Yadav, Siddhant

Objectives Long-term symptoms following infection with acute respiratory syndrome coronavirus-2 (SARS-CoV-2), termed post-acute sequelae of SARS-CoV-2 infection (PASC) or Long COVID (LC), persist beyond 90 days and may impact at least 10% of patients with acute infection. The exact cause of LC remains unknown, but several theories include persistent viral particles, immune dysfunction, and autonomic nervous system (ANS) imbalance, particularly involving the vagus nerve. Given the role of the vagus nerve in inflammation regulation, vagal nerve stimulation (VNS) is being explored as a treatment option. The present study aimed to evaluate the feasibility, safety, and exploratory effects of a handheld external transcutaneous cervical non-invasive VNS (tcVNS) on the primary endpoint of Post-COVID Functional Status (PCFS) grade, alongside secondary outcomes such as LC-related fatigue and other symptoms. Methods Participants from our Post COVID Care Clinic were randomized into treatment (tcVNS treatments two minutes, three times a day) and control (no VNS) groups for a study period of 12 weeks. Participants completed validated questionnaires, PET-CT scans, and inflammatory cytokines at baseline and 12 weeks. Results All randomized patients (8 tcVNS, 10 control) completed the 12-week study. Participants randomized to tcVNS were observed to have improvements in PHQ-9, PROMIS-F, and COMPASS-31 when compared to controls, but these differences were not statistically significant. Cortisol and DHEA were also observed to increase less in the tcVNS group when compared to the control group, but these changes were also not statistically significant. Conclusions tcVNS was well tolerated and may be a promising therapeutic approach for LC, a chronic disease with no approved treatments and very low rates of complete recovery.

Objective Long COVID (LC) refers to the long-term symptoms occurring after SARS-CoV-2 infection and resolution of the initial disease prodrome. While LC is increasingly recognized, knowledge about its biomarkers is still limited. This study examines imaging findings in 18 F-FDG PET-CT scans in 40 patients with LC from an academic LC Clinic, for potential imaging biomarkers. Methods This study included patients aged 18 and older with confirmed positive SARS-CoV-2 PCR test and at least 28 days post-symptom onset. 18 F-FDG PET-CT scans were performed, and brain metabolic activity was compared to a control database to generate Z-scores. Participants were grouped based on their clinical phenotype and Z-scores of different brain regions were analyzed using t-tests. Results The study group was mainly female (70%), with a median age of 53 years, and predominantly non-Hispanic White (90%). Most had pre-existing conditions such as gastrointestinal, cardiovascular, endocrine, and psychiatric disorders. The findings showed significant cerebral hypometabolism in 29 patients with fatigue and post-exertional malaise (PEM), particularly in the left sensorimotor cortex (p=0.0253) and bilateral primary visual cortex (right: p=0.0096, left: p=0.0016), which persisted up to two years after infection. Conclusions In summary, this study identified persistent cerebral hypometabolism in LC patients, especially those with fatigue with PEM, up to two years post-infection. These results suggest that 18 F-FDG PET-CT could be a valuable tool for diagnosing and managing LC. Further research is essential to confirm these findings and improve treatment strategies for patients with LC.

Abstract Background: Circulating levels of THC and CBD may be altered when administered with medications that strongly or moderately inhibit or induce CYP450 enzymes responsible for metabolizing both substances. THC and CBD levels can also theoretically be altered in individuals who carry germline genetic variants or atypical phenotypes of CYP450 enzymes. In individuals where drug and gene interactions occur together, there could be a heightened impact on the circulating levels of THC and CBD. Materials and Methods: We conducted a retrospective chart review using a database of participants who previously completed pharmacogenomic testing and reported oral cannabis use in a medical encounter. Two pharmacogenomic-trained pharmacists reviewed medications and atypical variants in each participant to characterize the predicted effect of cannabis-drug, cannabis-gene, and cannabis-drug-gene interactions on circulating levels of THC and CBD. Results: Oral cannabis use was confirmed in 71 participants, with an average age of 68.5 years and primarily White women. Regarding THC metabolism, drug-only interactions were noted in 1 participant; both drug and gene interactions were noted in 4 participants; single- or combination-gene-only interactions were noted in 38 participants; and 28 participants had no interactions. Concerning CBD metabolism, drug-only interactions were noted in 4 participants; both drug and gene interactions were noted in 4 participants; single- or combination-gene-only interactions were noted in 36 participants; and 27 participants had no interactions. Conclusion: This study is the first, to our knowledge, to conceptualize the potential impact of drugs and atypical phenotypes on altering circulating levels of THC and CBD in a clinical sample. The absence of published clinical outcomes in this field renders it challenging to estimate clinical significance of these findings. Until such data become available, leveraging the theoretical insights into drug interactions and atypical cannabis metabolism described in our study may serve as a tool to guide clinical care.

