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BACKGROUND: The choice of transcatheter aortic valve replacement (TAVR) prosthesis is crucial in optimizing short- and long-term outcomes. The objective of this study was to conduct a meta-analysis comparing outcomes of third-generation balloon-expandable valves (BEV) vs self-expanding valves (SEV). METHODS: Electronic databases were searched from inception to June 2023 for studies comparing third-generation BEV vs SEV. Primary outcome was all-cause mortality. Secondary outcomes included clinical and hemodynamic end points. Random-effects models were used to calculate pooled odds ratios (ORs) or weighted mean differences (WMDs). RESULTS: The meta-analysis included 16 studies and 10,174 patients (BEV, 5753 and SEV, 4421). There were no significant differences in 1-year all-cause mortality (OR, 1.15; 95% CI, 0.89-1.48) between third-generation BEV vs SEV. TAVR with third generation BEV was associated with a significantly lower risk of TIA/stroke (OR, 0.62; 95% CI, 0.44-0.87), permanent pacemaker implantation (OR, 0.55; 95% CI, 0.44-0.70), and ≥moderate paravalvular leak (PVL, OR, 0.43; 95% CI, 0.25-0.75), and higher risk of ≥moderate patient-prosthesis mismatch (OR, 3.76; 95% CI, 2.33-6.05), higher mean gradient (WMD, 4.35; 95% CI, 3.63-5.08), and smaller effective orifice area (WMD, -0.30; 95% CI, -0.37 to -0.23), compared with SEV. CONCLUSION: In this meta-analysis, TAVR with third-generation BEV vs SEV was associated with similar all-cause mortality, lower risk of TIA/stroke, permanent pacemaker implantation, and ≥moderate PVL, but higher risk of ≥moderate patient-prosthesis mismatch, higher mean gradient, and smaller effective orifice area. Large, adequately powered randomized trials are needed to evaluate long-term outcomes of TAVR with latest generations of BEV vs SEV.

Abstract Increased intracranial pressure (ICP) ≥15 mmHg is associated with adverse neurological outcomes, but needs invasive intracranial monitoring. Using the publicly available MIMIC-III Waveform Database (2000–2013) from Boston, we developed an artificial intelligence-derived biomarker for elevated ICP (aICP) for adult patients. aICP uses routinely collected extracranial waveform data as input, reducing the need for invasive monitoring. We externally validated aICP with an independent dataset from the Mount Sinai Hospital (2020–2022) in New York City. The AUROC, accuracy, sensitivity, and specificity on the external validation dataset were 0.80 (95% CI, 0.80–0.80), 73.8% (95% CI, 72.0–75.6%), 73.5% (95% CI 72.5–74.5%), and 73.0% (95% CI, 72.0–74.0%), respectively. We also present an exploratory analysis showing aICP predictions are associated with clinical phenotypes. A ten-percentile increment was associated with brain malignancy (OR = 1.68; 95% CI, 1.09-2.60), intracerebral hemorrhage (OR = 1.18; 95% CI, 1.07–1.32), and craniotomy (OR = 1.43; 95% CI, 1.12–1.84; P

Lymph node metastasis (LNM) is one of the major prognostic factors in human gastrointestinal carcinomas (GICs). The lymph node-positive patients have poorer survival than node-negative patients. LNM is directly associated with the recurrence and poor survival of patients with GICs. The early detection of LNM in patients and designing effective therapies to suppress LNM may significantly impact the survival of these patients. The rapid progress made in proteomic technologies could be successfully applied to identify molecular targets for cancers at high-throughput levels. LC-MS/MS analysis enables the identification of proteins involved in LN metastasis, which can be utilized for diagnostic and therapeutic applications. This review summarizes the studies on LN metastasis in GICs using proteomic approaches to date.

BackgroundThe sale of loose cigarettes or bidis can undermine the purpose of requiring health warning labels (HWLs) on cigarette packs and bidi bundles by diminishing their visibility and legibility. ObjectiveThis mixed-methods study aims to examine the association between purchase behavior (loose vs pack or bundle), HWL exposure, and responses to HWLs among Indian adults who smoke. MethodsData were analyzed from the 2018-2019 India Tobacco Control Policy Survey and from 28 in-depth interviews conducted with Indian adults who smoked in 2022. The Tobacco Control Policy Survey sample included tobacco users who bought cigarettes (n=643) or bidis (n=730), either loose or in packs or bundles at their last purchase. Ordinal regression models were fit separately for cigarettes and bidis, whereby HWL variables (noticing HWLs, reading and looking closely at HWLs, forgoing a cigarette or bidi because of HWLs, thinking about health risks of smoking, and thinking about quitting smoking cigarettes or bidis because of HWLs) were regressed on last purchase (loose vs packs or bundles). In-depth interviews with participants from Delhi and Mumbai who purchased loose cigarettes in the last month were conducted, and thematic analysis was used to analyze the interview data. ResultsSurvey findings indicated that about 74.3% (478/643) of cigarette users and 11.8% (86/730) of bidi users reported having bought loose sticks at their last purchase. Those who purchased loose cigarettes (vs packs) noticed HWLs less often (estimate –0.830, 95% CI –1.197 to –0.463, P

