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BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

Background Deep brain stimulation (DBS) is an effective surgical therapy for individuals with essential tremor (ET). However, DBS operates continuously, resulting in adverse effects such as postural instability or dysarthria. Continuous DBS (cDBS) also presents important practical issues including limited battery life of the implantable neurostimulator (INS). Collectively, these shortcomings impact optimal therapeutic benefit in ET. Objective The goal of the study was to establish a physiology-driven responsive DBS (rDBS) system to provide targeted and personalized therapy based on electromyography (EMG) signals. Methods Ten participants with ET underwent rDBS using Nexus-D, a Medtronic telemetry wand that acts as a direct conduit to the INS by modulating stimulation voltage. Two different rDBS paradigms were tested: one driven by one EMG (single-sensor) and another driven by two or more EMGs (multi-sensor). The feature(s) used in the rDBS algorithms was the pow2er in the participant's tremor frequency band derived from the sensors controlling stimulation. Both algorithms were trained on kinetic and postural data collected during DBS off and cDBS states. Results Using established clinical scales and objective measurements of tremor severity, we confirm that both rDBS paradigms deliver equivalent clinical benefit as cDBS. Moreover, both EMG-driven rDBS paradigms delivered less total electrical energy translating to an increase in the battery life of the INS. Conclusions The results of this study verify that EMG-driven rDBS provides clinically equivalent tremor suppression compared to cDBS, while delivering less total electrical energy. Controlling stimulation using a dynamic rDBS paradigm can mitigate limitations of traditional cDBS systems.

Background. The role of liver function tests (LFT) as prognostic factors in patients admitted with COVID-19 has not been fully investigated, particularly outside resource-rich countries. We aimed at evaluating the prognostic value of abnormal LFT on admission and during hospitalization of patients with COVID-19. Methods. We performed a retrospective study that included 298 adult patients hospitalized for COVID-19, between 05/2020 and 02/2021, in 6 hospitals from 5 countries in South America. We analyzed demographic and comorbid variables and laboratory tests on admission and during hospitalization. LFT over twice the upper limit of normal (ALEx2) were also evaluated in relation to a variety of factors on admission and during hospitalization. De novo-ALEx2 was defined as the presence of ALEx2 at one week of hospitalization in patients without ALEx2 on admission. Patients were followed until hospital discharge or death. Multivariable analysis was used to evaluate the association between ALEx2 on admission and during hospitalization and mortality. Results. Of the total of 298 patients, 60% were male, with a mean age of 60 years, and 74% of patients had at least one comorbidity. Of those, 137 (46%) patients were transferred to the intensive care unit and 66 (22.1%) patients died during hospitalization. ALEx2 on admission was present in 87 (29.2%) patients and was found to be independently associated with 1-week mortality (odds ratio (OR) = 3.55; 95% confidence interval (95%CI) 1.05–12.05). Moreover, 84 (39.8%) out of 211 patients without ALEx2 at admission developed de novo-ALEx2, which was independently associated with mortality during second week of hospitalization (OR = 6.09; 95%CI 1.28–29) and overall mortality (OR = 2.93, 95%CI 1.05–8.19). Conclusions. A moderate elevation of LFT during admission was associated with a poor short-term prognosis in patients hospitalized with COVID-19. In addition, moderate elevation of LFT at one week of hospitalization was an independent risk factor for overall mortality in these patients.

Acute-on-chronic liver failure (ACLF) is a rapidly progressive illness with high short-term mortality. Timely liver transplant (LT) may improve survival. We evaluated various indices for assessment of the severity of liver failure and their application for eligibility and timing of living donor LT (LDLT). Altogether 1021 patients were analyzed for the severity and organ failure at admission to determine transplant eligibility and 28 day survival with or without transplant. The ACLF cohort [mean age 44 ± 12.2 years, males 81%) was of sick patients; 55% willing for LT at admission, though 63% of them were ineligible due to sepsis or organ failure. On day 4, recovery in sepsis and/or organ failure led to an improvement in transplant eligibility from 37% at baseline to 63.7%. Delay in LT up to 7 days led to a higher incidence of multiorgan failure (p

Background: We described the demographics, cancer subtypes, comorbidities, and outcomes of patients with a history of cancer and coronavirus disease 2019 (COVID-19). Second, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza. Methods: We conducted a cohort study using eight routinely collected health care databases from Spain and the United States, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer were included: (i) diagnosed with COVID-19, (ii) hospitalized with COVID-19, and (iii) hospitalized with influenza in 2017 to 2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes. Results: We included 366,050 and 119,597 patients diagnosed and hospitalized with COVID-19, respectively. Prostate and breast cancers were the most frequent cancers (range: 5%–18% and 1%–14% in the diagnosed cohort, respectively). Hematologic malignancies were also frequent, with non-Hodgkin's lymphoma being among the five most common cancer subtypes in the diagnosed cohort. Overall, patients were aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 2% to 14% and from 6% to 26% in the diagnosed and hospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza (n = 67,743) had a similar distribution of cancer subtypes, sex, age, and comorbidities but lower occurrence of adverse events. Conclusions: Patients with a history of cancer and COVID-19 had multiple comorbidities and a high occurrence of COVID-19-related events. Hematologic malignancies were frequent. Impact: This study provides epidemiologic characteristics that can inform clinical care and etiologic studies.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide, and its prevalence increases continuously. As it predisposes to hepatocellular carcinoma both in the presence and in the absence of cirrhosis, it is not surprising that the incidence of NAFLD-related hepatocellular carcinoma would also rise. Some of the mechanisms involved in hepatocarcinogenesis are particular to individuals with fatty liver, and they help explain why liver cancer develops even in patients without cirrhosis. Genetic and immune-mediated mechanisms seem to play an important role in the development of hepatocellular carcinoma in this population. Currently, it is consensual that patients with NAFLD-related cirrhosis should be surveilled with ultrasonography every 6 mo (with or without alpha-fetoprotein), but it is known that they are less likely to follow this recommendation than individuals with other kinds of liver disease. Moreover, the performance of the methods of surveillance are lower in NAFLD than they are in other liver diseases. Furthermore, it is not clear which subgroups of patients without cirrhosis should undergo surveillance. Understanding the mechanisms of hepatocarcinogenesis in NAFLD could hopefully lead to the identification of biomarkers to be used in the surveillance for liver cancer in these individuals. By improving surveillance, tumors could be detected in earlier stages, amenable to curative treatments.

The prevalence of congenital uterine anomalies has been reported as 6.7% in the general population. The unicornuate uterus accounts for 2.4-13% of all Mullerian anomalies and has a prevalence of 1:1000. A unicornuate uterus may be present alone or with a rudimentary horn and 75-90% of rudimentary horns are non-communicating. A pregnancy in the rudimentary horn may lead to uterine rupture, haemoperitoneum with a high risk of maternal mortality. The association of a unicornuate uterus with a non-communicating uterine horn to the VACTERL association of defects (vertebral anomalies, anorectal malformations, cardiovascular anomalies, tracheoesophageal fistula, esophageal atresia, renal anomalies and limb defects) has been described only twice in the literature. We report a patient who was born with an extra thumb and had a trachea-bronchial remnant with oesophageal stenosis that were both operated on earlier, and they were associated with a non-communicating rudimentary uterine horn. To the best of our knowledge, this is the third case reported in the literature of a VACTERL association to a unicornuate uterus with a non-communicating functional rudimentary horn. Given the high risk for the patient if pregnant an early diagnosis is paramount. This case highlights the importance of considering Mullerian defects in the young patient born with components of the VACTERL association.

