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IntroductionOnline patient educational materials (OPEMs) help patients engage in their health care. The American Medical Association (AMA) recommends OPEM be written at or below the 6th grade reading level. This study assessed the readability of deep venous thrombosis OPEM in English and Spanish.MethodsGoogle searches were conducted in English and Spanish using "deep venous thrombosis" and "trombosis venosa profunda," respectively. The top 25 patient-facing results were recorded for each, and categorized into source type (hospital, professional society, other). Readability of English OPEM was measured using several scales including the Flesch Reading Ease Readability Formula and Flesch-Kincaid Grade Level. Readability of Spanish OPEM was measured using the Fernández-Huerta Index and INFLESZ Scale. Readability was compared to the AMA recommendation, between languages, and across source types.ResultsOnly one (4%) Spanish OPEM was written at an easy level, compared to 7 (28%) English OPEM (P = 0.04). More English (28%) OPEM were easy to read compared to Spanish (4%), with a significant difference in reading difficulty breakdown between languages (P = 0.04). The average readability scores for English and Spanish OPEM across all scales were significantly greater than the recommended level (P

ObjectiveDiabetic foot ulcers (DFUs) present a significant global health challenge, resulting in high morbidity and economic costs. Current available treatments often fail to achieve satisfactory healing rates, highlighting the need for novel therapies. This study evaluated the safety and efficacy of a novel autologous whole blood clot (AWBC)-a blood-based, biodegradable provisional matrix-in conjunction with standard of care (SoC) when compared to SoC alone in the treatment of hard-to-heal DFUs.MethodA multicentre, prospective, blinded assessor, randomised controlled trial was conducted at 16 sites across the US, South Africa and Turkey. A cohort of patients with hard-to-heal DFUs was enrolled and randomised to either the AWBC group or the control group. The primary endpoint was complete wound closure at 12 weeks, while secondary endpoints included time to heal and percentage area reduction (PAR) at four and eight weeks. Data were analysed using both intention-to-treat (ITT) and per-protocol (PP) populations.ResultsThe cohort included 119 patients. AWBC treatment resulted in a significantly higher healing rate compared to the control in both ITT (41% versus 15%, respectively; p=0.002) and PP populations (51% versus 18%, respectively; p=0.0075). AWBC treatment also resulted in a shorter mean time to heal and higher durability of wound closure. Safety analysis showed a similar incidence of adverse events (AEs) between groups, with no device-related AEs.ConclusionThe AWBC system, by modulating the wound microenvironment and providing a functional extracellular matrix, offered a promising new approach to treating hard-to-heal DFUs, demonstrating superior healing outcomes compared to SoC alone in this study.

OBJECTIVES: Our aim was to describe the epidemiology and outcomes of multisystem inflammatory syndrome in children (MIS-C) in Latin America. METHODS: We conducted an observational, retrospective, and prospective multicenter study that gathered information from 84 participating centers across 16 Latin American countries between August 1, 2020 and June 30, 2022. RESULTS: Of the 1239 reported children with MIS-C, 84.18% were previously healthy. The most frequent clinical manifestation in our studied population was abdominal pain (N = 804, 64.9%), followed by conjunctival injection (N = 784, 63.3%). The median duration of fever at the time of hospital admission was 5 days and a significant number of subjects required admission to an intensive care unit (N = 589, 47.5%). Most of the subjects (N = 1096, 88.7%) were treated with intravenous immunoglobulin, whereas 76.7% (N = 947) were treated with steroids, of whom 10.6% (N = 100) did not receive intravenous immunoglobulin. The death rate attributed to MIS-C was 4.88%, with a rate of 3.39% for those initially diagnosed with MIS-C and 8.85% for those whose admission diagnosis was not MIS-C (P

Clonal hematopoiesis (CH) is an age-associated phenomenon leading to an increased risk of both hematologic malignancy and nonmalignant organ dysfunction. Increasingly available genetic testing has made the incidental discovery of CH clinically common yet evidence-based guidelines and effective management strategies to prevent adverse CH health outcomes are lacking. To address this gap, the prospective CHIVE (clonal hematopoiesis and inflammation in the vasculature) registry and biorepository was created to identify and monitor individuals at risk, support multidisciplinary CH clinics, and refine taxonomy and standards of practice for CH risk mitigation. Data from the first 181 patients enrolled in this prospective registry recapitulate the molecular epidemiology of CH from biobank-scale retrospective studies, with DNMT3A, TET2, ASXL1, and TP53 as the most commonly mutated genes. Blood counts across all hematopoietic lineages trended lower in patients with CH. In addition, patients with CH had higher rates of end organ dysfunction, in particular chronic kidney disease. Among patients with CH, variant allele frequency was independently associated with the presence of cytopenias and progression to hematologic malignancy, whereas other common high-risk CH clone features were not clear. Notably, accumulation of multiple distinct high-risk clone features was also associated with cytopenias and hematologic malignancy progression, supporting a recently published CH risk score. Surprisingly, ∼30% of patients enrolled in CHIVE from CH clinics were adjudicated as not having clonal hematopoiesis of indeterminate potential, highlighting the need for molecular standards and purpose-built assays in this field. Maintenance of this well-annotated cohort and continued expansion of CHIVE to multiple institutions are underway and will be critical to understanding how to thoughtfully care for this patient population.