Background: In addition to the morbidity and mortality associated with acute infection, COVID-19 has been associated with persistent symptoms (>30 days), often referred to as Long COVID (LC). LC symptoms often cluster into phenotypes, resembling conditions such as fibromyalgia, postural orthostatic tachycardiac syndrome (POTS), and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). LC clinics have been established to best address the needs of LC patients and continuity of care. We developed a cross-sectional survey to assess treatment response through our LC Clinic (LCC). Methods: A 25-question survey (1-10 Likert scale) was expert- and content-validated by LCC clinicians, patients, and patient advocates. The survey assessed LC symptoms and the helpfulness of different interventions, including medications and supplements. A total of 852 LCC patients were asked to complete the survey, with 536 (62.9%) responding. Results: The mean time from associated COVID-19 infection to survey completion was 23.2 ± 6.4 months. The mean age of responders was 52.3 ± 14.1 (63% females). Self-reported symptoms were all significantly improved ( P < .001) from the initial visit to the LCC (baseline) to the time of the follow-up survey. However, only 4.5% (24/536) of patients rated all symptoms low (1-2) at the time of the survey, indicating low levels of full recovery in our cohort. The patients rated numerous interventions as being helpful, including low-dose naltrexone (45/77; 58%), vagal nerve stimulation (18/34; 53%), and fisetin (28/44; 64%). Conclusions: Patients report general improvements in symptoms following the initial LCC visit, but complete recovery rates remain low at 23.2 ± 6.4 months.

Background: Over 30% of patients with COVID-19 have persistent symptoms that last beyond 30 days and referred to as Long COVID. Long COVID has been associated with a persistent elevation in peripheral cytokines including interleukin-6, interleukin-1β, and tumor necrosis factor-α. This study reports cytokine profiles of patients in our clinic across SARS-COV-2 variant epochs. Methods: The clinical cytokine panel was analyzed in patients with Long COVID during periods that were stratified according to variant epoch. The 4 variant epochs were defined as: (1) wild-type through alpha, (2) alpha/beta/gamma, (3) delta, and (4) omicron variants. Results: A total of 390 patients had the clinical cytokine panel performed; the median age was 48 years (IQR 38-59) and 62% were female. Distribution by variant was wild-type and alpha, 50% (n = 196); alpha/beta/gamma, 7.9% (n = 31); delta, 18% (n = 72); and omicron, 23% (n = 91). Time to cytokine panel testing was significantly longer for the earlier epochs. Tumor necrosis factor-α ( P < .001) and interleukin 1β ( P < .001) were significantly more elevated in the earlier epochs (median of 558 days in wild-type through Alpha epoch vs 263 days in omicron epoch, P < .001)). Nucleocapsid antibodies were consistently detected across epochs. Discussion: When stratified by variant epoch, patients with early epoch Long COVID had persistently elevated peripheral pro-inflammatory cytokine levels when compared to later epoch Long COVID. Patients with Long COVID have similar clusters of symptoms across epochs, suggesting that the underlying pathology is independent of the peripheral cytokine signature.