Background: Alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH) are significant forms of liver disease and may progress to end-stage liver disease, cirrhosis and potentially malignant complications. The most difficult aspect of establishing a diagnosis of NASH is distinguishing it from ASH. Laboratory markers such as AST, ALT and GGT lack sufficient sensitivity and specificity. Aim: To study the clinical, biochemical and histological differences between non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH). Materials and Methods: Sixty histologically confirmed cases of non-alcoholic steatohepatitis and 38 cases of alcoholic steatohepatitis were included in the study. A modified form of scoring system proposed by Yip and Burt was used to grade histological features of NASH and ASH. Results: Mean age was 42.85 ± 12.36 years in ASH group and 35.07 ± 8.06 years for NASH group. Male: Female ratio was 37:1 in ASH and 4:1 in NASH. The mean ALT (P = 0.012), SAP (P = 0.003), serum bilirubin (P = 0.001), AST/ALT ratio (P = 0.03), steatosis (P < 0.001), ballooning degeneration of hepatocytes (P < 0.001), portal inflammation (P < 0.001), Mallory hyaline (P = 0.001), ductular proliferation and fibrosis (P < 0.001) showed a significant difference between ASH and NASH cases. Discussion: Older age, male sex, larger derangement of serum biochemistry, high serum bilirubin, AST/ALT > 1, more ballooning degeneration, portal inflammation, Mallory′s hyaline, hepatocytic and ductular cholestasis, ductular proliferation and higher stage of fibrosis favors a diagnosis of ASH. Younger age, high ALT, AST/ALT < 1, higher grade of steatosis and absence of extensive neutrophilic portal inflammation favors a diagnosis of NASH.

Xanthogranulomatous inflammation of gallbladder wall can extend and infiltrate adjacent organs which can be mistaken for malignancy on preoperative investigations and, intraoperatively, often leads to extensive surgical resections. Only the histopathologic examination of the specimen allows correct diagnosis. We hereby review clinicopathologic findings of six cases which underwent extensive surgeries on clinical, radiological and intraoperative suspicion of gallbladder carcinoma which turned out to be xanthogranulomatous cholecystitis (XGC). There was no evidence of malignancy on histopathologic examination. Xanthogranulomatous inflammation extended into liver, duodenum, colon and stomach in case 1; liver and colon in case 2; liver, duodenum, colon in case 3; stomach, duodenum, colon in case 4; stomach and duodenum in case 5 and duodenum and colon in case 6. Lymph nodes in all the six cases showed reactive hyperplasia. We present here the clinico-radiologic findings of these cases, techniques which may help differentiate between an XGC and a gallbladder carcinoma and also discuss the management of these cases.

Background: Tissue micro-array enables the analysis of a large number of tissues simultaneously. Widespread use of this technology is hampered by the high cost of commercial array instruments. We describe our experience of constructing tissue micro-array in a simple method using easily available and inexpensive instruments. Materials and Methods: We used an 11-19 gauge (G) bone marrow trephine biopsy needle/ small sized slotted screwdriver to punch holes in the wax blocks. Cores were taken from donor tissue blocks using a bone marrow trephine biopsy needle and arrayed into host paraffin wax blocks. A detailed database was constructed for each array constructed. Results: The array blocks were used over a period of one year as internal control for immunohistochemistry (IHC), quality control and research. It took about 10 minutes to construct a nine-dot array and about one hour for a 56-dot array. During IHC, the average loss of control dots was less than one per cent. We did not see any loss of antigenicity in the control sections even after four weeks storage. Discussion: Tissue array construction by the technique described here is inexpensive and reliable alternative to automated instruments. Because it is easy to modify the arrays by varying the core size, it is easy to adapt this to individual labs and requirements. We recommend using blocks with cores in 3 x 3 to 5 x 4 grids as controls in IHC and for standardizing antibodies and array blocks with a larger number of cores for research.

