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289 result(s) for "Agrawal, Gaurav"
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Impact of COVID-19 on cancer care in India: a cohort study
The COVID-19 pandemic has disrupted health-care systems, leading to concerns about its subsequent impact on non-COVID disease conditions. The diagnosis and management of cancer is time sensitive and is likely to be substantially affected by these disruptions. We aimed to assess the impact of the COVID-19 pandemic on cancer care in India. We did an ambidirectional cohort study at 41 cancer centres across India that were members of the National Cancer Grid of India to compare provision of oncology services between March 1 and May 31, 2020, with the same time period in 2019. We collected data on new patient registrations, number of patients visiting outpatient clinics, hospital admissions, day care admissions for chemotherapy, minor and major surgeries, patients accessing radiotherapy, diagnostic tests done (pathology reports, CT scans, MRI scans), and palliative care referrals. We also obtained estimates from participating centres on cancer screening, research, and educational activities (teaching of postgraduate students and trainees). We calculated proportional reductions in the provision of oncology services in 2020, compared with 2019. Between March 1 and May 31, 2020, the number of new patients registered decreased from 112 270 to 51 760 (54% reduction), patients who had follow-up visits decreased from 634 745 to 340 984 (46% reduction), hospital admissions decreased from 88 801 to 56 885 (36% reduction), outpatient chemotherapy decreased from 173634 to 109 107 (37% reduction), the number of major surgeries decreased from 17 120 to 8677 (49% reduction), minor surgeries from 18 004 to 8630 (52% reduction), patients accessing radiotherapy from 51 142 to 39 365 (23% reduction), pathological diagnostic tests from 398 373 to 246 616 (38% reduction), number of radiological diagnostic tests from 93 449 to 53 560 (43% reduction), and palliative care referrals from 19 474 to 13 890 (29% reduction). These reductions were even more marked between April and May, 2020. Cancer screening was stopped completely or was functioning at less than 25% of usual capacity at more than 70% of centres during these months. Reductions in the provision of oncology services were higher for centres in tier 1 cities (larger cities) than tier 2 and 3 cities (smaller cities). The COVID-19 pandemic has had considerable impact on the delivery of oncology services in India. The long-term impact of cessation of cancer screening and delayed hospital visits on cancer stage migration and outcomes are likely to be substantial. None. For the Hindi translation of the abstract see Supplementary Materials section.
Fecal Microbiota Transplantation: Indications, Methods, Evidence, and Future Directions
Fecal microbiota transplantation (FMT) has attracted great interest in recent years, largely due to the global Clostridium difficile infection (CDI) epidemic and major advances in metagenomic sequencing of the gastrointestinal (GI) microbiota, with growing understanding of its structure and function. FMT is now recommended as the most effective therapy for relapsing CDI and, with further refinement, may even be used in “first-time” CDI. There is interest also in other conditions related to GI dysbiosis—for example, inflammatory bowel disease, irritable bowel syndrome, obesity, and diabetes mellitus—although quality evidence is at present lacking. A few trials are now underway in FMT for ulcerative colitis. Many unanswered questions remain, including FMT methodology—for example, optimal route of administration, what makes a “good donor,” safety issues, and long-term effects of FMT.
Cell-free sorting of peroxisomal membrane proteins from the endoplasmic reticulum
Several yeast and mammalian peroxisomal membrane proteins (PMPs) are delivered to peroxisomes via the endoplasmic reticulum (ER). Fluorescence microscopy showed a focused assembly of PMPs in a specialized domain of the ER, referred to as the preperoxisomal ER. It is proposed that preperoxisomal vesicles containing PMPs bud from this domain to either fuse with preexisting peroxisomes or to mature into functional peroxisomes by uptake of peroxisomal membrane and matrix proteins. However, such vesicular entities are not identified nor are the biochemical requirements for the budding process known. We developed an in vitro cell-free ER-budding assay using Pichia pastoris and followed two endogenous PMPs, Pex11p and Pex3p during their ER exit. Both the PMPs were copackaged in the ER-budded vesicles that float on a Nycodenz gradient. PMP budding from the ER was dependent on ATP, temperature, cytosol, and Pex19p and generated preperoxisomal vesicles with an incomplete complement of PMPs. Surprisingly, Pex11p budding was independent of Pex3p; however, the budded vesicles were devoid of most of the PMPs otherwise present in the wild-type vesicles and might represent peroxisomal remnants. Our findings provide a biochemical platform to uncover the mechanism of PMP budding from the ER.
