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Background/Aims Association of sarcopenia with disease severity in ulcerative colitis (UC) is not clearly defined. We planned to estimate the prevalence of sarcopenia in patients with UC as per the revised definition and its relation with the disease severity. Methods A cross-sectional assessment of sarcopenia in patients with UC was performed. Disease activity was graded according to complete Mayo score. Hand grip strength was assessed with Jamar hand dynamometer, muscle mass using a dual energy X-ray absorptiometry scan, and physical performance with 4-m walk test. Sarcopenia was defined as a reduction of both muscle mass and strength. Severe sarcopenia was defined as reduced gait speed in presence of sarcopenia. Results Of 114 patients (62 males, mean age: 36.49±12.41 years), 32 (28%) were in remission, 46 (40.4%) had mild-moderate activity, and 36 (31.6%) had severe UC. Forty-three patients (37.7%) had probable sarcopenia, 25 (21.9%) had sarcopenia, and 14 (12.2%) had severe sarcopenia. Prevalence of sarcopenia was higher in active disease (2 in remission, 6 in active, and 17 in severe, P

Background: Chemometric analysis is also a powerful tool that can be used in the preliminary stages of analytical methods optimization, but is also efficient in data processing. These new approaches may be the key to the analysis of proteins, carbohydrate, sphignolipids, polyphenols in different food components. Although there are challenges in identifying and annotating those compounds due to the limited availability of analytical standards and structural diversity. Scope and approach: Chromatograms are a useful tool for learning more about the chemical make-up of the food being tested. This information can occasionally be implicit or presented in a subtle way. Therefore, to extract it, chemometric tools and data mining techniques are needed. A chromatogram's fingerprint allows for the possibility of performing both identity and quality testing on food. This viewpoint aims to offer a current assessment of chromatographic fingerprinting technique in the area of food authentication. Additionally, this methodology's limitations, absence from official analytical methods, and future directions are discussed. Novel techniques have been employed in the past few decades, ranging from high-pressure thin liquid chromatography (HPTLC) to mass spectrometry (MS) and other spectroscopic methods. In the last decade research developments, and the application of analytical methods in qualitative and quantitative studies of food components and their adulterants is reviewed in the present work. High-pressure Thin liquid chromatography (HPTLC) is hyphenated with high resolution mass spectrometry is particularly addressed due to its applicability in the targeted/untargeted metabolomic analysis of all food components. Key findings and conclusions: In the current study, the HPTLC-MS technique was used to examine food components and food adulteration. The HPTLC-MS hyphenated techniques were found to be an extremely helpful method for the detection of food adulterants as well as the various food components, such as protein, carbohydrates, lipids, essential oils, and flavonoids, which were found to be effective as medicinally.

Neutrophils, constituting 50%–70% of circulating leukocytes, play crucial roles in host defense and exhibit anti-tumorigenic properties. An elevated peripheral blood neutrophil-to-lymphocyte ratio is associated with decreased survival rates in cancer patients. In response to exposure to various antigens, neutrophils release neutrophil granular proteins, which combine to form web-like structures known as neutrophil extracellular traps (NETs). Previously, the relative percentage of NETs was found to be increased in resected tumor tissue samples from patients with gastrointestinal malignancies. The presence of NETs in peripheral blood is indicative of underlying pathological conditions. Hence, employing a non-invasive method to detect NETs in peripheral blood, along with other diagnostic tests, shows potential as a valuable tool not just for identifying different inflammatory disorders but also for assessing disease severity and determining patient suitability for surgical resection. While reliable methods exist for identifying NETs in tissue, accurately quantifying them in whole blood remains challenging. Many previous methods are time-consuming and rely on a limited set of markers that are inadequate for fully characterizing NETs. Therefore, we established a unique sensitive smear immunofluorescence assay based on blood smears to identify NETs in only as little as 2 μL of whole blood. To identify the NET complexes that have enhanced specificities, this combines the use of various antibodies against neutrophil-specific CD15, NET-specific myeloperoxidase (MPO), citrullinated histone H3 (Cit H3), and nuclear DNA. This protocol offers an easy, affordable, rapid, and non-invasive method for identifying NETs; thus, it can be utilized as a diagnostic marker and targeted through various therapeutic approaches for treating human malignancies.

Small bowel tumors are rare with nonspecific and protean clinical presentation. Early diagnosis of small bowel tumors is desirable as they can be associated with significant morbidity. In malignant small bowel tumors, delayed diagnosis may result in dissemination and metastasis leading to poor clinical outcomes. Imaging evaluation of small bowel can be challenging due to unpredictable luminal distension, peristalsis, and motion. In addition, the lack of distinction between the intraluminal lesions and intraluminal contents can be difficult at times. Computed tomography (CT) and magnetic resonance (MR) enterography are the most common imaging techniques for the evaluation of small bowel tumors. While these techniques may not be able to detect small tumors, they provide comprehensive evaluation of lumen, wall, and extramural structures in tumors more than 2 cm. Acquaintance of imaging appearance of common benign and malignant small bowel tumors may allow improved detection during evaluation of CT and MR enterography studies. In this review, we discuss the imaging appearances, approach, and differential diagnosis of small bowel tumors on cross-sectional imaging studies.

