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Background: Tuberculosis (TB) is long standing disease and SARS-COV-2 being global pandemic in current era. Interactions between SARS-COV-2 and TB needs analysis, as both has major infection-related morbidity and mortality worldwide. This study was conducted to evaluate impact of super imposing viral pandemic over chronic diseases like tuberculosis. Methodology: A Retrospective study done in 75 patients registered under RNTCP program at our centre. Epidemiological data, diagnostic timing of TB, duration of AKT, history of SARS-COV-2 symptoms and SARS-COV-2 diagnostic result were evaluated. Analysis conducted based on incidence of COVID-19 infection in active cases of TB. Results: Male: Female ratio was 1.88:1 with majority belongs to age group of 35 to 55years. Only 3 patients developed influenza like symptoms who tested negative for SARS-COV-2. None COVID-19 suspected or positive patient were reported amongst laboratory confirmed TB patients taking AKT, indicating TB drugs definitely have some impact on SARS-COV-2 virus. Conclusion: TB and COVID-19 co-infection has limited cases. Very few individuals who were exposed to SARS-COV-2 during AKT treatment developed influenza like symptoms, however tested negative for SARS-COV-2. A larger study is needed to understand any role played by TB infection or AKT drugs on covid-19 disease.

Background: Racial/ethnic disparities in cancer mortality are well described and are partly attributable to later stage of diagnosis. It is unclear to what extent reductions in the incidence of late-stage cancer could narrow these relative and absolute disparities. Methods: We obtained stage- and cancer-specific incidence and survival data from the Surveillance, Epidemiology, and End Results Program for persons ages 50 to 79 years between 2006 and 2015. For eight hypothetical cohorts of 100,000 persons defined by race/ethnicity and sex, we estimated cancer-related deaths if cancers diagnosed at stage IV were detected earlier, by assigning them outcomes of earlier stages. Results: We observed a 3-fold difference in the absolute burden of stage IV cancer between the group with the highest rate (non-Hispanic Black males, 337 per 100,000) and the lowest rate (non-Hispanic Asian/Pacific Islander females, 117 per 100,000). Assuming all stage IV cancers were diagnosed at stage III, 32–80 fewer cancer-related deaths would be expected across subgroups, a relative reduction of 13%–14%. Assuming one third of metastatic cancers were diagnosed at each earlier stage (I, II, and III), 52–126 fewer cancer-related deaths would be expected across subgroups, a relative reduction of 21%–23%. Conclusions: Across population subgroups, non-Hispanic Black males have the highest burden of stage IV cancer and would have the most deaths averted from improved detection of cancer before metastasis. Impact: Detecting cancer before metastasis could meaningfully reduce deaths in all populations, but especially in non-Hispanic Black populations. See related commentary by Loomans-Kropp et al., p. 512

Ultrasound offers a real-time 2-D view of structures within the human body. While many medical education programs have already dedicated a portion of their curriculum to ultrasound, others are concerned about cost, accessibility and limits to student practice. Student benefit may be affected by cognitive errors, which are in part owing to the mental heuristics required to visualize a 3-D structure by interpreting a 2-D image. A possible solution to eliminating subjectivity in ultrasound interpretation is the use of 3-D models to augment the traditional 2-D ultrasound experience. PubMed, Embase and Web of Science were searched for primary literature exploring relationships between 3-D modeling applications and their use in ultrasound education. The search and review process was guided by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist. Overall, 14 of the included 16 studies indicated a significant improvement in medical education of ultrasound with the intervention of 3-D modeling applications. This systematic review confirms that 3-D modeling applications benefit student learning in ultrasound education while illuminating the need for more research in this field.

Background: Obesity and diabetes are associated with a higher risk of heart failure (HF). The interrelationships between different measures of adiposity—overall obesity, central obesity, fat mass (FM)—and diabetes status for HF risk are not well-established. Methods: Participant-level data from the ARIC study (Atherosclerosis Risk in Communities; visit 5) and the CHS (Cardiovascular Health Study; visit 1) cohorts were obtained from the National Heart, Lung, and Blood Institute Biologic Specimen and Data Repository Information Coordinating Center, harmonized, and pooled for the present analysis, excluding individuals with prevalent HF. FM was estimated in all participants using established anthropometric prediction equations additionally validated using the bioelectrical impedance-based FM in the ARIC subgroup. Incident HF events on follow-up were captured across both cohorts using similar adjudication methods. Multivariable-adjusted Fine-Gray models were created to evaluate the associations of body mass index (BMI), waist circumference (WC), and FM with risk of HF in the overall cohort as well as among those with versus without diabetes at baseline. The population attributable risk of overall obesity (BMI≥30 kg/m 2 ), abdominal obesity (WC>88 and 102 cm in women and men, respectively), and high FM (above sex-specific median) for incident HF was evaluated among participants with and without diabetes. Results: The study included 10 387 participants (52.9% ARIC; 25.1% diabetes; median age, 74 years). The correlation between predicted and bioelectrical impedance-based FM was high ( R 2 =0.90; n=5038). During a 5-year follow-up, 447 participants developed HF (4.3%). Higher levels of each adiposity measure were significantly associated with higher HF risk (hazard ratio [95% CI] per 1 SD higher BMI=1.15 [1.05, 1.27], WC=1.22 [1.10, 1.36]; FM=1.13 [1.02, 1.25]). A significant interaction was noted between diabetes status and measures of BMI ( P interaction=0.04) and WC ( P interaction=0.004) for the risk of HF. In stratified analysis, higher measures of each adiposity parameter were significantly associated with higher HF risk in individuals with diabetes (hazard ratio [95% CI] per 1 SD higher BMI=1.29 [1.14–1.47]; WC=1.48 [1.29–1.70]; FM=1.25 [1.09–1.43]) but not those without diabetes, including participants with prediabetes and euglycemia. The population attributable risk percentage of overall obesity, abdominal obesity, and high FM for incident HF was higher among participants with diabetes (12.8%, 29.9%, and 13.7%, respectively) versus those without diabetes (≤1% for each). Conclusions: Higher BMI, WC, and FM are strongly associated with greater risk of HF among older adults, particularly among those with prevalent diabetes.

Recently, genitourinary reconstruction has experienced a renaissance. Over the past several years, there has been an expansion of the literature regarding the use of buccal mucosa for the repair of complex ureteral strictures and other pathologies. The appendix has been an available graft utilized for the repair of ureteral stricture disease and has been infrequently reported since the early 1900s. This review serves to highlight the use of the appendix for reconstruction in urology, particularly focusing on the anatomy and physiology of the appendix, historical use, and current applications, particularly in robotic upper tract reconstruction.

AIMS To evaluate the performance of the WATCH-DM risk score, a clinical risk score for heart failure (HF), in patients with dysglycaemia and in combination with natriuretic peptides (NPs). METHODS AND RESULTS Adults with diabetes/pre-diabetes free of HF at baseline from four cohort studies (ARIC, CHS, FHS, and MESA) were included. The machine learning- [WATCH-DM(ml)] and integer-based [WATCH-DM(i)] scores were used to estimate the 5-year risk of incident HF. Discrimination was assessed by Harrell's concordance index (C-index) and calibration by the Greenwood-Nam-D'Agostino (GND) statistic. Improvement in model performance with the addition of NP levels was assessed by C-index and continuous net reclassification improvement (NRI). Of the 8938 participants included, 3554 (39.8%) had diabetes and 432 (4.8%) developed HF within 5 years. The WATCH-DM(ml) and WATCH-DM(i) scores demonstrated high discrimination for predicting HF risk among individuals with dysglycaemia (C-indices = 0.80 and 0.71, respectively), with no evidence of miscalibration (GND P ≥0.10). The C-index of elevated NP levels alone for predicting incident HF among individuals with dysglycaemia was significantly higher among participants with low/intermediate (

