Development and validation of a tool for assessing adherence to gluten free diet in patients with Celiac disease (Celiac Disease: Compliance Assessment Test; CD-CAT).

OBJECTIVE: Life-long adherence to gluten-free diet (GFD) and its assessment is essential for celiac disease (CeD) patients. We have developed and validated a tool for assessing adherence to GFD which can be used by both physicians and dietitians. DESIGN: Phase-I: Development, content validation and assessment of reliability of tool. Phase-II: Validation of tool against standard dietary evaluation (SDE) (gold standard), IgA anti-tissue transglutaminase antibody (IgA-anti-tTG Ab) and gluten immunogenic peptides in urine (Urine-GIP). Overall, 380 biopsy-confirmed CeD patients [Derivation-cohort: n=100(Phase:I), n=210(Phase:II) and Independent validation cohort, n=70)were recruited. RESULTS: Of initial 90-point questionnaire, 84-items (CD-CAT.v1) were retained after content validation and pilot testing. In Phase:I, upon administering CD-CAT.v1on 100 patients, a comprehensive 35-items tool (CD-CAT.v2;α=0.86) was obtained after removing items with low test-retest reliability and item-rest correlation values. In Phase:II, upon administering CD-CAT.v2 on 210patients,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 CDAT (r=0.602, p=0.007) and moderate to weak correlation with urine GIP (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 CeD patients. Principal component analysis identified three relevant sub-scales 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 cut-off score of <19 from ROC-curve was further categorized as: 13=excellent,14-18=very good, 19-28=average and >28=poor adherence to GFD. CONCLUSION: 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.

Perplexing First Branchialcleft Anomalies-A Case Series with Review of Literature.

Incomplete obliteration of the branchial apparatus results in the formation of branchial cleft anomalies. First branchial cleft anomalies may persist anywhere in the first branchial arch, from the external auditory canal at the level of the bony cartilaginous junction to the submandibular triangle. The majority of cases present in childhood as an opening in the skin though they may present as cysts or neck masses, mostly mistaken for neck abscesses which leads to inadequate treatment and complications. Here different cases of first branchial cleft anomalies with variable presentation and treatment are illustrated. The need for proper diagnosis and adequate treatment cannot be overemphasized to avoid mismanagement and complications.

Correlation between intestinal stem cell niche changes and small bowel crypt failure in patients with treatment-naïve celiac disease.

OBJECTIVES: We hypothesized that crypt failure in the small bowel results in villous flattening in patients with celiac disease (CeD). We investigated whether alterations in the stem cell niche (ISC) are responsible for this phenomenon. MATERIALS AND METHODS: We included 92 duodenal (D2/3) biopsies from treatment-naive patients of CeD and 37 controls. All underwent screening for serum anti-tissue transglutaminase and endoscopic upper small bowel biopsy. Immunohistochemical markers were used to investigate ISC niche alterations, including LGR5 for crypt basal cells (CBC), Bmi1 for position 4+ cells, ß-Defensin for Paneth cells, R-spondin1 as WNT activator, transcription factor-4 as WNT transcription factor, BMP receptor1A as WNT inhibitor, fibronectin-1 as periepithelial stromal cell marker, H2AX as apoptosis marker, and Ki67 as proliferation marker. We also analyzed IgA anti-tTG2 antibody deposits by using dual-color immunofluorescence staining. RESULTS: We found that in biopsies from patients with treatment-naive CeD with modified Marsh grade 3a-3c changes, the epithelial H2AX apoptotic index was upregulated than in controls. LGR5+ crypt basal cells were upregulated in all modified Marsh grades compared to controls. However, the Ki67 proliferation index, expressions of WNT-activator RSPO1, and position-4 cell marker Bmi1 did not significantly alter in patients' biopsies as compared to controls ( P = 0.001). We also observed depletion of pericrypt stromal fibronectin-1 in patients with CeD compared to controls. In addition, we identified IgA anti-TG2 antibody deposits in pericrypt stroma. CONCLUSIONS: Our data suggests that ISC niche failure is a plausible hypothesis for villous flattening in patients with CeD, resulting from pericrypt IgA anti-TG2 antibody complex-mediated stromal depletion.

Clinical Profile, Intensive Care Needs and Predictors of Outcome Among Children Admitted with Non-COVID Severe Acute Respiratory Illness (SARI) During the Pandemic.