Abstract Background Ulcerative colitis is a relapsing and remitting disease that may be associated with flares. The causes of flares in the Indian setting are not well recognized. Methods The present prospective case-control study was conducted at a single center in North India. Cases were defined as patients admitted for flare of ulcerative colitis, while controls were patients in remission enrolled from the outpatient department. The basis of the diagnosis of flare was a simple clinical colitis activity index (SCCAI) of ≥ 5 and endoscopic activity, while remission was based on SCCAI

Abstract Gastrointestinal Tuberculosis (GITB) and Crohn’s disease (CD) are both chronic granulomatous diseases with a predilection to involve primarily the terminal ileum. GITB is often considered a disease of the developing world, while CD and inflammatory bowel disease are considered a disease of the developed world. But in recent times, the epidemiology of both diseases has changed. Differentiating GITB from CD is of immense clinical importance as the management of both diseases differs. While GITB needs anti-tubercular therapy (ATT), CD needs immunosuppressive therapy. Misdiagnosis or a delay in diagnosis can lead to catastrophic consequences. Most of the clinical features, endoscopic findings, and imaging features are not pathognomonic for either of these two conditions. The definitive diagnosis of GITB can be clinched only in a fraction of cases with microbiological positivity (acid-fast bacilli, mycobacterial culture, or PCR-based tests). In most cases, the diagnosis is often based on consistent clinical, endoscopic, imaging, and histological findings. Similarly, no single finding can conclusively diagnose CD. Multiparametric-based predictive models incorporating clinical, endoscopy findings, histology, radiology, and serology have been used to differentiate GITB from CD with varied results. However, it is limited by the lack of validation studies for most such models. Many patients, especially in TB endemic regions, are initiated on a trial of ATT to see for an objective response to therapy. Early mucosal response assessed at two months is an objective marker of response to ATT. Prolonged ATT in CD is recognized to have a fibrotic effect. Therefore, early discrimination may be vital in preventing the delay in the diagnosis of CD and avoiding a complicated course.

Dengue is one of the most critical diseases, caused by Dengue virus (DENV) serotypes (DENV-1 to DENV-4). Study aims to detect DENV in natural A. aegypti from endemic regions of Uttar Pradesh. From 2010- 2013, mosquitoes collected from Uttar Pradesh tested for Dengue virus serotypes by capsid-premembrane gene-based PCR analyzed for genotypes sequencing of the C-prM junction of DENV genome. A total of 4731, 53.54% (n=2671) A. aegypti and 46 % (n=2060) A. albopictus mosquitoes were collected. Of 226 mosquito pools, 10 pools of A. aegypti and 14 pools of A. albopictus were positive for DENV by PCR. All 24 isolates identified as DENV-I; Genotype (G)-III (n=8), G-V (n=1); DENV-2; G-IV (n=4); DENV-3; G-III (n=11). The overall minimum infection rate was much higher in A. albopictus mosquitoes and presence of MIR in male mosquitoes is an indicating natural vertical transmission and important observation in geographical area indicating natural vertical transmission.

Background and Purpose Transabdominal ultrasound (US)-based shear wave elastography (SWE) provides an attractive method of estimating pancreatic stiffness. There is limited data on the SWE values of the healthy pancreas in Indian subjects. The current study aimed to evaluate SWE of the normal pancreas. Methods We performed a study from January 2019 to March 2019. We included adult patients who presented for the US of the upper abdomen for vague abdominal symptoms, unrelated to the pancreas. The SWE values were obtained from the pancreatic head and body. The association of pancreatic SWE with age, gender, fatty liver, chronic liver disease, and cholelithiasis was recorded. Results During the study period, 205 subjects underwent SWE of the pancreas. The mean age of subjects was 41.3 (standard deviation [SD] 15.3) years. There were 93 males and 112 females. The mean SWE value in the head of the pancreas was 8.98 (SD 2.46 kPa), and that in the body region was 8.67 (SD 2.67 kPa). There was a positive correlation of SWE with age. The SWE of the pancreatic body was significantly higher in patients who had a fatty liver on US (p

Abstract Background Gastrointestinal strictures impact clinical presentation in abdominal tuberculosis and are associated with significant morbidity. Aim To conduct a systematic review of the prevalence of stricturing disease in abdominal and gastrointestinal tuberculosis and response to antitubercular therapy (ATT). Methods We searched Pubmed and Embase on 13th January 2022, for papers reporting on the frequency and outcomes of stricturing gastrointestinal tuberculosis. The data were extracted, and pooled prevalence of stricturing disease was estimated in abdominal tuberculosis and gastrointestinal (intestinal) tuberculosis. The pooled clinical response and stricture resolution (endoscopic or radiologic) rates were also estimated. Publication bias was assessed using the Funnel plot and Egger test. The risk of bias assessment was done using a modified Newcastle Ottawa Scale. Results Thirty-three studies reporting about 1969 patients were included. The pooled prevalence of intestinal strictures in abdominal tuberculosis and gastrointestinal TB was 0.12 (95%CI 0.07–0.20, I2 = 89%) and 0.27 (95% CI 0.21–0.33, I2 = 85%), respectively. The pooled clinical response of stricturing gastrointestinal tuberculosis to antitubercular therapy was 0.77 (95%CI 0.65–0.86, I2 = 74%). The pooled stricture response rate (endoscopic or radiological) was 0.66 (95%CI 0.40–0.85, I2 = 91%). The pooled rate of need for surgical intervention was 0.21 (95%CI 0.13–0.32, I2 = 70%), while endoscopic dilatation was 0.14 (95%CI 0.09–0.21, I2 = 0%). Conclusion Stricturing gastrointestinal tuberculosis occurs in around a quarter of patients with gastrointestinal tuberculosis, and around two-thirds of patients have a clinical response with antitubercular therapy. A subset of patients may need endoscopic or surgical intervention. The estimates for the pooled prevalence of stricturing disease and response to ATT had significant heterogeneity.

Transdermal drug delivery plays a significant part in the drug delivery system when compared to other routes of drug administration. The function of the stratum corneum (SC) is a barrier. Recently, numerous methods have been thrived to improve the perforation of drugs across the skin. The most effective method is to use enhancers since these agents enhance skin permeability. Natural penetration enhancers like essential oils demonstrate higher enhancement activity and are more widely accepted than synthetic penetration enhancers. High potential in the expansion and interaction with the SC intercellular lipids has led to an increasing interest in these oils as penetration enhancers. This article gives an overview of a few essential oils, including their mode of action and important parameters for permeation improvement. The present work can provide essential oils as alternative enhancers, and this could be useful in transdermal administration.