PURPOSE The prevalence of germline pathogenic variants (PVs) in established breast cancer predisposition genes in women in the general population over age 65 years is not well-defined. However, testing guidelines suggest that women diagnosed with breast cancer over age 65 years might have < 2.5% likelihood of a PV in a high-penetrance gene. This study aimed to establish the frequency of PVs and remaining risks of breast cancer for each gene in women over age 65 years. METHODS A total of 26,707 women over age 65 years from population-based studies (51.5% with breast cancer and 48.5% unaffected) were tested for PVs in germline predisposition gene. Frequencies of PVs and associations between PVs in each gene and breast cancer were assessed, and remaining lifetime breast cancer risks were estimated for non-Hispanic White women with PVs. RESULTS The frequency of PVs in predisposition genes was 3.18% for women with breast cancer and 1.48% for unaffected women over age 65 years. PVs in BRCA1, BRCA2, and PALB2 were found in 3.42% of women diagnosed with estrogen receptor (ER)–negative, 1.0% with ER-positive, and 3.01% with triple-negative breast cancer. Frequencies of PVs were lower among women with no first-degree relatives with breast cancer. PVs in CHEK2, PALB2, BRCA2, and BRCA1 were associated with increased risks (odds ratio = 2.9-4.0) of breast cancer. Remaining lifetime risks of breast cancer were ≥ 15% for those with PVs in BRCA1, BRCA2, and PALB2. CONCLUSION This study suggests that all women diagnosed with triple-negative breast cancer or ER-negative breast cancer should receive genetic testing and that women over age 65 years with BRCA1 and BRCA2 PVs and perhaps with PALB2 and CHEK2 PVs should be considered for magnetic resonance imaging screening.

PURPOSE: Coronavirus disease (COVID-19) sequelae in the transplant population are scarcely reported. Post-COVID-19 mucormycosis is one of such sequelae, which is a dreadful and rare entity. The purpose of this report was to study the full spectrum of this dual infection in kidney transplant recipients (KTR). METHODS: We did a comprehensive analysis of 11 mucormycosis cases in KTR who recovered from COVID-19 in IKDRC, Ahmedabad, Gujarat, India during the study period from Nov 2020 to May 2021. We also looked for the risk factors for mucormycosis with a historical cohort of 157 KTR who did not develop mucormycosis. RESULTS: The median age (interquartile range, range) of the cohort was 42 (33.5-50, 26-60) years with 54.5% diabetes. COVID-19 severity ranged from mild (n = 10) to severe cases (n = 1). The duration from COVID-19 recovery to presentation was 7 (7-7, 4-14) days. Ten cases were Rhino-orbital-cerebral-mucormycosis (ROCM) and one had pulmonary mucormycosis. Functional endoscopic sinus surgery (FESS) was performed in all cases of ROCM. The duration of antifungal therapy was 28 (24-30, 21-62) days. The mortality rate reported was 27%. The risk factors for post-transplant mucormycosis were diabetes (18% vs 54.5%; p-value = 0.01), lymphopenia [12 (10-18) vs 20 (12-26) %; p-value = 0.15] and a higher neutrophil-lymphocyte ratio [7 (4.6-8.3) vs 3.85 (3.3-5.8); p-value = 0.5]. CONCLUSION: The morbidity and mortality with post-COVID-19 mucormycosis are high. Post-transplant patients with diabetes are more prone to this dual infection. Preparedness and early identification is the key to improve the outcomes.

Aims: To study the impact of vestibular suppressant drugs (VSD) on provocative positional tests (PPT) in patients with benign paroxysmal positional vertigo (BPPV). Settings and Design: A prospective case-control observational study. Materials and Methods: Patients with a history suggestive of BPPV were tested for PPT. Patients with vertiginous symptoms and with nystagmus on PPT were classified as objective BPPV (O-BPPV, control group), while those without nystagmus with no alternate diagnosis were classified as subjective BPPV (S-BPPV, case group). Details of VSD treatment were noted in all the patients. In both groups, patients were instructed to discontinue VSD and were further assigned as the VSD and non-VSD subgroups. Patients were followed for 2 months with PPT every week. PPT positive patients were treated by vestibular rehabilitation maneuvers. Statistics: Student t-test with two-tailed, unpaired, was used for continuous scale and Chi-square test for categorical differences between the two groups. Results: 295 consecutive BPPV patients were enrolled in the study, 55 in the S-BPPV group and 240 in the O-BPPV group. Significantly higher proportion of patients in the S-BPPV group were on VSD at presentation, 80.00% vs. 53.75% (OR 2.52; 95% CI: 1.30–4.86), P = 0.006. In an unadjusted analysis of the S-BPPV group following discontinuation of VSD, PPT became positive in 79.54% of patients as compared to 18.19% in the non-VSD group (OR 35.0; 95% CI: 6.2–197.3), P < 0.001. Conclusion: A higher proportion of S-BPPV patients were receiving VSD in comparison to O-BPPV at the initial visit. The PPT converted positive four times higher after ceasing the VSD in S-BPPV patients. Study Design: Prospective case-control observational study.

Glioblastoma is an aggressive cancer with a notoriously poor prognosis. Recent advances in treatment have increased overall survival, though this may be accompanied by an increased incidence of leptomeningeal disease (LMD). LMD carries a particularly severe prognosis and remains a late stage manifestation of glioblastoma without satisfactory treatment. The objective of this review is to survey the literature on treatment of LMD in glioblastoma and to more fully characterize the current therapeutic strategies. The authors performed a systematic review following PRISMA criteria on PubMed and OVID databases. Articles that included adult patients with LMD from glioblastoma were retrieved and reviewed. LMD in glioblastoma patients is increasing in incidence, with reports of up to 21%. The overall survival without treatment is alarmingly brief, with patients surviving between 1.6–3.8 months. All studies showed that treatment does improve overall survival significantly, increasing to 11.7 months in one study. However, no one adjuvant or surgical therapy has been shown to improve survival in LMD significantly over another. Direct treatment methods include chemotherapy (standard, anti-angiogenic, intrathecal, immunotherapy), and radiation. Hydrocephalus is a complication in LMD that can be treated with ventriculoperitoneal shunt placement, however treating hydrocephalus and delivering intrathecal chemotherapy is a challenge. Though evidence remains lacking and there is no consensus, treatments show a trend towards improving survival and should be considered on a case-by-case basis. Further studies are necessary in the pursuit of a standard of care.

Pre-clinical evidence suggests bevacizumab (BV) depletes the GBM peri-vascular cancer-stem cell niche. This phase I/II study assesses the safety and efficacy of repeated doses of superselective intra-arterial cerebral infusion (SIACI) of BV after blood–brain barrier disruption (BBBD). Date of surgery was day 0. Evaluated patients received repeated SIACI bevacizumab (15 mg/kg) with BBBD at days 30 ± 7, 120 ± 7, and 210 ± 7 along with 6 weeks of standard chemoradiation. Response assessment in neuro-oncology criteria and the Kaplan–Meier product-limit method was used to evaluate progression free and overall survival (PFS and OS, respectively). Twenty-three patients with a median age of 60.5 years (SD = 12.6; 24.7–78.3) were included. Isocitrate dehydrogenase mutation was found in 1/23 (4%) patients. MGMT status was available for 11/23 patients (7 unmethylated; 3 methylated; 1 inconclusive). Median tumor volume was 24.0 cm3 (SD = 31.1, 1.7–48.3 cm3). Median PFS was 11.5 months (95% CI 7.7–25.9) with 6, 12, 24 and 60 month PFS estimated to be 91.3% (95% CI 69.5–97.8), 47.4% (26.3–65.9), 32.5% (14.4–52.2) and 5.4% (0.4–21.8), respectively. Median OS was 23.1 months (95% CI 12.2–36.9) with 12, 24, and 36 month OS as 77.3% (95% CI 53.6–89.9), 45.0% (22.3–65.3) and 32.1% (12.5–53.8), respectively. Repeated dosing of IA BV after BBBD offers an encouraging outcome in terms of PFS and OS. Phase III trials are warranted to determine whether repeated IA BV combined with Stupp protocol is superior to Stupp protocol alone for newly diagnosed GBM.