OBJECTIVES: To study the epidemiology of non-coronavirus disease-2019 (non-COVID-19) respiratory viral infections with respect to their clinical profile, intensive care needs and predictors of outcome once the non-pharmacological interventions (NPI) during the coronavirus disease-2019 (COVID-19) pandemic were relaxed. METHODS: Retrospective analysis of children with Severe Acute Respiratory Illness (SARI) who were SARS-CoV-2 negative, admitted to the Pediatric Emergency/Intensive Care Unit (PICU) from July 2021 through October 2021 was conducted. RESULTS: One hundred and thirty nine children with median age of 11 (4-28.5) mo were included. Besides respiratory symptoms in all, diarrhea was reported in 90 (64.7%) children. Nearly half (n = 66; 47%) presented in hypoxemic respiratory failure (SpO2 <88%). Fifty-two (37.4%) children had co-morbidities, commonest being congenital heart disease in 12 (23.1%). Baseline parameters revealed leukopenia (specifically lymphopenia) 39 (28%), elevated aspartate transaminase [Serum glutamic-oxaloacetic transaminase (SGOT)] in 108 (77.6%), elevated N-acetyl-cysteine-activated creatinine kinase (CK-NAC) 23 (79%) and lactate dehydrogenase (LDH) 15 (88%). Intensive care needs included mechanical ventilation 51 (36.6%), vasoactive support 34 (24.5%), and renal replacement therapy 10 (7.1%). Forty-two (30.2%) children developed multi-organ dysfunction syndrome (MODS). One hundred and three (74.1%) children were discharged, 31 (22.3%) died, and 5 (3.6%) left against medical advice. On multivariate regression analysis, elevated liver enzymes (>5 times normal), hypoxemic respiratory failure at admission, hypotensive shock and MODS predicted mortality. CONCLUSIONS: A surge in non-COVID SARI was observed once lockdown measures were relaxed. Nearly 1/3rd progressed to multi-organ failure and died. Elevated liver enzymes, hypoxemic respiratory failure at admission, hypotensive shock and MODS predicted death.

Intra-parotid Course and Variations in the Branching Pattern of Facial Nerve: Our Experience.

Facial nerve is responsible for the facial expressions and its preservation during parotidectomy is an important aspect for the operating surgeon. The nerve has a long course and the terminal part traverses through the parotid gland. The branching pattern of the nerve within the gland is highly complex and variable, making parotidectomy a challenging surgery. A cross-sectional record based study was conducted in a tertiary care hospital of a medical college in north India between November 2020 and December 2021 with an aim to describe the branching pattern of the facial nerve within the parotid gland. Patients of all age groups and both genders who underwent superficial parotidectomy for benign parotid gland tumors were taken into consideration. The branching pattern of the nerve was observed and recorded. Twenty patients were included in the study. In seventy percent cases the nerve divided into two main branches whereas in the rest, three branches emerged. In sixty five percent cases, the upper division (temporofacial) further divided into two branches whereas in rest it divided into three. The lower division (cervicofacial) divided into two subdivisions in majority of the cases. Multiple communications were found in the branches given off from the upper division and buccal branch had the most variable origin. A knowledge of branching pattern and the communications between the branches of facial nerve helps in avoiding an iatrogenic injury during parotidectomy and preserving the nerve function.

Falsely elevated anti-tissue transglutaminase antibodies in patients with immunoproliferative small intestinal diseases: A case series.

Immunoproliferative small intestinal disease (IPSID) is an uncommon disease of the small intestine. There is a similarity in the clinical presentations of enteropathic diseases, including celiac disease, tropical sprue, IPSID, and Whipple's disease. A differentiation between them is based on the use of a highly specific serological test for celiac disease and specific histological characteristics. We found that IgA-anti-tissue transglutaminase antibody (IgA-tTG Ab) is falsely elevated in a subset of patients with IPSID. The levels of IgA-tTG Ab fall with the treatment of IPSID. The healthcare professional should be aware of the conditions that lead to a false-positive anti-tTG Ab. Intestinal mucosal biopsies even in the presence of anti-tTG Ab should be done in endemic regions as they provide an opportunity for making a diagnosis of alternative and uncommon diseases before the diagnosis of celiac disease.

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.

Tracing the Anti-cancer Mechanism of Pleurotus osteratus by the Integrative Approach of Network Pharmacology and Experimental Studies.