Introduction: Ayurvedic formulations have a long history of use and have increased amazingly to follow the global interest in natural products. However, for many classical ayurvedic formulations, no quality parameters of standardization are available. Vyoshadi Churna, a classical Ayurvedic polyherbal formulation that cures indigestion and diarrhea, is being used since ancient times. However, there is no standard method available for its formulation and evaluation. Hence, the current study aims to develop the quality standards for Vyoshadi churna. Methods: The standard procedures for preparation and standardization of Churna described in Ayurvedic Pharmacopoeia of India (API) were used in the present study. Standardization includes pharmacognostical, chromatographic, and physico-chemical studies. The other essential studies were also done in accordance to API and World Health Organization guidelines to find the limits of microbial load, aflatoxin, heavy metals, and pesticide residue using modern analytical techniques such as gas chromatography-mass spectroscopy (MS) and inductively coupled plasma-MS/MS. Results: Vyoshadi Churna is of brown color and bitter in taste. Pharmacognostical studies have shown the characteristic features of almost each contributory crude drug. A unique chemical profile was also developed using toluene: ethyl acetate: methanol: formic acid (4:4:1:0.5) as the mobile phase to resolve maximum components. Furthermore, the standardized limits for the physicochemical studies, microbial load, heavy metals, aflatoxins, and pesticide residues were established and found in limits. Conclusion: This is for the first time when the standard operating procedure of Vyoshadi Churna was developed. Hence, the current technical work would be practically helpful for the future preparation and standardization study of Vyoshadi Churna.

Gill's use of Abelard to critique dominant trends in European semiotics finds its parallels in his extensive work on Buddhist philosophers Dignāga and Dharmakīrti, who posed an alternative notion of the sign to that developed by the more celebrated earlier grammarians from the Sanskrit tradition, Pāṇini and Bhrtihari. He places these heterodox Indian and French traditions of semiotics in creative dialogue to cultivate a semiotic theory that is at once universal in its applicability while also allowing for multiple, non-dominant forms of thought and creativity to emerge. Consequently, his ideas provide a new way for semiotics that would be particularly relevant for scholars working in postcolonial Asia. This interview is an abridged and edited excerpt taken from an interview conducted with Gill by Nishaant Choksi and Arka Chattopadhyay at a virtual seminar held at IIT-Gandhinagar on 31 March 2021. The entire recorded interview can be found at https://www.youtube.com/watch?v=jb6fG3_hvqg. A special thanks to Shruti Nair for her assistance in transcription.

Hepatic artery pseudoaneurysm in postcholecystectomy choleduodenal fistula is an extremely rare but clinically significant complication. A 52-year-old male presented with hematemesis and melena several weeks after open cholecystectomy for complicated gallstone disease. Upper gastrointestinal endoscopy revealed bleeding from the choledochoduodenal fistula site. On computed tomography angiography, a small right hepatic artery pseudoaneurysm close to fistula site was identified. Endovascular embolization failed due to nonopacification of the proximal right hepatic artery. Endoscopic ultrasound-guided embolization was also unsuccessful due to the small size of the aneurysm and inadequate visualization. Following this, percutaneous n-butyl cyanoacrylate glue was successfully injected into the pseudoaneurysm. The patient recovered and was planned for hepaticojejunostomy to restore biliary continuity.

Abstract Liver cirrhosis, alcoholic liver diseases, non-alcoholic fatty liver and steatohepatitis are the major risk factors for liver damage leading to hepatocellular carcinoma. Oxidative stress and insulin resistance are the main pathogenetic mechanisms leading the hepatic cell injury and damage in these patients. The present review is the first attempt which focuses on the biological activities of Bergenia ciliata to explore its benefits and possible applications in the treatment of liver ailments. Bergenia ciliata is an evergreen herb belonging to the family saxifragaceae and is regarded as a miracle herb due to its wide medicinal applications. The data published in India and other nations are methodically reviewed and summarized in this article. It covers the facts collected from scientific journals, theses and online bibliographical databases: PubMed, Scopus, Google Scholar and Web of Science from year 1995–2020. The phytochemical studies on B. ciliata have shown the presence of many phytochemicals belonging to phenols, flavonoids, fatty acid, glycosides, terpenoids, etc. Due to the presence of a multitude of these bioactives, the whole plant of B. ciliata has numerous medicinal applications such as diuretic, antipyretic, α-glucosidase, antiviral, antibacterial, anti-inflammatory and insecticidal activity. Therefore in the present study, we invite the attention of scientists and researchers to carry out further clinical and toxicological studies on this valuable plant in order to discover and develop novel hepatoprotective medicine with fewer side effects on human beings.

Abstract Introduction Stricturing gastrointestinal tuberculosis (GITB) may result in persistent symptoms even after antitubercular therapy (ATT) and may require surgical intervention. Data on efficacy and safety of endoscopic dilatation for management GITB related strictures is scarce. Methods A retrospective analysis of database of patients who underwent endoscopic balloon dilatation for suspected or proven gastrointestinal tuberculosis was performed. The analysis included the site of involvement, technical success, clinical success (response), relapse and requirement of surgery in these patients. Results Out of 34 patients (47.1% males, mean age 31.9 ± 12.9 years), eventually four patients were diagnosed to have Crohn’s disease while the rest had GITB. Initial technical success was achieved in 30 (88.2%) patients. Initial clinical success was achieved in 28 (82.3%) patients. Median number of dilatation sessions required to obtain symptomatic relief were 2.5 (1–5) per patient. Two patients with initial clinical success had recurrence of symptoms over follow up of 1 year, out of which one patient was managed with repeat endoscopic balloon dilatation successfully. Of 30 patients with technical success, 16 (53.4%) were on ATT when they underwent dilatation while two were in intestinal obstruction. Eventually 7 patients required surgical intervention for various reasons. Conclusion Non-fluoroscopic endoscopic balloon dilatation is an acceptable and fairly safe modality for symptomatic tuberculous strictures of gastrointestinal tract.

