patients on biologics.

Of 32,904,480 patients in the database, we identified 140,540 patients with CD and 115,260 patients with UC, of whom 25,840 (18%) and 9,050 (7.8%) patients received biologics, respectively. The pundergo bowel resection when compared to those who never received biologics. This data suggests that biologics may impact surgical rates in IBD.Microscopic colitis (MC) is a chronic inflammatory disease of the colon that presents with chronic, nonbloody watery diarrhea and only few or no endoscopic abnormalities. Histologic examination discriminates lymphocytic colitis (LyC; presence of ≥20 intraepithelial lymphocytes per 100 surface epithelial cells) and collagenous colitis (CC; colonic subepithelial collagen band >10 μm in diameter).1,2 MC not otherwise specified describes a subgroup of patients who do not fulfill the diagnostic criteria for either CC or LyC.1,2 Population-based epidemiologic data regarding MC are scarce. We aimed to evaluate the clinical presentation at diagnosis, incidence, and prevalence of MC in Cantons of Vaud and Fribourg, Switzerland.
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that may lead to cirrhosis and liver failure, but data on overall mortality in AIH are conflicting.

This was a nationwide population-based cohort study in Sweden from 1969-2017 of 6,016 adults with AIH and 28,146 matched general population reference individuals. AIH was defined by a combination of a medical diagnosis of AIH plus a liver biopsy from any of Sweden's 28 pathology departments. Through Cox regression, we estimated hazard ratios (HRs) for overall and cause-specific death. Liver transplant was included in our main outcome of death.

During follow-up, 3,185 individuals with AIH died (41.4/1000 person-years) compared with 10,477 reference individuals (21.9/1000 person-years). The 10-year cumulative incidence of death was 32.3% (95%CI = 31.1-33.6) for AIH individuals and 14.1% (95%CI = 13.7-14.5) for reference individuals. This corresponded to an adjusted HR of 2.29 (95%CI = 2.17-2.41), which remained elevated ≥20 years follow-up. AIH individuals with cirrhosis on biopsy had a high risk of death (HR = 4.55; 95%CI = 3.95-5.25), while mortality in patients with fibrosis, inflammation without fibrosis, or necrosis did not differ. Portal hypertension and overlap with cholestatic liver diseases were also associated with death. AIH was associated with an increased risk of death from cardiovascular disease (HR = 1.27; 95%CI = 1.15-1.40), liver disease (HR = 66.24; 95%CI = 48.19-91.03) and extrahepatic malignancy (HR = 1.69; 95%CI = 1.51-1.89). In a sibling comparison, AIH individuals remained at increased risk of death.

AIH is associated with a 2-fold increased risk of death. Risks were particularly high in individuals with cirrhosis, portal hypertension, and overlap with cholestatic liver disease.
AIH is associated with a 2-fold increased risk of death. TPX-0046 Risks were particularly high in individuals with cirrhosis, portal hypertension, and overlap with cholestatic liver disease.
Second forward view (SFV) examination of the right colon (RC) in colonoscopy was suggested to improve the adenoma detection rate (ADR), but multicenter data to inform its routine use remain limited. We performed an international multicenter randomized trial comparing SFV vs a standard single forward view examination of the RC on adenoma detection.

Asymptomatic individuals undergoing screening or surveillance colonoscopies from 6 Asia Pacific regions were invited for study. A forward view examination of the RC was first performed in all patients, followed by randomization at the hepatic flexure to either SFV examination of the RC and standard withdrawal examination from the hepatic flexure to rectum, or a standard withdrawal colonoscopy (SWC) examination from the hepatic flexure to rectum. The primary outcome was RC ADR.

Between 2016 and 2019, there were 1011 patients randomized (SFV group, 502 patients; SWC group, 509 patients). Forty-five endoscopists performed the colonoscopies. The RC ADR was significantly higher in the SFV group than in the SWC group (27.1% vs 21.6%; P= .042). The whole-colon ADR was high in both groups (49.0% vs 45.0%; P=.201). The SFV examination identified 58 additional adenomas in 49 patients (9.8%), leading to a change in surveillance recommendations in 15 patients (3.0%). The median overall withdrawal time was 1.5 minutes longer in the SFV group (12.0 vs 10.5 min; P < .001). Older age, male sex, ever smoking, and longer RC withdrawal time were independent predictors of right-sided adenoma detection.