Profound remission in Crohn’s disease requiring no further treatment for 3–23 years: a case series
Background Crohn’s disease (CD) is rising in incidence and has a high morbidity and increased mortality. Current treatment use immunosuppressives but efficacy is suboptimal, and relapse is common. It has been shown that there is an imbalance present in the gut microbiome (dysbiosis) in CD with a possible infective aetiology— Mycobacterium avium subsp. paratuberculosis (MAP) being the most proposed. Antibacterial therapy and Faecal Microbiota Transplantation (FMT) are emerging treatments which can result in clinical and endoscopic remission, if employed correctly. The objective of this study was to report on the treatment and clinical outcomes of patients with CD in prolonged remission. Results Ten patients were identified to have achieved prolonged remission for 3–23 years (median 8.5 years). Of these, 7/10 took targeted Anti-MAP therapy (AMAT) for a median 36 months and then ceased AMAT treatment. After stopping AMAT five patients underwent Faecal Microbiota Transplantation (FMT) (average four infusions). In 4/7, AMAT was combined with infliximab (mean of six infusions) that was withdrawn within 6 months after fistulae resolution. One patient achieved deep mucosal healing with AMAT alone. Of the 3/10 patients not prescribed AMAT, one had a combination of anti-inflammatory agents and a single antibiotic (metronidazole) followed by FMT. The other two received only FMT for Clostridioides difficile Infection. Conclusions Prolonged remission has been achieved for 3–23 years with individualised treatments, with the majority using AMAT ± infliximab and FMT. Treatment with antibiotics and/or FMT provides a potential new avenue for treatment of CD. These findings should stimulate thinking, investigations and better therapy against MAP and the dysbiosis of the gut flora, to enable higher rates of prolonged remission.
An Unusual Case of Uninterrupted Inferior Vena Cava with Accessory Hemizygous Channel: An Incidental Finding in a Child
Azygos or hemizygous continuation of inferior vena cava (IVC) is diagnosed in the presence of intrahepatic interruption of IVC. We report a case of a 4-year-old, male child presenting with a history of poor weight gain. A detailed evaluation of the child revealed a diagnosis of hemizygous continuation of uninterrupted, but severely obstructed, IVC. This incidental finding has rarely been reported in the literature.
Geographic distribution of inflammatory bowel disease in the UK: A spatially explicit survey
Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the gastrointestinal (GI) tract, with two main forms: Crohn’s disease (CD) and ulcerative colitis (UC). While CD can affect any part of the digestive system, UC predominately affects the colon and rectum. The incidence and prevalence rates of IBD cases are increasing worldwide, including in Europe where the UK has one of the highest incidence and prevalence rates. This study reports on a new survey of IBD cases in the UK, involving 5,452 respondents. The survey was promoted periodically by multiple IBD organizations across the UK over 307 days (01 Dec 2021–03 Oct 2022) and collected data on participants’ IBD diagnoses and histories. The distributions of CD and UC cases were examined on a grid scale and based on these distributions, relative risk was calculated and mapped in regions where CD and UC cases were recorded. In addition, age- and sex-standardized morbidity rates (ASMRs) for CD and UC were calculated. The results of this UK-wide IBD study reveal an even geographical distribution of reported IBD cases and relative risk across the UK. The ASMR analysis revealed that the reported morbidity rate for women (in the 20–59 age range) was much higher than the morbidity rate for men in both CD and UC cases. In addition, the CD:UC ratio, which has the advantage of normalizing for possible sampling biases, revealed a cluster of large values (i.e., relative risk of CD) in the North-West England which may require further investigation.
843 Crohn’s Strictures Open With Anti-Mycobacterial Antibiotic Therapy (AMAT): A Retrospective Review
INTRODUCTION:Approximately one third of patients with Crohn’s disease (CD) will develop strictures within 10 years of diagnosis, commonly in the terminal ileum and ileocecal valve (ICV). Strictures often lead to abdominal pain, obstruction and are a risk factor for developing internal fistulae and cancer. Current treatment involves endoscopic balloon dilatation or strictureplasty. However, this may result in postoperative complications or recurrence. Recent evidence suggests that Mycobacterium avium ssp paratuberculosis may be a causative agent of CD and anti-mycobacterial antibiotic therapy (AMAT) has been shown to induce remission significantly better than placebo. The effects of AMAT on strictures has not been reported.AIM:To report the outcomes of AMAT in patients with CD and an ileal stricture/s.METHODS:This is a single centre retrospective (January 1995-December 2018) case review of patients diagnosed with CD, who had ileal stricture on colonoscopy and were treated with AMAT which comprised a combination of clarithromycin, rifabutin, and clofazimine, some with added ethambutol, ciprofloxacin, metronidazole or tinidazole. Symptoms, colonoscopy reports, biochemistry and concurrent medications were reviewed and recorded at pre-treatment and 6, 12, 18 and >24 months on treatment.RESULTS:Forty-three patients (24 male, 16-56 yrs) with an average age of 31 yrs, and 5 yrs (0-27 yrs) after diagnosis were included. At pre-treatment, 17 patients had stricturing of the ICV, 25 had stricturing of the ileum and one had stricturing in both the ileum and ICV. Of the patients who had follow up colonoscopy data (N = 32), after >24 months of AMAT, 22/32 patients (69%) had complete resolution and 2/32 patients had partial resolution of their strictures. Interestingly, after resolution of stricture on AMAT one patient ceased treatment. At 36 month follow up post cessation of AMAT the patient’s ileocecal stricture had returned. Further treatment with AMAT resulted in resolution of the stricture.CONCLUSION:AMAT for CD is effective in opening Crohn’s strictures avoiding the need for repeated dilatations or surgery. These observations suggest that stricturing in CD may be mediated by mycobacterial infection, as reported in tuberculosis strictures. To our knowledge, CD strictures have not previously been reported to open using medical therapy. Further prospective documentation is required to better define this positive effect of AMAT, including rate of resolution.