Introduction: Neurogenic pulmonary edema is a rare and potentially life-threatening condition that can present as severe pulmonary edema after significant neurologic insults. This is the first documented instance that shows a plausible causal link between cannabis consumption, psychogenic polydipsia, and the subsequent development of neurogenic pulmonary edema associated with status epilepticus secondary to acute hyponatremia.Case Report: We report a case of a 34-year-old female who presented to the emergency department altered and postictal after a witnessed new-onset seizure. She developed significant respiratory distress that required intubation. Her sodium was 121 millimoles per liter (mmol/L), from 137 mmol/L 36 hours prior on routine outpatient labs. Further history revealed excessive water ingestion after eating a cannabis edible prior to the seizure.Conclusion: This case highlights the importance of recognizing neurogenic pulmonary edema in connection with psychogenic polydipsia, severe hyponatremia, and status epilepticus subsequent to cannabis consumption.

Routine sampling of pregnant women at first antenatal care (ANC) visits could make Plasmodium falciparum genomic surveillance more cost-efficient and convenient in sub-Saharan Africa. We compare the genetic structure of parasite populations sampled from 289 first ANC users and 93 children from the community in Mozambique between 2015 and 2019. Samples are amplicon sequenced targeting 165 microhaplotypes and 15 drug resistance genes. Metrics of genetic diversity and relatedness, as well as the prevalence of drug resistance markers, are consistent between the two populations. In an area targeted for elimination, intra-host genetic diversity declines in both populations (p = 0.002-0.007), while for the ANC population, population genetic diversity is also lower (p = 0.0004), and genetic relatedness between infections is higher (p = 0.002) than control areas, indicating a recent reduction in the parasite population size. These results highlight the added value of genomic surveillance at ANC clinics to inform about changes in transmission beyond epidemiological data.

ObjectiveThoracic outlet syndrome (TOS) has life-changing impacts on young athletes. As the level of competition increases between the high school (HS) and collegiate (CO) stage of athletics, the impact of TOS may differ. Our objective is to compare surgical outcomes of TOS in HS and CO athletes.MethodsThis was a retrospective review of HS and CO athletes within a prospective surgical TOS database. The primary outcome was postoperative return to sport. Secondary outcomes were resolution of symptoms assessed with somatic pain scale (SPS), QuickDASH, and Derkash scores. Categorical and continuous variables were compared using χ2 and analysis of variance, respectively. Significance was defined as P < .05.ResultsThirty-two HS and 52 CO athletes were identified. Females comprised 82.9% HS and 61.5% CO athletes (P = .08). Primary diagnoses were similar between groups (venous TOS: HS 50.0% vs CO 42.3%; neurogenic TOS: 43.9% vs 57.7%; pectoralis minor syndrome: 6.3% vs 0.0%) (P = .12). Pectoralis minor syndrome was a secondary diagnosis in 3.1% and 3.8% of HS and CO athletes, respectively (P = 1.00). The most common sports were those with overhead motion, specifically baseball/softball (39.3%), volleyball (12.4%), and water polo (10.1%), and did not differ between groups (P = .145). Distribution of TOS operations were similar in HS and CO (First rib resection: 94.3% vs 98.1%; scalenectomy: 0.0% vs 1.9%, pectoralis minor tenotomy: 6.3% vs 0.0%) (P = .15). Operating room time was 90.0 vs 105.3 minutes for HS and CO athletes, respectively (P = .14). Mean length of stay was 2.0 vs 1.9 days for HS and CO athletes (P = .91). Mean follow-up was 6.9 months for HS athletes and 10.5 months for CO athletes (P = .39). The majority of patients experienced symptom resolution (HS 80.0% vs CO 77.8%; P = 1.00), as well as improvement in SPS, QuickDASH, and Derkash scores. Return to sport was similar between HS and CO athletes (72.4% vs 73.3%; P = .93). Medical disability was reported in 100% HS athletes and 58.3% CO athletes who did not return to sport (P = .035).ConclusionsDespite increased level of competition, HS and CO athletes demonstrate similar rates of symptom resolution and return to competition. Of those that did not return to their sport, HS athletes reported higher rates of medical disability as a reason for not returning to sport compared with CO athletes.