The present study identified the probable mechanism behind the anti-cancer activity of the hexane fraction of Pleurotus osteratus (HFPO) using network pharmacology and experimental validation. HFPO myco-metabolites targets and targets related to the cancer were mined from the online web server, and overlapping targets were screened. Out of the 74 overlapping targets, 33 targets were identified in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of cancer. Furthermore, the main active myco-metabolites and hub targets were identified by network analysis of the compound-targets network and protein-protein interaction (PPI), respectively. Molecular docking results showed good binding affinity of the hub targets with their respective myco-metabolites. HFPO induced in-vitro anti-cancer activity by affecting the PI3K-AKT-mTOR pathway, besides time-dependent cell cytotoxicity and apoptotic cell body formation. Additionally, tumor volume reduction was observed in HFPO-treated Ehrlich ascites carcinoma (EAC) bearing Swiss albino mice. Overall, HFPO induces anti-cancer potential by modulating the PI3K-AKT-mTOR signaling pathway.

Expression of Vascular Endothelial Growth Factor in Patients With Premalignant Lesions and Squamous Cell Carcinoma of Oral Cavity.

To evaluate and compare expression of VEGF in patients of premalignant lesions and squamous cell carcinoma of oral cavity. The cross sectional observational study is undertaken at the department of otorhionolaryngology and pathology, PGIMER and Dr RML Hospital, New Delhi,from 1st Nov 2017 to 31st March 2019,with a sample size of 30 cases each of premalignant lesions and oral squamous cell carcinoma immunohistochemistry by polymer method. In the participants with oral SCC, VEGF expression of Score 1 was observed in verrucous and well differentiated tumor, Score 2 in moderately differentiated SCC & Score 3 in poorly differentiated SCC with a p value of 0.0001. The observed difference and value of proportion p, is statically significant. In this study we concluded that VEGF expression increases as the lesion progresses from premalignant lesions to oral squamous cell carcinoma and is strongly associated with lymph node status (N-staging). Thus, VEGF can be a target in chemotherapy and its therapeutic implications in the HNSCC needs further research. Levels of Evidence 1A: Systematic review of randomized control trials.

A lumpy bumpy stomach: The more the murkier.

This report describes the radiological and endoscopic findings in a 54-year-old male who presented with epigastric pain. The patient underwent an upper gastrointestinal (GI) barium study followed by axial imaging, which demonstrated nodular gastric wall thickening. The classic findings of aggressive primary gastric diffuse large B-Cell lymphoma are presented with a brief review differentiating the pathological subtypes, important for patient prognostication and planning of therapy.

Experimental Analysis of Steel Circular Hollow Section under Bending Loads: Comprehensive Study of Mechanical Performance.

The present study aimed at evaluating the mechanical performance under bending loads of circular hollow sections of steel. Different bending tests have been carried out by applying two-point loads, to determine and examine the effects of the diameter, the thickness of the section, and the span of the beam on the performance of the steel tube. The effects of square opening and variation in the number of openings on the performance of these sections have also been examined. Ten samples of hollow circular beams of varying thickness (2 mm, 3 mm, and 6 mm), varying diameter (76.2 mm, 101.6 mm, and 219 mm), and varying span (1000 mm, 1500 mm, and 2000 mm) were fabricated and tested for pre-failure and post-failure stages. The dimensions of the reference specimen considered were 3 mm in thickness, 101.6 mm in diameter, and 1500 mm in span. The results have shown that on increasing the section thickness by 200%, ductility and bearing strength were enhanced by 58.04% and 81.75%, respectively. Meanwhile, decreasing the section thickness by 67%, ductility and bearing strength were reduced by 64.86% and 38.87%, respectively. Moreover, on increasing the specimen diameter and on decreasing span, a significant increase in bearing strength and stiffness was observed; however, ductility was reduced. Meanwhile, on increasing the span of the specimen, all the parameters observed, i.e., bearing strength, stiffness, and ductility, decreased. On observing the ultimate strength of each specimen with square opening, the ultimate strength was reduced by 17.88%, 19.71%, and 14.23% for one, two-, and three-square openings, respectively. Moreover, the ductility was significantly reduced by 72.40%, 67.71%, and 60.88% for one, two-, and three-square openings/apertures, respectively, and led to the sudden failure of these specimens. The local buckling failure dominated for specimens having a D/t ratio more than 50 and showed very negligible levels of ovalization of the cross-section. Local buckling failure was observed to be prevented after providing the circular rings in the specimen, since bearing strength increased compared with the specimen without rings.