Background: Children have different natural history of Hepatitis B virus (HBV) infection. They commonly develop asymptomatic chronic carrier state which is less frequently seen in adults. We describe a rare case of acute on chronic liver failure (ACLF) in the course of concurrent autoimmune hepatitis (AIH) and HBV infection and replication of HBV following the treatment for autoimmune hepatitis. Case Report: A 15 year old male child presented with jaundice and altered sensorium. Physical examination showed hepatosplenomegaly. The liver function tests were markedly altered. Serology was positive for anti liver kidney microsomal antibody (LKM), hepatitis B surface antigen (HBsAg) and immunoglobulin M (IgM) anti hepatitis B core antigen (HBc Ag). Liver biopsy showed chronic hepatitis with features of acute exacerbation. Patient was started on treatment with azathioprine and prednisolone for AIH following which clinical and biochmemical improvement was noted. After two years of continued treatment a repeat biopsy performed showed fairly reduced histological activity, but marked replication of the HBV (immunohistochemistry for HBsAg and anti HBcAg showed diffuse cytoplasmic and nuclear positivity respectively). These findings suggest viral replication although the patient was clinically stable. At six months follow-up after the second biopsy and cessation of azathioprine and prednisolone, there were raised liver enzymes and viral load, hence the patient was started on antiviral drug Entecavir to which there was good response and the patient is presently doing well. Conclusion: We describethe rare co occurrence of HBV infection and AIH with marked HBV replication following the treatment for AIH

IntroductionBanning the sales of loose cigarettes is recommended by Article 16 of the World Health Organization – Framework Convention on Tobacco Control. This study aims to understand the perceptions of cigarette users and tobacco vendors regarding such a ban.MethodsUsing a systematic recruitment and interview protocol, we interviewed cigarette users (n = 28) and tobacco vendors (n = 28) from two Indian cities where sales of loose cigarettes were banned (Mumbai) or not banned (Delhi). Separate semi-structured interview guides were used for users and vendors. Interview questions focused on reasons for purchasing loose cigarettes, preference for buying and selling loose vs. packs, thoughts on the necessity of banning loose cigarettes, and the perceived impact of the policy ban for vendors and cigarette users. We performed thematic analysis and used NVivo for organizing transcript coding.ResultsThe main reasons users cited for purchasing loose cigarettes were financial constraints, social restrictions (fear of getting caught), and limiting cigarette consumption. In Mumbai, awareness of the existing ban was poor among both users and vendors. Those who were aware did not think the policy had been implemented. Users thought that loose cigarettes promoted smoking initiation and prevented them from quitting. Both users and vendors reported that a ban on loose cigarettes would reduce cigarette consumption and promote quit attempts as it would not be possible for everyone to purchase packs because of financial and social reasons.ConclusionUsers in both cities reported easy access to and widespread availability of loose cigarettes. Low awareness of the ban in Mumbai suggested inadequate enforcement. A country-wide ban on the sale of loose cigarettes could be highly effective in preventing smoking initiation and promoting quitting.

Background Many patients with severe aortic stenosis (AS) and an indication for aortic valve replacement (AVR) do not undergo treatment. The reasons for this have not been well studied in the transcatheter AVR era. We sought to determine how patient- and process-specific factors affected AVR use in patients with severe AS. Methods and Results We identified ambulatory patients from 2016 to 2018 demonstrating severe AS, defined by aortic valve area [Formula: see text]1.0 cm2. Propensity scoring analysis with inverse probability of treatment weighting was used to evaluate associations between predictors and the odds of undergoing AVR at 365 days and subsequent mortality at 730 days. Of 324 patients with an indication for AVR (79.3±9.7 years, 57.4% men), 140 patients (43.2%) did not undergo AVR. The odds of AVR were reduced in patients aged >90 years (odds ratio [OR], 0.24 [95% CI, 0.08-0.69]; P=0.01), greater comorbid conditions (OR, 0.88 per 1-point increase in Combined Comorbidity Index [95% CI, 0.79-0.97]; P=0.01), low-flow, low-gradient AS with preserved left ventricular ejection fraction (OR, 0.11 [95% CI, 0.06-0.21]), and low-gradient AS with reduced left ventricular ejection fraction (OR, 0.18 [95% CI, 0.08-0.40]) and were increased if the transthoracic echocardiogram ordering provider was a cardiologist (OR, 2.46 [95% CI, 1.38-4.38]). Patients who underwent AVR gained an average of 85.8 days of life (95% CI, 40.9-130.6) at 730 days. Conclusions The proportion of ambulatory patients with severe AS and an indication for AVR who do not receive AVR remains significant. Efforts are needed to maximize the recognition of severe AS, especially low-gradient subtypes, and to encourage patient referral to multidisciplinary heart valve teams.