BackgroundOnline resources are a valuable source of information for patients and have been reported to improve engagement and adherence to medical care. However, readability of online patient educational materials (OPEMs) is crucial for them to serve their intended purpose. The American Medical Association (AMA) recommends that OPEM be written at or below the sixth grade reading level. To avoid disparities in access to comprehensible health information on peripheral artery disease (PAD), it is imperative that the readability of PAD OPEM is appropriate for both English-speaking and Spanish-speaking patients. The aim of this study is to evaluate the readability of PAD OPEM in Spanish and compare to English-language OPEM.MethodsWe conducted a Google search in English and Spanish using "peripheral arterial disease" and "enfermedad arterial periferica", respectively, and the top 25 patient-accessible articles were collected for each. Articles were categorized by source type: hospital, professional society, or other. Readability of English-language OPEM was measured using the Flesch Reading Ease Readability Formula, Automated Readability Index, Coleman-Liau Index, Flesch-Kincaid Grade Level, Gunning Fog, Linsear Write Formula, and the Simple Measure of Gobbledygook Index. Readability of Spanish OPEM was measured using the Fernández-Huerta Index and Índice Flesch-Szigriszt Scale. Readability of the articles was compared to the AMA recommendation, between English- and Spanish-language, and across sources using statistical tests appropriate to the data.ResultsOPEM from professional societies represented the fewest number of English- (n = 7, 28%) and Spanish-language (n = 6, 24%) articles. Most English-speaking (n = 18, 72%) and Spanish-language (n = 20, 80%) OPEM were considered difficult as measured by the Flesch Reading Ease Readability Formula and Fernández-Huerta Index, respectively, but did not significantly differ between languages (P = 0.59). There were no significant differences in the average readability of all readability measurements across sources (hospital, professional society, or other). All the average readability grade levels for English-speaking and Spanish-language OPEM was significantly higher than the sixth grade reading level (P

Remyelination after white matter injury (WMI) often fails in diseases such as multiple sclerosis because of improper recruitment and repopulation of oligodendrocyte precursor cells (OPCs) in lesions. How OPCs elicit specific intracellular programs in response to a chemically and mechanically diverse environment to properly regenerate myelin remains unclear. OPCs construct primary cilia, specialized signaling compartments that transduce Hedgehog (Hh) and G-protein-coupled receptor (GPCR) signals. We investigated the role of primary cilia in the OPC response to WMI. Removing cilia from OPCs genetically via deletion of Ift88 results in OPCs failing to repopulate WMI lesions because of reduced proliferation. Interestingly, loss of cilia does not affect Hh signaling in OPCs or their responsiveness to Hh signals but instead leads to dysfunctional cyclic AMP (cAMP)-dependent cAMP response element-binding protein (CREB)-mediated transcription. Because inhibition of CREB activity in OPCs reduces proliferation, we propose that a GPCR/cAMP/CREB signaling axis initiated at OPC cilia orchestrates OPC proliferation during development and in response to WMI.

BACKGROUND: Antiplatelet agents are central in the management of vascular disease. The use of dual antiplatelet therapy (DAPT) for the management of thromboembolic complications must be weighed against bleeding risk in the perioperative setting. This balance is critical in patients undergoing cardiac or non-cardiac surgery. The management of patients on DAPT for any indication (including stents) is not clear and there is limited evidence to guide decision-making. This review summarizes current evidence since 2015 regarding the occurrence of major adverse events associated with continuing, suspending, or varying DAPT in the perioperative period. METHODS: A research librarian searched PubMed and Cochrane from November 30, 2015 to May 17, 2022, for relevant terms regarding adult patients on DAPT for any reason undergoing surgery, with a perioperative variation in DAPT strategy. Outcomes of interest included the occurrence of major adverse cardiac events, major adverse limb events, all-cause death, major bleeding, and reoperation. We considered withdrawal or discontinuation of DAPT as stopping either aspirin or a P2Y12 inhibitor or both agents; continuation of DAPT indicates that both drugs were given in the specified timeframe. RESULTS: Eighteen observational studies met the inclusion criteria. No RCTs were identified, and no studies were judged to be at low risk of bias. Twelve studies reported on CABG. Withholding DAPT therapy for more than 2 days was associated with less blood loss and a slight trend favoring less transfusion and surgical re-exploration. Among five observational CABG studies, there were no statistically significant differences in patient death across DAPT management strategies. Few studies reported cardiac outcomes. The remaining studies, which were about procedures other than exclusively CABG, demonstrated mixed findings with respect to DAPT strategy, bleeding, and ischemic outcomes. CONCLUSION: The evidence base on the benefits and risks of different perioperative DAPT strategies for patients with stents is extremely limited. The strongest signal, which was still judged as low certainty evidence, is that suspension of DAPT for greater than 2 days prior to CABG surgery is associated with less bleeding, transfusions, and re-explorations. Different DAPT strategies association with other outcomes of interest, such as MACE, remains uncertain. SYSTEMATIC REVIEW REGISTRATION: A preregistered protocol for this review can be found on the PROSPERO International Prospective Register of systematic reviews ( http://www.crd.york.ac.uk/PROSPERO/ ; registration number: CRD42022371032).

