Development and Validation of a Tool for Assessing Adherence to Gluten-Free Diet in Patients With Celiac Disease.

INTRODUCTION: Life-long adherence to gluten-free diet (GFD) and its assessment is essential for patients with celiac disease (CeD). We have developed and validated a tool for assessing adherence to GFD which can be used by both physicians and dietitians. METHODS: Phase 1: Development, content validation, and assessment of reliability of tool. Phase 2: Validation of tool against standard dietary evaluation (SDE) (gold standard), immunoglobulin A - anti-tissue transglutaminase antibodies (IgA anti-tTG Ab), and gluten immunogenic peptides in urine. Overall, 380 biopsy-confirmed patients with CeD (derivation cohort: n = 100 [phase 1], n = 210 [phase 2] and independent validation cohort, n = 70) were recruited. RESULTS: Of an initial 90-point questionnaire, 84 items (Celiac Disease: Compliance Assessment Test [CD-CAT.v1]) were retained after content validation and pilot testing. In phase 1, upon administering CD-CAT.v1 on 100 patients, a comprehensive 35-item tool (CD-CAT.v2; α = 0.86) was obtained after removing items with low test-retest reliability and item-rest correlation values. In phase 2, upon administering CD-CAT.v2 on 210 patients, 22 items were removed having low correlation values (R < 0.4) with SDE. Finally, a 13-item tool (CD-CAT.v3; α = 0.84) was obtained with high criterion validity with SDE ( r = 0.806, P < 0.001), moderate convergent validity with celiac disease adherence test ( r = 0.602, P = 0.007), and moderate to weak correlation with urine gluten immunogenic peptides ( r = 0.46, P = 0.001) and IgA anti-tTG Ab ( r = 0.39, P = 0.008), respectively. The final 13-item tool also strongly correlated with SDE ( r = 0.78, P < 0.001) in an independent validation cohort of 70 patients with CeD. Principal component analysis identified 3 relevant subscales with a cumulative variance of 62%. The sensitivity and specificity of CD-CAT.v3 were 80% and 91%, respectively, with an area under curve of 0.905 with SDE. The obtained cutoff score of <19 from the receiver operating characteristic curve was further categorized as 13 = excellent, 14-18 = very good, 19-28 = average, and >28 = poor adherence to GFD. DISCUSSION: CD-CAT is a new and rapid tool for monitoring dietary adherence to GFD with high sensitivity and specificity, which can be administered by both physicians and dietitians.

Thromboelastography-Guided versus Standard-of-Care or On-Demand Platelet Transfusion in Patients with Cirrhosis and Thrombocytopenia Undergoing Procedures: A Randomized Controlled Trial.

PURPOSE: To determine the rate of platelet transfusion in patients with cirrhosis and severe thrombocytopenia (platelet counts <50 × 109/L) undergoing high-risk invasive procedures when prescribed by thromboelastography (TEG) compared with empirical and on-demand transfusion strategies. MATERIALS AND METHODS: This was a single-center, single-blinded, randomized controlled trial. Patients with cirrhosis and severe thrombocytopenia undergoing high-risk invasive procedures were randomized into 3 groups: TEG group, transfusions based on TEG parameters; standard of care (SOC) group, 3 units of random donor platelets before procedure; and on-demand group, transfusions based on procedural adverse events/clinician's discretion. The primary outcome was periprocedural platelet transfusion in each arm. RESULTS: Eighty-seven patients were randomized (29 in each group) with no significant differences in demographics/coagulation profile/procedures. The median platelet count was 33 × 109/L (interquartile range, 26-43 × 109/L). Percutaneous liver biopsy was the most common procedure (46, 52.9%). Significantly lower number of patients in the TEG group received platelets (4 cases, 13.8%; 95% CI, 3.9-31.7) compared with SOC group (100%; 95% CI, 88.1-100; P < .001). Four patients in the on-demand group received platelets (13.8%; 95% CI, 3.9-31.7). Minor (World Health Organization [WHO] Grade 2) procedure-related bleeding occurred in 3 (10%; 95% CI, 2.2-27.4) patients in the TEG-guided transfusion group compared with 1 (3.4%; 95% CI, 0.1-17.8) patient each in the SOC and on-demand groups (P = .43), although the study was not powered for comparison of bleeding rates. No bleeding-related mortality was observed in any of the 3 groups. CONCLUSIONS: TEG-prescribed transfusion reduced prophylactic transfusions in patients with cirrhosis and severe thrombocytopenia undergoing high-risk invasive procedures. The study was not powered for comparison of bleeding rates.