Myopia is a widespread and complex refractive error in which a person's ability to see distant objects clearly is impaired. Its prevalence rate is increasing worldwide, and as per WHO, it is projected to increase from 22% in 2000 to 52% by 2050. It is more prevalent in developed, industrial areas and affects individuals of all ages. There are a number of treatments available for the control of myopia, such as glasses, contact lenses, laser surgery, and pharmaceuticals agents. However, these treatments are less beneficial and have significant side effects. A novel molecule, 7-methylxanthine (7-MX), has been found to be a highly beneficial alternate in the treatment of myopia and excessive eye elongation. Many preclinical and clinical studies showed that 7-MX is effective for the treatment of myopia and is presently under phase II of clinical investigation. We have also investigated preclinical toxicity studies such as acute, sub-acute, sub-chronic, and chronic on rats. In these studies, 7-MX was found to be non-toxic as compared to other reported anti-myopic agents. Moreover, as an ideal drug, 7-MX is observed to have no or low toxicity, brain permeability, non-allergic, higher oral administration efficacy, and low treatment costs and thus qualifies for the long-term treatment of myopia. This review article on 7-MX as an alternative to myopia treatment will highlight recent findings from well-designed preclinical and clinical trials and propose a potential future therapy.

Background: SARSCoV-2, a coronavirus that causes COVID-19, is spreading rapidly. By the middle of August-2021, it has affected over 3 million confirmed cases in India. The main aim of this study was to examine the clinical profile of COVID-19 patients and their length of stay during treatment in a hospital. Materials and Methods: It was a hospital-based retrospective study conducted by using a total enumeration technique in July–August 2021 at Nehru Hospital, Postgraduate Institute of Medical Education and Research (PGIMER) in India. The present study was conducted on 72 COVID-19 patients who took treatment in 4C and 5C wards. Structured questionnaires were used to collect data, which included bio-demographic factors and questions about their treatment and length of stay. Results: The majority of the 72 COVID-19 positive patients were men (62%), belonged to the age group of 41–60 years (35%), had SpO2 levels ranging from 91%–95% (45%), and received room air O2 therapy (63%) during their treatment in the hospital. Female patients had a longer length of stay (7.33 days), patients under the age of 20 years had the longest hospital stay (11.5 days), patients with SpO2 less than 70% had the longest hospital stay (8 days), and patients who received oxygen using a non-rebreathing mask had the longest hospital stay (11 days). Conclusion: To avoid panic situations, regular admission and discharge of patients was essential due to the considerable increase in cases during the second wave. Patient length of stay was reduced as a consequence of collaboration and cooperation among all physicians, residents, staff nurses, and paramedics, with the goal of discharging the patient after a room air trial and follow up if needed.

ABSTRACT Background: Advanced achalasia cardia (AC) represents the end stage in the natural history of AC. Role of per oral endoscopic myotomy (POEM) in this technically difficult subset is emerging. Methods: Retrospective review of the patients who had undergone POEM for advanced AC with sigmoid esophagus. We assessed the technical success, clinical success and adverse event rate. Pre and post POEM Eckardt score (ES), integrated relaxation pressure-4sec (IRP-4), lower oesophageal sphincter pressure (LESP) and height and width of barium column at 5 minutes were noted. Results: Of the 85 patients who underwent POEM for AC, 10 patients had advanced AC with sigmoid esophagus of which eight were sigmoid and two were advanced sigmoid. The clinical and technical success was 100% with significant reduction of ES, IRP-4, LESP and height and width of barium column at 5 minutes. One patient had a minor adverse event in the form of mucosal injury that was closed with hemoclips. At a median follow up of 17 months there was no recurrence. Conclusion: Our study demonstrates POEM to be a safe and effective modality of treatment in this technically difficult subset of AC with sigmoid morphology.

Chimeric antigen receptor (CAR) T-cell therapy has emerged recently as a standard of care treatment for patients with relapsed or refractory acute lymphoblastic leukemia (ALL) and several subtypes of B-cell non-Hodgkin lymphoma (NHL). However, its use remains limited to highly specialized centers, given the complexity of its administration and its associated toxicities. We previously reported our experience in using a novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy in the peri-transplant setting, where it exhibited an excellent safety profile with encouraging survival outcomes. We have since modified the SB CD19 CAR construct to improve its efficacy and shorten its manufacturing time. We report here the phase 1 clinical trial safety results. Fourteen heavily treated patients with relapsed/refractory ALL and NHL were infused. Overall, no serious adverse events were directly attributed to the study treatment. Three patients developed grades 1-2 cytokine release syndrome and none of the study patients experienced neurotoxicity. All dose levels were well tolerated and no dose-limiting toxicities were reported. For efficacy, 3 of 8 (38%) patients with ALL achieved CR/CRi (complete remission with incomplete count recovery) and 1 (13%) patient had sustained molecular disease positivity. Of the 4 patients with DLBCL, 2 (50%) achieved CR. The SB-based CAR constructs allow manufacturing of targeted CAR T-cell therapies that are safe, cost-effective and with encouraging antitumor activity.

The in vivo persistence of adoptively transferred T cells is predictive of antitumor response. Identifying functional properties of infused T cells that lead to in vivo persistence and tumor eradication has remained elusive. We profiled CD19-specific chimeric antigen receptor (CAR) T cells as the infusion products used to treat large B cell lymphomas using high-throughput single-cell technologies based on time-lapse imaging microscopy in nanowell grids (TIMING), which integrates killing, cytokine secretion, and transcriptional profiling. Our results show that the directional migration of CD19-specific CAR T cells is correlated with multifunctionality. We showed that CD2 on T cells is associated with directional migration and that the interaction between CD2 on T cells and CD58 on lymphoma cells accelerates killing and serial killing. Consistent with this, we observed that elevated CD58 expression on pretreatment tumor samples in patients with relapsed or refractory large B cell lymphomas treated with CD19-specific CAR T cell therapy was associated with complete clinical response and survival. These results highlight the importance of studying dynamic T cell–tumor cell interactions in identifying optimal antitumor responses.