SPECIAL ARTICLE COVID-19: ENT Manifestations in Patients Suffering from COVID- 19: Study from a COVID Hospital in North India

Abstract Introduction COVID-19 has been one of the worst pandemics faced by the human civilization, and otorhinolaryngological manifestations are commonly seen in this disease. Objective The present study was done to profile the ear, nose, and throat (ENT) manifestations in patients diagnosed with COVID-19. An attempt has also been made to assess whether there was any difference between the symptoms of different strains of COVID-19. A brief review of the current knowledge of the transmission of the disease and its treatment has also been done. Methods A cross-sectional, record-based study was conducted in a COVID hospital of India between May and July 2020. Descriptive statistics were used and appropriate parametric/nonparametric tests were applied to assess the association between various variables. Results Out of 250 patients, 80 cases were asymptomatic and 170 were symptomatic. Most of the symptomatic patients had sore throat and nasal congestion. Conclusion Knowledge of the ENT manifestations of COVID-19 is essential for its early identification and to devise appropriate prevention protocols for the benefit of health care workers (HCWs) and of the general population.

Clinical and microbiological evaluation of 940-nm diode laser as an adjunct to modified Widman flap for the management of chronic periodontitis: A 6-month randomized split-mouth clinical trial.

Background. The present randomized clinical trial aimed to determine the additive clinical and microbiological benefits of diode laser (DL) with modified Widman flap (MWF) to manage chronic periodontitis. Methods. Seventy-two sites in 36 healthy non-smoking patients diagnosed with chronic periodontitis were randomly assigned to the test group (MWF + active DL) or control group (MWF + sham DL). Clinical (probing pocket depth [PPD], clinical attachment level [CAL]) and microbiological (colony-forming units [CFUs]) measurements were recorded at baseline and 6- and 6-month postoperative intervals. Results. Compared to baseline, 6-month results showed significant changes in clinical and microbiological parameters in both groups. However, the intergroup comparison revealed significantly lower PPD (1.90±0.48 mm vs. 2.35±0.41 mm), CAL (4.43±0.57 mm vs. 4.93±0.58 mm), and CFUs for Porphyromonas gingivalis (6.32±0.18 vs. 8.88 ±1.88), Prevotella intermedia (7.62±1.86 vs. 8.12±1.78), and Aggregatibacter actinomycetemcomitans (6.43±1.44 vs. 7.24±1.22) in the test group after six months. Conclusion. Within the limitations, the present study confirmed the useful role of DL with MWF to manage chronic periodontitis.

Combination chemotherapy versus temozolomide for patients with methylated MGMT (m-MGMT) glioblastoma: results of computational biological modeling to predict the magnitude of treatment benefit.

BACKGROUND: A randomized trial in glioblastoma patients with methylated-MGMT (m-MGMT) found an improvement in median survival of 16.7 months for combination therapy with temozolomide (TMZ) and lomustine, however the approach remains controversial and relatively under-utilized. Therefore, we sought to determine whether comprehensive genomic analysis can predict which patients would derive large, intermediate, or negligible benefits from the combination compared to single agent chemotherapy. METHODS: Comprehensive genomic information from 274 newly diagnosed patients with methylated-MGMT glioblastoma (GBM) was downloaded from TCGA. Mutation and copy number changes were input into a computational biologic model to create an avatar of disease behavior and the malignant phenotypes representing hallmark behavior of cancers. In silico responses to TMZ, lomustine, and combination treatment were biosimulated. Efficacy scores representing the effect of treatment for each treatment strategy were generated and compared to each other to ascertain the differential benefit in drug response. RESULTS: Differential benefits for each drug were identified, including strong, modest-intermediate, negligible, and deleterious (harmful) effects for subgroups of patients. Similarly, the benefits of combination therapy ranged from synergy, little or negligible benefit, and deleterious effects compared to single agent approaches. CONCLUSIONS: The benefit of combination chemotherapy is predicted to vary widely in the population. Biosimulation appears to be a useful tool to address the disease heterogeneity, drug response, and the relevance of particular clinical trials observations to individual patients. Biosimulation has potential to spare some patients the experience of over-treatment while identifying patients uniquely situated to benefit from combination treatment. Validation of this new artificial intelligence tool is needed.

High Prevalence of Biofilms on Retrieved Implants from Aseptic Pseudarthrosis Cases.