Objective To determine the dose-dependent effect of contemporary marijuana exposure on female menstrual cyclicity and reproductive endocrine physiology in a nonhuman primate model. Design Research animal study. Setting Research institute environment. Animals Adult female rhesus macaques (6–12 years of age; n = 8). Intervention(s) Daily delta-9-tetrahydrocannabinol (THC) edible at medically and recreationally relevant contemporary doses. Main Outcome Measure(s) Menstrual cycle length (MCL), anti-Mullerian hormone, prolactin, basal follicle-stimulating hormone (FSH), estradiol (E2) and progesterone, luteinizing hormone (LH), and thyroid-stimulating hormone. Result(s) The average before THC weight was 6.9 kg (standard deviation, 0.8), and at the highest THC dosing, the average weight was 7.2 kg (standard deviation, 0.8). With increasing THC dosing, MCL and FSH concentrations increased, while basal E2 concentration was stable. The average MCL concentration increased 4.0 days for each mg/7 kg/day of THC (95% CI, 1.4–6.6 days). Follicle-stimulating hormone concentration increased significantly with increasing THC dose, 0.34 ng/mL for each mg/7 kg/day of THC (95% CI, 0.14–0.57 ng/mL). No significant trends were observed between THC dosing and average basal progesterone, anti-Mullerian hormone, prolactin, LH, or thyroid-stimulating hormone concentrations. Conclusion(s) In rhesus macaques, a dose response toward increased MCL and basal FSH concentrations but plateau of basal E2 and LH concentrations was observed with increasing THC dosing, suggesting ovulatory dysfunction. Further studies are needed to determine the effects of a longer duration of exposure and whether the significant increase in MCL and FSH concentrations results in reduced fecundity.

This paper reports the proceedings from the first consensus meeting on the management of mild‐to‐moderate gastroesophageal reflux disease (GERD) in the Southeast Asian (SEA) region. Seventeen statements were drawn up by a steering committee that focused on epidemiology, mechanism of action, diagnostic investigations, and treatment. Voting on the recommendations used the Delphi method with two rounds of voting among the 10 panel members. The consensus panel agreed that GERD is mostly a mild disease in the SEA region with predominantly non‐erosive reflux disease (NERD). Complicated GERD and Barrett's esophagus are infrequently seen. The panel recommended endoscopy in patients with alarm or refractory symptoms but cautioned that the incidence of gastric cancer is higher in SEA. pH and impedance measurements were not recommended for routine assessment. The acid pocket is recognized as an important pathogenic factor in GERD. Lifestyle measures such as weight reduction, avoidance of smoking, reduction of alcohol intake, and elevation of the head of the bed were recommended but strict avoidance of specific foods or drinks was not. Alginates was recommended as the first‐line treatment for patients with mild‐to‐moderate GERD while recognizing that proton‐pump inhibitors (PPIs) remained the mainstay of treatment of GERD. The use of alginates was also recommended as adjunctive therapy when GERD symptoms were only partially responsive to PPIs., Algorithm for the management of mild‐to‐moderate gastroesophageal reflux disease in the Southeast Asian region derived from the consensus statements and recommendations of an expert panel.

We evaluated the dynamics of hepatic encephalopathy (HE) and ammonia estimation in acute-on-chronic liver failure (ACLF) patients due to a paucity of evidence. ACLF patients recruited from the APASL-ACLF Research Consortium (AARC) were followed up till 30 days, death or transplantation, whichever earlier. Clinical details, including dynamic grades of HE and laboratory data, including ammonia levels, were serially noted. Of the 3009 ACLF patients, 1315 (43.7%) had HE at presentation; grades I–II in 981 (74.6%) and grades III–IV in 334 (25.4%) patients. The independent predictors of HE at baseline were higher age, systemic inflammatory response, elevated ammonia levels, serum protein, sepsis and MELD score (p

Chronic infections due to hepatitis B and hepatitis C viruses are responsible for most cases of hepatocellular carcinoma (HCC) worldwide, and this association is likely to remain during the next decade. Moreover, viral hepatitis-related HCC imposes an important burden on public health in terms of disability-adjusted life years. In order to reduce such a burden, some major challenges must be faced. Universal vaccination against hepatitis B virus, especially in the neonatal period, is probably the most relevant primary preventive measure against the development of HCC. Moreover, considering the large adult population already infected with hepatitis B and C viruses, it is also imperative to identify these individuals to ensure their access to treatment. Both hepatitis B and C currently have highly effective therapies, which are able to diminish the risk of development of liver cancer. Finally, it is essential for individuals at high-risk of HCC to be included in surveillance programs, so that tumors are detected at an early stage. Patients with hepatitis B or C and advanced liver fibrosis or cirrhosis benefit from being followed in a surveillance program. As hepatitis B virus is oncogenic and capable of leading to liver cancer even in individuals with early stages of liver fibrosis, other high-risk groups of patients with hepatitis B are also candidates for surveillance. Considerable effort is required concerning these strategies in order to decrease the incidence and the mortality of viral hepatitis-related HCC.

Multiple predictive models of mortality exist for acute-on-chronic liver failure (ACLF) patients that often create confusion during decision-making. We studied the natural history and evaluated the performance of prognostic models in ACLF patients.Prospectively collected data of ACLF patients from APASL-ACLF Research Consortium (AARC) was analyzed for 30-day outcomes. The models evaluated at days 0, 4, and 7 of presentation for 30-day mortality were: AARC (model and score), CLIF-C (ACLF score, and OF score), NACSELD-ACLF (model and binary), SOFA, APACHE-II, MELD, MELD-Lactate, and CTP. Evaluation parameters were discrimination (c-indices), calibration [accuracy, sensitivity, specificity, and positive/negative predictive values (PPV/NPV)], Akaike/Bayesian Information Criteria (AIC/BIC), Nagelkerke-RThirty-day survival of the cohort (n = 2864) was 64.9% and was lowest for final-AARC-grade-III (32.8%) ACLF. Performance parameters of all models were best at day 7 than at day 4 or day 0 (p 0.05 for C-indices of all models except NACSELD-ACLF). On comparison, day-7 AARC model had the numerically highest c-index 0.872, best accuracy 84.0%, PPV 87.8%, RAPASL-ACLF is often a progressive disease, and models assessed up to day 7 of presentation reliably predict 30-day mortality. Day-7 AARC model is a statistically robust tool for classifying risk of death and accurately predicting 30-day outcomes with relatively lower prediction errors. Day-7 AARC score 12 may be used as a futility criterion in APASL-ACLF patients.

Background Peripheral artery disease (PAD) is recognized as a significant predictor of mortality and adverse cardiovascular outcomes in patients with coronary heart disease (CHD). In fact, coexisting PAD and CHD is strongly associated with a greater coronary event recurrence compared with either one of them alone. High-density lipoprotein (HDL)-mediated cholesterol efflux capacity (CEC) is found to be inversely associated with an increased risk of incident CHD. However, this association is not established in patients with PAD in the context of secondary prevention. In this sense, our main aim was to evaluate the association between CEC and PAD in patients with CHD and whether the concurrent presence of PAD and T2DM influences this association. Methods CHD patients (n = 1002) from the CORDIOPREV study were classified according to the presence or absence of PAD (ankle-brachial index, ABI ≤ 0.9 and ABI > 0.9 and Results The presence of PAD determined low CEC in non-T2DM and newly-diagnosed T2DM patients. Coexisting PAD and newly-diagnosed T2DM provided and additive effect providing an impaired CEC compared to non-T2DM patients with PAD. In established T2DM patients, the presence of PAD did not determine differences in CEC, compared to those without PAD, which may be restored by glucose-lowering treatment. Conclusions Our findings suggest an inverse relationship between CEC and PAD in CHD patients. These results support the importance of identifying underlying mechanisms of PAD, in the context of secondary prevention, that provide potential therapeutic targets, that is the case of CEC, and establishing strategies to prevent or reduce the high risk of cardiovascular events of these patients. Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT00924937. Unique Identifier: NCT00924937

BACKGROUND: The impact of statins on COVID-19 outcomes is important given the high prevalence of their use among individuals at risk for severe COVID-19. Our aim is to assess whether patients receiving chronic statin treatment who are hospitalized with COVID-19 have reduced in-hospital mortality if statin therapy is maintained during hospitalization. METHODS: This work is a cross-sectional, observational, retrospective multicenter study that analyzed 2921 patients who required hospital admission at 150 Spanish centers included in the nationwide SEMI-COVID-19 Network. We compared the clinical characteristics and COVID-19 disease outcomes between patients receiving chronic statin therapy who maintained this therapy during hospitalization versus those who did not. Propensity score matching was used to match each statin user whose therapy was maintained during hospitalization to a statin user whose therapy was withdrawn during hospitalization. RESULTS: After propensity score matching, continuation of statin therapy was associated with lower all-cause mortality (OR 0.67, 0.54-0.83, p < 0.001); lower incidence of acute kidney injury (AKI) (OR 0.76,0.6-0.97, p = 0.025), acute respiratory distress syndrome (ARDS) (OR 0.78, 0.69- 0.89, p < 0.001), and sepsis (4.82% vs 9.85%, p = 0.008); and less need for invasive mechanical ventilation (IMV) (5.35% vs 8.57, p < 0.001) compared to patients whose statin therapy was withdrawn during hospitalization. CONCLUSIONS: Patients previously treated with statins who are hospitalized for COVID-19 and maintain statin therapy during hospitalization have a lower mortality rate than those in whom therapy is withdrawn. In addition, statin therapy was associated with a decreased probability that patients with COVID-19 will develop AKI, ARDS, or sepsis and decreases the need for IMV.