Impact of delay in the diagnosis on the severity of celiac disease.

BACKGROUND AND AIM: Celiac disease (CeD) has now become a global disease with a worldwide prevalence of 0.67%. Despite being a common disease, CeD is often not diagnosed and there is a significant delay in its diagnosis. We reviewed the impact of the delay in the diagnosis on the severity of manifestations of CeD. METHODS: We reviewed clinical records of 726 consecutive patients with CeD from the Celiac Clinic database and the National Celiac Disease Consortium database. We extracted specific data including the demographics, symptoms at presentation, time of onset of symptoms, time to diagnosis from the onset of the symptoms, and relevant clinical data including fold-rise in anti-tissue transglutaminase antibody (IgA anti-tTG Ab) and severity of villous and crypt abnormalities as assessed using modified Marsh classification. RESULTS: The median duration between the onset of symptoms and the diagnosis of CeD was 27 months (interquartile range 12-60 months). A longer delay in the diagnosis of CeD from the onset of symptoms was associated with lower height for age, lower hemoglobin, higher fold rise in IgA Anti tTG titers, and higher severity of villous and crypt abnormalities. About 18% of patients presented with predominantly non-gastrointestinal complaints and had a longer delay in the diagnosis of CeD. CONCLUSIONS: There is a significant delay in the diagnosis of CeD since the onset of its symptoms. The severity of celiac disease increases with increasing delay in its diagnosis. There is a need to keep a low threshold for the diagnosis of CeD in appropriate clinical settings.

Validation of no-biopsy pathway for the diagnosis of celiac disease in Asian adults: a multicenter retrospective study.

BACKGROUND AND AIM: While European Society of Pediatric Gastroenterology Hepatology and Nutrition advocates a no-biopsy pathway for the diagnosis of celiac disease (CeD) in children if IgA anti-tissue transglutaminase antibody (anti-tTG ab) titer is ≥10-fold upper limit of normal (ULN) and have a positive IgA anti-endomysial antibody (EMA); the data for anti-tTG Ab titer-based diagnosis of CeD in adults is still emerging. We planned to validate if IgA anti-tTG Ab titer ≥10-fold predicts villous abnormalities of modified Marsh grade ≥2 in Asian adult patients with CeD. METHODS: We recruited 937 adult patients with positive anti-tTG Ab from two databases, including AIIMS Celiac Clinic and Indian National Biorepository. The diagnosis of definite CeD was made on the basis of a positive anti-tTG Ab and the presence of villous abnormalities of modified Marsh grade ≥2. RESULTS: Of 937 adult patients with positive anti-tTG Ab, 889 (91.2%) showed villous abnormalities of modified Marsh grade ≥2. Only 47.6% of 889 adults with CeD had anti- tTG Ab titers of ≥10-fold. The positive predictive value (PPV) and specificity of anti tTG Ab titer ≥10-fold for predicting modified Marsh grade ≥2 were 99.8% and 98%, respectively. At anti-tTG Ab titer ≥11-fold, specificity and PPV were 100% for predicting villous abnormalities of modified Marsh grade ≥2. CONCLUSIONS: Approximately 50% of adults with CeD may benefit from the no biopsy pathway, reducing the health burden and risks of gastroscopy/anesthesia.

Energy-efficient resistive switching synaptic devices based on patterned Ag nanotriangles with tunable gaps fabricated using plasma-assisted nanosphere lithography.