Objective: Age is the strongest contributor to 10-year predicted atherosclerotic cardiovascular disease (ASCVD) risk. Some older adults have a predicted ASCVD risk ≥7.5 %, without established risk factors. We sought to compare ASCVD incidence among adults with predicted ASCVD risk ≥7.5 %, with and without established ASCVD risk factors, to adults with predicted risk

Abstract Lymph node (LN) metastasis is the earliest sign of metastatic spread and an established predictor of poor outcome in gallbladder cancer (GBC). Patients with LN positive GBC have a significantly worse survival (median survival- 7 months) than patients with LN negative disease (median survival- ~ 23 months) in spite of standard treatment which includes extended surgery followed by chemotherapy, radiotherapy and targeted therapy. This study aims at understanding the underlying molecular processes associated with LN metastasis in GBC. Here, we used iTRAQ-based quantitative proteomic analysis using tissue cohort comprising of primary tumor of LN negative GBC (n = 3), LN positive GBC (n = 4) and non-tumor controls (Gallstone disease, n = 4), to identify proteins associated with LN metastasis. A total of 58 differentially expressed proteins (DEPs) were found to be specifically associated with LN positive GBC based on the criteria of p value ≤ 0.05, fold change ≥ 2 and unique peptides ≥ 2. These include the cytoskeleton and associated proteins such as keratin, type II cytoskeletal 7 (KRT7), keratin type I cytoskeletal 19 (KRT19), vimentin (VIM), sorcin (SRI) and nuclear proteins such as nucleophosmin Isoform 1 (NPM1), heterogeneous nuclear ribonucleoproteins A2/B1 isoform X1 (HNRNPA2B1). Some of them are reported to be involved in promoting cell invasion and metastasis. Bioinformatic analysis of the deregulated proteins in LN positive GBC using STRING database identified ‘neutrophil degranulation’ and ‘HIF1 activation’ to be among the top deregulated pathways. Western blot and IHC analysis showed a significant overexpression of KRT7 and SRI in LN positive GBC in comparison to LN negative GBC. KRT7, SRI and other proteins may be further explored for their diagnostics and therapeutic applications in LN positive GBC.

Background Right ventricular ejection fraction (RVEF) and end‐diastolic volume (RVEDV) are not readily assessed through traditional modalities. Deep learning–enabled ECG analysis for estimation of right ventricular (RV) size or function is unexplored. Methods and Results We trained a deep learning–ECG model to predict RV dilation (RVEDV >120 mL/m2), RV dysfunction (RVEF ≤40%), and numerical RVEDV and RVEF from a 12‐lead ECG paired with reference‐standard cardiac magnetic resonance imaging volumetric measurements in UK Biobank (UKBB; n=42 938). We fine‐tuned in a multicenter health system (MSHoriginal [Mount Sinai Hospital]; n=3019) with prospective validation over 4 months (MSHvalidation; n=115). We evaluated performance with area under the receiver operating characteristic curve for categorical and mean absolute error for continuous measures overall and in key subgroups. We assessed the association of RVEF prediction with transplant‐free survival with Cox proportional hazards models. The prevalence of RV dysfunction for UKBB/MSHoriginal/MSHvalidation cohorts was 1.0%/18.0%/15.7%, respectively. RV dysfunction model area under the receiver operating characteristic curve for UKBB/MSHoriginal/MSHvalidation cohorts was 0.86/0.81/0.77, respectively. The prevalence of RV dilation for UKBB/MSHoriginal/MSHvalidation cohorts was 1.6%/10.6%/4.3%. RV dilation model area under the receiver operating characteristic curve for UKBB/MSHoriginal/MSHvalidation cohorts was 0.91/0.81/0.92, respectively. MSHoriginal mean absolute error was RVEF=7.8% and RVEDV=17.6 mL/m2. The performance of the RVEF model was similar in key subgroups including with and without left ventricular dysfunction. Over a median follow‐up of 2.3 years, predicted RVEF was associated with adjusted transplant‐free survival (hazard ratio, 1.40 for each 10% decrease; P=0.031). Conclusions Deep learning–ECG analysis can identify significant cardiac magnetic resonance imaging RV dysfunction and dilation with good performance. Predicted RVEF is associated with clinical outcome.