BackgroundPerioperative care after surgery for thoracic outlet syndrome (TOS) involves multimodal pain control. Pain catheters with bupivacaine infusion are a modality to minimize perioperative narcotic use. Our study aims to compare surgically placed pain catheters (SP) with erector spinae pain catheters (ESP) placed by the anesthesia pain service.MethodsRetrospective review of a prospectively maintained surgical TOS database identified patients undergoing transaxillary first rib resection (FRR) who had either SP or ESP placed for pain control. Patients were matched for age and gender. Data collected included demographics, operative details, and perioperative pain medication use. Narcotic pain medication doses were converted to milligram morphine equivalents (MME) for comparison between groups. Pain medications were collected for several time points: intraoperatively, for each post-operative day (POD), and for the entire hospital stay.ResultsEighty-eight total patients were selected for comparison: 44 patients in the SP and ESP groups. Patients in each group did not differ with regards to age, BMI, gender, diagnosis, or comorbidities. There were no differences in preoperative narcotic use, preoperative pain score, or QuickDASH score. All patients underwent FRR. Concurrent cervical rib resection was performed in 6.8% SP and 6.8% ESP patients (p=1.00), pectoralis minor tenotomy in 34.1% SP and 29.5% ESP patients (p=0.65), and venogram in 31.8% SP and 31.8% ESP patients (p=1.00). Mean OR time was 90.0 minutes in SP and 105.3 minute in ESP cases (p=0.15). Mean length of stay was 1.9 days for SP and 1.8 days for ESP patients (p=0.56). There were no significant differences in intraoperative narcotics dosing in MME (SC: 22.1 vs ESP: 25.3, p=0.018). On POD 0, there were no differences in total narcotics dosing (MME) (SC: 112.0 vs ESP: 100.7, p=0.59), or in the use of acetaminophen, NSAIDS, or muscle relaxants. A similar trend in narcotics dosing was observed on POD 1 (SP: 58.6 vs ESP: 69.7, p=0.43), and POD 2 (SP: 23.5 vs ESP: 71.3, p=0.23). On POD 1, there was a higher percentage of SP patients taking NSAIDs (63.6% vs 40.9%, p=0.024), however, this difference was not observed on POD 2. There were no differences in acetaminophen or muscle relaxant use on POD 1 or 2. Total hospital stay MME was similar between groups (SC: 215.9 vs ESP: 250.9, p=0.23) CONCLUSION: Pain catheters with bupivacaine infusions are helpful adjuncts in postoperative pain control after FRR for TOS. This study compares SP to ESP, and demonstrates no difference in narcotics use between SP and ESP groups. SC should be used for pain control in facilities which do not have an anesthesia pain service available for ESP placement.

In response to concerns about healthcare access and long wait times within the Veterans Health Administration (VA), Congress passed the Choice Act of 2014 and the Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act of 2018 to create a program for patients to receive care in non-VA sites of care, paid by VA. Questions remain about the quality of surgical care between these sites in specific and between VA and non-VA care in general. This review synthesizes recent evidence comparing surgical care between VA and non-VA delivered care across the domains of quality and safety, access, patient experience, and comparative cost/efficiency (2015 to 2021). Eighteen studies met the inclusion criteria. Of 13 studies reporting quality and safety outcomes, 11 reported that quality and safety of VA surgical care were as good as or better than non-VA sites of care. Six studies of access did not have a preponderance of evidence favoring care in either setting. One study of patient experience reported VA care as about equal to non-VA care. All 4 studies of cost/efficiency outcomes favored non-VA care. Based on limited data, these findings suggest that expanding eligibility for veterans to get care in the community may not provide benefits in terms of increasing access to surgical procedures, will not result in better quality, and may result in worse quality of care, but may reduce inpatient length of stay and perhaps cost less.

The COVID-19 pandemic affected the main Amazon cities dramatically, with Iquitos City reporting the highest seroprevalence of anti-SARS-CoV-2 antibodies during the first COVID-19 wave worldwide. This phenomenon raised many questions about the possibility of a co-circulation of dengue and COVID-19 and its consequences. We carried out a population-based cohort study in Iquitos, Peru. We obtained a venous blood sample from a subset of 326 adults from the Iquitos COVID-19 cohort (August 13-18, 2020) to estimate the seroprevalence of anti-dengue virus (DENV) and anti-SARS-CoV-2 antibodies. We tested each serum sample for anti-DENV IgG (serotypes 1, 2, 3, and 4) and SARS-CoV-2 antibodies anti-spike IgG and IgM by ELISA. We estimated an anti-SARS-CoV-2 seroprevalence of 78.0% (95% CI, 73.0-82.0) and an anti-DENV seroprevalence of 88.0% (95% CI, 84.0-91.6), signifying a high seroprevalence of both diseases during the first wave of COVID-19 transmission in the city. The San Juan District had a lower anti-DENV antibody seroprevalence than the Belen District (prevalence ratio, 0.90; 95% CI, 0.82-0.98). However, we did not observe these differences in anti-SARS-CoV-2 antibody seroprevalence. Iquitos City presented one of the highest seroprevalence rates of anti-DENV and anti-SARS-CoV-2 antibodies worldwide, but with no correlation between their antibody levels.

