Longitudinal Progression of Patients with Long COVID Treated in a Post-COVID Clinic: A Cross-Sectional Survey.

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.

Pro Inflammatory Cytokines Profiles of Patients With Long COVID Differ Between Variant Epochs.

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-1ß, 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 1ß (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.

Inflammatory Arthritis After COVID-19: A Case Series.

BACKGROUND Some patients who have recovered from acute infection with SARS-CoV-2 develop persistent symptoms that have been termed post-COVID syndrome (PoCoS). PoCoS can affect the musculoskeletal system, with arthralgia and myalgia being common. Preliminary evidence suggests that PoCoS is an immune-mediated condition that not only predisposes but also precipitates pre-existing inflammatory joint diseases such as rheumatoid arthritis and reactive arthritis. Here, we describe a series of patients who presented to our Post-COVID Clinic and were found to have inflammatory arthritis (reactive and rheumatoid arthritis). CASE REPORT We present 5 patients who developed joint pain several weeks after recovery from acute SARS-CoV-2 infection. These patients were seen in our Post-COVID Clinic and came from locations across the United States. All 5 patients were women, with age of diagnosis of COVID-19 disease between 19 and 61 years (mean 37.8 years). All patients presented with joint pain as the primary concern to the Post-COVID Clinic. Abnormal joint imaging was present in all patients. Treatments varied and included non-steroidal anti-inflammatory drugs, acetaminophen, corticosteroids, immunomodulators (golimumab), methotrexate, leflunomide, and hydroxychloroquine. CONCLUSIONS COVID-19 disease is a potential cause of inflammatory arthritis, with both rheumatoid arthritis and reactive arthritis demonstrated in our PoCoS population. Care must be taken to identify these conditions, as there are treatment ramifications.

Osteonecrosis in Inflammatory Bowel Disease: Clinical Features, Risk Factor Analysis, and Outcomes.

BACKGROUND: Avascular 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. METHODS: In 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. RESULTS: Eighty-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. CONCLUSIONS: Most patients with IBD-AVN had multifocal involvement. Most had received CS, but many patients had other risk factors including arthropathy.

This single-center, case-control study of inflammatory bowel disease patients with osteonecrosis showed that while corticosteroid use was likely a risk factor, especially among ulcerative colitis patients, other risk factors included estrogen use among Crohn's disease patients, arthropathy, and osteoporosis.

A Rare Case of Transposition of Great Arteries Uncovered With Progressive Rheumatic Aortic Stenosis.

The authors describe a case of transposition of great arteries with a large atrial septal defect with fusion of tricuspid valve leaflets and severe aortic stenosis. The latter two were likely rheumatic in etiology. The patient's condition improved after atrial switch and aortic valve replacement surgery. (Level of Difficulty: Intermediate.).

Incidence and Outcomes of Home Parenteral Nutrition in Patients With Crohn Disease in Olmsted County, Minnesota.

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.

Outcome of endoscopic resection of colonic polyps larger than 10 mm in patients with inflammatory bowel disease.

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.

Hyperglycemia During Home Parenteral Nutrition Administration in Patients Without Diabetes.

BACKGROUND: Parenteral nutrition (PN) is a life-sustaining therapy in appropriate clinical settings. In the hospital setting, some nondiabetic patients develop hyperglycemia and subsequently require long-term insulin while receiving PN. Whether similar hyperglycemia is seen in the outpatient setting is unclear. METHODS: We studied patients enrolled in the Mayo Clinic Home Parenteral Nutrition (HPN) program between January 1, 2010, and December 31, 2012. Patients were excluded if they had diabetes mellitus type 2 (DM2), had previously received HPN, had taken corticosteroids, or were at risk for refeeding syndrome. RESULTS: Of 144 enrolled patients, 93 met inclusion criteria with 39 patients requiring the addition of insulin to HPN. The mean age of the insulin-requiring group (IR) was higher than that of the non-insulin-requiring group (NIR) (60.74 ± 13.62 years vs 48.97 ± 17.62 years, P < .001). There were 17 (44%) men in the IR group and 26 (48%) men in the NIR group. Mean blood glucose at baseline before starting the infusion was 131.82 ± 49.55 mg/dL in IR patients and 106.16 ± 59.01 mg/dL in NIR patients ( P = .03). In the stepwise multivariate analysis for assessing the risk for developing hyperglycemia, HR for age was 1.020 (1.010-1.031), P < .001. CONCLUSIONS: Hyperglycemia is a common finding with the use of PN in both the hospital and ambulatory setting in patients without a previous diagnosis of DM2. Age was the most significant predictor of the requirement of insulin in the present study. When hyperglycemia is managed appropriately with insulin therapy, the long-term complications can be minimized.