The development of synaptic devices featuring metallic nanostructures with brain-analog hierarchical architecture, capable of mimicking cognitive functionalities, has emerged as a focal point in neuromorphic computing. However, existing challenges, such as inconsistent and unpredictable switching, high voltage requirements, unguided filament formation, and detailed fabrication processes, have impeded technological progress in the domain. The present study addresses some of these challenges by leveraging periodic nanostructures of Ag fabricated via plasma-assisted nanosphere lithography (NSL). The triangular nanostructures with a preferred orientation offer enhanced localized electric fields, facilitating low voltage electromigration at the sharp edges to guide predictive filament formation. A thorough investigation into gap control between the nanostructures through oxygen plasma treatment enables the attainment of an optimized low switching voltage of 0.86 V and retention at an ultra-low current compliance of 100 nA. The optimized device consumes low power, typically in the fJ range, akin to biological neurons. Furthermore, the device showcases intriguing synaptic characteristics, including controlled transition from short- to long-term potentiation, associative learning, etc., projecting its potential in perceptive learning, memory formation, and brain-inspired computing. COMSOL Multiphysics simulation, supported by ex situ electron microscopic imaging, confirms the controlled and predictable filament formation facilitated by electric field enhancement across the strategic nanostructures. Thus, the work highlights the potential of NSL-based cost-effective fabrication techniques for realizing efficient and biomimetic synaptic devices for neuromorphic computing applications.

Role of antioxidants in modulating anti-tumor T cell immune resposne.

It has been well established that in addition to oxygen's vital in cellular respiration, a disruption of oxygen balance can lead to increased stress and oxidative injury. Similarly, reduced oxygen during tumor proliferation and invasion generates a hypoxic tumor microenvironment, resulting in dysfunction of immune cells and providing a conducive milieu for tumors to adapt and grow. Strategies to improve the persistence tumor reactive T cells in the highly oxidative tumor environment are being pursued for enhancing immunotherapy outcomes. To this end, we have focused on various strategies that can help increase or maintain the antioxidant capacity of T cells, thus reducing their susceptibility to oxidative stress/damage. Herein we lay out an overview on the role of oxygen in T cell signaling and how pathways regulating oxidative stress or antioxidant signaling can be targeted to enhance immunotherapeutic approaches for cancer treatment.

Sieving out non-celiac gluten sensitivity amongst patients with irritable bowel syndrome.

OBJECTIVES: It is challenging to make diagnosis of non-celiac gluten sensitivity/non-celiac wheat sensitivity (NCGS/NCWS) in clinical practice, since there is no biomarker and diagnosis is based on response to gluten-free-diet (GFD). We used anti-gliadin antibody (AGA) for screening patients with IBS for gluten-sensitivity. METHODS: 492 Adult-patients with IBS underwent screening for celiac disease and gluten-sensitivity using IgA anti-tissue transglutaminase antibody and IgA-AGA and IgG-AGA, respectively. Patients with positive AGA (IgA and/or IgG) were invited to follow GFD, those willing were put on GFD for 6-weeks. Responsive patients were given gluten re-challenge. Diagnosis of NCGS was confirmed if they had recurrence of symptoms. RESULTS: Of 492 patients with IBS, AGA was positive in 61(12.4 %), hence suspected to have gluten-sensitivity. Of 31 who agreed to participate and followed GFD for 6-weeks, 17 (54.8 %) had complete (>30 % improvement) and 10(32.2 %) had partial (>20 % improvement) response. All 17 complete-responders were given gluten re-challenge for 6-weeks, symptoms recurred in all and hence were confirmed to have NCGS/NCWS. Significant decrease in AGA levels occurred almost in all GFD-responders. CONCLUSIONS: 12.4 % IBS patients have biological evidence of gluten/wheat-sensitivity. Almost 87 % patients with IBS having AGA responded to GFD. The value of AGA may further be explored as a biomarker for screening for the presence of NCGS, before recommending this test for the clinical practice.

Gastrointestinal tract involvement in patients with potential celiac disease beyond the small intestine: An early proof with IgA anti-tissue transglutaminase-2 antibody deposits.