The purpose of this study was to examine the applicability of the use of samples in dried blood spot (DBS) for the definitive diagnosis of Fabry disease (FD) in males and females and to compare the diagnostic role of α-galactosidase A activity (α-Gal A), levels of lyso-Gb3 and sequencing of the GLA gene in screening patients with suspected FD. Measurement of α-Gal A activity in suspected FD patients in DBS was made followed by lyso-Gb3 determination and GLA gene sequencing. Of the 2381 subjects analyzed, FD was confirmed in 24 patients. Thirteen different variants were considered like pathogenic, five of which had not been previously described (c.143A > G; c.455A > C; c.487G > T; c.554delA; c.1045_1046insA). None of the patients with normal enzyme activity had FD confirmation. The DBS measurement of α-Gal A was more sensitive than lyso-Gb3 levels in both men and women. Definitive diagnosis of FD from a single DBS is possible, allowing samples to be easily sent from anywhere to the reference laboratory.

Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disease of the colon, characterized by relapsing and remitting symptoms. Although traditionally viewed as a Western disease, the incidence and prevalence of UC is increasing in developing regions, including Asian countries.A PubMed search identified articles describing epidemiology, disease burden, patient demographics, clinical characteristics, risk factors, and treatment of UC across Asia. We review the epidemiology and disease course of UC across Asia, including region-specific factors that may aid development of more cost-effective treatment approaches tailored to the needs of Asian populations.The opinion of non-Pfizer-affiliated practicing gastroenterologists is that epidemiological data from the last four decades have shown 1.5-fold to almost 20-fold increases in the incidence and prevalence of UC in some Asian countries, although prevalence remains generally lower than in the West. As the prevalence of UC rises, so will overall healthcare costs. Disparities in healthcare systems and funding mean that different Asian countries face unique challenges in how best to use available resources, including selection from a growing number of emerging treatment options. More clinical trial and real-world data are required to help define treatment approaches that will most benefit Asian populations.

BACKGROUND Metabolic risk factors may impact the severity and outcome of alcoholic liver disease. The present study evaluated this effect in patients with alcohol-associated acute-on-chronic liver failure (ACLF). METHODOLOGY One thousand two hundred and sixteen prospectively enrolled patients with ACLF (males 98%, mean age 42.5 ± 9.4 years, mean CTP, MELD and AARC scores of 12 ± 1.4, 29.7 ± 7 and 9.8 ± 2 respectively) from the Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) database were analysed retrospectively. Patients with or without metabolic risk factors were compared for severity (CTP, MELD, AARC scores) and day 30 and 90 mortality. Information on overweight/obesity, type 2 diabetes mellitus (T2DM), hypertension and dyslipidaemia were available in 1028 (85%), 1019 (84%), 1017 (84%) and 965 (79%) patients respectively. RESULTS Overall, 392 (32%) patients died at day 30 and 528 (43%) at day 90. Overweight/obesity, T2DM, hypertension and dyslipidaemia were present in 154 (15%), 142 (14%), 66 (7%) and 141 (15%) patients, respectively, with no risk factors in 809 (67%) patients. Patients with overweight/obesity had higher MELD scores (30.6 ± 7.1 vs 29.2 ± 6.9, P = .007) and those with dyslipidaemia had higher AARC scores (10.4 ± 1.2 vs 9.8 ± 2, P = .014). Overweight/obesity was associated with increased day 30 mortality (HR 1.54, 95% CI 1.06-2.24, P = .023). None of other metabolic risk factors, alone or in combination, had any impact on disease severity or mortality. On multivariate analysis, overweight or obesity was significantly associated with 30-day mortality (aHR 1.91, 95% CI 1.41-2.59, P

Inflammatory bowel disease (IBD) has increased in incidence and prevalence in Asian countries since the end of the 20th century. Moreover, differences in the cause, phenotypes, and natural history of IBD between the East and West have been recognized. Therefore, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have established recommendations on medical management of IBD in Asia. Initially, the committee members drafted 40 recommendations, which were then assessed according to Grading of Recommendations Assessment, Development and Evaluation. Eight statements were rejected as this indicated that consensus had not been reached. The recommendations encompass pretreatment evaluation; medical management of active IBD; medical management of IBD in remission; management of IBD during the periconception period and pregnancy; surveillance strategies for colitis-associated cancer; monitoring side effects of thiopurines and methotrexate; and infections in IBD.

Asia has intermediate-to-high prevalence and high morbidity of hepatitis B virus (HBV) infection. The use of guideline-recommended nucleos(t)ide analogs with high barrier to resistance, such as entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), is one of the key interventions for curbing HBV infection and associated morbidity in Asia. However, there are some challenges to the use of ETV and TDF; while ETV is associated with high resistance in lamivudine (LAM)-exposed (especially LAM-refractory) patients; bone and renal safety issues are a major concern with TDF. Hence, a panel of twenty-eight expert hepatologists from Asia convened, reviewed the literature, and developed the current expert opinion-based review article for the use of TAF in the resource-constrained settings in Asia. This article provides a comprehensive review of two large, phase 3, double-blind, randomized controlled trials of TAF versus TDF in HBeAg-negative (study 0108) and HBeAg-positive (study 0110) chronic HBV patients (> 70% Asians). These studies revealed as follows: (1) non-inferiority for the proportion of patients who had HBV DNA

Background In patients who are not suitable for traditional access routes for transcatheter aortic valve replacement (TAVR) due to severe peripheral vascular disease (PVD) or prohibitive surgical risk, carotid artery (CA) access is an emerging route for TAVR. This study represents the most up to date on outcomes of carotid access TAVR. Methods A systematic review was conducted as per the Preferred Reporting Instructions for Systematic Reviews and Meta-analysis (PRISMA). We performed a thorough electronic search through Pubmed, SCOPUS and Embase databases. Statistical analyses were performed using SPSS version 24 (IBM Corporation, Armonk, New York, USA). Results A total of 15 non-randomized studies were included in this systematic review comprising of patients that received TAVR via 4 vascular access sites, transcarotid (TC) (N = 1035), transfemoral (TF) (N = 1116), transapical (TAP) (N = 307), transaortic (TAO) (N = 176) and transaxillary (TAX) (N = 90). In the Transcarotid cases, device success was achieved in 95.6% of patients (n = 748). The 30-day and 1-yr mortality was 4.2% and 10.5% respectively. 15.3% of patients required new pacemaker implantation. In-hospital stroke or TIA occurred in 4% of cases. 30-day stroke or TIA occurred in 5% of cases. There were no hemorrhagic strokes. 30-day Mortality was significantly higher in the Transaortic group (12.1%) compared to the Transcarotid group (2.6%) [RR = 2.93 95% CI = 1.15–7.58; p = 0.027]. There were no differences in outcomes between the Transcarotid group and the Transapical or Transaxillary groups. Conclusion The most contemporary data on Carotid access TAVR shows impressive device success, low rates of stroke and pacemaker implantation and an acceptable 30-day and 1-year mortality. 30-day mortality was significantly lower in TC compared to TAO patients.

Introduction: Previous studies have linked chronic pelvic pain (CPP) to appendix pathologies. However, few studies have investigated appendix pathology specifically in the context of CPP that is right-side predominant (R-CPP). We hypothesized that women with R-CPP have higher rates of appendix pathology compared with women with CPP that is not right-side predominant (N-CPP). Methods: We conducted a retrospective case–control study of 220 women who underwent diagnostic laparoscopy and planned or incidental appendectomy for CPP and suspected endometriosis between January 2015 and December 2018 at a tertiary care center in Saint Louis, MO. Results: No significant difference in abnormal appendix pathology was found between women with R-CPP and women with N-CPP (30.9% vs 34.5%, p = 0.74, odds ratio = 0.85, 95% CI: (0.44, 1.62)). Gross abnormalities of the appendix were documented in 40 of 220 patients (18.2%), with the most common abnormal gross findings being adhesions (8.2%), followed by abnormal lesions (7.3%). Conclusion: In this study, the presence of abnormal pathology within the appendix did not correlate with R-CPP, indicating triage based on predominant pain location cannot help identify patients with underlying appendix pathology. However, consistent with previous studies, we identified a high rate of abnormal appendix pathology overall, supporting the practice of many surgeons to perform routine appendectomy in women with CPP.