Background and aims: Although young children's gaze behaviors in experimental task contexts have been shown to be potential biobehavioral markers relevant to autism spectrum disorder (ASD), we know little about their everyday gaze behaviors. The present study aims (1) to document early gaze behaviors that occur within a live, social interactive context among children with and without ASD and their parents, and (2) to examine how children's and parents' gaze behaviors are related for ASD and typically developing (TD) groups. A head-mounted eye-tracking system was used to record the frequency and duration of a set of gaze behaviors (such as sustained attention [SA] and joint attention [JA]) that are relevant to early cognitive and language development. Methods: Twenty-six parent--child dyads (ASD group =13, TD group =13) participated. Children were between the ages of 3 and 8 years old. We placed head-mounted eye trackers on parents and children to record their parent- and child-centered views, and we also recorded their interactive parent--child object play scene from both a wall- and ceiling-mounted camera. We then annotated the frequency and duration of gaze behaviors (saccades, fixation, SA, and JA) for different regions of interest (object, face, and hands), and attention shifting. Independent group t-tests and ANOVAs were used to observe group comparisons, and linear regression was used to test the predictiveness of parent gaze behaviors for JA. Results: The present study found no differences in visual experiences between children with and without ASD. Interestingly, however, significant group differences were found for parent gaze behaviors. Compared to parents of ASD children, parents of TD children focused on objects and shifted their attention between objects and their children's faces more. In contrast, parents of ASD children were more likely to shift their attention between their own hands and their children. JA experiences were also predicted differently, depending on the group: among parents of TD children, attention to "objects" predicted JA, but among parents of ASD children, attention to their children predicted JA. Conclusion: Although no differences were found between gaze behaviors of autistic and TD children in this study, there were significant group differences in parents' looking behaviors. This suggests potentially differential pathways for the scaffolding effect of parental gaze for ASD children compared with TD children. Implications: The present study revealed the impact of everyday life, social interactive context on early visual experiences, and point to potentially different pathways by which parental looking behaviors guide the looking behaviors of children with and without ASD. Identifying parental social input relevant to early attention development (e.g., JA) among autistic children has implications for mechanisms that could support socially mediated attention behaviors that have been documented to facilitate early cognitive and language development and implications for the development of parent-mediated interventions for young children with or at risk for ASD.

Abstract Background Extramedullary plasmacytoma is an uncommon entity that most commonly involves nasopharynx or upper respiratory tract. Involvement of the gastrointestinal tract occurs in approximated 10% of cases. Isolated primary plasmacytoma of colon is rare and only 7 well documented cases have been reported in the literature. Case presentation We present a case of 42 year male who presented with diarrhea. Multiple colonic strictures were found on investigation. Colonoscopic biopsy was not helpful in making any specific diagnosis. Patient underwent subtotal colectomy. Isolated primary colonic plasmacytoma was found on histopathological examination. Conclusion Plasmacytoma is known to occur in extra osseous sites. Primary colonic plasmacytoma, however, is a rare clinical entity. Primary colonic plasmacytoma may have varying clinical presentations including multiple colonic strictures that may mimic colonic tuberculosis or inflammatory bowel disease. Although these cases are rare, treating physician as well as radiologist, and pathologist should be aware of this entity.

Background: A majority of the patients with gall bladder cancer (GBCa) present at an advanced stage and have poor survival. The aim is to retrospectively study the role of guided FNA in the diagnosis of GBCa in a superspecialty institute and to describe the cytomorphologic spectrum of gall bladder (GB) lesions in the North Indian population. Materials and Methods: All suspected cases of GBCa who underwent guided FNA from the primary GB mass or metastatic liver space-occupying lesion from 2017 to 2019 were included. The aspirate smears were retrieved and analyzed for cytomorphological features independently by two cytopathologists. The neoplastic lesions were classified according to the WHO 2019 classification. Results: Of 489 cases, fine needle aspiration cytology (FNAC) was diagnostic in 463 cases (94.6%), of which 417 (90.1%) were positive for malignancy, 35 (7.5%) were inflammatory, and 11 (2.4%) were inconclusive for malignancy. Adenocarcinoma not otherwise specified (NOS) was the most common type seen in 330 cases (79.1%) and 87 (20.9%) were unusual variants. These included papillary adenocarcinoma (22, 5.2%), mucinous adenocarcinoma (12, 2.8%), signet ring carcinoma (2,0.4%), adenosquamous carcinoma (8, 1.9%), squamous cell carcinoma (10, 2.4%), neuroendocrine neoplasms (7, 1.7%), undifferentiated carcinoma (24, 5.7%) and non-Hodgkin lymphoma (2,0.4%), respectively. Immunohistochemistry on the cell block confirmed the diagnosis wherever possible. Histopathology was discordant in 5 out of 33 cases. Conclusion: Guided FNAC is a sensitive investigation that plays a crucial role in confirming the diagnosis and deciding the further treatment options in advanced-stage GBCa patients. The uncommon variants of GBCa can be reliably categorized on cytology.