BackgroundFrailty is a known risk factor for adverse outcomes following surgery and affects at least 3 of every 10 US Veterans aged 65 years and older. We designed a study to characterize the association between frailty and complications after endovascular aneurysm repair (EVAR) compared to open aneurysm repair (OAR) at our regional Veterans Affairs Medical Center.MethodsVeterans who underwent either OAR or EVAR at our institution between January 1, 2000 and December 31, 2020 were identified. We examined medical history, procedure characteristics, perioperative complications, and frailty as measured by the 5-factor modified frailty index (mFI-5). Frailty was defined as an mFI-5 score ≥2. Primary endpoints were postoperative complications, duration of surgery, and length of hospital stay. Tests of association were performed with t-test and chi-squared analysis.ResultsOver the 21-year period, we identified 314 patients that underwent abdominal aortic aneurysm (AAA) repair with 115 (36.6%) OAR and 199 EVAR (63.4%) procedures. Patients undergoing EVAR were older on average (72.1 years vs. 70.2 years) and had a higher average mFI-5 compared to the open repair group (1.49 vs. 1.23, P = 0.036). When comparing EVAR and OAR cohorts, patients undergoing OAR had a larger AAA diameter (6.5 cm, standard deviation [SD]: 1.5) compared to EVAR (5.5 cm, SD: 1.1 P

BackgroundMultisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments.MethodsThe Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370.FindingsWe enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2-11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75-1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58-1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91-1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70-1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11-0·20]; p

BackgroundVeterans are disproportionately affected by housing insecurity (HI), which can lead to adverse health outcomes and reduced life expectancy. We sought to examine the impact of HI on the outcomes of veterans who underwent abdominal aortic aneurysm (AAA) repair at our regional Veterans Affairs medical center.MethodsRetrospective chart review was performed on patients who underwent AAA repair at our institution between January 1, 2000, and December 31, 2020. We examined medical history, procedure details, hospitalization course, and postoperative outcomes. Primary endpoints were a 30-day mortality and median survival. Secondary endpoints were hospital length of stay, readmission rate, and perioperative complications. Hypothesis testing was performed with t-test and chi-squared analysis. Survival analysis was conducted using Kaplan-Meier estimation.ResultsOf the 314 veterans that underwent AAA repair (mean age of 71.4 ± 7.8 years, 99.7% male) over the 21-year period, we identified 39 (12.4%) patients with a history of HI. The HI was associated with a positive smoking history (100% vs. 88.0%, P = 0.022), lower rate of hypertension diagnosis (69.2% vs. 84.0%, P = 0.024), and increased rate of surgical site infections (SSI) (10.3% vs. 1.8%, P = 0.016). The median postoperative survival was lower in the HI group (7.6 years [CI 6.0-11.2] vs. 8.9 [CI 6.9-10.3]).ConclusionsHI was associated with reduced median postoperative survival, greater readmission rate, and increased risk of SSI following AAA repair.

ObjectiveWe compared the functional outcomes among adolescent athletes with venous thoracic outlet syndrome (VTOS) and neurogenic TOS (NTOS) after thoracic outlet decompression.MethodsWe performed a single-institution retrospective review of a prospective database of adolescent athletes (aged 13-19 years) from June 1, 1996 to December 31, 2021 who had undergone operative decompression for TOS. The demographic data, preoperative symptoms, operative details, and postoperative outcomes were compared. The primary outcome was the postoperative return to sport. The secondary outcomes included symptom resolution and assessment of the somatic pain scale, QuickDASH, and Derkash scores. The Fisher exact test and t test were used to evaluate the categorical and continuous variables, respectively. A logistic regression model was constructed to adjust for the influence of preoperative factors and return to sport.ResultsA total of 60 patients (40.0% with VTOS and 60.0% with NTOS) were included. The average age of the VTOS patients was 17.2 years vs 16.6 years for the NTOS patients (P = .265). The NTOS patients were more likely to be female (88.9% vs 62.5%; P = .024). The NTOS patients had more frequently presented with pain (97.2% vs 70.8%; P = .005), paresthesia (94.4% vs 29.1%; P = .021), and weakness (67.7% vs 12.5%; P = .004) but had less often reported swelling (25.0% vs 95.8%; P < .001). At presentation, the NTOS patients had also reported a longer symptom duration (17.7 months vs 3.1 months; P < .001). Transaxillary first rib resection with subtotal scalenectomy was performed for 100% of the VTOS patients and 94.4% of the NTOS patients undergoing cervical rib resection (2.8%) or scalenectomy alone (2.8%). Additionally, 11.1% of the NTOS patients had undergone combined first rib resection and cervical rib resection. For the VTOS patients, postoperative venography showed patent subclavian veins in 27.8%. In addition, 44.4% had required venoplasty, 16.8% had required thrombolysis, and 11% were chronically occluded. No significant differences were found in blood loss, operative time, or length of stay between the groups. No surgical complications occurred. The average follow-up was 6.3 months. Significant differences were found between the VTOS and NTOS groups for the pre- and postoperative somatic pain scale, QuickDASH, and Derkash scores. Complete symptom resolution had occurred in 83.3% of the VTOS and 75% of the NTOS patients (P = .074). No statistically significant difference in the return to sport was observed between the two groups (VTOS, 94.4%; vs NTOS, 73.9%; P = .123). Of the NTOS patients, 10.0% had had other concomitant injuries and 5.0% had had medical conditions that had precluded their return to sport. Logistic regression found no significant relationship between the preoperative somatic pain scale score, QuickDASH score, or duration of symptoms and the return to sport.ConclusionsAdolescent athletes with VTOS and NTOS can have good functional outcomes, and most will be able to return to sport after surgery. Greater initial symptom severity and concomitant injuries were observed in adolescents with NTOS. Of those who had not returned to sport postoperatively, three of seven had had unrelated health issues that had prevented their return to sport.