Hidradenitis Suppurativa in Patients With Inflammatory Bowel Disease: A Population-Based Cohort Study in Olmsted County, Minnesota.

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) may be at higher risk for hidradenitis suppurativa (HS). We studied the risk and clinical characteristics of HS in a population-based cohort of patients with IBD. METHODS: We identified all cases of HS (confirmed by biopsy and/or dermatologic evaluation) in a population-based inception cohort of Olmsted County, Minnesota, residents diagnosed with IBD between 1970 and 2004 and followed up through August 2013. We estimated the incidence rate ratio of HS in patients with IBD compared with the general population, and described the clinical characteristics, risk factors, and management of HS. RESULTS: In 679 IBD patients followed up over a median of 19.8 years, we identified 8 patients with HS (mean age, 44.4 ± 8.3 y; 7 women; 6 obese). Compared with the general population, the incidence rate ratio of HS in IBD was 8.9 (95% confidence interval, 3.6-17.5). The 10- and 30-year cumulative incidence of HS was 0.85% and 1.55%, respectively. Five patients had Crohn's disease, 4 of whom had perianal disease; of 3 patients with ulcerative colitis, 2 had undergone ileal pouch-anal anastomosis. Axillae, groin, and thighs were the most common sites of involvement. Six patients had Hurley stage 2 disease (recurrent abscesses with sinus tracts and scarring, involving widely separated areas), and required a combination of antibiotics and surgery; none of the patients were treated with anti-tumor necrosis factor-α agents. CONCLUSIONS: In this population-based study, patients with IBD were approximately 9 times more likely to develop HS than the general population, with a female predisposition.

Effect of Medications on Risk of Cancer in Patients With Inflammatory Bowel Diseases: A Population-Based Cohort Study from Olmsted County, Minnesota.

OBJECTIVES: To estimate the overall risk of cancer in a population-based cohort of patients with inflammatory bowel disease (IBD) and how IBD-related medications modify this risk. METHODS: We identified all incident cancers (excluding nonmelanoma skin cancer) after IBD diagnosis in a cohort of 839 patients diagnosed as having IBD from January 1, 1940, through December 31, 2004, in Olmsted County, Minnesota, and followed up for a median 18 years through December 31, 2011 (122 patients taking biologic agents at last follow-up). We calculated standardized incidence ratios (SIRs) with 95% CIs of all cancers and compared cancer risk in patients treated with immunomodulators (IMMs) and biologics with that of patients not exposed to these medications, using an incidence rate ratio (IRR). RESULTS: One hundred nine patients developed 135 cancers. The 10-year cumulative probability of cancer was 3.8%. Patients with Crohn disease (SIR, 1.6; 95% CI, 1.2-2.1) but not ulcerative colitis (SIR, 1.1; 95% CI, 0.8-1.4) had an increased overall risk of cancer compared with the general population. Patients treated with IMMs (relative to IMM-naive patients) had an increased risk of melanoma (IRR, 5.3; 95% CI, 1.1-24.8) (and a numerically higher risk of hematologic malignant tumors [IRR, 4.2; 95% CI, 0.9-19.2]), although this risk returned to baseline on discontinuation of IMM treatment. Patients treated with biologics (relative to biologic-naive patients) had a numerically higher risk of hematologic malignant tumors (IRR, 5.3; 95% CI, 0.7-40.5). There was no significant increase in the risk of gastrointestinal malignancies in patients with IBD compared with the general population. CONCLUSIONS: We observed an increased risk of melanoma in IMM-treated patients with IBD, and this risk returned to baseline after discontinued use of the medications.

A population-based study of incidence, risk factors, clinical spectrum, and outcomes of ischemic colitis.