The COVID‐19 pandemic, secondary to SARS‐CoV‐2, has resulted in high mortality and morbidity worldwide. As inflammatory bowel disease (IBD) is a chronic disease, and most patients are on long‐term immunosuppressive agents, there is understandable concern, particularly in terms of therapy. In view of this, experts in IBD across the Asia Pacific region were invited to put together recommendations based on their experience and the currently available data. In general, most IBD therapies (with a few exceptions) can be continued safely, and the general consensus is that maintaining disease control should remain the main principle of management. In addition, social distancing measures and the appropriate use of personal protective equipment should be strictly adhered to. During the current pandemic, face‐to‐face clinic follow ups and non‐urgent procedures should be kept to a minimum., This is a concerted effort by the members of the Asian Pacific Association of Gastroenterology Inflammatory Bowel Disease (IBD) Workgroup members to provide guidance on IBD management (all‐in‐one succinct review paper) during the difficult COVID‐19 pandemic.

Atherosclerosis is the primary cause of renal artery stenosis. Atherosclerotic renal artery stenosis (ARAS) is associated with three clinical problems: renovascular hypertension, ischemic nephropathy and cardiac destabilization syndrome which pose huge healthcare implications. There is a significant rate of natural disease progression with worsening severity of renal artery stenosis when renal revascularization is not pursued in a timely manner. Selective sub-groups of individuals with ARAS have had good outcomes after percutaneous renal artery stenting (PTRAS). For example, individuals that underwent PTRAS and had improved renal function were reported to have a 45% survival advantage compared to those without improvement in their renal function. Advances in the imaging tools have allowed for better anatomic and physiologic measurements of ARAS. Measuring translesional hemodynamic gradients has allowed for accurate assessment of ARAS severity. Renal revascularization with PTRAS provides a survival advantage in individuals with significant hemodynamic renal artery stenosis lesions. It is important that we screen, diagnosis, intervene with invasive and medical treatments appropriately in these high-risk patients.

Asia has an intermediate-to-high prevalence of and high morbidity and mortality from hepatitis B virus (HBV) infection. Optimization of diagnosis and initiation of treatment is one of the crucial strategies for lowering disease burden in this region. Therefore, a panel of 24 experts from 10 Asian countries convened, and reviewed the literature, to develop consensus guidance on diagnosis and initiation of treatment of HBV infection in resource-limited Asian settings. The panel proposed 11 recommendations related to diagnosis, pre-treatment assessment, and indications of therapy of HBV infection, and management of HBV-infected patients with co-infections. In resource-limited Asian settings, testing for hepatitis B surface antigen may be considered as the primary test for diagnosis of HBV infection. Pre-treatment assessments should include tests for complete blood count, liver and renal function, hepatitis B e-antigen (HBeAg), anti-HBe, HBV DNA, co-infection markers and assessment of severity of liver disease. Noninvasive tests such as AST-to-platelet ratio index, fibrosis score 4 or transient elastography may be used as alternatives to liver biopsy for assessing disease severity. Considering the high burden of HBV infection in Asia, the panel adopted an aggressive approach, and recommended initiation of antiviral therapy in all HBV-infected, compensated or decompensated cirrhotic individuals with detectable HBV DNA levels, regardless of HBeAg status or alanine transaminase levels. The panel also developed a simple algorithm for guiding the initiation of treatment in noncirrhotic, HBV-infected individuals. The recommendations proposed herein, may help guide clinicians, to optimize the diagnosis and improvise the treatment rates for HBV infection in Asia.

Kristin Kostka,1,2 Talita Duarte-Salles,3 Albert Prats-Uribe,4 Anthony G Sena,5,6 Andrea Pistillo,3 Sara Khalid,4 Lana YH Lai,7 Asieh Golozar,8,9 Thamir M Alshammari,10 Dalia M Dawoud,11 Fredrik Nyberg,12 Adam B Wilcox,13,14 Alan Andryc,5 Andrew Williams,15 Anna Ostropolets,16 Carlos Areia,17 Chi Young Jung,18 Christopher A Harle,19 Christian G Reich,1,2 Clair Blacketer,5,6 Daniel R Morales,20 David A Dorr,21 Edward Burn,3,4 Elena Roel,3,22 Eng Hooi Tan,4 Evan Minty,23 Frank DeFalco,5 Gabriel de Maeztu,24 Gigi Lipori,19 Hiba Alghoul,25 Hong Zhu,26 Jason A Thomas,13 Jiang Bian,19 Jimyung Park,27 Jordi Martínez Roldán,28 Jose D Posada,29 Juan M Banda,30 Juan P Horcajada,31 Julianna Kohler,32 Karishma Shah,33 Karthik Natarajan,16,34 Kristine E Lynch,35,36 Li Liu,37 Lisa M Schilling,38 Martina Recalde,3,22 Matthew Spotnitz,14 Mengchun Gong,39 Michael E Matheny,40,41 Neus Valveny,42 Nicole G Weiskopf,21 Nigam Shah,29 Osaid Alser,43 Paula Casajust,42 Rae Woong Park,27,44 Robert Schuff,21 Sarah Seager,1 Scott L DuVall,35,36 Seng Chan You,45 Seokyoung Song,46 Sergio Fernández-Bertolín,3 Stephen Fortin,5 Tanja Magoc,19 Thomas Falconer,16 Vignesh Subbian,47 Vojtech Huser,48 Waheed-Ul-Rahman Ahmed,33,49 William Carter,38 Yin Guan,50 Yankuic Galvan,19 Xing He,19 Peter R Rijnbeek,6 George Hripcsak,16,34 Patrick B Ryan,5,16 Marc A Suchard,51 Daniel Prieto-Alhambra4 1IQVIA, Cambridge, MA, USA; 2OHDSI Center at The Roux Institute, Northeastern University, Portland, ME, USA; 3Fundació Institut Universitari per a la recerca a l’Atenció Primà ria de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain; 4Centre for Statistics in Medicine, NDORMS, University of Oxford, Oxford, UK; 5Janssen Research & Development, Titusville, NJ, USA; 6Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands; 7School of Medical Sciences, University of Manchester, Manchester, UK; 8Regeneron Pharmaceuticals, Tarrytown, NY, USA; 9Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; 10College of Pharmacy, Riyadh Elm University, Riyadh, Saudi Arabia; 11National Institute for Health and Care Excellence, London, UK; 12School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 13Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, WA, USA; 14Unviersity of Washington Medicine, Seattle, WA, USA; 15Tufts Institute for Clinical Research and Health Policy Studies, Boston, MA, USA; 16Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, USA; 17Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; 18Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Daegu Catholic University Medical Center, Daegu, South Korea; 19University of Florida Health, Gainesville, FL, USA; 20Division of Population Health and Genomics, University of Dundee, Dundee, UK; 21Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA; 22Universitat Autònoma de Barcelona, Barcelona, Spain; 23O’Brien Institute for Public Health, Faculty of Medicine, University of Calgary, Calgary, Canada; 24IOMED, Barcelona, Spain; 25Faculty of Medicine, Islamic University of Gaza, Gaza, Palestine; 26Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 27Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, South Korea; 28Director of Innovation and Digital Transformation, Hospital del Mar, Barcelona, Spain; 29Department of Medicine, School of Medicine, Stanford University, Redwood City, CA, USA; 30Georgia State University, Department of Computer Science, Atlanta, GA, USA; 31Department of Infectious Diseases, Hospital del Mar, Institut Hospital del Mar d’Investigació Mèdica (IMIM), Universitat Autònoma de Barcelona, Universitat Pompeu Fabra, Barcelona, Spain; 32United States Agency for International Development, Washington, DC, USA; 33Botnar Research Centre, NDORMS, University of Oxford, Oxford, UK; 34New York-Presbyterian Hospital, New York, NY, USA; 35VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT, USA; 36Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA; 37Biomedical Big Data Center, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 38Data Science to Patient Value Program, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; 39Institute of Health Management, Southern Medical University, Guangzhou, People’s Republic of China; 40Tennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, TN, USA; 41Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA; 42Real-World Evidence, TFS, Barcelona, Spain; 43Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 44Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, South Korea; 45Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, South Korea; 46Department of Anesthesiology and Pain Medicine, Catholic University of Daegu, School of Medicine, Daegu, South Korea; 47College of Engineering, The University of Arizona, Tucson, AZ, USA; 48National Library of Medicine, National Institutes of Health, Bethesda, MD, USA; 49College of Medicine and Health, University of Exeter, St Luke’s Campus, Exeter, UK; 50DHC Technologies Co. Ltd., Beijing, People’s Republic of China; 51Departments of Biostatistics, Computational Medicine, and Human Genetics, University of California, Los Angeles, CA, USACorrespondence: Daniel Prieto-Alhambra, Botnar Research Centre, Windmill Road, Oxford, OX37LD, UK, Email daniel.prietoalhambra@ndorms.ox.ac.ukPurpose: Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) Characterizing Health Associated Risks and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD.Patients and Methods: We conducted a descriptive retrospective database study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11th June 2020 and are iteratively updated via GitHub. We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19, and 113,627 hospitalized with COVID-19 requiring intensive services.Results: We aggregated over 22,000 unique characteristics describing patients with COVID-19. All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts and are readily available online. Globally, we observed similarities in the USA and Europe: more women diagnosed than men but more men hospitalized than women, most diagnosed cases between 25 and 60 years of age versus most hospitalized cases between 60 and 80 years of age. South Korea differed with more women than men hospitalized. Common comorbidities included type 2 diabetes, hypertension, chronic kidney disease and heart disease. Common presenting symptoms were dyspnea, cough and fever. Symptom data availability was more common in hospitalized cohorts than diagnosed.Conclusion: We constructed a global, multi-centre view to describe trends in COVID-19 progression, management and evolution over time. By characterising baseline variability in patients and geography, our work provides critical context that may otherwise be misconstrued as data quality issues. This is important as we perform studies on adverse events of special interest in COVID-19 vaccine surveillance.Keywords: OHDSI, OMOP CDM, descriptive epidemiology, real world data, real world evidence, open science