Schmincke described lymphoepithelioma as an undifferentiated carcinoma with abundant lymphoid stroma in the nasopharynx. Tumors with a similar histomorphology in extrapharyngeal areas have been referred to as lymphoepithelioma-like carcinoma (LELC). The association of an Ebstein-Barr virus (EBV) infection with lymphoepithelioma is well established in the nasopharynx but not so well at the extrapharyngeal sites. Only four cases of LELC have been reported in the gall bladder, of which all were negative for the EBV. This paper reports the first case of an EBV-associated mixed gall bladder carcinoma exhibiting a distinct phenotype of LELC and adenocarcinoma with mucinous differentiation. The EBV was confirmed by the strong granular membranous and cytoplasmic expression of LMP-1 (latent membrane protein-1) on immunohistochemistry and nuclear EBER RNA on chromogen in-situ hybridization in the tumor. This is the first case of LELC positive for EBV in the gall bladder. LELC has a more favorable prognosis than conventional adenocarcinoma or squamous cell carcinoma, irrespective of the site. Although a higher T stage and nodal metastasis were exceptional in the present case in contrast to the previous cases, the EBV-associated lymphocytic response might limit the disease spread and confer better overall survival and prognosis in these patients. Nevertheless, more prospective studies with a larger cohort will be needed to understand the pathogenesis, biological behavior, and prognosis of this rare entity.

BackgroundResearch clearly demonstrates social determinants of health (SDOH) impact health outcomes. Provider consideration of patient SDOH in prevention and treatment planning is critical for improved health care quality and health equity. Despite awareness of the connections between SDOH and improved population health, research demonstrates few providers document patient SDOH. ObjectiveThis qualitative study aimed to better understand the barriers and facilitators of SDOH assessment, documentation, and referral in different health care settings and roles. MethodsIndividual semistructured interviews were conducted with practicing health care providers in South Carolina between August 25, 2022, and September 2, 2022. Participants were recruited via community partners’ web-based newsletters or listservs using a purposive sampling design. An interview guide with 19 questions was used to explore the following research question: How do SDOH impact patient health and what are the facilitators and barriers experienced by multidisciplinary health care providers assessing and documenting patient SDOH? ResultsParticipants (N=5) included a neonatal intensive care unit registered nurse, a nurse practitioner, a certified nurse midwife, a family and preventive medicine physician, and a counselor (licensed clinical social worker) with careers spanning 12 to 32 years. Participant responses are presented according to the following 5 themes: participants’ understanding of SDOH for the patient population, assessment and documentation practices, referrals to other providers and community-based resources, barriers and facilitators of SDOH assessment and documentation, and SDOH assessment and documentation training preferences. Overall, participants were aware of the importance of including patient SDOH in assessment and intervention but noted a variety of institutional and interpersonal barriers to assessment and documentation, including time constraints, perceptions of stigma around discussion of SDOH, and limited referral protocols. ConclusionsIncentivizing inclusion of patient SDOH in health care must be facilitated from the top down, so assessment and documentation can be universally implemented in a pragmatic way that works for providers in a variety of roles and settings for the betterment of health care quality, health equity, and improved population health outcomes. Partnering with community organizations can serve to augment health care organizations’ resource and referral availability for addressing patients’ social needs.

Autoimmune hepatitis (AIH) is a chronic, relapsing and remitting, immune-mediated liver disease that progresses to cirrhosis if left untreated. A significant number of patients may present with acute hepatitis or acute liver failure, which are often misdiagnosed as toxic liver injury. AIH shows a preponderance in young women but may be seen in children and the elderly. Diagnosis requires the integration of clinical, biochemical, and serologic parameters, along with supportive liver histology and exclusion of other causes of liver disease. Liver biopsy is a prerequisite for diagnosis of AIH, to assess severity and stage of disease, exclude other entities, and recognize any concurrent morbidities. No single biomarker or histologic feature is pathognomonic for AIH. The diagnostic and histologic criteria have undergone several modifications since the original scoring system was proposed by the International Autoimmune Hepatitis Group (IAIHG) in 1993. Recently, the IAIHG has proposed consensus recommendations for histologic criteria, relevant for both acute and chronic AIH. This review article will describe the evolving diagnostic criteria for AIH, with their limitations and utility, and with an emphasis on the role of liver histology in the diagnosis and management of AIH.

