COVID-19 convalescent plasma therapy decreases inflammatory cytokines: a randomized controlled trial.

IMPORTANCE: This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect. This decrease in IL-6 levels after early CCP treatment suggests a possible role of inflammation in COVID-19 progression. The evidence of IL-6 involvement brings insight into the possible mechanisms involved in CCP treatment mitigating SARS-CoV-2 severity.

Dynamics of inflammatory responses after SARS-CoV-2 infection by vaccination status in the USA: a prospective cohort study.

BACKGROUND: Cytokines and chemokines play a critical role in the response to infection and vaccination. We aimed to assess the longitudinal association of COVID-19 vaccination with cytokine and chemokine concentrations and trajectories among people with SARS-CoV-2 infection. METHODS: In this longitudinal, prospective cohort study, blood samples were used from participants enrolled in a multi-centre randomised trial assessing the efficacy of convalescent plasma therapy for ambulatory COVID-19. The trial was conducted in 23 outpatient sites in the USA. In this study, participants (aged ≥18 years) were restricted to those with COVID-19 before vaccination or with breakthrough infections who had blood samples and symptom data collected at screening (pre-transfusion), day 14, and day 90 visits. Associations between COVID-19 vaccination status and concentrations of 21 cytokines and chemokines (measured using multiplexed sandwich immunoassays) were examined using multivariate linear mixed-effects regression models, adjusted for age, sex, BMI, hypertension, diabetes, trial group, and COVID-19 waves (pre-alpha or alpha and delta). FINDINGS: Between June 29, 2020, and Sept 30, 2021, 882 participants recently infected with SARS-CoV-2 were enrolled, of whom 506 (57%) were female and 376 (43%) were male. 688 (78%) of 882 participants were unvaccinated, 55 (6%) were partly vaccinated, and 139 (16%) were fully vaccinated at baseline. After adjusting for confounders, geometric mean concentrations of interleukin (IL)-2RA, IL-7, IL-8, IL-15, IL-29 (interferon-λ), inducible protein-10, monocyte chemoattractant protein-1, and tumour necrosis factor-α were significantly lower among the fully vaccinated group than in the unvaccinated group at screening. On day 90, fully vaccinated participants had approximately 20% lower geometric mean concentrations of IL-7, IL-8, and vascular endothelial growth factor-A than unvaccinated participants. Cytokine and chemokine concentrations decreased over time in the fully and partly vaccinated groups and unvaccinated group. Log10 cytokine and chemokine concentrations decreased faster among participants in the unvaccinated group than in other groups, but their geometric mean concentrations were generally higher than fully vaccinated participants at 90 days. Days since full vaccination and type of vaccine received were not correlated with cytokine and chemokine concentrations. INTERPRETATION: Initially and during recovery from symptomatic COVID-19, fully vaccinated participants had lower concentrations of inflammatory markers than unvaccinated participants suggesting vaccination is associated with short-term and long-term reduction in inflammation, which could in part explain the reduced disease severity and mortality in vaccinated individuals. FUNDING: US Department of Defense, National Institutes of Health, Bloomberg Philanthropies, State of Maryland, Mental Wellness Foundation, Moriah Fund, Octapharma, HealthNetwork Foundation, and the Shear Family Foundation.

Imaging Utilization Patterns and Injury Characteristics Associated with Electric Standing Scooters in a Major Urban Area.

BACKGROUND: The recent proliferation of electric standing scooters in major urban areas of the United States has been accompanied by injuries of varying severity and nature, representing a growing public health concern. OBJECTIVE: Our aim was to characterize imaging utilization patterns for injuries associated with electric scooter (e-scooter) use, including their initial emergency department (ED) management. METHODS: We conducted a retrospective review of the electronic medical record for all patients presenting to affiliated EDs for e-scooter-related injuries between July 2018 and April 2020. Demographics, date and time of presentation, imaging study type, resultant injury, and procedural details were recorded. RESULTS: Ninety-seven patients were included; mean age was 27.6 years. Of these, 55 patients (57%) had injuries identified on imaging and 40% of all imaging studies were positive. Most identified injuries (61%) were musculoskeletal, with a small number of neurological (2%) and genitourinary (1%) injuries. The highest prevalence of presentations occurred in August; most patients (72%) presented between 3 pm and 1 am and granular peaks were between 12 am and 1 am and 5 pm and 6 pm. CONCLUSIONS: Patients presenting with e-scooter injuries have a high likelihood of injury to the radial head, nasal bone, and malleoli. Emergency physicians should be especially vigilant for injuries in these areas at presentation. Visceral injuries are uncommon but may be severe enough to warrant surgery.