BackgroundThoracic outlet syndrome (TOS) is an infrequent condition which results in disability in use of upper extremity. While TOS is often associated with manual labor, industrial workers, and accidents, it has not been reported in a physician (MD) population. Given the investment of time and effort in training to become a MD, the impact of TOS may be devastating. Our objective is to report the presentation and outcome of TOS in MDs.MethodsA prospectively surgical database was reviewed for MDs who sought care of disabling TOS between 1997 and 2022. Demographic, clinical, outcome and pathological data were reviewed. Outcomes were assessed based on Somatic Pain Scale (SPS), Quick Disabilities of Arm, Shoulder and Hand (DASH) scores, and Derkash scores. Results were also assessed based on return to employment.ResultsA total of 19 MDs were identified, from 1,687 TOS cases. The group included 13 (63%) men, 6 (31%) women, average age 45 years (range 27-57). Presentations included 1 (5.3%) arterial TOS (ATOS), 9 (47.4%) venous TOS (VTOS), and 9 (47.4) neurogenic TOS (NTOS). All patients were right-handed, and symptomatic side was dominant hand in 7 (37%) patients. Etiologies included repetitive motion injury, athletic injury, and congenital bony abnormalities. Repetitive motion was associated with 3/9 (33%) NTOS. Significant athletic activities were noted in 12 of 19 (63%) MDs, including 8/9 (89%) VTOS and 4/9 (44%) NTOS. Athletic activities associated with VTOS included triathletes (2), rock climbing (1), long distance swimming (2), and weightlifting (3). Of the 9 NTOS cases, 3 were associated with weightlifting and 1 with skiing. Congenital causes included 1 (5%) abnormal first rib and 1 (5%) cervical rib. Time from symptom onset to consultation varied significantly according to diagnosis: ATOS 6 days, VTOS 97 days, and NTOS 2,335 days (P

Oxygen-deficient marine waters referred to as oxygen minimum zones (OMZs) or anoxic marine zones (AMZs) are common oceanographic features. They host both cosmopolitan and endemic microorganisms adapted to low oxygen conditions. Microbial metabolic interactions within OMZs and AMZs drive coupled biogeochemical cycles resulting in nitrogen loss and climate active trace gas production and consumption. Global warming is causing oxygen-deficient waters to expand and intensify. Therefore, studies focused on microbial communities inhabiting oxygen-deficient regions are necessary to both monitor and model the impacts of climate change on marine ecosystem functions and services. Here we present a compendium of 5,129 single-cell amplified genomes (SAGs) from marine environments encompassing representative OMZ and AMZ geochemical profiles. Of these, 3,570 SAGs have been sequenced to different levels of completion, providing a strain-resolved perspective on the genomic content and potential metabolic interactions within OMZ and AMZ microbiomes. Hierarchical clustering confirmed that samples from similar oxygen concentrations and geographic regions also had analogous taxonomic compositions, providing a coherent framework for comparative community analysis.