Gastrointestinal tuberculosis (GITB) and Crohn’s disease (CD) are close mimics. This prospective study aimed to evaluate the diagnostic performance of perfusion computed tomography (CT) in differentiating GITB from CD. Consecutive patients with ileocaecal thickening underwent perfusion CT of the ileocaecal region between January 2019 and July 2020. Two radiologists (blinded to the final diagnosis) independently assessed blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability at perfusion CT. These parameters were compared among the patients with GITB as well as active and inactive CD. Receiver operating characteristic curves were utilized for determining the diagnostic performance of perfusion CT. Interclass correlation coefficient and Bland–Altman analysis were performed to compare the observations of the two radiologists. During the study period, 34 patients underwent perfusion CT. Eight patients had diagnoses other than intestinal tuberculosis or CD. Thus, 26 patients (mean age 36 ± 14 years, 18 males) with GITB (n = 11), active CD (n = 6), and inactive CD (n = 9) were evaluated. BF, MTT, and permeability showed significant differences among the groups, while BV did not differ significantly among the groups. BF and permeability had 100% sensitivity and 100% specificity, while MTT had 61.5–100% sensitivity and 70–100% specificity for differentiating GITB from active CD and active from inactive CD. The interclass correlation coefficient for perfusion CT parameters was 0.88–1. Perfusion CT is a novel imaging technique that can improve the diagnostic performance of differentiating tuberculosis from CD.

Abdominal tuberculosis and its protean manifestations still create a diagnostic challenge for clinicians and remain an important concern in the developing world. Crohn’s disease, which is being increasingly recognised in countries where intestinal tuberculosis is prevalent, needs to be differentiated as the two diseases resemble each other in their clinical presentation, and in their radiological, endoscopic, and histological findings. New diagnostic modalities and scoring systems have facilitated the differentiation of Crohn’s disease from intestinal tuberculosis with good accuracy. Randomised trials have shown 6 months of therapy to be equivalent to longer durations of treatment for patients with abdominal tuberculosis. This review focusses on the recent advances in diagnosis and management of abdominal tuberculosis.

Pancreatitis is one of the important medical conditions. Gastrointestinal (GI) complications of pancreatitis are important and lead to significant morbidity and mortality. Diagnosis of these complications is difficult and may require a strong clinical suspicion coupled with various imaging features. This review provides an extensive update of the whole spectrum of GI complication of pancreatitis, both acute and chronic, from inflammation, ischemia, and necrosis to obstruction, perforation, and GI fistulae. The focus is on the clinical and imaging features of this less commonly described aspect of pancreatitis.

Background Chyle leak is an uncommon form of ascites occurring due to the accumulation of lipid‐rich lymph into the peritoneal cavity. Traumatic injury to the lymphatic system due to pancreaticobiliary surgery can lead to this phenomenon. Method We retrospectively evaluated the data of 159 patients of pancreticobiliary surgery from January 2012 to December 2016. Five patients (5/137, 3.6%) sustained a chylous leak following pancreaticoduodenectomy and one patient (1/22, 4.5%) sustained a chylous leak following Roux‐en‐Y hepaticojejunostomy for postcholecystectomy biliary stricture. Results Average daily output was 441 mL (range: 150–800 mL/day), and total duration of output was 16.5 days (range: 4–35 days). Mean hospital stay increased to 19.1 days (range: 10–40 days). All the patients were successfully managed conservatively with a combination of customized enteral feeds, supplemental parenteral nutrition, and octreotide. One patient required additional percutaneous drainage. Conclusion Chyle leak can be successfully treated with conservative management but at the cost of increased hospital stay.

Background and Aim Abdominal tuberculosis is an important form of extrapulmonary tuberculosis. Evidence from clinical trials suggests that 6 months of antitubercular therapy (ATT) is sufficient for abdominal tuberculosis. Methods We report real‐world experience with 6 months of ATT based on a retrospective analysis of patients with abdominal tuberculosis seen at a large tertiary care hospital in India. Results Of 101 patients, 93 with complete records were included. The mean age was 35.90 ± 14.06 years, and 53 were males (56.98%). A total of 42 patients (45.16%) had intestinal involvement, 24 (25.08%) had peritoneal, 22 (23.65%) had combined involvement, and 5 patients (5.37%) had isolated lymph nodal involvement. Six patients received prolonged ATT. Six patients developed ATT‐induced hepatitis. Of 64 patients with intestinal involvement, 45 had stricturing disease (70.3%), of whom 7 (15.5%) required surgery due to refractory symptoms. Overall, there was one death, and eight patients (including one with massive gastrointestinal bleeding) needed surgery. Conclusion Six months of ATT is associated with objective clinical response in most of the patients of abdominal tuberculosis.

Antibiotic resistance is one of our most serious global health threats. The adverse effects of overusing and misusing antibiotics are highly publicized in the health professional literature. Antibiotic abuse occurs during routine endodontic treatment and there are deficiencies in knowledge regarding prescribing antibiotic and appropriate prophylactic antibiotic use. Multidisciplinary coordination and cooperation among dentists, pharmacists, and patients is needed to curb antibiotic abuse. As endodontists, we can become part of the solution to the antibiotic resistance crisis and deal with it conclusively. This review article discusses antibiotic resistance resulting from antibiotic abuse during endodontic treatment, various factors contributing to it, and measures required for stopping antibiotic abuse in endodontic treatment. A web-based research on MedLine was performed with terms Review Articles published in the last 10 year's dental journals in English for literature researching, extracting, and synthesizing data. Relevant articles were shortlisted. Important cross-reference articles were also reviewed.