Background: IgA anti-tissue transglutaminase-2 antibody (anti-TG2Ab) deposits in intestinal and extraintestinal organs have been used to link the respective pathological changes in these organs with celiac disease (CeD). Aims: To know if parts of intestine other than the duodenum, such as esophagus, stomach, and colon, have any pathology related to potential CeD or have mucosal IgA anti-TG2 Ab deposits. Settings and Design: A prospective case-control study conducted from April 2018 to December 2019. Materials and Methods: Nine patients with potential CeD and 27 age- and gender-matched patients with irritable bowel syndrome were recruited as cases and controls, respectively. Mucosal biopsies were collected from esophagus, stomach, duodenum, and rectosigmoid regions, histological changes were evaluated, and IgA anti-TG2 Ab deposits were analyzed in these regions by two-color immunohistochemical staining. Statistics: Data were analyzed using statistical software Stata 14.0. Results: No distinct difference in mucosal lymphocytosis were identified between biopsies of patients with potential CeD and controls at the following sites: esophagus (11.1% vs 0%, P = 0.079), stomach (14.3% vs 7.7%, P = 0.590), and rectum (20% vs 0%, P = 0.067). Co-localized IgA anti-TG2Ab deposits were observed more in potential CeD than in controls at esophagus 22.2% (2/9) vs 0%, P = 0.012; stomach 66.7% (6/9) vs 11.5% (3/26), P < 0.001; and duodenum 66.7% (6/9) vs 0%, P < 0.001 but not at rectum 0% (0/4) vs 0% (0/25). Conclusion: Although histological changes are not distinct, a subset of subjects with potential CeD has pan-intestinal involvement other than in the duodenum.

Incidence and Predictors of Liver-Related Events in Patients With Nonalcoholic Fatty Liver Disease.

Background: Nonalcoholic fatty liver disease (NAFLD) is the commonest type of liver disease worldwide. We aimed to assess the incidence and predictors of liver-related events (LREs) and mortality in NAFLD patients. Methods: NAFLD patients (n = 957) evaluated between January 2000 and November 2021 were included. Patients were categorised as noncirrhosis (NC), compensated cirrhosis (CC) and decompensated cirrhosis (DC), and the incidence of LRE and mortality were estimated and compared. Results: The proportions of NC, CC and DC were 87.8% (n = 840), 8.8% (n = 84) and 3.4% (n = 33), respectively. The median follow-up duration was 3.9 (3.0-5.7) years, and the total cumulative duration was 4633 person-years. The incidence of LRE per 100 person-years was 0.14, 2.72 and 10.24 in patients with NC, CC and DC, respectively. The incidence of mortality was 0.12, 1.05 and 4.24 per 100 person-years, respectively, in the 3 groups. The causes of mortality in the 3 groups were liver related in 1/5 (20%), 3/4 (75%) and 6/9 (66.7%), respectively. Overall, the mortality rate was higher in those with diabetes than those without diabetes (log-rank P value = 0.005). On further analysis, diabetes was associated with poor outcomes only in NC group (log-rank P value = 0.036), and not in CC (log-rank P value = 0.353) or DC groups (log-rank P value = 0.771). On multivariate Cox proportional hazard analysis, age (hazard ratio [HR] 1.070), hypertension (HR 4.361) and DC (HR 15.036) were independent predictors of poor outcomes. Liver stiffness measurement, bilirubin, CC and DC were independent predictors of LRE. Conclusion: In our study of NAFLD from India, the incidence of LRE was found to be similar to that seen in Western studies. In NC NAFLD, diabetes was associated with poor outcomes.

Communicating Visualizations without Visuals: Investigation of Visualization Alternative Text for People with Visual Impairments.

Alternative text is critical in communicating graphics to people who are blind or have low vision. Especially for graphics that contain rich information, such as visualizations, poorly written or an absence of alternative texts can worsen the information access inequality for people with visual impairments. In this work, we consolidate existing guidelines and survey current practices to inspect to what extent current practices and recommendations are aligned. Then, to gain more insight into what people want in visualization alternative texts, we interviewed 22 people with visual impairments regarding their experience with visualizations and their information needs in alternative texts. The study findings suggest that participants actively try to construct an image of visualizations in their head while listening to alternative texts and wish to carry out visualization tasks (e.g., retrieve specific values) as sighted viewers would. The study also provides ample support for the need to reference the underlying data instead of visual elements to reduce users' cognitive burden. Informed by the study, we provide a set of recommendations to compose an informative alternative text.