Abstract The authors examined the proportion of US adults that would have their high blood pressure (BP) status changed if systolic BP (SBP) and diastolic BP (DBP) were measured with systematic bias and/or random error versus following a standardized protocol. Data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES; n = 5176) were analyzed. BP was measured up to three times using a mercury sphygmomanometer by a trained physician following a standardized protocol and averaged. High BP was defined as SBP ≥130 mm Hg or DBP ≥80 mm Hg. Among US adults not taking antihypertensive medication, 32.0% (95%CI: 29.6%,34.4%) had high BP. If SBP and DBP were measured with systematic bias, 5 mm Hg for SBP and 3.5 mm Hg for DBP higher and lower than in NHANES, the proportion with high BP was estimated to be 44.4% (95%CI: 42.6%,46.2%) and 21.9% (95%CI 19.5%,24.4%). Among US adults taking antihypertensive medication, 60.6% (95%CI: 57.2%,63.9%) had high BP. If SBP and DBP were measured 5 and 3.5 mm Hg higher and lower than in NHANES, the proportion with high BP was estimated to be 71.8% (95%CI: 68.3%,75.0%) and 48.4% (95%CI: 44.6%,52.2%), respectively. If BP was measured with random error, with standard deviations of 15 mm Hg for SBP and 7 mm Hg for DBP, 21.4% (95%CI: 19.8%,23.0%) of US adults not taking antihypertensive medication and 20.5% (95%CI: 17.7%,23.3%) taking antihypertensive medication had their high BP status re‐categorized. In conclusions, measuring BP with systematic or random errors may result in the misclassification of high BP for a substantial proportion of US adults.

Only a few small studies have shown the association between high ankle-brachial pressure index (ABI >1.4) and adverse cardiovascular (CV) events and mortality. Although there is abundant literature depicting the association between ABI and overall systemic atherosclerosis, it typically focuses on low ABI. Furthermore, historically, many studies focusing on peripheral artery disease have excluded high ABI participants. We aimed to study the mortality outcomes of persons with high ABI in the National Health and Nutrition Examination Survey (NHANES). We obtained ABI from participants aged ≥40 years for survey years 1999 to 2004. We defined low a ABI as ≤0.9, normal ABI as 0.9 to 1.4, and high ABI as >1.4 or if the ankle pressures were >245 mm Hg. Demographics, various comorbidities, and laboratory test results were obtained at the time of the survey interview. Multivariable adjusted hazard ratios (HRs) along with 95% confidence intervals (CIs) were calculated for CV and all-cause mortality via Cox proportional hazards regression. Mortality was linked to all NHANES participants for follow-up through December 31, 2019, by the Centers for Disease Control and Prevention. We identified 7639 NHANES participants with available ABI. Of these, 6787 (89%) had a normal ABI, 646 (8%) had a low ABI, and 206 (3%) had elevated ABI. Of participants with high ABI, 50% were men, 15% were African Americans, 10% were current smokers, 56% had hypertension, 33% had diabetes, 15% had chronic kidney disease (CKD), and 18% had concomitant coronary artery disease (CAD). Diabetes (odds ratio [OR], 2.4; 95% CI, 1.7-3.2), CAD (OR, 1.6; 95% CI, 1.0-2.4), and CKD (OR, 1.5; 95% CI, 1.0-2.3) at baseline were associated with having a high ABI, respectively. A high ABI was associated independently with elevated CV (HR, 2.6; 95% CI, 2.1-3.1; P <.0001) and all-cause mortality (HR, 2.5; 95% CI, 2.2-2.8; P <.0001) after adjusting for covariates, including diabetes, CKD, CAD, current smoking, cancer, and hypertension. A high ABI is associated with an elevated CV and all-cause mortality, similar to patients with PAD. High ABI participants should receive the same attention and aggressive medical therapies as patients with PAD. [ABSTRACT FROM AUTHOR]

Gastric hyperplastic polyps (GHP) account for a majority of benign gastric polyps. Most of the GHPs are

Gallbladder cancer (GBC) is an aggressive malignancy of the gastrointestinal tract with a poor prognosis. It is important to understand the molecular processes associated with the pathogenesis of early stage GBC and identify proteins useful for diagnostic and therapeutic strategies. Here, we have carried out an iTRAQ-based quantitative proteomic analysis of tumor tissues from early stage GBC cases (stage I, n=7 and stage II, n=5) and non-tumor controls (n=6) from gallstone disease (GSD). We identified 357 differentially expressed proteins (DEPs) based on ≥ 2 unique peptides and ≥ 2 fold change with p value < 0.05. Pathway analysis using the STRING database showed, ‘neutrophil degranulation’ to be the major upregulated pathway that includes proteins such as MPO, PRTN3, S100A8, MMP9, DEFA1, AZU, and ‘ECM organization’ to be the major downregulated pathway that includes proteins such as COL14A1, COL1A2, COL6A1, COL6A2, COL6A3, BGN, DCN. Western blot and/or IHC analysis confirmed the elevated expression of MPO, PRTN3 and S100A8 in early stage of the disease. Based on the above results, we hypothesize that there is an increased neutrophil infiltration in tumor tissue and neutrophil degranulation leading to degradation of extracellular matrix (ECM) proteins promoting cancer cell invasion in the early stage GBC. Some of the proteins (MPO, MMP9, DEFA1) associated with ‘neutrophil degranulation’ showed the presence of ‘signal sequence’ suggesting their potential as circulatory markers for early detection of GBC. Overall, the study presents a protein dataset associated with early stage GBC.