Background: The relationship between diabetes mellitus and tuberculosis (TB) has received increasing attention, and diabetes may be associated with poor outcomes in pulmonary TB. Clinical relevance of HbA1c measurement in abdominal TB is unknown. Methods: We did a retrospective study of consecutive patients diagnosed with abdominal TB and treated with antitubercular therapy for 6 months. Patients were categorized as those with normal HbA1c (

Background Adoptive cell therapy based on the infusion of chimeric antigen receptor (CAR) T cells has shown remarkable efficacy for the treatment of hematologic malignancies. The primary mechanism of action of these infused T cells is the direct killing of tumor cells expressing the cognate antigen. However, understanding why only some T cells are capable of killing, and identifying mechanisms that can improve killing has remained elusive.Methods To identify molecular and cellular mechanisms that can improve T-cell killing, we utilized integrated high-throughput single-cell functional profiling by microscopy, followed by robotic retrieval and transcriptional profiling.Results With the aid of mathematical modeling we demonstrate that non-killer CAR T cells comprise a heterogeneous population that arise from failure in each of the discrete steps leading to the killing. Differential transcriptional single-cell profiling of killers and non-killers identified CD137 as an inducible costimulatory molecule upregulated on killer T cells. Our single-cell profiling results directly demonstrate that inducible CD137 is feature of killer (and serial killer) T cells and this marks a different subset compared with the CD107apos (degranulating) subset of CAR T cells. Ligation of the induced CD137 with CD137 ligand (CD137L) leads to younger CD19 CAR T cells with sustained killing and lower exhaustion. We genetically modified CAR T cells to co-express CD137L, in trans, and this lead to a profound improvement in anti-tumor efficacy in leukemia and refractory ovarian cancer models in mice.Conclusions Broadly, our results illustrate that while non-killer T cells are reflective of population heterogeneity, integrated single-cell profiling can enable identification of mechanisms that can enhance the function/proliferation of killer T cells leading to direct anti-tumor benefit.

Background and Objectives: Influenza A/H1N1pdm09 causes respiratory illness and remains a concern for public health. Since its first emergence in 2009, the virus has been continuously circulating in the form of its genetic variants. Influenza A/H1N1pdm09 surveillance is essential for uncovering emerging variants of epidemiologic and vaccine efficacy. The present study attempts in silico analysis and molecular characterization of Influenza A (H1N1) pdm09 virus circulating and causing major outbreaks in central India during 2009-2019. Materials and Methods: We have investigated the antigenic drift analysis of 96 isolates’ hemagglutinin (HA) gene sequences (59 central Indian and 37 local Indian and 28 global reference HA gene sequences) of Influenza A/H1N1pdm09 viruses from 2009 to 2019. The study includes mutational (Multiple sequence Alignment), phylogenetic (Maximum Likelihood Method), and statistical analysis (Covariance and correlation) of HA sequences submitted in NCBI, IRD and GISAID from central India. Results: Phylogenetic analysis indicated maximum clustering of central Indian HA gene sequences in genogroup 6B. Analysis of amino acid sequence alignment revealed changes in receptor binding site (RBS). The frequency of S220T amino acid substitution was found to be high followed by S202T, K300E A273T, K180Q. The Karl Pearson correlation coefficient (r) and covariance between the number of mutations and the death toll was found +0.246 and +100.3 respectively. Conclusion: The study identifies the continuous genetic variations in the HA gene sequences of circulating Influenza A/H1N1pdm09 in central India from the year 2009 to 2019. Further suggesting importance of monitoring the gradual evolution of the virus with regards to an increase in virulence, pathogenicity and vaccine efficacy timely.

Two different field experiments were conducted at Punjab Agricultural University, Regional Research Station, Bathinda, (1) to manage optimum source-sink relationship through mepiquat chloride (MC) in Bt cotton hybrid and (2) to find feasibility of MC application on non hybrid compact cotton genotype under high density planting system (HDPS) with varied nitrogen levels. Raw data for growth and yield parameters was recorded from each treatment and statistically analysed. In experiment (1), application of MC 75 g active ingredient per hectare (a.i./ha) irrespective of splits between 60 and 90 days after sowing (DAS) was effective for significant reduction in plant height, increase in bolls per plant as compared to control and de-topping treatments. All these led to significantly highest seed cotton yield (SCY) and monetary returns under MC 75 g a.i./ha as compared to de-topping treatment. In experiment (2) of high density planting of cotton, sympods per plant, bolls per plant, SCY as well as nitrogen use efficiency (NUE) and monetary returns were increased significantly with 25% increase in recommended dose of nitrogen. Among the growth retardants, application of MC 20 g a.i./ha once and twice reduced plant height, increased sympods and boll per plant significantly which led to significantly higher SCY production as compared to control. Similarly, NUE and monetary returns were also significantly higher under MC treatments as compared to control. Application of MC 75 g a.i./ha in either two or three splits on Bt cotton hybrid under normal plant density and MC 20–40 g a.i./ha on non Bt compact genotype under high plant density optimized source-sink relationship which improve crop productivity and profitability.

Tubercular aortitis presenting as primary aortoenteric fistula (AEF) is a rare entity. We present a 78-year-old male who presented with upper gastrointestinal bleed and also had abdominal pain and pulsating abdominal mass and on evaluation was found to have tubercular AEF which was successfully repaired with surgery and the patient recovered with antitubercular therapy along with the surgery. This case highlights the importance of high index of suspicion with early institution of surgical repair along with antitubercular therapy for tubercular AEF with good results.

Aortoenteric fistula (AEF) is an uncommon entity with high morbidity and mortality associated with it. Primary AEF can occur in the presence of aortic aneurysm but it is less common as compared to the secondary type, which is associated with the presence of prosthetic graft used for repair of aortic aneurysm or aortic bypass for occlusive disease. Multiple strategies have been described in the literature which needs to be individualized to each patient. This patient had undergone aortobifemoral bypass twice in the past, which makes anatomy hostile, followed by graft infection and graft enteric (jejunum) erosion leading to very challenging case to treat. The patient was managed in two stages, first axillobifemoral bypass followed by explantation of two grafts. He is doing fine at >12 months of follow-up.

Genetically engineered T cells that express chimeric antigen receptors (CAR+) are heterogeneous and thus, understanding the immunotherapeutic efficacy remains a challenge in adoptive cell therapy. We developed a high-throughput single-cell methodology, Timelapse Imaging Microscopy In Nanowell Grids (TIMING) to monitor interactions between immune cells and tumor cells in vitro. Using TIMING we demonstrated that CD4+ CAR+ T cells participate in multi-killing and benefit from improved resistance to activation induced cell death in comparison to CD8+ CAR+ T cells. For both subsets of cells, effector cell fate at the single-cell level was dependent on functional activation through multiple tumor cells.