Background Limited data exist on the incidence and outcome of early coronavirus disease 2019 (COVID-19) in kidney transplantation recipients (KTR). Methods A retrospective multicenter research study was conducted across 12 centers in India. We explored the symptomatology, demographic, laboratory findings, and outcome of COVID-19 within 30 days of transplantation. The outcome was compared with the overall KTR and waitlisted patients acquiring COVID-19. Results The incidence of early COVID-19 was 2.6% (n = 22) for the cumulative 838 renal transplants performed since nationwide lockdown in March 2020 until May 2021. Overall, 1049 KTR were diagnosed with COVID-19 and 2% of those had early COVID-19. The median age of the early COVID-19 cohort was 43 (31-46) years. COVID-19 severity ranged from asymptomatic (18.2%), mild (59.1%), moderate (9.1%), and severe (13.6%). Among clinical symptoms, dyspnea and anosmia were frequent, and in laboratory parameters, neutrophil lymphocyte ratio, high-sensitivity C-reactive protein, and D -dimer were higher in patients requiring oxygen. The mortality in early COVID-19 was not higher than overall KTR (4.5% vs 8.5%; P = 1). COVID-19 severity (23.9% vs 15.7%; P = .0001) and mortality (15.5% vs 8.5%; P = .001) among waitlisted patients (n = 1703) were higher compared with overall KTR. Conclusions We report higher burden of COVID-19 in waitlisted patients compared with KTR and a favorable outcome in early COVID-19 in KTR. Our report will help the transplant physicians in dealing with the ongoing dilemma of halting or resuming transplantation in the COVID-19 era.

Chronic pain clinical trials have historically assessed benefit and risk outcomes separately. However, a growing body of research suggests that a composite metric that accounts for benefit and risk in relation to each other can provide valuable insights into the effects of different treatments. Researchers and regulators have developed a variety of benefit-risk composite metrics, although the extent to which these methods apply to randomized clinical trials (RCTs) of chronic pain has not been evaluated in the published literature. This article was motivated by an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials consensus meeting and is based on the expert opinion of those who attended. In addition, a review of the benefit-risk assessment tools used in published chronic pain RCTs or highlighted by key professional organizations (ie, Cochrane, European Medicines Agency, Outcome Measures in Rheumatology, and U.S. Food and Drug Administration) was completed. Overall, the review found that benefit-risk metrics are not commonly used in RCTs of chronic pain despite the availability of published methods. A primary recommendation is that composite metrics of benefit-risk should be combined at the level of the individual patient, when possible, in addition to the benefit-risk assessment at the treatment group level. Both levels of analysis (individual and group) can provide valuable insights into the relationship between benefits and risks associated with specific treatments across different patient subpopulations. The systematic assessment of benefit-risk in clinical trials has the potential to enhance the clinical meaningfulness of RCT results.

Outcomes for adult spinal deformity continue to improve as new technologies become integrated into clinical practice. Machine learning, robot-guided spinal surgery, and patientspecific rods are tools that are being used to improve preoperative planning and patient satisfaction. Machine learning can be used to predict complications, readmissions, and generate postoperative radiographs which can be shown to patients to guide discussions about surgery. Robot-guided spinal surgery is a rapidly growing field showing signs of greater accuracy in screw placement during surgery. Patient-specific rods offer improved outcomes through higher correction rates and decreased rates of rod breakage while decreasing operative time. The objective of this review is to evaluate trends in the literature about machine learning, robot-guided spinal surgery, and patient-specific rods in the treatment of adult spinal deformity.

Introduction:Anticholinergics are associated with cognitive side effects and dementia. Agents such as trospium, fesoterodine and darifenacin have been shown to be less likely to cross the b...

BACKGROUND: Data on clinical characteristics and outcomes of people living with HIV (PLWH) hospitalized with coronavirus disease 2019 (COVID-19) who develop acute kidney injury (AKI) are limited. SETTING: Large tertiary health care system in the Bronx, NY. METHODS: We performed a retrospective cohort study of 83 PLWH and 4151 patients without HIV hospitalized with COVID-19 from March 10, 2020, to May 11, 2020. We compared the clinical characteristics and outcomes associated with AKI by HIV serostatus and evaluated HIV-related factors for AKI among PLWH. AKI was defined and staged using Kidney Disease Improving Global Outcomes criteria. RESULTS: The incidence of AKI in hospitalized patients with COVID-19 did not differ significantly by HIV serostatus (54.2% in PLWH vs 49.5% in patients without HIV, P = 0.6). Despite a higher incidence of stage 3 AKI (28.9% vs 17.1% P = 0.05) in PLWH compared with those without HIV, there was no significant difference in the need for renal replacement therapy (22.2% vs 13.4% P = 0.12), renal recovery (76.9% vs 82.5% P = 0.61), or dependence on renal replacement therapy (7.7% vs 3.8% P = 0.27). CD4 T-cell count, HIV-1 RNA viral suppression, and antiretroviral therapy use were not associated with AKI. AKI was associated with increased need for invasive ventilation and in-hospital death, but HIV was not an independent risk factor of in-hospital death after AKI [adjusted hazard ratio 1.01 (95% CI: 0.59 to 1.72), P = 0.98]. CONCLUSIONS: HIV-related factors were not associated with increased risk of AKI in PLWH hospitalized with COVID-19. PLWH hospitalized with COVID-19 had more stage 3 AKI, but outcomes after AKI were similar to those without HIV.

PURPOSE This study assessed the joint association of pathogenic variants (PVs) in breast cancer (BC) predisposition genes and polygenic risk scores (PRS) with BC in the general population. METHODS A total of 26,798 non-Hispanic white BC cases and 26,127 controls from predominately population-based studies in the Cancer Risk Estimates Related to Susceptibility consortium were evaluated for PVs in BRCA1, BRCA2, ATM, CHEK2, PALB2, BARD1, BRIP1, CDH1, and NF1. PRS based on 105 common variants were created using effect estimates from BC genome-wide association studies; the performance of an overall BC PRS and estrogen receptor–specific PRS were evaluated. The odds of BC based on the PVs and PRS were estimated using penalized logistic regression. The results were combined with age-specific incidence rates to estimate 5-year and lifetime absolute risks of BC across percentiles of PRS by PV status and first-degree family history of BC. RESULTS The estimated lifetime risks of BC among general-population noncarriers, based on 10th and 90th percentiles of PRS, were 9.1%-23.9% and 6.7%-18.2% for women with or without first-degree relatives with BC, respectively. Taking PRS into account, more than 95% of BRCA1, BRCA2, and PALB2 carriers had > 20% lifetime risks of BC, whereas, respectively, 52.5% and 69.7% of ATM and CHEK2 carriers without first-degree relatives with BC, and 78.8% and 89.9% of those with a first-degree relative with BC had > 20% risk. CONCLUSION PRS facilitates personalization of BC risk among carriers of PVs in predisposition genes. Incorporating PRS into BC risk estimation may help identify > 30% of CHEK2 and nearly half of ATM carriers below the 20% lifetime risk threshold, suggesting the addition of PRS may prevent overscreening and enable more personalized risk management approaches.

Background Single-center data demonstrates that regional analgesia (RA) techniques are associated with reduced risk of delirium in older patients with multiple rib fractures. We hypothesized that a similar effect between RA and delirium would be identified in a larger cohort of patients from multiple level I trauma centers. Methods Retrospective data from seven level I trauma centers were collected for intensive care unit (ICU) patients 65 years or older with ≥3 rib fractures from January 2012 to December 2016. Those with a head and/or spine injury Abbreviated Injury Scale (AIS) score of ≥ 3 or a history of dementia were excluded. Delirium was defined as one positive Confusion Assessment Method for the Intensive Care Unit score in the first 7 days of ICU care. Poisson regression with robust standard errors was used to determine the association of RA (thoracic epidural or paravertebral catheter) with delirium incidence. Results Data of 574 patients with a median age of 75 years (interquartile range [IQR], 69-83), Injury Severity Score of 14 (IQR, 11-18), and ICU length of stay of 3 days (IQR, 2-6 days) were analyzed. Among the patients, 38.9% were women, 15.3% were non-White, and 31.4% required a chest tube. Regional analgesia was used in 19.3% patients. Patient characteristics did not differ by RA use; however, patients with RA had more severe chest injury (chest AIS, flail segment, hemopneumothorax, thoracostomy tube). In univariate analysis, there was no difference in the likelihood of delirium between the RA and no RA groups (18.9% vs. 23.8% p = 0.28). After adjusting for age, sex, Injury Severity Score, maximum chest AIS, thoracostomy tube, ICU length of stay, and trauma center, RA was associated with reduced risk of delirium (incident rate ratio [IRR], 0.65; 95% confidence interval [CI], 0.44-0.94) but not with in-hospital mortality (IRR, 0.42; 95% CI, 0.14-1.26) or respiratory complications (IRR, 0.70; 95% CI, 0.42-1.16). Conclusion In this multicenter cohort of injured older adults with multiple rib fractures, RA use was associated with a 35% lower risk of delirium. Further studies are needed to standardize protocols for optimal pain management and prevention of delirium in older adults with severe thoracic injury. Level of evidence Therapeutic, level IV; Epidemiologic, level III.