Medical errors education: A prospective study of a new educational tool.

Medical errors training is an important yet often overlooked aspect of medical education. A medical errors educational session was developed for rotating medical students (MSs) with prospective analysis of the educational tool. Students completed the same 12-question test before and after the educational session and a long-term posttest 1 to 12 months later. Control students who did not take part in the session completed the test twice with a 6-month interval. In all, 51 students completed a pretest and a short-term posttest, and 35 students completed a long-term posttest. Test scores for the study group increased significantly from a pretest mean of 29.3% to a short-term posttest mean of 73.7% ( P < .001) and a long-term posttest mean of 49.1% (P < .001). Long-term test scores for 24 control group students were significantly lower (P < .001). This brief educational intervention led to statistically significant improved performance in general understanding of medical errors and could be a useful tool to enhance MS awareness and proactive handling of medical errors.

Medical errors education for students of surgery: a pilot study revealing the need for action.

BACKGROUND: Medical errors training is an important yet often overlooked aspect of surgical education. In response to a perceived deficiency in medical errors training at our institution, we implemented an educational session on medical errors concepts for the benefit of rotating medical students. MATERIALS AND METHODS: Medical students completed the same 12-question test before and after the 90-minute educational session. Pretest and posttest scores were compared for evidence of enhanced understanding. No personal identifiers were used, and students were provided unlimited time to complete the tests. Six groups of medical students (who ranged from 5 to 8 students per session) completed the educational session. All sessions were moderated by the same surgical resident and attending surgeon, who used a standard slide presentation. Test scores were analyzed with SPSS statistical software (version 14.0; SPSS Inc., Cary, NC), which employed the paired samples t-test (alpha = 0.05). RESULTS: Test scores increased significantly from a pretest mean of 27.3% correct (3.28 of 12 possible, SD = 1.57) to a mean posttest score of 70.1% (8.41, SD = 1.52) (p < 0.001). CONCLUSIONS: This retrospective pilot study demonstrated that a brief educational intervention led to statistically significant improved performance on a general understanding of medical errors. The study also revealed the dearth of baseline knowledge in our participating medical students on the subject. We believe that these results underscore the need for action in providing improved and ongoing education in medical errors concepts to enhance medical student awareness and proactive handling of medical errors.

The cost effectiveness of laparoscopic versus open gastric bypass surgery.

BACKGROUND: Over the last decade, laparoscopic gastric bypass (LGBP) has been proven to be a safe and well-tolerated approach to the Roux-en-Y gastric bypass, despite its increased cost when compared to the open approach (OGBP). This increased expense has led many to question whether LGBP is a cost effective alternative to OGBP. The aim of this study is to determine which approach is most cost effective, considering costs associated with the operation itself, perioperative complications, and income lost during convalescence. METHODS: A PubMed search of the National Library of Medicine online journal database was conducted. Studies that met predetermined criteria for selection were included in the analyses of patient demographics, perioperative complications, length of hospital stay, excess weight loss, and time to recovery. Data on 6,425 OGBP and 5,867 LGBP patients were used to compare the outcomes associated with each approach. RESULTS: Significant differences were found in the perioperative complication profiles, time to recovery, and overall expense of the two approaches. OGBP was associated with an increased incidence of major perioperative complications, especially extraintestinal complications, and greater perioperative mortality. LGBP was associated with shorter hospital stays, increased incidence of intestinal complications, and a 2.25% incidence of conversion to OGBP. Patient demographics and percent excess weight loss (%EWL) at 3 years follow-up were found to be similar with both OGBP and LGBP. CONCLUSION: LGBP is a cost effective alternative to OGBP for surgical weight loss. Despite the increased cost of LGBP, patients suffer fewer expensive and lifethreatening perioperative complications.

Interleukin-6 induces thermotolerance in cultured Caco-2 cells independent of the heat shock response.