AbstractBackgroundAvascular necrosis (AVN) is a known adverse event associated with corticosteroid (CS) usage. Inflammatory bowel disease (IBD) is often treated with a CS for induction of remission. We sought to describe clinical features and outcomes of IBD patients with AVN.MethodsIn this retrospective, single-center, case-control study, patients with IBD who had a diagnosis of osteonecrosis, aseptic necrosis, or AVN from 1976 to 2009 were included, and each was matched with up to 2 controls (IBD but no AVN) on age, sex, IBD subtype, geographic area of residence, and date of IBD diagnosis. We abstracted risk factor data from the medical records. Conditional logistic regression was performed accounting for minor differences in age and date of first IBD visit to assess the relationship between putative risk factors and AVN, expressed as odds ratio and 95% confidence interval.ResultsEighty-five patients were diagnosed with IBD-AVN and were matched with 163 controls. The mean age at AVN diagnosis was 47.5 years. AVN was diagnosed a median of 12.2 years after IBD diagnosis, and the control group was followed for a median of 15 years after IBD diagnosis to ensure that they did not have AVN. Ten percent of patients with AVN did not have any CS exposure. History of arthropathy or estrogen use in Crohn’s disease and use of CS, osteoporosis, and history of arthropathy in ulcerative colitis were significantly associated with AVN.ConclusionsMost patients with IBD-AVN had multifocal involvement. Most had received CS, but many patients had other risk factors including arthropathy.

Abstract Background We sought to estimate the incidence of home parenteral nutrition (HPN) use in a population-based cohort of patients with Crohn disease (CD), and to assess clinical outcomes and complications associated with HPN. Methods We used the Rochester Epidemiology Project (REP) to identify residents of Olmsted County, who were diagnosed with CD between 1970 and 2011, and required HPN. Results Fourteen out of 429 patients (3.3%) with CD received HPN (86% female). Eleven patients (79%) had moderate–severe CD and 12 patients (86%) had fistulizing disease. Thirteen patients (93%) underwent surgery, primarily due to obstruction. Among CD incidence cases, the cumulative incidence of HPN from the date of CD diagnosis was 0% at 1 year, 0.5% at 5 years, 0.8% at 10 years, and 2.4% at 20 years. Indications for HPN included short bowel syndrome in 64%, malnutrition in 29%, and bowel rest in 21%. The median duration of HPN was 2.5 years. There was an average weight gain of 1.2 kg at 6 months, an average weight loss of 1.4 kg at 1 year, and a further weight loss of 2.2 kg at 2 years from the start of HPN. Patients were hospitalized a mean of 5 times after the start of HPN, mainly due to catheter-related bloodstream infections and thrombosis. Conclusions Less than 4% of patients with CD need HPN. Most have moderate to severe disease with short bowel syndrome or malnutrition. Possible reasons for the patients’ weight loss could be noncompliance, and increased metabolic needs because of active disease.

Abstract Background and study aims There are limited published data on endoscopic removal of colorectal polyps by endoscopic mucosal resection (EMR) and endoscopic mucosal dissection (ESD) in patients with inflammatory bowel disease (IBD). Patients and methods We performed a retrospective review of patients with colonic IBD and colonic polyps >10mm who underwent EMR and/or ESD at our institution between January 1, 2012 and June 31, 2016. Results Ninety-seven patients with pathology-confirmed IBD (median disease duration 16 years) were included. Mild or moderate active colitis (in background biopsies) was seen in 85 %. Of the total 124 polyps, location was ascending colon in 44 %, transverse in 15 % and sigmoid in 18.5 %; of the total, 55 % were < 20 mm and 45 % were ≥20mm in maximal diameter. Using the Paris classification, 56 % of polyps were polypoid sessile (Is) polyps, while 38 % were non-polypoid (IIa, IIb, IIc). EMR was used in 118 polyps, three required ESD, and three by combined EMR-ESD. Seventy-two percent were resected en-bloc; 28 % underwent piecemeal resection. Histology included low-grade dysplasia in 75, serrated adenoma in 31, and tubular adenoma in 14 polyps. Chromoendoscopy was used in 33 (26.6 %). Adverse events occurred in three patients. Colectomy was performed in 11 patients within 12 months. Recurrence was seen in 20 polyps, 11 of which were successfully resected en-bloc using EMR. Polyps ≥ 20 mm and polyps treated with APC were found to have a statistically significantly higher risk of recurrence. Conclusion This study demonstrates the efficacy and safety of endoscopic resection of large polyps in patients with IBD, making them effective alternatives to colectomy.