Introduction: Modified Epley’s maneuver is the recommended treatment for the Posterior Canal (PC) BPPV. To enhance the efficacy of this maneuver, an easy to perform visual aid device (DizzyFIX) guided modified Epley’s maneuver was studied. Material and Methods: This prospective, double-blind, randomized study included consecutive patients with PC-BPPV based on clinical history, neuro-otological examination, and positive Dix- Hallpike (DHP) test from January 2018 to March 2019 at a neurology clinic of western India. Patients were randomly assigned treatment with either visual aid device assisted modified Epley’s maneuver, which constituted the case group or by a placebo device guided modified Epley’s maneuver, which constituted the control group. DizzyFIX was used as a visual aid device in the case group. Patients were followed up at one hour and 24 hours with DHP by the blinded examiners to observe for remission. Results: Out of 280 patients (140 patients in each group), 6 from the case, and 2 from the controls were lost from the follow-up. Overall, 134 cases were compared to 138 controls. The success rate of remission in the case and the control group at one-hour was 79.19% vs. 48.30%, respectively, with a p-value of 0.003. Similarly, the success rate in the case and control group at 24 hours was 95.27% vs. 80.62%, respectively, with a p-value of 0.011. At 1 hour, unadjusted Odd Ratio (OR) was 4.13, (C.I. 95% 2.02- 8.46) and at 24 hours, it was 4.37, (C.I. 95% 1.39-13.77), which was significant even after adjustment of co-variables (OR 4.02, C.I. 95% 2.34- 8.26) and (OR 4.11, C.I. 95% 2.30- 14.26), respectively. Conclusion: For short term treatment of PC-BPPV, DizzyFIX assisted modified Epley’s maneuver is more efficacious than unassisted modified Epley’s maneuver.

Background Glenoid loosening is the most common long-term complication of total shoulder arthroplasty (TSA) and frequently necessitates revision. Though arthroscopic glenoid removal is an accepted treatment option for glenoid loosening, there is a paucity of outcomes literature available. The purpose of this study was to report the long-term clinical and radiographic outcomes of arthroscopic glenoid removal for failed or loosened glenoid component in TSA. We hypothesized that arthroscopic glenoid removal would produce acceptable clinical and patient-reported outcomes while limiting the need for further revisions. Methods This was a retrospective analysis of 11 consecutive patients undergoing 12 arthroscopic glenoid removals for symptomatic glenoid loosening by a single orthopedic surgeon between March 2005 and March 2018. Indication for arthroscopic glenoid removal included symptomatic glenoid loosening with radiographic evidence of a 1-2 mm radiolucent line around the glenoid. Shoulder range of motion, functionality (American Shoulder and Elbow Surgeons, Simple Shoulder Test), and pain (visual analog scale [VAS]) were evaluated. Radiographs were assessed for glenohumeral subluxation, humeral superior migration, and glenohumeral offset following glenoid removal. Results The mean follow-up period since arthroscopic glenoid removal was 55 months (range, 20-172 months). Glenoid component removal significantly reduced forward elevation, with a mean decrease from 147 ± 13° preoperatively to 127 ± 29° postoperatively (P= .031). However, there was no significant change in external rotation (44 ± 9° vs. 43 ± 19°; P= .941) or internal rotation (L4 vs. L4; P= .768). Importantly, glenoid removal significantly decreased VAS pain scores from 7 ± 3 preoperatively to 5 ± 3 postoperatively (P= .037). Additionally, improvement in ASES approached statistical significance, increasing from 33 ± 25 preoperatively to 53 ± 28 postoperatively (P= .055). With regard to radiographic outcomes, there was no evidence of glenohumeral subluxation and humeral superior migration developed in 1 patient. However, there was significant medialization of the greater tuberosity relative to the acromion, with a mean lateral offset of 6 ± 7 mm preoperatively and −2 ± 4 mm postoperatively (P= .002). Two patients required conversion to reverse TSA for persistent pain. There were no complications. Discussion These findings suggest that arthroscopic glenoid removal for symptomatic glenoid loosening is a viable option to improve pain while limiting the need for additional reoperations and decreasing the risks associated with revision arthroplasty. However, continual follow-up to monitor medialization is recommended. Level of Evidence Level IV; Case Series; Treatment Study

Objectives COVID-19 has emerged as a global pandemic with significant impacts on health care systems. The present study was conducted to analyze the effects of the COVID-19 pandemic on nephrology and transplant services and clinical training at our center. Materials and methods This observational study was conducted at the Institute of Kidney Disease and Research Centre (Ahmedabad, India). Our institute is one of the largest tertiary care centers of its kind in India with around 400 total inpatient beds for nephrology, urology, and transplant patients. In 2019, our center had annual outpatient and inpatient numbers of 132 181 and 7471, respectively, and conducted 412 renal transplant procedures. For this study, monthly data on number of outpatients, inpatients, and patients undergoing renal transplant, as well as various nonelective procedures, conducted in 2019 and 2020 were collected and analyzed. We investigated the impact of the COVID-19 pandemic on various non-COVID-19-related health care facilities and on clinical training and research activities at our institute. Results During the 2020 COVID-19 period, the number of outpatients and inpatients was greatly reduced compared with data from 2019. A similar decrease was seen in patients undergoing hemodialysis, renal transplant, and nonelective procedures at our center. The COVID-19 period also greatly affected clinical training of residents enrolled at our institute and research activities, as a result of focus on COVID-19 as a priority. Conclusions The effects of reduced numbers of outpatients and inpatients on workflow, as well as reduced numbers of renal transplants and nonelective procedures on the health of our patients, are unknown. Hence, a strategic scheme is needed to develop new health care models that can help manage the COVID-19 pandemic at present and any further waves arising in the future.

To determine the efficacy and safety of inferior vena cava (IVC) filters in preventing pulmonary embolism (PE) in high-risk patients undergoing hip or knee arthroplasty.2857 hip or knee arthroplasty procedures between January 2013 and December 2018 were retrospectively reviewed. Patients with a preoperative history of venous thromboembolism (VTE), either PE or deep venous thrombosis (DVT), were categorized as high-risk patients. The incidence of overall VTE, PE, and DVT were compared between patients with filters and those without. The subgroup analysis was also performed by patient risk, and filter status and the incidence of VTE, PE, and DVT were compared. Variables such as filter placement, history of hypercoagulability etcetra were evaluated as risk factors for the development of postoperative VTE.In the high-risk group, the use of IVC filters was significantly associated with a lower incidence of pulmonary embolism (0.8% vs 5.5%, P = .028). When compared with the low-risk group, the high-risk group had significantly higher incidence of PE (3.8% vs 2.0%, P = .038), DVT (11.6% vs 5.3%, P.001), and overall VTE (15.0% vs 6.8%, P.001). The history of VTE was associated with postoperative VTE (P.001), PE (P = .042), and DVT (P.001). There was no significant correlation between filter placement and postoperative VTE, DVT, or PE in the low-risk group. Filter retrieval was successful in 100% (96/96) of attempted patients with no complications.The use of IVC filters is significantly associated with a lower incidence in pulmonary embolism in high-risk arthroplasty patients. High-risk patients demonstrated an incidence of postoperative VTE over two times greater than other patients. Prophylactic placement of IVC filters in hip/knee arthroplasty is safe.