ObjectiveOnline resources can be a valuable source of information for patients and have been shown to result in more inquiry during medical office visits, following physician medical recommendation more closely, and making self-directed lifestyle changes. The accessibility to these resources is limited by the readability level of the article and the literacy level of the population. Peripheral artery disease (PAD) is estimated to affect between 8 and 12 million people in the United States with greater disease severity among under insured or uninsured populations. As PAD continues to increase in prevalence, it is imperative that patients have access to comprehensible patient-centered health information. This study aims to evaluate the readability of online PAD patient education materials.MethodsThe search engine Google was used to collect the first 25 patient-accessible online articles pertaining to the search term "peripheral artery disease." Articles were then categorized by source type: hospital, professional society, or other. Readability was measured using the following tests: Automated Readability Index, Coleman-Liau Index, Flesch-Kincaid Grade Level, Gunning Fog, Linsear Write Formula, and the SMOG Index. Statistical analyses were performed using Statistical Analysis Software, with P values less than .05 being statistically significant.ResultsTwenty-five articles were categorized by source and statistically analyzed. The average readability of PAD patient education materials was 10.8 and significantly above the American Medical Association, National Institutes of Health, and US Department of Health and Human Services recommended reading level of sixth grade. Readability scores among source categories were not significantly different.ConclusionsCommonly available online PAD resources are written at a grade level above that currently recommended by medical societies. Hospitals, professional societies, and other stakeholders in PAD patient education should take into consideration the readability of their materials to make medicine more accessible. Readable articles may combat the historic and structural racism often found in our health care system that marginalizes those with lower health literacy. It is imperative to develop patient education at an appropriate level to enrich patient autonomy.

BackgroundWe hypothesize among patients undergoing lower extremity amputation, access to pre-, and post operative rehabilitation services; as well as improved medical care, have led to higher rates of postoperative ambulation, and improved survival.MethodsRetrospective single center review of all major lower extremity amputations performed at the Greater Los Angeles Veterans Affairs Healthcare System from 2000-2020 stratified into multiyear cohorts. We abstracted demographics, operative indication, comorbidities, preoperative medical management, perioperative complications, discharge location, and pre and postoperative ambulatory status. Odds of ambulation after amputation were analyzed using multivariate logistic regression. Survival was analyzed using multivariate logistic regression and Kaplan-Meier survival analysis. Multivariate logistic predictors were selected based on prior literature and clinical experience.ResultsWe identified 654 operations in our study, noting fewer amputations performed in the latest 3 cohort years as compared to the initial cohort (2000-2004). Patients undergoing below-knee amputations (BKA) had 2.7 times (P

ObjectiveManagement of Paget-Schroetter syndrome (PSS) with first rib resection (FRR) and venoplasty is successful in re-establishing subclavian vein (SCV) patency in most cases. However, in cases with subacute or chronic venous occlusion, SCV patency may not be achieved. Thus, the role for FRR remains controversial in cases of subacute or chronic SCV occlusion. Our goal is to determine whether FRR is beneficial in PSS patients with subacute or chronic SCV occlusion.MethodsA prospectively maintained thoracic outlet syndrome (TOS) database was searched for patients undergoing FRR who were identified as having SCV occlusion on preoperative venography between 2012 and 2021. Preoperative and postoperative venous patency were determined by venography. Standardized functional outcomes were assessed using the Quick Disability Arm, Shoulder, Hand (QuickDASH-QDS) and Somatic Pain Scale (SPS) before and after FRR. The Derkash outcome score was recorded after FRR.ResultsOver the study period, 966 TOS operations were performed; of these, 401 were for venous TOS, and 33 patients were identified with subacute or chronic preoperative SCV occlusion verified by venography. The median age was 29 years, with 73% men. Eighteen patients had attempted thrombolysis; eight were performed at our institution, and ten performed at a referring facility. The median time from the symptom onset of SCV occlusion to FRR was 78 days for all patients. For the group that achieved venous patency after FRR, the time from SCV occlusion to FRR was 71 days, and it was 106 days for the group that remained occluded after FRR. All underwent postoperative venography and percutaneous attempt at SCV recanalization. Recanalization was successful in 64% (21) and unsuccessful in 36% (12). All patients experienced improvement in SPS and QDS. For all patients, the average SPS improved from 1.69 preoperatively to 0.25 postoperatively and the average QDS improved from 27.63 preoperatively to 10.19 postoperatively (P > .05). For patients who were successfully recanalized, the final SPS was 0.18 and the final QDS was 11.22 (P > .05). In patients who failed to achieve recanalization, the final SPS was 0.40 and the final QDS was 9.06 (P > .05). All postoperative Derkash outcome scores were excellent and good, with none fair or poor.ConclusionsIn patients with subacute or chronic preoperative SCV occlusion, surgical decompression and postoperative angioplasty resulted in re-establishing SCV patency in 64% of patients. Symptomatic patients clinically improve after surgical decompression regardless of whether venous patency is successfully re-established. These results indicate that symptomatic patients with PSS should be considered for TOS decompression even if their SCV is occluded in the subacute or chronic presentation.