Antecedentes y objetivo: La endocarditis infecciosa (EI) es una infección de mal pronóstico, con una mortalidad intrahospitalaria que va del 15-20%. La terapia óptima requiere antibioticoterapia efectiva por tiempo prolongado y cirugía valvular en algunos casos. El objetivo de este estudio fue revisar la epidemiología y desenlaces de pacientes con EI en un centro de referencia en la Ciudad de México. Métodos: Cohorte retrospectiva de pacientes admitidos al Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán con diagnóstico de EI en un periodo de 10 años, de enero de 2009 a enero de 2019. Se incluyeron a pacientes que cumplían la definición de diagnóstico definitivo de endocarditis infecciosa de acuerdo a los criterios modificados de Duke. Resultados: Se incluyeron a 62 pacientes (50.85 ± 17.46 años, 40.3% mujeres). Todos los casos tuvieron cultivos positivos, siendo S. aureus el microorganismo más frecuente (34%). El 58.1% de los pacientes recibió tratamiento quirúrgico y 41.9% recibió únicamente tratamiento médico. La mortalidad a 30 días fue de 25.8% y a 12 meses fue de 41.9%. Comparando los grupos de tratamiento médico y quirúrgico, se encontró que 50% y 36% de cada grupo, respectivamente, habían fallecido a los 12 meses. Conclusiones: Encontramos una alta prevalencia de EI asociada a los cuidados de la salud, principalmente en relación a accesos intravasculares. Casi todos los pacientes presentaban un criterio quirúrgico al momento del diagnóstico. Los pacientes con diabetes mellitus tipo 2 y función sistólica del ventrículo derecho disminuida presentaron una mayor mortalidad a 12 meses.

Purpose: The primary purpose of this study was to assess vascular retinal findings temporally related to COVID-19 vaccination. With greater information regarding all possible future adverse events, we hope to understand the real dimension and relevance of what was presented. Methods: Eleven patients with visual complaints after COVID-19 vaccination were enrolled. Data on the following were included: age, sex, vaccine, time of symptom onset, systemic findings, medical history, best-corrected visual acuity, and ocular findings by slit-lamp biomicroscopy as well as multimodal retinal imaging (color fundus, red-free photography, spectral-domain optical coherence tomography, optical coherence tomography angiography, and fluorescein-angiography). Inclusion criteria were the presence of ophthalmologic signs within 30 days after the first or second dose of any COVID-19 vaccine. Results: Of 11 patients, five had arterial occlusion (45.4%), four had venous occlusion (36.4%), and two (18.2%) had nonspecific vascular alterations suggestive of retinal ischemia such as cotton-wool spots. The mean age was 57 (SD = 16; range: 27-84) years. The mean time of symptoms onset was 10 (SD = 5.4; range: 3-16) days. Nine patients were female (81.8%). Systemic risk factors were observed in 36.4% of patients. Two patients had both neurological and visual symptoms, with arterial occlusion. Overall, 36.4% patients had COVID-19 in the previous year. Seven patients (63.6%) received ChAdOx1 nCoV- 19 (AZD1222) vaccine. Conclusions: Our data suggest that retinal events temporally related to COVID-19 vaccination are possible but are very rare. The relationship of these events with post-COVID-19 vaccination warrants further attention to derive a meaningful conclusion. RESUMO Objetivos: o principal objetivo deste estudo foi descrever pacientes com achados vasculares retinianos temporalmente relacionados à vacinação contra COVID-19. Com maior notificação de possíveis eventos adversos similares, esperamos compreender a real dimensão e relevância do que foi apresentado. Métodos: Onze pacientes com queixas visuais após vacinação contra COVID-19 foram estudados. Os dados analisados foram: idade, gênero, tipo de vacinação, tempo de aparecimento de sintomas, achados sistêmicos, antecedentes pessoais, acuidade visual com melhor correção, biomicroscopia e imagem retiniana multimodal (retinografia colorida, red-free, SD-OCT, OCTA e angiofluoresceinografia). Os critérios de inclusão foram a presença de alterações oftalmológicas ocorridas dentro de 30 dias após a primeira ou segunda dose de qualquer vacina contra COVID-19. Resultados: Onze pacientes foram incluídos: 5 com oclusão arterial (45,4%), 4 com oclusão venosa (36,4%) e 2 (18,2%) com alterações não específicas vasculares sugestivas de isquemia retiniana como exsudatos algodonosos. A idade média dos pacientes foi de 57 anos (DP=16; com intervalo de 27 a 84 anos). A média de tempo de aparecimento de sintomas após a vacinação foi de 10 dias (DP=5,4; com intervalo de 3 a 16 dias). Nove dos onze pacientes eram do sexo feminino (81,8%). Fatores de risco sistêmicos foram observados em 36,4% dos pacientes. Dois pacientes tiveram sintomas neurológicos e visuais, com oclusão arterial. 36,4% dos pacientes tiveram infecção prévia por COVID-19 no último ano. Sete pacientes (63,6%) receberam a vacina ChAdOx1 nCoV-19 (AZD1222). Conclusões: nossos dados sugerem que eventos retinianos temporalmente relacionados à vacinação contra COVID-19 são possíveis, porém raros. A relação entre estes eventos pós-vacinais exigem futura atenção antes de maiores conclusões.

Non-alcoholic fatty liver disease (NAFLD) is the first cause of chronic liver disease worldwide. The spectrum is broad from hepatocellular carcinoma, cirrhosis, fibrosis, fatty liver, non-alcoholic steatohepatitis (NASH). NASH is a condition associated with the metabolic syndrome, overweight, obesity, dyslipidemia and type 2 diabetes mellitus. It is a dynamic condition that can regress to isolated steatosis or progress to fibrosis and cirrhosis. Statins exert anti-inflammatory, proapoptotic, and antifibrotic effects. It´s has been proposed that this drugs could have a relevant role in NASH. In this review we provide an overview of current evidence, from mechanisms of statins involved in the modulation of NASH to human trials about the use of statins to treat or attenuate NASH.

This cohort study investigates the rate of pediatrician recommendations for behavioral treatment for preschoolers with an attention-deficit/hyperactivity disorder diagnosis or symptoms.