Background There is limited current knowledge on feasibility and safety of kidney transplantation in COVID-19 survivors. Methods We present a retrospective cohort study of 75 kidney transplants in patients who recovered from polymerase chain reaction (PCR) confirmed COVID-19 performed across 22 transplant centers in India from July 3, 2020 to January 31, 2021. We detail demographics, clinical manifestations, immunosuppression regimen, laboratory findings, treatment and outcomes. Patients with a previous diagnosis of COVID-19 were accepted after documenting 2 negative SARS-CoV-2 PCR tests, normal chest imaging with complete resolution of symptom for at least 28 days and significant social distancing for 14 days prior to surgery. Results Clinical severity in patients ranged from asymptomatic (n=17, 22.7%), mild(n=36,48%), moderate(n=15,20%) and severe(n=7,9.3%) disease. Median duration between PCR positive to transplant was 60 days (overall) and, increased significantly from asymptomatic, mild, moderate and severe disease (49,57,83,94 days, P-value 0.019) respectively. All recipients and donors were asymptomatic with normal creatinine after surgery at a median (interquartile range) follow up of 81 (56-117) days without any complications relating to surgery or COVID-19. Patient and graft survival was 100%, and acute rejection was reported in 6.6%. Conclusions Prospective kidney transplant recipients post-COVID-19 can be considered for transplantation after comprehensive donor and recipient screening before surgery using a combination of clinical, radiologic, and laboratory criteria, careful pre-transplant evaluation, and individualized risk-benefit analysis. Further large-scale prospective studies with longer follow-up will better clarify our initial findings. Till date, this remains the first largest study of kidney transplantation in COVID-19 survivors.Supplemental Visual Abstract; http://links.lww.com/TP/C180.

OBJECTIVE To assess the prevalence, magnitude, and disclosure status of industry funding in editorial boards of surgery journals. SUMMARY OF BACKGROUND DATA Financial conflicts of interest (COI) can bias research. While authors seeking to publish in peer-reviewed surgery journals are required to provide COI disclosures, editorial board members' COI disclosures are generally not disclosed to readers. METHODS We present a cross-sectional analysis of industry funding to editorial board members of high-impact surgery journals. We reviewed top US-based surgery journals by impact factor to determine the presence of financial COI in members of each journal's editorial board. The prevalence and magnitude of COI was determined using 2018 industry reported payments found in the CMS Open Payments database. Journal websites were also reviewed looking for the presence of editorial board disclosure statements. RESULTS A total of 1,002 names of editorial board members from the top 10 high-impact American surgery journals were identified. Of 688 individual physicians based in the USA, 452 (65.7%) were found to have received industry payments in 2018, totaling $21,916,503 with a median funding amount per physician of $1,253 (IQR $156 - $10,769). Funding levels varied by surgical specialty and journal. Editorial board disclosure information was found in only 3.3% of physicians. CONCLUSIONS Industry funding to editorial board members of high impact surgery journals is prevalent and underreported. Mechanisms of disclosure for COI are needed at the editorial board level to provide readers full transparency. This would acknowledge this COI of editorial board members, and thereby attempt to potentially further reduce the risk of bias in editorial decisions.

Background Low cardiorespiratory fitness (CRF), high body mass index, and excess visceral adiposity are each associated with impairment in left ventricular (LV) peak circumferential strain (Ecc), an intermediate phenotype that precedes the development of clinical heart failure (HF). However, the association of regional fat distribution and CRF with Ecc independent of each other and other potential confounders is not known. Methods Participants from the Dallas Heart Study Phase 2 who underwent dual energy X-ray absorptiometry assessment of regional fat distribution, CRF assessment by submaximal treadmill test, and Ecc quantification by tissue-tagged cardiovascular magnetic resonance were included in the analysis. The cross-sectional associations of measures of regional adiposity, namely visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and lower-body fat (LBF) with Ecc after adjustment for CRF and other potential confounders (independent variables) were assessed using multivariable linear regression analysis. Results The study included 1089 participants (55% female, 39% black). In the unadjusted analysis, higher VAT was associated with greater impairment in Ecc. After adjustment for baseline risk factors, CRF, parameters of LV structure and function, and other fat depots such as SAT and LBF, higher VAT remained associated with greater impairment in Ecc (β: 0.19, P = 0.002). SAT and LBF were not significantly associated with Ecc, however, CRF remained associated with Ecc in the fully adjusted model including all fat depots (β: − 0.15, P Conclusions VAT and CRF are each independently associated with impairment in Ecc, suggesting that higher VAT burden and low CRF mediate pathological cardiac remodeling through distinct mechanisms.

Background To conduct a meta-analysis to assess the safety and efficacy of prophylactic transcatheter arterial embolization (PTAE) for the treatment of high-risk bleeding peptic ulcers after achieving endoscopic hemostasis. Methods PubMed and Cochrane Library were queried for full-text articles published up to December 2019. The following keywords were used: “prophylactic embolization”, “supplement embolization”, “gastrointestinal bleeding”, and “ulcer bleeding”. High-risk ulcers were defined based on endoscopic findings (i.e., large ulcers, Forrest class I-IIb) and/or clinical presentation (i.e., hypotension, decreased hemoglobin during endoscopy). Only comparative studies investigating PTAE versus conservative treatment after achieving endoscopic hemostasis were included. Baseline study characteristics, rebleeding rate, need for surgery, mortality, and PTAE-related complication rates were investigated. Quantitative analyses were performed with Stata 15.1. Results Among the five included original studies, a total of 265 patients received PTAE and 617 were managed conservatively after endoscopy. The rebleeding rate (6.8% vs 14.3%, p = 0.003) and mortality (4.5% vs 8.8%, p = 0.032) of patients from the PTAE group were lower than the control group. PTAE also reduced the cumulative need for future surgical intervention (3.0% vs 14.4%, p = 0.005). The PTAE-related major and minor events were 0.75% and 14.4%, respectively. Conclusion PTAE had therapeutic potentials in reducing rebleeding risk, need for surgical intervention, and morality in high-risk peptic ulcers after achieving endoscopic hemostasis. The embolization-associated adverse events were minimal. Future studies should aim to increase the sample size and resources for performing endovascular interventions.

Female urethral strictures are rare, but underdiagnosed pathologies that can cause voiding dysfunction. These strictures are best managed with open reconstruction, as endoscopic treatments have high rates of failure. A flap urethroplasty can be performed with vaginal, labial or bladder tissue. Meanwhile, graft urethroplasties can utilize vaginal, labial, buccal or lingual tissue. It is important to consider the etiology and type of stricture, local vascularity, and prior attempts at repair when selecting the type of repair. Multiple different techniques have been described with theoretical advantages to each one. While some studies have reviewed a few of the reconstructive techniques to treat female urethral strictures, no single study has accounted for each individual technique. In this review, we discuss techniques captured by a number of systematic reviews and other articles. We will herein focus on reviewing and describing each unique technique of reconstruction in the setting of female urethral stricture.

Background: About half of children with nephrolithiasis and/or nephrocalcinosis (NL/NC) have an underlying metabolic cause. Next-generation sequencing (NGS) is increasingly being used as a clinical tool in diagnosing inherited renal diseases. Objective: The objective of the study was to retrospectively analyze the utility of NGS in the diagnosis and management of children with NL/NC at a tertiary care referral nephrology center in western India. Methods: All children ?18 years with NL/NC, where an NGS was sent from September 2016 to September 2020, were included in the study. Clinical exome sequencing covering 8882 genes was done in 13 children. The test result was interpreted as per the American College of Medical Genetics classification: No pathogenic variant, a variant of unknown significance (VUS), and likely pathogenic and pathogenic variant. Results: The median age (IQR) of the cohort at the onset of disease was 11 months (4.25–102). History of consanguinity was present in 3 children (23%). Eight children had NC 7 had NL, 7 had the end-stage renal disease (ESRD) at presentation. Seven out of 8 children with NC had ESRD. Eleven children (84.6%) had an identifiable monogenic genetic cause: 9 had pathogenic, 2 had likely pathogenic variants detected in 5 genes: AGXT, GRHPR, HOGA1, CLDN16, and HPRT1. Two VUS were detected in two children in BBS4 and KCNJ1 gene. Primary hyperoxaluria (PH) Type 1 was the most common diagnosis in 6 children. Other diagnoses were Lesch–Nyhan syndrome in 2, PH 2, PH3, and FHHNC in 1 each. Conclusion: The yield of NGS in children with NL/NC was remarkably high. NGS was useful in diagnosis and management of children with NL/NC.