Introduction: Data on the use of Xpert Mtb/Rif for the diagnosis of intestinal tuberculosis is sparse. We report on the utility of Xpert Mtb/Rif testing for diagnosis of intestinal tuberculosis (ITB) in patients with ileocecal ulcers Methodology: We performed a retrospective analysis of patients with ileocecal ulcers and suspected to have ITB and in whom testing of intestinal tissue for Xpert Mtb/Rif was performed. The patients were divided into two groups: those with a final diagnosis of intestinal tuberculosis and those with other diagnosis. These patients were compared for clinical features and presentation. The sensitivity, specificity, positive predictive value, and negative predictive value of Xpert Mtb/Rif for the diagnosis of ITB were calculated. Results: Of the 40 patients studied, 23 were women and the mean age was 32.92 ± 12.78 years. Abdominal pain was present in 33 (88.5%) patients and diarrhea in 12 (30%). A total of 25 patients had underlying ITB whereas 15 patients had other diagnoses (Crohn’s disease, amebiasis, nonspecific ileitis, etc.). The sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of GeneXpert-Mtb/Rif was 32% (CI: 14.95–53.50%), 100% (78.2–100), 46.88% (40.27–53.59%), 100 & 57.50 (40.89–72.89%) respectively. Conclusion: A positive GeneXpert-Mtb/Rif helps in the diagnosis of ITB, but the sensitivity is low.

Despite polio eradication, nonpolio enterovirus (NPEV) detection amid polio surveillance, which is considered to have implications in paralysis, requires attention. The attributes of NPEV infections in nonpolio-AFP (NPAFP) cases from Uttar Pradesh (UP), India, remain undetermined and are thus investigated. A total of 1839 stool samples collected from patients with acute flaccid paralysis (AFP) from UP, India, between January 2010 and October 2011 were analyzed as per the WHO algorithm. A total of 359 NPAFP cases yielded NPEVs, which were subjected to microneutralization assay, partial VP1 gene-based molecular serotyping and phylogenetic analysis. Demographic and clinical-epidemiological features were also ascertained. Echoviruses (29%) and Coxsackievirus (CV)-B (17%) were the most common viruses identified by the microneutralization assay. The molecular genotyping characterized the NPEVs into 34 different serotypes, corresponding to Enterovirus (EV)-A (1.6%), EV-B (94%) and EV-C (5.3%) species. The rarely described EV serotypes, such as EV-C95, CV-A20, EV-C105, EV-B75, EV-B101, and EV-B107, were also identified. NPEV-associated AFP was more prevalent in younger male children, peaked in the monsoon months and was predominantly found in the central part of the state. The NPEV strains isolated in the study exhibited genetic diversity from those isolated in other countries. These form part of a different cluster or subcluster existing in cocirculation, limited to India only. This study augments the understanding of epidemiological features and demonstrates the extensive diversity exhibited by the NPEV strains in NPAFP cases from the polio-endemic region. It also underscores the need or effective long-term strategies to monitor NPEV circulation and its associated health risks in the post-polio eradication era.

Tuberculosis is a common clinical problem which can involve virtually any organ and mimic a multitude of clinical conditions. Colonic tuberculosis is a type of intestinal tuberculosis which involves the colon and mimics inflammatory bowel disease. Occasionally, it is also confused with colonic malignancy. We report the case of a young female who presented with abdominal pain, bleeding per rectum. Abdominal X-ray showed evidence of thumb-printing. A possibility of ischemic colitis was entertained. However, further investigation unraveled the presence of tubercular colitis. The patient improved with anti-tubercular therapy. Colonic tuberculosis can mimic a number of clinical entities and should be considered in differential diagnosis of colonic lesions in endemic areas.

Nonpolio acute flaccid paralysis is increasing in India. To determine viral causes, we conducted cell culture and molecular analysis identification of nonpolio human enteroviruses associated with acute flaccid paralysis during March–August 2010 in northern India. The predominant nonpolio enterovirus found was echovirus 13, a serotype rarely isolated in India.

Adoptive immunotherapy infusing T cells with engineered specificity for CD19 expressed on B- cell malignancies is generating enthusiasm to extend this approach to other hematological malignancies, such as acute myelogenous leukemia (AML). CD123, or interleukin 3 receptor alpha, is overexpressed on most AML and some lymphoid malignancies, such as acute lymphocytic leukemia (ALL), and has been an effective target for T cells expressing chimeric antigen receptors (CARs). The prototypical CAR encodes a VH and VL from one monoclonal antibody (mAb), coupled to a transmembrane domain and one or more cytoplasmic signaling domains. Previous studies showed that treatment of an experimental AML model with CD123-specific CAR T cells was therapeutic, but at the cost of impaired myelopoiesis, highlighting the need for systems to define the antigen threshold for CAR recognition. Here, we show that CARs can be engineered using VH and VL chains derived from different CD123-specific mAbs to generate a panel of CAR+ T cells. While all CARs exhibited specificity to CD123, one VH and VL combination had reduced lysis of normal hematopoietic stem cells. This CAR's in vivo anti-tumor activity was similar whether signaling occurred via chimeric CD28 or CD137, prolonging survival in both AML and ALL models. Co-expression of inducible caspase 9 eliminated CAR+ T cells. These data help support the use of CD123-specific CARs for treatment of CD123+ hematologic malignancies.