Endothelial dysfunction is a key player in both the onset and development of atherosclerosis. No study has examined whether healthy dietary patterns can improve microvascular endothelial function in patients with coronary heart disease (CHD) in the long-term and whether this relationship can affect patient’s risk of CHD recurrence. In the CORDIOPREV study, a randomized, double-blind, controlled trial, dietary intervention with either the Mediterranean diet or a low-fat diet was implemented in 1,002 CHD patients. A laser-doppler flowmetry was performed at baseline and after 6 years of follow up in 664 patients, evaluating the effects of this dietary intervention on microvascular basal flow and reactive hyperaemia area, as well as on the risk of CHD recurrence, based on the TRS2P risk score. Basal flow (97.78 ± 2.79 vs. 179.31 ± 5.06 arbitrary perfusion units, 83.38% increase, p p p > 0.05 for the diet-effect). When patients were stratified to low, moderate or high-risk of recurrence, basal flow was similarly increased in all three groups. However, reactive hyperaemia area was improved to a greater extent in patients at the low-risk group compared with those at moderate or high-risk. No differences were observed between diets. Healthy dietary patterns can improve microvascular endothelial function and this improvement persists in the long-term. Patients with a low-risk of CHD recurrence show a greater improvement in reactive vasodilation to ischemia than patients in the moderate or high-risk groups.

Patients with autoimmune diseases were advised to shield to avoid COVID-19, but information on their prognosis is lacking. We characterised 30-day outcomes and mortality after hospitalisation with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza.Multinational network cohort study.Electronic health records data from Columbia University Irving Medical Center (CUIMC) (NYC, United States [US]), Optum [US], Department of Veterans Affairs (VA) (US), Information System for Research in Primary Care-Hospitalisation Linked Data (SIDIAP-H) (Spain), and claims data from IQVIA Open Claims (US) and Health Insurance and Review Assessment (HIRA) (South Korea).All patients with prevalent autoimmune diseases, diagnosed and/or hospitalised between January and June 2020 with COVID-19, and similar patients hospitalised with influenza in 2017-2018 were included.30-day complications during hospitalisation and death.We studied 133,589 patients diagnosed and 48,418 hospitalised with COVID-19 with prevalent autoimmune diseases. The majority of participants were female (60.5% to 65.9%) and aged ≥50 years. The most prevalent autoimmune conditions were psoriasis (3.5 to 32.5%), rheumatoid arthritis (3.9 to 18.9%), and vasculitis (3.3 to 17.6%). Amongst hospitalised patients, Type 1 diabetes was the most common autoimmune condition (4.8% to 7.5%) in US databases, rheumatoid arthritis in HIRA (18.9%), and psoriasis in SIDIAP-H (26.4%).Compared to 70,660 hospitalised with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2% to 4.3% versus 6.3% to 24.6%).Patients with autoimmune diseases had high rates of respiratory complications and 30-day mortality following a hospitalization with COVID-19. Compared to influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality. Future studies should investigate predictors of poor outcomes in COVID-19 patients with autoimmune diseases.Patients with autoimmune conditions may be at increased risk of COVID-19 infection andcomplications.There is a paucity of evidence characterising the outcomes of hospitalised COVID-19 patients with prevalent autoimmune conditions.Most people with autoimmune diseases who required hospitalisation for COVID-19 were women, aged 50 years or older, and had substantial previous comorbidities.Patients who were hospitalised with COVID-19 and had prevalent autoimmune diseases had higher prevalence of hypertension, chronic kidney disease, heart disease, and Type 2 diabetes as compared to those with prevalent autoimmune diseases who were diagnosed with COVID-19.A variable proportion of 6% to 25% across data sources died within one month of hospitalisation with COVID-19 and prevalent autoimmune diseases.For people with autoimmune diseases, COVID-19 hospitalisation was associated with worse outcomes and 30-day mortality compared to admission with influenza in the 2017-2018 season.

Hepatocellular carcinoma (HCC) represents a major cause of morbidity and mortality in the world, but this problem is especially significant in low-resource countries where HCC screening recommendations and strategies are limited. We describe a rare complication of newly diagnosed HCC in a patient with untreated hepatitis B virus (HBV) infection, underscoring the importance of improving screening strategies and promoting early diagnosis of HCC in Sub-Saharan Africa.

Introduction Cholangiocarcinoma (CCA) includes a heterogeneous group of biliary cancers with dismal prognosis and increasing incidence. Information on epidemiology and risk factors are scarce, particularly in Latin America. Aim Describe and analyze a multicentric cohort of CCA patients from Latin America. Methods The Ibero-Latin American Research Network on Cholangiocarcinoma (ILARN-CCA) Registry and ESCALON consortium (www.escalon.eu) collected data from patients diagnosed from 2010 and onwards. Results 183 patients with histologically/cytologically confirmed CCA were included from 5 tertiary hospitals (Brazil,Argentina,Chile,Ecuador and Peru). Median age at diagnosis was 62 years-old (IQR:25-87) and 55.7% were women. Most frequent risk factors were overweight/obesity (n=68;31.1%), diabetes (n=35;19.1%), NAFLD (n=14;7.7%), viral hepatitis (n=5;2.7%), cirrhosis (n=4;2.2%), gallstones (n=10;5.5%), primary sclerosing cholangitis (n=11;6%) and 21.3%(n=39) had no known-risk factor. Intrahepatic CCA was the predominant type (n=73;39.9%), followed by distal (n=49;26.8%) and perihilar (n=38;20.8%). Regional lymph-node invasion was found in 74 (40.4%) and metastasis in 79 (43.2%) patients. Upon diagnosis, 88 patients (48.1%) required upfront biliary stenting prior to main treatments, consisting in resection (n=39;21.3%) or palliative modalities (n=135;73.8%). Recurrence occurred in 64.1%(n=25), with median time-to-recurrence of 13.5 months (95%CI:6.5-18.8). Chemotherapy was delivered to 120 patients (Gemcitabine+Cisplatin:n=105;87.5%) with a median progression-free survival of 4.2 months (95%CI:3.4-4.9). Median overall survival of the entire cohort was 8.2 months (n=183;95%CI:6.3-10.2), 22.5 (n=39;95%CI:11.6-34.1) under surgery, 10.4 (n=87;95%CI:8.4-13.6) under chemotherapy and 2.5 (n=30;95%CI:1.5-3.9) without active treatments (log-rank p Conclusion CCA is associated to diverse etiologies in Latin-America, particularly metabolic disorders. Surgical resection shows favorable outcome, highlighting the need of surveillance strategies in individuals at risk.

To evaluate clinical characteristics of patients admitted to the hospital with coronavirus disease 2019 (COVID-19) in Southern United States and development as well as validation of a mortality risk prediction model.Southern Louisiana was an early hotspot during the pandemic, which provided a large collection of clinical data on inpatients with COVID-19. We designed a risk stratification model to assess the mortality risk for patients admitted to the hospital with COVID-19. Data from 1673 consecutive patients diagnosed with COVID-19 infection and hospitalized between March 1, 2020, and April 30, 2020, was used to create an 11-factor mortality risk model based on baseline comorbidity, organ injury, and laboratory results. The risk model was validated using a subsequent cohort of 2067 consecutive hospitalized patients admitted between June 1, 2020, and December 31, 2020.The resultant model has an area under the curve of 0.783 (95% CI, 0.76 to 0.81), with an optimal sensitivity of 0.74 and specificity of 0.69 for predicting mortality. Validation of this model in a subsequent cohort of 2067 consecutively hospitalized patients yielded comparable prognostic performance.We have developed an easy-to-use, robust model for systematically evaluating patients presenting to acute care settings with COVID-19 infection.