BACKGROUND: The objective of this study was to determine the healthcare resource utilization for people living with HIV (PLWH) presenting to the emergency department (ED) across the HIV Care Continuum. METHODS: This prospective study enrolled PLWH presenting to an urban ED between June 2016 and March 2017. Subjects were categorized as being linked to care, retained in care, on antiretroviral therapy (ART), and virally suppressed (

Context: Distal end radius fractures are among the commonest fractures encountered in public health care. These injuries are associated with osteoporosis, articular damage, comminution and complex fracture pattern. These fractures should be managed according to fracture configuration and functional demand of patient. Material and Methods: 110 patients with distal end radius fractures were managed with different surgical fixation. Out of them 58 were operated by locking plates, 44 were operated by percutaneous k wire pinning and external fixation was done in 8 patients. Mean age of study population was 46.4 year (range 20-75year) with slight male dominance. All patients were assessed post operatively by clinical and radiological methods in forms of DASH score, VAS pain score, range of motion at wrist joint, operative complication of each treatment modality, pinch and grip strength of both hands. Results: Patients managed with plating had significantly better function, strength and range of motion as compared with patients operated with K-wiring or distractor in all 8 types of fractures (p

Pathological hand tremor (PHT) is a common symptom of Parkinson’s disease (PD) and essential tremor (ET), which affects manual targeting, motor coordination, and movement kinetics. Effective treatment and management of the symptoms relies on the correct and in-time diagnosis of the affected individuals, where the characteristics of PHT serve as an imperative metric for this purpose. Due to the overlapping features of the corresponding symptoms, however, a high level of expertise and specialized diagnostic methodologies are required to correctly distinguish PD from ET. In this work, we propose the data-driven $$\text {NeurDNet}$$ NeurDNet model, which processes the kinematics of the hand in the affected individuals and classifies the patients into PD or ET. $$\text {NeurDNet}$$ NeurDNet is trained over 90 hours of hand motion signals consisting of 250 tremor assessments from 81 patients, recorded at the London Movement Disorders Centre, ON, Canada. The $$\text {NeurDNet}$$ NeurDNet outperforms its state-of-the-art counterparts achieving exceptional differential diagnosis accuracy of $$95.55\%$$ 95.55 % . In addition, using the explainability and interpretability measures for machine learning models, clinically viable and statistically significant insights on how the data-driven model discriminates between the two groups of patients are achieved.

Background: Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. Methods: We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values-8 as genome-wide significant, and p-values-5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants.Results: None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values5. The strongest evidence was found for rs4674019 (p-value=2.27x10-7), which showed genome-wide significant interaction (p-value=3.8x10-8) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen-progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. Conclusions: In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT–breast cancer risk association.

Purpose/Objective(s) I125 Eye Plaque brachytherapy is the standard treatment for medium size uveal melanomas. As a result, most patients have late radiation toxicities (RTT) such as radiation-induced maculopathy (RM), radiation-induced neovascular glaucoma/iris neovascularization (RNGI) and radiation-induced optic neuropathy (RON) that result in vision loss. While tumor size, location and radiation dose have been identified as predictors of radiation toxicity, we hypothesize demographics, pre-treatment tumor characteristics and post-operative complications may also impact radiation toxicities. Materials/Methods An IRB-approved retrospective chart review was performed from 2011-2019 to evaluate patients with posterior uveal melanomas who were treated with brachytherapy at a single institution in the Southeast with a large Hispanic population, with a minimum of 3 months follow-up. We collected patient demographics, pre-treatment tumor characteristics, tumor margin to fovea/optic disk and post-operative complications as potential predictors of RTT. RTT was defined as an event of RM, RNGI, or RON following plaque removal. Univariable analysis (UVA) and multivariable analysis (MVA) were performed using logistic regression model to examine the associations between study variables and the development of RTT. Odds ratios (ORs) and corresponding P-values were reported. All tests were two-sided and statistical significance was considered when P Results A total of 262 patients were evaluated over 8 years. Median follow up was 33.5 months (range 3.02 – 97.31). 178 pts (67.9%) had RTT. 131 pts (50.0%) developed RM. 19 pts (7.3%) developed RNGI. 56 pts (21.4%) developed RO. 41 pts (15.8%) identified as Hispanic. UVA found shorter distance to fovea (OR = 0.97, P = 0.025), post-operative subretinal fluid/exudative retinal detachment (RD) (OR = 2.89, P = 0.002) and vitreous hemorrhage (OR = 3.73, P = 0.002) are associated with RTT and Hispanic ethnicity is not significantly associated with RTT when compared to non-Hispanics (OR = 1.54, P = 0.219). MVA found shorter distance to fovea (OR = 0.95, P = 0.004), post-operative subretinal fluid/exudative RD (OR = 3.14, P = 0.006) and vitreous hemorrhage (OR = 4.50, P = 0.003) are associated with increased RTT. Conclusion These data suggest that shorter distance to fovea and post-operative complications such as subretinal fluid/exudative RD and vitreous hemorrhage are associated with increased risk of RTT. This study can serve as prognostic tools to better counsel patients on the risks and benefits of brachytherapy and allow for early intervention in the management of RTT. These data need to be validated in a prospective trial investigating post-operative complications and subsequent RTT after the treatment of posterior uveal melanomas. Author Disclosure V.A. Peters: None. A. Gurayah: None. D. Kwon: None. W. Zhao: None. W. Jin: Stock; Vit Inc. Partnership; Vit Inc. N.V. Patel: None. A.M. Markoe: None. Z. Correa: None. M.T. Studenski: None. J. Harbour: None. S. Samuels: None.

To study factors causing postoperative change of PI after surgical correction of ASD and to assess the effect of this variability on postoperative PI-LL mismatch. PI is used as an individual constant to define lumbar lordosis (LL) correction goal (PI-LL 10°) associated with a |∆PI|> 6°, P = 0.05. Sacroiliac fixation diminished PI variability only during the first postoperative year. Preoperative variability and postoperative instability of PI diminish the applicability of the PI–LL

BACKGROUND: The PrEP cascade outlines sequential steps to maximize PrEP’s impact and highlights potential intervention targets to improve PrEP implementation. We evaluate the PrEP cascade in the Together 5,000 study (T5K). METHODS: T5K is an internet-based, U.S. national cohort study of PrEP-eligible men and trans persons who have sex with men who were not taking PrEP at enrollment. Using longitudinal data from baseline (2017–2018) and year one follow-up (2018–2019, n=4,229), we evaluated five steps of the PrEP cascade—PrEP contemplation: believes they are a good candidate for PrEP; PrEParation: plans to initiate PrEP; PrEP action: speaks to a provider about PrEP; PrEP initiation: receives a prescription for PrEP; and PrEP maintenance: continues to take PrEP. We compared the cascade across geographic region and identified factors associated with gaps in the cascade. RESULTS: After one year, 1092 (26%) participants had initiated PrEP, 709 (17%) were still using PrEP, and 177 (4%) were no longer clinically indicated for PrEP. Participants in the South and Midwest were less likely to speak to a provider about PrEP or initiate PrEP. Baseline characteristics associated with lower odds of PrEP initiation at year one include: not having a college degree; earning

The average age at menarche declined in European and U.S. populations during the 19th and 20th centuries. The timing of pubertal events may have broad implications for chronic disease risks in aging women. Here we tested for associations of recalled menarcheal age with risks of 19 cancers in 536,450 women [median age, 60 years (range, 31–39 years)] in nine prospective U.S. and European cohorts that enrolled participants from 1981 to 1998. Cox regression estimated multivariable-adjusted HRs and 95% confidence intervals (CI) for associations of the age at menarche with risk of each cancer in each cohort and random-effects meta-analysis was used to generate summary estimates for each cancer. Over a median 10 years of follow-up, 60,968 women were diagnosed with a first primary incident cancer. Inverse linear associations were observed for seven of 19 cancers studied. Each additional year in the age at menarche was associated with reduced risks of endometrial cancer (HR = 0.91; 95% CI, 0.89–0.94), liver cancer (HR = 0.92; 95% CI, 0.85–0.99), melanoma (HR = 0.95; 95% CI, 0.93–0.98), bladder cancer (HR = 0.96; 95% CI, 0.93–0.99), and cancers of the colon (HR = 0.97; 95% CI, 0.96–0.99), lung (HR = 0.98; 95% CI, 0.96–0.99), and breast (HR = 0.98; 95% CI, 0.93–0.99). All but one of these associations remained statistically significant following adjustment for baseline body mass index. Similarities in the observed associations between menarche and seven cancers suggest shared underlying causes rooted early in life. We propose as a testable hypothesis that early exposure to sex hormones increases mid-life cancer risks by altering functional capacities of stem cells with roles in systemic energy balance and tissue homeostasis. Significance: Age at menarche is associated with risk for seven cancers in middle-aged women, and understanding the shared underlying causal pathways across these cancers may suggest new avenues for cancer prevention.