INTRODUCTION: Recent literature has associated pseudarthrosis and pedicle screw loosening with subchronic infection at the pedicle of the vertebra. The positive culture results of a previous retrieval analysis show that such patients have a high frequency of bacterial contamination. The objective of this study is to visually capture the architecture of these undiagnosed infections, which have been described in other studies as biofilms on supposedly "aseptic" screw loosening. METHODS: Explants from 10 consecutive patients undergoing revision spine surgery for pseudarthrosis were collected and fixed in glutaraldehyde solution. Each of these implants was imaged thoroughly by using scanning electron microscopy and x-ray spectroscopy to evaluate the architecture of the biofilm. Additionally, eight patient swabs from tissues around the implants were sent for cultures to assess bacterial infiltration in tissues beyond the biofilm. The implants were also analyzed using energy dispersive x-ray spectroscopy. The exclusion criteria included clinically diagnosed infection (current or previous) and/or mechanical failure of the implant due to falls/accidents. RESULTS: The study was successful in capturing the visual architecture of the biofilm on retrieved implants. A total of 77% of pseudarthrosis cases presented with loose pedicle screws, which were diagnosed by a preoperative computed tomography scan showing radiolucency along the screw track and were confirmed intraoperatively, and 72% of the cases showed biofilm on explants. CONCLUSIONS: In the absence of the clinical presentation of infection, impregnated bacteria could form a biofilm around an implant, and this biofilm can remain undetected via contemporary diagnostic methods, including swabbing. Implant biofilm is frequently present in "aseptic" pseudarthrosis cases.

Relapse rate following withdrawal of anti-TNF therapy in patients with inflammatory bowel disease: A real-life cohort from northern India.

BACKGROUND: The decision to withdraw anti-tumor necrosis factor (anti-TNF) therapy in patients with inflammatory bowel disease (IBD) remains controversial, especially in the developing world, where its long-term use is restrained by side effects and prohibitive cost. Present study evaluated the relapse rate and its predictors following anti-TNF withdrawal in a cohort of IBD patients from northern India. METHODS: Patients with IBD who received anti-TNF therapy (induction and beyond), and were under follow-up at All India Institute of Medical Sciences, New Delhi, from January 2005 to July 2018 were included. Demographic features, disease characteristics, duration, response to anti-TNF therapy, and relapse rate after its withdrawal were analyzed. RESULTS: Among 4600 patients with IBD under follow-up, 90 (1.9%) received anti-TNF therapy, of whom 11 were excluded (8-complete records unavailable; 3-received only single dose). Of 79 patients (mean age-40.1 ± 14.2 years; 53.2% males; 31 [39.2%] ulcerative colitis, 47 [59.5%] Crohn's disease; median follow-up-24 [12-39] months), 9 (11.4%) were primary non-responders, 19 (24.1%) had secondary loss of response, and 51 (64.5%) maintained clinical response on anti-TNF. Anti-TNF was withdrawn in 45 (57%) patients (major causes: financial burden-16.5%; tubercular reactivation-12.7%), of whom 33 were in clinical remission. Over a median follow-up of 26 (7.5-45) months, 15 patients (45.5%) relapsed. Most of them responded to antibiotics, steroids, or anti-TNF agents; only 3 required surgery. On Kaplan-Meier analysis, long disease duration prior to therapy was a significant predictor of relapse (hazard ratio [HR] = 1.33, p = 0.034). CONCLUSION: Almost 50% patients with IBD in clinical remission relapse within a year of anti-TNF withdrawal. However, most of these patients have a favorable disease course and respond to medical therapy.

Implant Retention or Removal for Management of Surgical Site Infection After Spinal Surgery.

STUDY DESIGN: A literature review. OBJECTIVE: To summarize the implant removal rate, common bacterial organisms found, time of onset, ratio of superficial to deep infection, and regurgitating the prevalence among all the retrospective and prospective studies on management and characterization of surgical site infections (SSIs). METHODS: PubMed was searched for articles published between 2000 and 2018 on the management or characterization of SSIs after spinal surgery. Only prospective and retrospective studies were included. RESULTS: A total of 49 articles were found relevant to the objective. These studies highlighted the importance of implant removal to avoid recurrence of SSI. The common organisms detected were methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermis, Staphylococcus epidermis, Staphylococcus aureus, and Propionibacterium acnes, with prevalence of 1% to 15%. A major proportion of all were deep SSI, with minority reporting on late-onset SSI. CONCLUSION: Long-term antibiotics administration, and continuous irrigation and debridement were common suggestion among the authors; however, the key measure undertaken or implied by most authors to avoid risk of recurrence was removal or replacement of implants for late-onset SSI.