Objective: To report a case of thyroglossal duct carcinoma with concurrent papillary thyroid carcinoma Methods: Design: Case Report Setting: Tertiary National University Hospital Patient: One Results: A 46-year-old woman was diagnosed with thyroglossal duct carcinoma after undergoing a Sistrunk procedure. Due to presence of thyroid nodules, the patient underwent second stage thyroidectomy with central neck dissection which revealed papillary thyroid carcinoma. Conclusion: Thyroglossal duct carcinomas are rare entities and there is no current consensus regarding their management. Difficulties arise in the diagnosis of these tumors as they present similarly to benign thyroglossal duct cysts. Most cases are diagnosed postoperatively. Proper preoperative assessment including head and neck examination, biopsy, and radiologic imaging is necessary to recognize patients who could benefit from more aggressive management. Keywords: thyroglossal carcinoma; thyroglossal duct cyst; papillary thyroid carcinoma

Nonalcoholic fatty liver disease (NAFLD) is now the most common liver condition. Predicting its progression could help clinicians manage and potentially prevent complications. We evaluated the independent and joint effects of metabolic traits on the risk of cirrhosis and hepatocellular carcinoma (HCC) among patients with NAFLD.We assembled a retrospective cohort of patients with NAFLD diagnosed at 130 facilities in the Veterans Administration between January 1, 2004, and December 31, 2008, with follow-up through December 31, 2015. We performed competing risk-adjusted cause-specific Cox models to evaluate the effects of metabolic traits (diabetes, hypertension, dyslipidemia, obesity) as additive or combined indicators on time to develop cirrhosis or HCC or a composite endpoint of both. Of the 271,906 patients, 22,794 developed cirrhosis, and 253 developed HCC during a mean of 9 years follow-up. At baseline, the mean body mass index was 31.6 (SD, 5.6), 28.7% had diabetes, 70.3% had hypertension, and 62.3% had dyslipidemia with substantial overlap among these traits. The risk of progression was the lowest in patients with only one or no metabolic trait. There was a stepwise increase in risk with each additional metabolic trait. Compared with patients with no metabolic trait, patients with both hypertension and dyslipidemia had 1.8-fold higher risk of progression to cirrhosis/HCC (hazard ratio [HR] = 1.8, 95% confidence interval [CI] = 1.59-2.06); the risk was 2.6-fold higher in patients with diabetes, obesity, dyslipidemia, and hypertension (HR = 2.6, 95% CI = 2.3-2.9). These associations were stronger for HCC. Diabetes had the strongest association with HCC in this cohort.Each additional metabolic trait increased the risk of cirrhosis and HCC in patients with NAFLD. Diabetes conferred the highest risk of progression to HCC. Patients with diabetes and coexisting hypertension and obesity may be important targets for secondary prevention.

Background There is limited data regarding the use of emergency departments (EDs) for infectious disease screening and vaccination in resource-limited regions. In these settings, EDs are often the only contact that patients have with the healthcare system, turning an ED visit into an opportune time to deliver preventative health services. Methods In this pilot study, patients that met inclusion criteria were prospectively tested for hepatitis B surface antigen test (HBsAg). Previously unvaccinated patients who tested negative for HBsAg were offered HBV vaccination. The study setting was a public infectious disease hospital in Cordoba, Argentina. The primary outcomes were new HBV diagnoses, as well as vaccination completion between screening modalities (Point-of-Care-Testing-POCT vs. laboratory testing) and same vs. different day vaccination. Results We screened 100 patients for HBV (75 POCT & 25 laboratory). The median age of participants was 35 years (IQR 24-52) and 55% were male. No patients tested positive for HBsAg. All patients who completed first dose vaccination were initially screened with the POCT. No patients screened with laboratory testing returned for vaccination. Patients who were scheduled for vaccination the same day were more likely to complete vaccination compared to those scheduled for another day (75% vs. 14%, p Conclusion Our study supports the use of HBV POCTs in the ED in conjunction with vaccination of HBV-negative individuals. In regions with low HBV endemicity, direct vaccination without HBsAg testing may be more cost effective. We believe that this acute-care screening model is applicable to other resource-limited settings.

Supplemental Digital Content is available in the text., The presence of mutations of BRAF, NRAS, and KIT genes is recognized as playing a role during carcinogenesis. Our study aims to evaluate and review other studies that present the frequency of mutations of BRAF, NRAS, and KIT genes for different populations, and analyse correlation to their clinical-pathological characteristics and to the demographics of melanoma. Thirty-two articles were selected from a collection of published literature studying 6299 patients. The parameters for correlation to different variables were calculated by odds ratio, for random and single effects. 38.5% of patients present BRAF gene mutations, 16.4% in NRAS, and 10% in KIT. Mutations of the BRAF gene were correlated to superficial spreading melanoma (odds ratio = 1.31), localization in the torso (odds ratio = 1.42) and presence of metastases. Mutations in NRAS were correlated to nodular melanoma (odds ratio = 1.57), localized in the limbs (odds ratio = 1.31). Mutations of the KIT gene were correlated to mucosal melanoma (odds ratio = 1.59). Populations in Brazil, the US, Sweden, Italian, and Australia were found to be correlated to mutations of BRAF and melanoma. Populations in Italy, Sweden, Spain, and the US were found to be correlated to mutations of NRAS. Populations in Japan, China, Turkey, Canada, and Russia were found to be correlated to mutations of KIT. Data correlated to the presence of melanoma and population type is due to the amount of studies performed across of globe.

Incident depression has been reported to be associated with poor prognosis in patients with cardiovascular disease (CVD), which might be associated with beta-blocker therapy. Because early detection and intervention can alleviate the severity of depression, we aimed to develop a machine learning (ML) model predicting the onset of major depressive disorder (MDD). A model based on L1 regularized logistic regression was trained against the South Korean nationwide administrative claims database to identify risk factors for the incident MDD after beta-blocker therapy in patients with CVD. We identified 50,397 patients initiating beta-blockers for CVD, with 774 patients developing MDD within 365 days after initiating beta-blocker therapy. An area under the receiver operating characteristic curve (AUC) of 0.74 was achieved. A history of non-selective beta-blockers and factors related to anxiety disorder, sleeping problems, and other chronic diseases were the most strong predictors. AUCs of 0.62&ndash, 0.71 were achieved in the external validation conducted on six independent electronic health records and claims databases in the USA and South Korea. In conclusion, an ML model that identifies patients at high-risk for incident MDD was developed. Application of ML to identify susceptible patients for adverse events of treatment may serve as an important approach for personalized medicine.

Renal artery stenosis (RAS) is a common cause of secondary hypertension (HTN) and may lead to resistant (refractory) HTN despite guideline directed medical therapy. Although randomized controlled trials comparing medical therapy to medical therapy and renal artery stenting have shown no benefit with renal artery stenting, according to comparative effectiveness reviews by the Agency for Healthcare Research and Quality, the trials did not enroll patients with the most severe RAS who would be more likely to benefit from renal stenting. Because of limitations of conventional angiography, it is important to assess the hemodynamic severity of moderate (50%-70%) RAS lesions with a hemodynamic measurement. We review techniques to optimize patient selection, to minimize procedural complications, and to facilitate durable patency of renal stenting. We also review the current ACC/AHA Guidelines and SCAI Appropriate Use Criteria as they relate to renal stenting.

Presentation of the interesting case of a patient suffering from castrate-resistant prostate cancer (CRPC) with bone metastasis, who received concomitant treatment with abiraterone acetate (AA) and radium-223. The patient experienced significant clinical improvement in his quality of life and pain relief after beginning the aforementioned treatment, without being affected by adverse toxicities. Currently, the correct selection of patients to receive radium-223 treatment is still a clinical challenge in the case of CRPC with metastasis. In this article, we discuss the future prospects of this treatment, reviewing current evidence about concomitant therapies with radium-223 and its present state, based upon the recent recommendations from the Pharmacovigilance Risk Assessment Committee (PRAC), and the data presented in the ERA-223 study. Based on our clinical experience, we provide practical orientation for the integration of this radiopharmaceutical in the therapeutic plan for this group of patients. We conclude, despite some of the positive results and our excellent experience, that it would be wise to wait for the results of the clinical trials that are studying the safety and benefits of the combined use of radium-223 with new hormone therapies. Bearing in mind that to date, the only published large-scale randomised trial that investigated the combination of AR-axis-targeted therapy with Ra-223 is negative, the harms of the combination outweighed any benefits in ERA-223. Nonetheless, in order to recommend whether or not this treatment should be used, it is essential to define the patient profile that could benefit from this therapeutic option.