Reciprocal SOX2 regulation by SMAD1-SMAD3 is critical for anoikis resistance and metastasis in cancer.

Growth factors in tumor environments are regulators of cell survival and metastasis. Here, we reveal the dichotomy between TGF-ß superfamily growth factors BMP and TGF-ß/activin and their downstream SMAD effectors. Gene expression profiling uncovers SOX2 as a key contextual signaling node regulated in an opposing manner by BMP2, -4, and -9 and TGF-ß and activin A to impact anchorage-independent cell survival. We find that SOX2 is repressed by BMPs, leading to a reduction in intraperitoneal tumor burden and improved survival of tumor-bearing mice. Repression of SOX2 is driven by SMAD1-dependent histone H3K27me3 recruitment and DNA methylation at SOX2's promoter. Conversely, TGF-ß, which is elevated in patient ascites, and activin A can promote SOX2 expression and anchorage-independent survival by SMAD3-dependent histone H3K4me3 recruitment. Our findings identify SOX2 as a contextual and contrastingly regulated node downstream of TGF-ß members controlling anchorage-independent survival and metastasis in ovarian cancers.

Management of COVID-19 from the pulmonologist's perspective: a narrative review.

Introduction: The COVID-19 pandemic has provided global challenges to health-care facilities in ensuring the delivery of care to patients. Tremendous international collaboration has enabled the swift formulation of evidence-based guidelines that aim to clarify day-to-day issues faced by physicians and other health-care providers on the frontlines.Areas covered: In order to provide answers to the common questions and dilemmas faced by physicians and policymakers, especially those handling pulmonary manifestations of COVID-19, the authors made a list of pertinent clinical topics that were reviewed between 21st of August, 2020 to 30th of August, 2020 by the authors using online databases that included PubMed, EBSCO, and the Cochrane Library. Literature was reviewed and included based on relevance to the topics selected. The review was aimed to serve as a quick reference for addressing practical issues faced during patient care in the ongoing pandemic with a brief account of the management of COVID-19 patients as per international guidelines.Expert opinion: As more evidence continues to generate regarding the optimal methods of managing COVID-19 cases while caring for non-COVID patients concurrently, physicians will need to constantly reeducate themselves to keep pace with a rapidly evolving landscape of therapeutic options.

Expanded dengue syndrome in secondary dengue infection: A case of biopsy proven rhabdomyolysis induced acute kidney injury with intracranial and intraorbital bleeds.

Dengue fever is endemic in the Indian subcontinent and can have myriad presentations. The term expanded dengue syndrome (EDS) is used for atypical manifestations in dengue fever. We present a rare case of EDS in a patient with secondary dengue infection who developed rhabdomyolysis induced acute kidney injury (RAKI) along with intracranial and intraorbital bleeds. Patient was successfully managed in our institute and was discharged in stable condition. To the best of our knowledge, this is the only reported case of simultaneous occurrence of these complications in a dengue patient. This case is being presented to make clinicians aware of the spectrum of dengue infection.

Diagnostic Stability of Acute and Transient Psychotic Disorders in Developing Country Settings: An Overview.

Acute and transient psychotic disorders (ATPD), introduced in the International Classification of Diseases (ICD-10) diagnostic system in 1992, are not receiving much attention in developing countries. Therefore, the main objective of this article is to review the literature related to the diagnostic stability of ATPD in developing countries. A PubMed search was conducted to review the studies concerned with this issue in the context of developing countries, as diagnostic stability is more of a direct test of validity of psychiatric diagnoses. Four publications were found. According to the literature search, the stability percentage of the ICD-10 ATPD diagnosis is 63-100%. The diagnostic shift is more commonly either towards bipolar disorder or schizophrenia, if any. Shorter duration of illness (<1 month) and abrupt onset (<48 hours) predict a stable diagnosis of ATPD. Based on available evidence, the diagnosis of ATPD appears to be relatively stable in developing countries. However, it is difficult to make a definitive conclusion, as there is a substantial lack of literature in developing country settings.