In this multicenter trial, SFV examination significantly increased the RC ADR in screening and surveillance colonoscopies. Routine RC SFV examination should be considered. ClinicalTrials.gov ID NCT03121495.
In this multicenter trial, SFV examination significantly increased the RC ADR in screening and surveillance colonoscopies. Routine RC SFV examination should be considered. ClinicalTrials.gov ID NCT03121495.Copper nanoparticles were synthesized using Manilkara zapota leaf extract. The synthesis of the nanoparticle was primarily visualized when the colour of the reaction mixture turned into reddish-brown. Biosynthesized nanoparticles were characterized by UV-vis, FT-IR, XRD, SEM and EDX. The UV spectra showed maximum absorption at 584 nm. FT-IR studies showed stretching frequency at 592.76 cm-1, which is the fingerprint region for Cu-O bond. The crystallinity of the synthesized copper nanoparticles (Mz-Cu NPs) was revealed through XRD analysis. The synthesized Mz-Cu NPs were spherical with an average size of 18.9-42.5 nm and it was shown by SEM analysis. EDX analysis displayed that the nano sample contains 58 % of copper. The antimicrobial property of the synthesized nanoparticles was evaluated against fungal plant pathogens Rhizoctonia solani (MTCC 12232), Sclerotium oryzae (MTCC 12230) and bacterial species, namely Bacillus subtilis (ATCC 23857), Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 25923), Vibrio harveyi (ATCC 35084), Vibrio parahaemolyticus (ATCC 33845). In in-vitro haemolytic assay, the particle showed 5.73, 3.34, 0.5 % hemolysis at 100, 50, 25 μg/mL concentration respectively. In the antiproliferative assay, the IC50 values of MCF7 and Vero cells were found to be 53.89 and 883.69 μg/μl. The particle degraded Methyl violet, Malachite green and Coomassie brilliant blue by 92.2, 94.9 and 78.8 %, within 50, 40 and 60 min, respectively, through its photocatalytic activity.
To evaluate retinal thickness, area of foveal avascular zone (FAZ), flow area and flow density of choriocapillaris, vessel density of both superficial capillary plexus (SCP) and deep capillary plexus (DCP) of eyes with adult-onset foveomacular vitelliform dystrophy (AOFVD) using optical coherence tomography angiography (OCT-A) and compare the results with healthy controls.

17 eyes of 14 patients diagnosed with AOFVD and 17 eyes of 17 healthy subjects were enrolled in this study. All patients underwent a complete ophthalmological examination and a 6 x 6 mm macular OCT-A scanning. Quantiative results of retinal thickness, retinal vessel density of SCP and DCP, FAZ area, flow area and flow density of choriocapillaris were analyzed.

No statistically significant differences were noted in the vessel density of the SCP, except for the parafoveal nasal sector (P = 0.048). Similarly, no statistically significant differences were observed in the vessel density of the DCP, except for the parafoveal (P = 0.037) and the parafoveal temporal (P = 0.048) sectors. The choriocapillaris flow area and the flow density were significantly lower in the patients with AOFVD than in the healthy controls (P = 0.001 for both). The mean FAZ area and the retinal thickness measurements were comparable in both groups.

Patients with AOFVD show vascular abnormalities that can be detected with OCT-A. OCT-A, as a noninvasive imaging modality, could provide a new perspective for understanding the pathophysiology of AOFVD and could also be useful in the follow-up of these patients and in the management of the disease progression.
Patients with AOFVD show vascular abnormalities that can be detected with OCT-A. OCT-A, as a noninvasive imaging modality, could provide a new perspective for understanding the pathophysiology of AOFVD and could also be useful in the follow-up of these patients and in the management of the disease progression.
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