BACKGROUND & AIMS: Little is known about progression of ischemic colitis (IC) among unselected patients. We aimed to estimate the incidence, risk factors, and natural history of IC in a population-based cohort in Olmsted County, Minnesota. METHODS: We performed a retrospective population-based cohort and nested case-control study of IC. Each IC case was matched to 2 controls from the same population on the basis of sex, age, and closest registration number. Conditional logistic regression, the Kaplan-Meier method, and proportional hazards regression were used to assess comorbidities, estimate survival, and identify characteristics associated with survival, respectively. RESULTS: Four hundred forty-five county residents (median age, 71.6 years; 67% female) were diagnosed with IC from 1976 through 2009 and were matched with 890 controls. The age-adjusted and sex-adjusted incidence rates of IC nearly quadrupled from 6.1 cases/100,000 person-years in 1976-1980 to 22.9/100,000 in 2005-2009. The odds for IC were significantly higher among subjects with atherosclerotic diseases; odds ratios ranged from 2.6 for individuals with coronary disease to 7.9 for individuals with peripheral vascular disease. Of IC cases, 59% survived for 5 years (95% confidence interval, 54%-64%), compared with 90% of controls (95% confidence interval, 88%-92%). Age >40 years, male sex, right-sided colon involvement, concomitant small bowel involvement, and chronic obstructive pulmonary disease were all independently associated with mortality (P < .05). CONCLUSIONS: The incidence of IC increased during the past 3 decades in a population-based cohort in Minnesota. IC typically presents in older patients with multiple comorbidities and is associated with high in-hospital mortality (11.5%) and rates of surgery (17%).

The rationale for combining an online audiovisual curriculum with simulation to better educate general surgery trainees.

BACKGROUND: Surgery interns' training has historically been weighted toward patient care, operative observation, and sleeping when possible. With more protected free time and less clinical time, real educational hours for trainees in 2013 are precious. METHODS: We created a 20-session (3 hours each) simulation curriculum (with pre- and post-tests) and a 24/7 online audiovisual (AV) curriculum for surgery interns. Friday morning simulation sessions emphasize operative skills and judgment. AV clips (using operating room, whiteboard, and simulation center videos) take learners through 20 different general surgery operations with follow-up quizzes. We report our early experience with this novel setup. RESULTS: Thirty-two surgical interns (2012-2013) attended simulation sessions on 20 separate subjects (hernia, breast, hepatobiliary, endocrine, etc). Post-test scores improved (P < .05) and trainees enjoyed using surgical skills for 3 hours each Friday morning (mean, >4.5; Likert scale, 1-5). The AV curriculum feedback is similar (mean, >4.3) and usage is available 24/7 preparing learners for both operating room and simulation sessions. Most simulation sessions utilize low-fidelity models to keep costs <$50 per session. Scores on our semiannual Surgical Olympics (mean score of 49.6 in July vs 82.9 in January; P < .05) improved significantly, suggesting that interns are improving their surgical skills and knowledge. CONCLUSION: Residents enjoy and learn from the step-by-step, in-house, AV curriculum and both appreciate and thrive on the 'hands-on' simulation sessions mimicking operations they see in real operating rooms. The cost of these programs is not prohibitive and the programs offer simulated repetitions for duty-hour-regulated trainees.

Inflammatory bowel disease is associated with an increased risk of melanoma: a systematic review and meta-analysis.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) has been associated with an increased risk of nonmelanoma skin cancer, particularly among patients treated with thiopurines. It is unclear whether IBD affects risk for melanoma. We performed a systematic review and meta-analysis of cohort studies to determine the risk of melanoma in patients with IBD. METHODS: We conducted a systematic search of bibliographic databases through March 2013. Cohort studies reporting incident melanoma after IBD diagnosis and an estimate of incidence rate ratio or standardized incidence rate were included in the analysis. Pooled relative risk (RR) estimates with 95% confidence intervals (CIs) were calculated using the random-effects model. RESULTS: Our analysis included 12 studies, comprising a total of 172,837 patients with IBD; 179 cases of melanoma were reported from 1940 to 2009. The pooled crude incidence rate of melanoma in patients with IBD was 27.5 cases/100,000 person-years (95% CI, 19.9-37.0). Overall, IBD was associated with a 37% increase in risk of melanoma (12 studies: RR, 1.37; 95% CI, 1.10-1.70). The risk was increased among patients with Crohn's disease (7 studies: RR, 1.80; 95% CI, 1.17-2.75) and ulcerative colitis (7 studies: RR, 1.23; 95% CI, 1.01-1.50). The risk of melanoma was higher in studies performed before introduction of biologic therapies (before 1998) (8 studies: RR, 1.52; 95% CI, 1.02-2.25) but not in studies performed after 1998 (2 studies: RR, 1.08; 95% CI, 0.59-1.96). CONCLUSIONS: Based on a meta-analysis, IBD has been associated with an increased risk of melanoma, independent of the use of biologic therapy. Patients diagnosed with IBD should be counseled on their risk for melanoma.