Unipolar mania: recent updates and review of the literature.

Introduction. Unipolar mania (UM) has received less than the expected attention, when compared to its contemporary mood disorders, unipolar depression (UD) and bipolar disorder (BD). Method. The literature search included PUBMED and PSYCINFO databases. Cross-searches of key references were made to identify other articles of importance. Results. There seems to be a bipolar subgroup with a stable, unipolar recurrent manic course. Although UM does not have significant differences from bipolar mania in terms of sociodemographic variables, there are certain significant differences in clinical features. UM is reported to have more grandiosity, psychotic symptoms, and premorbid hyperthymic temperament, but less rapid cycling, suicidality, seasonality, and comorbid anxiety disorders. It seems to have a better course of illness with better social and professional adjustment. However, its response to lithium prophylaxis is found to be poor as compared to classical BD and valproate could be a better choice in this case. Conclusion. The available literature suggests that UM has certain differences from classical BD. The evidence, however, is insufficient to categorize it as separate diagnostic entity. However, considering UM as a course specifier of BD would be a reasonable step.

An Overview of Risk Factors Associated to Post-partum Depression in Asia.

Post partum depression (PPD) is an important complication of child-bearing. It requires urgent interventions as it can have long-term adverse consequences if ignored, for both mother and child. If PPD has to be prevented by a public health intervention, the recognition and timely identification of its risk factors is must. We in this review have tried to synthesize the results of Asian studies examining the risk factors of PPD. Some risk factors, which are unique to Asian culture, have also been identified and discussed. We emphasize on early identification of these risk factors as most of these are modifiable and this can have significant implications in prevention of emergence of post partum depression, a serious health issue of Asian women.

Psychosocial Functioning in Depressive Patients: A Comparative Study between Major Depressive Disorder and Bipolar Affective Disorder.

Introduction. Major depressive disorder (MDD) and bipolar affective disorder (BAD) are among the leading causes of disability. These are often associated with widespread impairments in all domains of functioning including relational, occupational, and social. The main aim of the study was to examine and compare nature and extent of psychosocial impairment of patients with MDD and BAD during depressive phase. Methodology. 96 patients (48 in MDD group and 48 in BAD group) were included in the study. Patients were recruited in depressive phase (moderate to severe depression). Patients having age outside 18-45 years, psychotic symptoms, mental retardation, and current comorbid medical or axis-1 psychiatric disorder were excluded. Psychosocial functioning was assessed using Range of Impaired Functioning Tool (LIFE-RIFT). Results. Domains of work, interpersonal relationship, life satisfaction, and recreation were all affected in both groups, but the groups showed significant difference in global psychosocial functioning score only (P = 0.031) with BAD group showing more severe impairment. Conclusion. Bipolar depression causes higher global psychosocial impairment than unipolar depression.

Study of Inter-relationship of Depression, Seizure Frequency and Quality of Life of People with Epilepsy in India.

Epilepsy is a chronic neurological disorder that can have profound physical, social and psychological consequences. We aimed to assess the clinical predictors of quality of life of people with epilepsy. We recruited 31 patients suffering from epilepsy in this cross-sectional study. Their clinical profile was recorded. Quality Of Life in Epilepsy (QOLIE-31) was used to assess quality of life of our patients. Depression was screened by Neurological Disorders Depression Inventory in Epilepsy (NDDI-E). Among all the clinical variables, only seizure frequency significantly correlated with seizure worry (P=0.002), emotional well-being (P=0.026) and social functions (P=0.013) subscales of QOLIE-31. NDDIE score showed a significant negative correlation with all the subscales of QOLIE-31 except medication effects (P=0.993). A significant positive correlation was also noted between seizure frequency and NDDI-E score (r=0.417, P=0.020). Seizure frequency and depression are the most important predictors of quality of life in epilepsy patients. The management of patients with epilepsy should not only be aimed at just preventing seizures but the treating clinicians should also be cognizant about depression which itself can significantly affect the quality of life of patients.