There are limited clinical data on feasibility and safety of convalescent plasma therapy in kidney transplant recipients with severe COVID-19. The present study was conducted to explore the feasibility of convalescent plasma treatment in 10 kidney transplant recipients with severe COVID-19.The prospective observational cohort study was conducted at the Institute of Kidney Disease and Research Centre, Ahmedabad, India. All patients were admitted to the intensive care unit and received antiviral therapy, glucocorticoids, and other supportive care. Two doses of 200 mL each of convalescent plasma with neutralization activity of1:640 were transfused into patients 24 hours apart following the World Health Organization blood transfusion protocol. The endpoints were the improvement of clinical symptoms and laboratory parameters within 1 day and 7 days after convalescent plasma transfusion.The patients showed resolution of clinical symptoms, and there was a significant decrease in inflammatory markers (P.05) within 7 days of convalescent plasma transfusion. Of the 10 patients, 9 patients had full recovery and 1 patient died.Convalescent plasma therapy is highly safe and clinically feasible and reduces mortality in kidney transplant recipients with severe COVID-19. Larger clinical registries and randomized clinical trials should be conducted to further explore the clinical outcomes associated with convalescent plasma use in kidney transplant recipients with severe COVID-19.

Background: In the current pandemic of COVID-19, hydroxychloroquine (HCQ) is recommended as an experimental drug for prophylaxis and treatment of the illness. Although it is a safe drug, it can rarely produce a severe drug reaction ‘drug rash with eosinophilia and systemic symptoms syndrome (DRESS)’, and to differentiate it from systemic viral infections is challenging. Case Presentation: A 45-year old male nurse working in a COVID-19 ward consumed HCQ weekly for two weeks for prevention of SARS-COV-2 illness. He presented with fever, pruritic maculopapular palmar rash, cervical lymphadenopathy for 12 hours and was quarantined as a suspected COVID-19 case. His laboratory tests revealed lymphopenia, eosinophilia, atypical lymphocytes, raised liver enzymes along with IgM negative, IgG positive rapid antibody test of SARS-COV-2. However, his throat swabs for SARS-COV-2 by real-time PCR were negative on day 1 and 7. He was finally diagnosed as definite DRESS based on the RegiSCAR score of six. He responded to levocetirizine 5 mg OD and oral prednisolone 60 mg daily tapered over 7 days. Conclusion: DRESS due to HCQ is ‘probable’, ‘of moderate severity’, and ‘not preventable’ adverse effect mimicking SARS-COV-2 illness.

Summary Background There is a paucity of evidence to support safe and effective management of patients with acute severe ulcerative colitis during the COVID-19 pandemic. We sought to identify alterations to established conventional evidence-based management of acute severe ulcerative colitis during the early COVID-19 pandemic, the effect on outcomes, and any associations with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes. Methods The PROTECT-ASUC study was a multicentre, observational, case-control study in 60 acute secondary care hospitals throughout the UK. We included adults (≥18 years) with either ulcerative colitis or inflammatory bowel disease unclassified, who presented with acute severe ulcerative colitis and fulfilled the Truelove and Witts criteria. Cases and controls were identified as either admitted or managed in emergency ambulatory care settings between March 1, 2020, and June 30, 2020 (COVID-19 pandemic period cohort), or between Jan 1, 2019, and June 30, 2019 (historical control cohort), respectively. The primary outcome was the proportion of patients with acute severe ulcerative colitis receiving rescue therapy (including primary induction) or colectomy. The study is registered with ClinicalTrials.gov , NCT04411784 . Findings We included 782 patients (398 in the pandemic period cohort and 384 in the historical control cohort) who met the Truelove and Witts criteria for acute severe ulcerative colitis. The proportion of patients receiving rescue therapy (including primary induction) or surgery was higher during the pandemic period than in the historical period (217 [55%] of 393 patients vs 159 [42%] of 380 patients; p=0·00024) and the time to rescue therapy was shorter in the pandemic cohort than in the historical cohort (p=0·0026). This difference was driven by a greater use of rescue and primary induction therapies with biologicals, ciclosporin, or tofacitinib in the COVID-19 pandemic period cohort than in the historical control period cohort (177 [46%] of 387 patients in the COVID-19 cohort vs 134 [36%] of 373 patients in the historical cohort; p=0·0064). During the pandemic, more patients received ambulatory (outpatient) intravenous steroids (51 [13%] of 385 patients vs 19 [5%] of 360 patients; p=0·00023). Fewer patients received thiopurines (29 [7%] of 398 patients vs 46 [12%] of 384; p=0·029) and 5-aminosalicylic acids (67 [17%] of 398 patients vs 98 [26%] of 384; p=0·0037) during the pandemic than in the historical control period. Colectomy rates were similar between the pandemic and historical control groups (64 [16%] of 389 vs 50 [13%] of 375; p=0·26); however, laparoscopic surgery was less frequently performed during the pandemic period (34 [53%] of 64] vs 38 [76%] of 50; p=0·018). Five (2%) of 253 patients tested positive for SARS-CoV-2 during hospital treatment. Two (2%) of 103 patients re-tested for SARS-CoV-2 during the 3-month follow-up were positive 5 days and 12 days, respectively, after discharge from index admission. Both recovered without serious outcomes. Interpretation The COVID-19 pandemic altered practice patterns of gastroenterologists and colorectal surgeons in the management of acute severe ulcerative colitis but was associated with similar outcomes to a historical cohort. Despite continued use of high-dose corticosteroids and biologicals, the incidence of COVID-19 within 3 months was low and not associated with adverse COVID-19 outcomes. Funding None.

Background Widespread reports suggest the characteristics and disease course of coronavirus disease 2019 (COVID-19) and influenza differ, yet detailed comparisons of their clinical manifestations are lacking. Objective Comparison of the epidemiology and clinical characteristics of COVID-19 patients during the pandemic with those of influenza patients in previous influenza seasons at the same hospital Design Admission rates, clinical measurements, and clinical outcomes from confirmed COVID-19 cases between March 1 and April 30, 2020, were compared with those from confirmed influenza cases in the previous five influenza seasons (8 months each) beginning September 1, 2014. Setting Large tertiary care teaching hospital in Boston, MA Participants Laboratory-confirmed COVID-19 and influenza inpatients Measurements Patient demographics and medical history, mortality, incidence and duration of mechanical ventilation, incidences of vasopressor support and renal replacement therapy, and hospital and intensive care admissions. Results Data was abstracted from medical records of 1052 influenza patients and 582 COVID-19 patients. An average of 210 hospital admissions for influenza occurred per 8-month season compared to 582 COVID-19 admissions over 2 months. The median weekly number of COVID-19 patients requiring mechanical ventilation was 17 (IQR: 4, 34) compared to a weekly median of 1 (IQR: 0, 2) influenza patient (p=0.001). COVID-19 patients were significantly more likely to require mechanical ventilation (31% vs 8%) and had significantly higher mortality (20% vs. 3%; p