Cumulative incidence and risk factors for hospitalization and surgery in a population-based cohort of ulcerative colitis.

BACKGROUND: We sought to identify clinical and demographic features influencing hospitalization and colectomy in a population-based inception cohort of ulcerative colitis. METHODS: Between 1970 and 2004, a total of 369 patients (58.5% males) from Olmsted County, MN, were followed from diagnosis for 5401 person-years. The cumulative probability of hospitalization and colectomy were estimated using the Kaplan-Meier method. Cox proportional hazards regression was used to identify factors associated with hospitalization and colectomy. RESULTS: The cumulative probability of first hospitalization was 29.4% at 5 years (95% confidence interval [CI], 24.5%-34.1%), 38.7% at 10 years (33.1%-43.8%), 49.2% at 20 years (42.7%-55.2%), and 52.3% at 30 years (45.1%-59.7%). The incidence rate of hospitalizations decreased over the last 4 decades, although cumulative probability of first hospitalization increased with successive decades of diagnosis. Early need for corticosteroids (hazard ratio [HR], 1.8; 95% CI, 1.1%-2.7%) and early need for hospitalization (HR, 1.5; 95% CI, 1.02-2.4) were independent predictors of hospitalization after 90 days of illness. The cumulative probability of colectomy from the time of diagnosis was 13.1% at 5 years (95% CI, 9.4%-16.6%), 18.9% at 10 years (95% CI, 14.4%-23.2%), and 25.4% at 20 years (95% CI, 19.8%-30.8%). Male gender (HR, 2.1; 95% CI, 1.3-3.5), diagnosis in the 1990s (HR, 2.0; 95% CI, 1.01-4.0), and diagnosis in 2000 to 2004 (HR, 3.7; 95% CI, 1.7-8.2) were significantly associated with colectomy risk. CONCLUSIONS: Colectomy rates were comparable to reports from northern Europe. The numbers of hospitalizations show a decreasing trend. Male gender and being diagnosed in the 2000 to 2004 period predicted colectomy while extensive colitis predicted future hospitalizations.

Predictors of chronic groin discomfort after laparoscopic totally extraperitoneal inguinal hernia repair.

BACKGROUND: Chronic groin discomfort is an undesired complication of laparoscopic totally extraperitoneal (TEP) inguinal hernia repairs. We examined whether perioperative factors may be associated with an increased risk of developing this problem and if their recognition could lead to preventive strategies. STUDY DESIGN: We performed a retrospective review of 1 surgeon's experience with 1,479 TEP repairs on 976 patients from 1995 to 2009. A mailed survey, which included a groin discomfort questionnaire (Carolinas Comfort Scale), was distributed to all patients. Symptom severity grading (range 0, none to 5, severe) was used to sort individual responses. Perioperative factors were compared between asymptomatic and symptomatic patients with varying levels of discomfort. RESULTS: There were 691 patients (71%) who provided complete responses to the questionnaire. Median follow-up was 5.7 years (range 0 to 14.4 years). The majority (n = 543, 79%) denied any symptoms of mesh sensation, pain, or movement limitation. In the remaining 148 (21%) patients, symptoms were most often mild (n = 108), followed by mild but bothersome (n = 25), and 15 patients (2%) had moderate or severe symptoms. Symptomatic patients were younger (median age 52 vs 57 years, p = 0.002) and were more likely to have had the TEP repair for recurrent hernias (24% vs 17%, p = 0.035). Operative diagnosis, bilateral exploration, mesh fixation techniques, perioperative complications, American Society of Anesthesiologists grade, and length of hospital stay were not associated with chronic groin discomfort. CONCLUSIONS: The majority of patients are asymptomatic after a laparoscopic TEP inguinal hernia repair. Most of the symptomatic patients do not have any bothersome symptoms. Given that younger age and a repair for recurrent hernia were predictors of chronic groin discomfort, we counsel these patients about their increased risks.