T cells modified with chimeric antigen receptors (CARs) targeting CD19 demonstrated clinical activity against some B-cell malignancies. However, this is often accompanied by a loss of normal CD19+ B cells and humoral immunity. Receptor tyrosine kinase-like orphan receptor-1 (ROR1) is expressed on sub-populations of B-cell malignancies and solid tumors, but not by healthy B cells or normal post-partum tissues. Thus, adoptive transfer of T cells specific for ROR1 has potential to eliminate tumor cells and spare healthy tissues. To test this hypothesis, we developed CARs targeting ROR1 in order to generate T cells specific for malignant cells. Two Sleeping Beauty transposons were constructed with 2nd generation ROR1-specific CARs signaling through CD3ζ and either CD28 (designated ROR1RCD28) or CD137 (designated ROR1RCD137) and were introduced into T cells. We selected for T cells expressing CAR through co-culture with γ-irradiated activating and propagating cells (AaPC), which co-expressed ROR1 and co-stimulatory molecules. Numeric expansion over one month of co-culture on AaPC in presence of soluble interleukin (IL)-2 and IL-21 occurred and resulted in a diverse memory phenotype of CAR+ T cells as measured by non-enzymatic digital array (NanoString) and multi-panel flow cytometry. Such T cells produced interferon-γ and had specific cytotoxic activity against ROR1+ tumors. Moreover, such cells could eliminate ROR1+ tumor xenografts, especially T cells expressing ROR1RCD137. Clinical trials will investigate the ability of ROR1-specific CAR+ T cells to specifically eliminate tumor cells while maintaining normal B-cell repertoire.

Adoptive transfer of T cells expressing a CD19-specific chimeric antigen receptor (CAR) is being evaluated in multiple clinical trials. Our current approach to adoptive immunotherapy is based on a second generation CAR (designated CD19RCD28) that signals through a CD28 and CD3-ζ endodomain. T cells are electroporated with DNA plasmids from the Sleeping Beauty (SB) transposon/transposase system to express this CAR. Stable integrants of genetically modified T cells can then be retrieved when co-cultured with designer artificial antigen presenting cells (aAPC) in the presence of interleukin (IL)-2 and 21. Here, we reveal how the platform technologies of SB-mediated transposition and CAR-dependent propagation on aAPC were adapted for human application. Indeed, we have initiated clinical trials in patients with high-risk B-lineage malignancies undergoing autologous and allogeneic hematopoietic stem-cell transplantation (HSCT). We describe the process to manufacture clinical grade CD19-specific T cells derived from healthy donors. Three validation runs were completed in compliance with current good manufacturing practice for Phase I/II trials demonstrating that by 28 days of co-culture on γ-irradiated aAPC ∼10(10) T cells were produced of which >95% expressed CAR. These genetically modified and propagated T cells met all quality control testing and release criteria in support of infusion.

Clinical trials targeting CD19 on B-cell malignancies are underway with encouraging anti-tumor responses. Most infuse T cells genetically modified to express a chimeric antigen receptor (CAR) with specificity derived from the scFv region of a CD19-specific mouse monoclonal antibody (mAb, clone FMC63). We describe a novel anti-idiotype monoclonal antibody (mAb) to detect CD19-specific CAR(+) T cells before and after their adoptive transfer. This mouse mAb was generated by immunizing with a cellular vaccine expressing the antigen-recognition domain of FMC63. The specificity of the mAb (clone no. 136.20.1) was confined to the scFv region of the CAR as validated by inhibiting CAR-dependent lysis of CD19(+) tumor targets. This clone can be used to detect CD19-specific CAR(+) T cells in peripheral blood mononuclear cells at a sensitivity of 1∶1,000. In clinical settings the mAb is used to inform on the immunophenotype and persistence of administered CD19-specific T cells. Thus, our CD19-specific CAR mAb (clone no. 136.20.1) will be useful to investigators implementing CD19-specific CAR(+) T cells to treat B-lineage malignancies. The methodology described to develop a CAR-specific anti-idiotypic mAb could be extended to other gene therapy trials targeting different tumor associated antigens in the context of CAR-based adoptive T-cell therapy.

Leiomyosarcoma of the gallbladder is a rare entity, constituting about 1.4 per 1000 gallbladder malignancies. Literature review shows female preponderance in sixth decade of life, due to unknown reasons. We report one such rare case of a 50-year-old female admitted with pain in right upper abdomen. On examination, mass was felt in right hypochondrium. The ultrasound abdomen showed mass with loss of interface with liver and cholelithiasis. CECT abdomen showed polypoidal gallbladder malignancy with ill-defined interface with liver. She was operated upon with diagnosis of carcinoma gallbladder; extended cholecystectomy was done. Histopathological examination revealed spindle-cell proliferation and possibility of malignant tumor of mesenchymal origin was kept. This was later confirmed on immunohistochemistry.

NK cells have therapeutic potential for a wide variety of human malignancies. However, because NK cells expand poorly in vitro, have limited life spans in vivo, and represent a small fraction of peripheral white blood cells, obtaining sufficient cell numbers is the major obstacle for NK-cell immunotherapy. Genetically-engineered artificial antigen-presenting cells (aAPCs) expressing membrane-bound IL-15 (mbIL15) have been used to propagate clinical-grade NK cells for human trials of adoptive immunotherapy, but ex vivo proliferation has been limited by telomere shortening. We developed K562-based aAPCs with membrane-bound IL-21 (mbIL21) and assessed their ability to support human NK-cell proliferation. In contrast to mbIL15, mbIL21-expressing aAPCs promoted log-phase NK cell expansion without evidence of senescence for up to 6 weeks of culture. By day 21, parallel expansion of NK cells from 22 donors demonstrated a mean 47,967-fold expansion (median 31,747) when co-cultured with aAPCs expressing mbIL21 compared to 825-fold expansion (median 325) with mbIL15. Despite the significant increase in proliferation, mbIL21-expanded NK cells also showed a significant increase in telomere length compared to freshly obtained NK cells, suggesting a possible mechanism for their sustained proliferation. NK cells expanded with mbIL21 were similar in phenotype and cytotoxicity to those expanded with mbIL15, with retained donor KIR repertoires and high expression of NCRs, CD16, and NKG2D, but had superior cytokine secretion. The mbIL21-expanded NK cells showed increased transcription of the activating receptor CD160, but otherwise had remarkably similar mRNA expression profiles of the 96 genes assessed. mbIL21-expanded NK cells had significant cytotoxicity against all tumor cell lines tested, retained responsiveness to inhibitory KIR ligands, and demonstrated enhanced killing via antibody-dependent cell cytotoxicity. Thus, aAPCs expressing mbIL21 promote improved proliferation of human NK cells with longer telomeres and less senescence, supporting their clinical use in propagating NK cells for adoptive immunotherapy.