Background and aims Although young children's gaze behaviors in experimental task contexts have been shown to be potential biobehavioral markers relevant to autism spectrum disorder (ASD), we know little about their everyday gaze behaviors. The present study aims (1) to document early gaze behaviors that occur within a live, social interactive context among children with and without ASD and their parents, and (2) to examine how children's and parents’ gaze behaviors are related for ASD and typically developing (TD) groups. A head-mounted eye-tracking system was used to record the frequency and duration of a set of gaze behaviors (such as sustained attention [SA] and joint attention [JA]) that are relevant to early cognitive and language development. Methods Twenty-six parent–child dyads (ASD group = 13, TD group = 13) participated. Children were between the ages of 3 and 8 years old. We placed head-mounted eye trackers on parents and children to record their parent- and child-centered views, and we also recorded their interactive parent–child object play scene from both a wall- and ceiling-mounted camera. We then annotated the frequency and duration of gaze behaviors (saccades, fixation, SA, and JA) for different regions of interest (object, face, and hands), and attention shifting. Independent group t-tests and ANOVAs were used to observe group comparisons, and linear regression was used to test the predictiveness of parent gaze behaviors for JA. Results The present study found no differences in visual experiences between children with and without ASD. Interestingly, however, significant group differences were found for parent gaze behaviors. Compared to parents of ASD children, parents of TD children focused on objects and shifted their attention between objects and their children's faces more. In contrast, parents of ASD children were more likely to shift their attention between their own hands and their children. JA experiences were also predicted differently, depending on the group: among parents of TD children, attention to objects predicted JA, but among parents of ASD children, attention to their children predicted JA. Conclusion Although no differences were found between gaze behaviors of autistic and TD children in this study, there were significant group differences in parents’ looking behaviors. This suggests potentially differential pathways for the scaffolding effect of parental gaze for ASD children compared with TD children. Implications The present study revealed the impact of everyday life, social interactive context on early visual experiences, and point to potentially different pathways by which parental looking behaviors guide the looking behaviors of children with and without ASD. Identifying parental social input relevant to early attention development (e.g., JA) among autistic children has implications for mechanisms that could support socially mediated attention behaviors that have been documented to facilitate early cognitive and language development and implications for the development of parent-mediated interventions for young children with or at risk for ASD. Note: This paper uses a combination of person-first and identity-first language, an intentional decision aligning with comments put forth by Vivanti (Vivanti, 2020), recognizing the complexities of known and unknown preferences of those in the larger autism community.

Gallbladder cancer (GBC) is the sixth most common gastrointestinal tract cancer with a very low overall survival and poor prognosis. Profiling of cancer-derived extracellular vesicles (EVs) is an emerging strategy for identification of candidate biomarkers for the detection and prognosis of the disease. The aim of the study was to analyse the protein content from GBC cell line- derived EVs with emphasis on proteins which could be used as candidate biomarkers for the detection of GBC. NOZ and OCUG-1 cell lines were cultured and EVs were isolated from conditioned media. LC-MS/MS analysis of total EV proteins led to the identification of a total of 268 proteins in both the cell lines. Of these, 110 proteins were identified with ≥2 unique peptides with ≥2 PSMs in at least two experimental and technical replicate runs. STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) database was used to perform bioinformatics analysis of 110 proteins which showed ‘cell adhesion molecule binding’, ‘integrin binding’, ‘cadherin binding’ among the top molecular functions and ‘focal adhesion’ to be among the top pathways associated with the EV proteins. A total of 42 proteins including haptoglobin (HP), pyruvate kinase (PKM), annexin A2 (ANXA2), thrombospondin 1 (THBS1), were reported to be differentially abundant in GBC tissue. Of these, 16 proteins were reported to be differentially abundant in plasma and plasma-derived EVs. We infer these proteins to be highly important to be considered as potential circulatory biomarkers for the detection of GBC. To check the validity of this hypothesis, one of the proteins, haptoglobin (HP) as a representative case, was analysed in plasma by quantitative Enzyme- linked immunosorbent assay (ELISA) and we observed its increased levels in GBC in comparison to controls (p value= 0.0063). Receiver operating characteristic (ROC) curve analysis for GBC vs controls showed an Area under the ROC Curve (AUC) of 0.8264 for HP with 22% sensitivity against 100% specificity. We propose that HP along with other candidate proteins may be further explored for their clinical application.