In Argentina, the scorpion species Tityus trivittatus has been the species most commonly associated with serious injury and death.We performed a retrospective study of cases of T trivittatus envenomation that presented to the emergency department at an infectious disease hospital in Cordoba, Argentina, between December 2014 and February 2015. All cases were taxonomically confirmed using criteria established in the Argentine Ministry of Health national guidelines. The primary outcome was classification of clinical presentation (mild/moderate/severe). Classification of clinical presentation was performed in a post hoc fashion using the national guidelines and compared to the classification of clinical presentation given to patients at the time of diagnosis in the emergency department.We included 450 individuals with T trivittatus envenomation. The median age of was 36 y (interquartile range 25-52), and 57% were female. In the emergency department, only 5 patients (1%) were diagnosed as moderate cases and received antivenom; all other cases were diagnosed as mild. Conversely, in our post hoc classification of clinical presentations, 280 patients had mild presentations, 170 had moderate presentations, and no patients had severe presentations. In our cohort, there were no deaths, no inpatient hospital admissions, and no requirements for continuous cardiac monitoring. We found that age50 y, (odds ratio [OR] 2.5, P0.001), time from sting to presentation120 min (OR 2.6, P=0.02), and pre-existing hypertension (OR=3.9, P0.001) were all independently associated with worse post hoc classification severity.Our study exposed factors associated with moderate presentations of scorpion envenomation and proposes the option of conservative treatment for affected adults.

Adherence to a healthy dietary pattern positively influences clinical outcomes in cardiovascular prevention, but long-term adherence is difficult to maintain. We evaluated 5-year changes in dietary habits, adherence achieved, and its maintenance in a cohort of coronary patients from the CORDIOPREV study. 1002 coronary patients were randomized to a Mediterranean diet (n = 502) or a low-fat diet (n = 500) and received individual-group-telephone visits and personalized dietary advice. A validated food-frequency questionnaire, a 14-point Mediterranean diet adherence screener, and a 9-point low-fat diet adherence score were used. Dietary adherence was categorized into Low, Medium, and High Adherence. Changes in nutrient intake, food consumption, and adherence were analyzed on a yearly basis. The maintenance of long-term dietary adherence was evaluated using data after the first year and fifth year. From baseline to 5 years, significant increases were observed in overall dietary adherence (Mediterranean diet from 8.9 to 11.4; low-fat diet from 3.9 to 7.1) and in the percentage of patients considered High Adherence (Mediterranean diet from 41 to 89%; low-fat diet from 4 to 67%). When we evaluated the maintenance of adherence, patients considered Low and Medium Adherence at 1 year increased their adherence at the 5 years with both diets and patients considered High Adherence maintained their adherence with a Mediterranean diet, but decreased their adherence with a low-fat diet. A comprehensive dietary intervention results in an overall long-term improvement and maintenance of adherence to the Mediterranean and low-fat diets. In our population, the Mediterranean diet group achieved a high level of adherence in the short term which was maintained in the long term.

Background/Aims There has been major progress in our understanding of the irritable bowel syndrome (IBS), and novel treatment classes have emerged. The Rome IV guidelines were published in 2016 and together with the growing body of Asian data on IBS, we felt it is timely to update the Asian IBS Consensus. Methods Key opinion leaders from Asian countries were organized into 4 teams to review 4 themes: symptoms and epidemiology, pathophysiology, diagnosis and investigations, and lifestyle modifications and treatments. The consensus development process was carried out by using a modified Delphi method. Results Thirty-seven statements were developed. Asian data substantiate the current global viewpoint that IBS is a disorder of gut-brain interaction. Socio-cultural and environmental factors in Asia appear to influence the greater overlap between IBS and upper gastrointestinal symptoms. New classes of treatments comprising low fermentable oligo-, di-, monosacharides, and polyols diet, probiotics, non-absorbable antibiotics, and secretagogues have good evidence base for their efficacy. Conclusions Our consensus is that all patients with functional gastrointestinal disorders should be evaluated comprehensively with a view to holistic management. Physicians should be encouraged to take a positive attitude to the treatment outcomes for IBS patients. (J Neurogastroenterol Motil 2019;25:343-362)

The Asia-Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia-Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of inflammatory bowel disease workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing, and future revisions are likely as new data continue to emerge.

Goals:We aim to describe the efficacy, safety profile, and variables associated with survival in patients with hepatocellular carcinoma (HCC) treated with sorafenib in South America.Background:Sorafenib has been shown to improve survival in patients with advanced HCC. There are few data on sorafenib use for HCC in South America.Study:We performed a retrospective analysis of HCC cases treated with sorafenib from 8 medical centers in 5 South American countries, between January 2010 and June 2017. The primary endpoint was overall survival (OS), which was defined as time from sorafenib initiation to death or last follow-up. Risk factors for decreased OS were assessed using Cox proportional hazard regression and log-rank tests.Results:Of 1336 evaluated patients, 127 were treated with sorafenib and were included in the study. The median age of individuals was 65 years (interquartile range, 55 to 71) and 70% were male individuals. Median OS in all patients was 8 months (interquartile range, 2 to 17). Variables associated with survival on multivariate analysis were platelets >//

Summary Background There is an urgent need for biomarkers to better stratify patients with idiopathic pulmonary fibrosis by risk for lung transplantation allocation who have the same clinical presentation. We aimed to investigate whether a specific immune cell type from patients with idiopathic pulmonary fibrosis could identify those at higher risk of poor outcomes. We then sought to validate our findings using cytometry and electronic health records. Methods We first did a discovery analysis with transcriptome data from the Gene Expression Omnibus at the National Center for Biotechnology Information for 120 peripheral blood mononuclear cell (PBMC) samples of patients with idiopathic pulmonary fibrosis. We estimated percentages of 13 immune cell types using statistical deconvolution, and investigated the association of these cell types with transplant-free survival. We validated these results using PBMC samples from patients with idiopathic pulmonary fibrosis in two independent cohorts (COMET and Yale). COMET profiled monocyte counts in 45 patients with idiopathic pulmonary fibrosis from March 12, 2010, to March 10, 2011, using flow cytometry; we tested if increased monocyte count was associated with the primary outcome of disease progression. In the Yale cohort, 15 patients with idiopathic pulmonary fibrosis (with five healthy controls) were classed as high risk or low risk from April 28, 2014, to Aug 20, 2015, using a 52-gene signature, and we assessed whether monocyte percentage (measured by cytometry by time of flight) was higher in high-risk patients. We then examined complete blood count values in the electronic health records (EHR) of 45 068 patients with idiopathic pulmonary fibrosis, systemic sclerosis, hypertrophic cardiomyopathy, or myelofibrosis from Stanford (Jan 01, 2008, to Dec 31, 2015), Northwestern (Feb 15, 2001 to July 31, 2017), Vanderbilt (Jan 01, 2008, to Dec 31, 2016), and Optum Clinformatics DataMart (Jan 01, 2004, to Dec 31, 2016) cohorts, and examined whether absolute monocyte counts of 0·95 K/μL or greater were associated with all-cause mortality in these patients. Findings In the discovery analysis, estimated CD14+ classical monocyte percentages above the mean were associated with shorter transplant-free survival times (hazard ratio [HR] 1·82, 95% CI 1·05–3·14), whereas higher percentages of T cells and B cells were not (0·97, 0·59–1·66; and 0·78, 0·45–1·34 respectively). In two validation cohorts (COMET trial and the Yale cohort), patients with higher monocyte counts were at higher risk for poor outcomes (COMET Wilcoxon p=0·025; Yale Wilcoxon p=0·049). Monocyte counts of 0·95 K/μL or greater were associated with mortality after adjusting for forced vital capacity (HR 2·47, 95% CI 1·48–4·15; p=0·0063), and the gender, age, and physiology index (HR 2·06, 95% CI 1·22–3·47; p=0·0068) across the COMET, Stanford, and Northwestern datasets). Analysis of medical records of 7459 patients with idiopathic pulmonary fibrosis showed that patients with monocyte counts of 0·95 K/μL or greater were at increased risk of mortality with lung transplantation as a censoring event, after adjusting for age at diagnosis and sex (Stanford HR=2·30, 95% CI 0·94–5·63; Vanderbilt 1·52, 1·21–1·89; Optum 1·74, 1·33–2·27). Likewise, higher absolute monocyte count was associated with shortened survival in patients with hypertrophic cardiomyopathy across all three cohorts, and in patients with systemic sclerosis or myelofibrosis in two of the three cohorts. Interpretation Monocyte count could be incorporated into the clinical assessment of patients with idiopathic pulmonary fibrosis and other fibrotic disorders. Further investigation into the mechanistic role of monocytes in fibrosis might lead to insights that assist the development of new therapies. Funding Bill & Melinda Gates Foundation, US National Institute of Allergy and Infectious Diseases, and US National Library of Medicine.