In recent studies, induction of the heat shock response increased IL-6 production in gut mucosa in vivo and in cultured Caco-2 cells in vitro. The heat shock response is associated with increased survival of cells exposed to otherwise lethal hyperthermia, so called thermotolerance, but the role of IL-6 in the induction of thermotolerance is not known. We tested the hypothesis that treatment of cultured Caco-2 cells with IL-6 results in the development of thermotolerance. Cells were treated with human recombinant IL-6 for 1h followed by 3 h recovery in cytokine-free medium whereafter cells were exposed to heat stress (48 degrees C for 2 h). In untreated cells, the heat stress resulted in an approximately 80% cell death. In cells treated with IL-6, cell viability after heat stress was significantly improved and was doubled at an IL-6 concentration of 20 ng/ml. Treatment of the cells with other cytokines (IL-4, IL-10, IL-1beta, or TNFalpha) did not induce thermotolerance, suggesting that the effect of IL-6 may be specific for this cytokine. The induction of thermotolerance by IL-6 was blocked by an IL-6 receptor antibody, suggesting that the development of thermotolerance was receptor-mediated. Treatment of cells with IL-6 did not induce an heat shock response as suggested by unaltered heat shock protein 70 and 90 levels and unaffected heat shock factor DNA binding activity. In addition, the IL-6-induced thermotolerance was not inhibited by quercetin. The present study provides the first evidence of IL-6-induced thermotolerance and suggests that this effect of IL-6 is independent of the heat shock response.

Interleukin-10 activates the transcription factor C/EBP and the interleukin-6 gene promoter in human intestinal epithelial cells.

BACKGROUND: Interleukin (IL)-6 is produced by enterocytes in response to sepsis and after treatment with IL-1beta. The IL-6 promoter contains binding sites for multiple transcription factors, including nuclear factor-kappaB and C/EBP. The anti-inflammatory cytokine IL-10 downregulates nuclear factor-kappaB activity, but its effects on C/EBP activation and IL-6 production in the enterocyte are not known. METHODS: Caco-2 cells were treated with IL-1beta, IL-10, or a combination of the cytokines. C/EBP DNA binding activity was determined by electrophoretic mobility shift assay and IL-6 levels by enzyme-linked immunosorbent assay. IL-6 promoter activation was assessed by luciferase assay. RESULTS: IL-10 treatment of cultured Caco-2 cells resulted in increased C/EBP DNA binding activity. Supershift analysis revealed upregulated DNA binding activity of C/EBP-beta but not C/EBP-delta. To examine if the increased DNA binding reflected gene activation, cells were transfected with a wild-type IL-6 promoter luciferase construct or with a mutated C/EBP binding site. IL-10 potentiated IL-1 beta-induced IL-6 promoter activity. Replacing the wild-type promoter with the promoter containing a mutated C/EBP DNA binding sequence blocked the effect of IL-10. When cells were treated with 0.5 ng/mL of IL-1 beta for 24 hours, IL-6 production increased, and this response to IL-1 beta was potentiated several-fold by IL-10. CONCLUSIONS: IL-10 may activate the IL-6 gene in stimulated enterocytes by upregulating the expression and activity of C/EBP.

Interposition of a jejunal segment as an alternative one-stage operation for acute left colon obstruction.

PURPOSE: Much debate surrounds the one-stage surgical management of acute left colon obstruction. Many surgeons are still reluctant to perform primary anastomosis in unprepared bowel fearing the risk of anastomotic dehiscence. Although intraoperative lavage and subtotal colectomy have recently proved effective for preventing fecal loading, both of these procedures have drawbacks and the search for additional alternative surgical procedures continues. We conducted an experimental study to examine a new one-stage operation, consisting of the interposition of a jejunal segment to the resection site of the colon, to manage acute left colon obstruction. METHODS: The colons of 20 domestic pigs were obstructed, and 2 days later, segmental resection and either primary colo-colonic anastomosis or interposition of a jejunal segment was performed. Autopsies were done 6 weeks after the operations and the anastomotic regions were subjected to bursting pressure analysis. RESULTS: The operating time was longer in the interposition group at 49 +/- 14 vs 38 +/- 12 min ( P < 0.01). There was no mortality or clinical signs of anastomotic dehiscence in either group. A perianastomotic abscess was detected on autopsy in one animal from the primary colo-colonic anastomosis group. The bursting pressures of the jejunocolic anastomoses were significantly higher ( P < 0.001) than those of the primary colo-colonic anastomoses. CONCLUSIONS: These experimental results suggest that jejunal interposition may be a feasible alternative to primary colonic anastomosis to create intestinal continuity after resection for acute obstruction of the left colon.