Type 2 diabetes is a heterogeneous disease process with variable trajectories of CVD risk. We aimed to evaluate four phenomapping strategies and their ability to stratify CVD risk in individuals with type 2 diabetes and to identify subgroups who may benefit from specific therapies. Participants with type 2 diabetes and free of baseline CVD in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial were included in this study (N = 6466). Clustering using Gaussian mixture models, latent class analysis, finite mixture models (FMMs) and principal component analysis was compared. Clustering variables included demographics, medical and social history, laboratory values and diabetes complications. The interaction between the phenogroup and intensive glycaemic, combination lipid and intensive BP therapy for the risk of the primary outcome (composite of fatal myocardial infarction, non-fatal myocardial infarction or unstable angina) was evaluated using adjusted Cox models. The phenomapping strategies were independently assessed in an external validation cohort (Look Action for Health in Diabetes [Look AHEAD] trial: n = 4211; and Bypass Angioplasty Revascularisation Investigation 2 Diabetes [BARI 2D] trial: n = 1495). Over 9.1 years of follow-up, 789 (12.2%) participants had a primary outcome event. FMM phenomapping with three phenogroups was the best-performing clustering strategy in both the derivation and validation cohorts as determined by Bayesian information criterion, Dunn index and improvement in model discrimination. Phenogroup 1 (n = 663, 10.3%) had the highest burden of comorbidities and diabetes complications, phenogroup 2 (n = 2388, 36.9%) had an intermediate comorbidity burden and lowest diabetes complications, and phenogroup 3 (n = 3415, 52.8%) had the fewest comorbidities and intermediate burden of diabetes complications. Significant interactions were observed between phenogroups and treatment interventions including intensive glycaemic control (p-interaction = 0.042) and combination lipid therapy (p-interaction

Background: Autoimmune polyglandular syndrometype-2 (APS-2) is an uncommon endocrine disorder of Addison’s disease with an autoimmune thyroid disorder and/or type 1 diabetes mellitus. The diagnosis is more challenging when a patient presents with nonspecific neuropsychiatric features with hypothyroidism in the setting of unrecognized Addison’s disease. Case Report: We report a case of subclinical autoimmune hypothyroidism presented with nonspecific neuropsychiatric symptoms precipitated by stress. Despite levothyroxine treatment, her symptoms deteriorated and she was admitted with persistent vomiting and hypovolemic shock. Clinical features and laboratory parameters were suggestive of underlying adrenocortical insufficiency. Preexisting autoimmune hypothyroidism combined with Addison's disease confirmed the diagnosis of unrecognized APS-2. She remarkably improved and her thyroid function tests also normalized with the treatment of corticosteroids only. Review of the Literature: We identified only five published case reports of our title by searching the database. Neufeld and Betterle have reported their data of APS-2 and concluded that a full- blown clinical picture of two or more components of the syndrome is like the tip of the iceberg. Conclusion : The patients of one major component of APS-2 should be screened for other components of the disease to pick up latent cases. Addison’s disease should be ruled out in patients of hypothyroidism who are intolerant to levothyroxine.

Background Reverse total shoulder arthroplasty is a common treatment for patients with rotator cuff arthropathy who have failed a prior rotator cuff repair. Latissimus dorsi transfer can be performed simultaneously to reverse total shoulder arthroplasty for patients with preoperative external rotation deficiency. Current literature is limited with several studies providing functional and pain improvements at short-term follow-up; however, there is a deficit in data regarding mid-term outcomes. The purpose of this study was to evaluate the clinical and radiographic outcomes following reverse total shoulder arthroplasty with latissimus dorsi transfer with mid-term follow-up. We hypothesized significant improvement in external rotation and shoulder functionality for patients with preoperative external rotation lag. Methods We retrospectively reviewed patients who underwent reverse total shoulder arthroplasty with latissimus dorsi transfer. Preoperative and postoperative changes in range of motion were assessed. American Shoulder and Elbow Surgeon Score and the Simple Shoulder Test were used to evaluate changes in shoulder function while pain scores were assessed using the Visual Analog Scale (VAS). Radiographs were reviewed for rotator cuff arthropathy, fatty infiltration, scapular notching, baseplate loosening, and osteolysis. We reported frequency and mean ± standard deviation for categorical and continuous variables, respectively. Means were compared using the paired Student's t-test and proportions using the Chi-square test. Results Fifteen patients met the inclusion criteria. The mean age of the cohort was 71.7 ± 8.4 years (range 51.2–87.8 years) with a mean follow-up of 6.3 ± 4.1 years (range 1.0–14.5 years). Reverse total shoulder arthroplasty with latissimus dorsi transfer improved external rotation (−7 ± 21.3° to 38 ± 15.8°; p value = 0.001). There was no statistically significant difference regarding forward flexion (116.3 ± 45.4° to 133.7 ± 14.7°; p value = 0.17) and internal rotation (T12 to L2; p value = 0.57). The procedure led to an increase in American Shoulder and Elbow Surgeon Score scores (37 ± 19 to 62 ± 22; p = 0.005) and Simple Shoulder Test scores (2 ± 2 to 6 ± 3; p value = 0.001) with a significant reduction in Visual Analog Scale scores (5 ± 3 to 2 ± 3; p value = 0.022). The procedure corrected external rotation lag in 10 patients. Radiographically, rotator cuff arthropathy was found to be grade 3 in two patients, grade 4 A in four patients, grade 4B in eight patients, and grade 5 in one patient. On postoperative imaging, scapular notching was found in six patients (40%). Twelve patients had cortical humeral erosion at the site of the latissimus dorsi transfer. Only one patient experienced a shoulder-related complication which was aseptic baseplate loosening and required a revision reverse total shoulder arthroplasty with allograft. Conclusions In this study, patients undergoing reverse total shoulder arthroplasty with latissimus dorsi transfer experienced improvements in range of motion, functional scores, and pain at mid-term follow-up. The shoulder-related complication rate was low. Level of evidence: IV; Case series.

Prior work has shown associations between blood transfusion (BT) and inferior outcomes during resection for colorectal cancer liver metastases (CRLM). Herein, we describe short and long-term outcomes relating to perioperative BT in routine clinical practice.All CRLM resections in Ontario, Canada from 2002 to 2009 were identified using the Ontario Cancer Registry. Log-binomial regression and Cox regression were used to explore factors associated with receipt of BT and the association of BT with 5-year cancer specific (CSS) and overall survival (OS), respectively.The study included 1310 patients; 31% (403/1310) had perioperative BT. Transfused patients had longer median length of stay (9 vs. 7 days, p 0.001), higher 90-day mortality (9% vs. 1%, p 0.001), greater 90-day readmission (28% vs. 16%, p 0.001), and inferior 5-year CSS (41% vs. 48%, p = 0.001) and OS (38% vs. 47%, p 0.001). Transfusion was independently associated with inferior CSS (HR = 1.35, 95% CI: 1.11-1.63) and OS (HR = 1.30, 95% CI: 1.10-1.53), however, excluding 90-day postoperative deaths showed these associations were no longer significant.Perioperative BT is common in patients undergoing resection of CRLM. While transfusion is associated with greater morbidity, mortality, and inferior survival, after excluding early postoperative deaths, BT does not appear to be independently associated with CSS or OS.

AIMS: Comprehensive echocardiography assessment of right ventricular (RV) impairment has not been reported in critically ill patients with COVID-19. We detail the specific phenotype and clinical associations of RV impairment in COVID-19 acute respiratory distress syndrome (ARDS). METHODS: Transthoracic echocardiography (TTE) measures of RV function were collected in critically unwell patients for associations with clinical, ventilatory and laboratory data. RESULTS: Ninety patients (25.6% female), mean age 52.0 ± 10.8 years, veno-venous extracorporeal membrane oxygenation (VVECMO) (42.2%) were studied. A significantly higher proportion of patients were identified as having RV dysfunction by RV fractional area change (FAC) (72.0%,95% confidence interval (CI) 61.0-81.0) and RV velocity time integral (VTI) (86.4%, 95 CI 77.3-93.2) than by tricuspid annular plane systolic excursion (TAPSE) (23.8%, 95 CI 16.0-33.9), RVS' (11.9%, 95% CI 6.6-20.5) or RV free wall strain (FWS) (35.3%, 95% CI 23.6-49.0). RV VTI correlated strongly with RV FAC (p ≤ 0.01). Multivariate regression demonstrated independent associations of RV FAC with NTpro-BNP and PVR. RV-PA coupling correlated with PVR (univariate p