IntroductionAccess to surgical service is limited by provider availability and geographic barriers. Telemedicine ensures that patients can access medical care.ObjectiveThe objective is to describe our use of telemedicine in delivering vascular surgery services to remote locations before and during the COVID-19 pandemic.MethodsWe conducted a retrospective chart review analyzing care delivered at six vascular surgery telemedicine clinics over a 22-month period. We examined vascular diagnoses, recommended interventions, referrals placed, and emergency department visits within 30 days of evaluation. We calculated travel distance saved for patients between their local clinic and our main hospital.ResultsWe identified 94 patients and 144 telemedicine visits, with an average of 1.5 visits per patient (SD = 0.73). The most common referrals were for peripheral artery disease (20.2%) and abdominal aortic aneurysm (14.9%). Three patients were immediately referred to the emergency department due to concern for acute limb ischemia (2) or questionable symptomatic AAA (1). Telemedicine visit recommendations were distributed between no intervention (n = 30, 31.9%), medical management (n = 41, 43.6%), and surgical intervention (n = 23, 24.5%).The surgical intervention cohort was most commonly referred to arterial revascularization (n = 4), venous ablation (n = 4), and arteriovenous fistula procedures (n = 4). Fourteen patients came to our main hospital for surgery and four to local providers. Average travel distance saved per telemedicine visit was 104 miles (SD = 43.7).ConclusionsTelemedicine provided safe, efficient care during the COVID-19 pandemic and saved patients an average of 104 travel miles per visit.

Steven-Johnson syndrome (SJS) is a rare condition commonly associated with exposure to antibiotics. We have presented the case of a 76-year-old man with end-stage renal disease who had developed SJS after endovascular thrombectomy of hemodialysis access. He had developed epithelial erosions of the mucosal membranes, hemorrhagic bullae to the palmar and plantar surfaces, and erosions of the genitalia. The findings from biopsies of the lip and palm were suggestive of a drug reaction. He developed SJS three times after exposure to iodinated contrast. The one time he did not develop SJS, he had undergone open thrombectomy with no contrast exposure.

ObjectivesCongenital abnormalities of the first rib (ABNFR) are a rare cause of thoracic outlet syndrome (TOS). The range of abnormalities have not been clearly documented in the literature. Surgical decompression in these patients presents with increased complexity secondary to anomalous anatomy. Our goal is to review an institutional experience of first rib resection (FRR) performed for ABNFRs, to present a novel classification system, and to analyze outcomes according to clinical presentation.MethodsA prospectively collected database was used to identify individuals with ABNFRs who underwent FRR for TOS between 1990-2021. These individuals were identified both by preoperative imaging and intraoperative descriptions of the first rib after resection. Demographic, clinical, perioperative and pathological data were reviewed. ABNFRs were classified into 3 categories according to anatomical criteria: (I) Hypoplastic, (II) Fused, and (III) Hyperplastic. Outcomes were rated using the standardized Quick Disability of Arm Shoulder and Hand Scores (QDS), Somatic Pain Scores (SPS) and Derkash Scores (DkS).ResultsAmong the 2200 cases of TOS, there were 19 patients (0.8%) with ABNFR who underwent FRR. Average age at surgery was 30.5 (range 11-74), including 13 men and 6 women. Presentations included 9 arterial (ATOS), 6 neurogenic (NTOS), and 4 venous (VTOS) cases. There were 6 class I, 6 class II, and 7 class III ABNFRs. Among 6 NTOS patients there were 4 abnormal nerve conduction tests and 5 positive anterior scalene muscle blocks. Among the 9 patients with ATOS, thrombolysis was attempted in 5 patients, and of these, 3 ultimately required surgical thrombectomy. Of 4 VTOS cases, 2 were managed with thrombolysis, and 2 with anticoagulation alone. The approach for FRR was transaxillary in all patients. Secondary procedures included 1 pectoralis minor tenotomy, 1 scalenectomy, and 1 contralateral rib resection. No major neurological or vascular complications occurred. There was 1 patient who required surgical evacuation of a hematoma. Intraoperative chest tube placement was required in 5 patients secondary to pleural entry during dissection. There was an overall improvement in symptoms over an average follow-up of 7.4 months. QDS reduced from 49.7 pre-op to 22.1 (P < 0.05). SPS improved from 3.4 pre-op to 1.8. DkS scores were good to excellent in 79% of patients. Residual symptoms were noted in 7, and ATOS accounted for 5 (70%) of these. All patients were able to return to work.ConclusionsDespite increased complexity, ABNFRs may be safely resected via transaxillary approach with low incidence of complications, very good symptom relief, and excellent outcomes. Congenital ABNFRs may by classified into 3 categories (hypoplastic, fused, and hyperplastic) with a variety of presentations, including ATOS, NTOS, and VTOS. Classification of ABNFRs allows concise description of abnormal anatomy which facilitates comparison between series and provides direction for surgical management to ultimately optimize patient outcomes.

BackgroundEndovenous ablation techniques have replaced greater saphenous vein (GSV) ligation and stripping for treatment of venous insufficiency. Our objective was to investigate our initial procedural experience and clinical presentation of patients undergoing mechanochemical ablation (MOCA) at a single institution. We hypothesized that closure level and success rate improved over time and were comparable to other endovenous ablation techniques.MethodsWe retrospectively reviewed all MOCA procedures performed at the Greater Los Angeles Veterans Affairs Hospital from 2015 - 2020. Variables included CEAP and VCSS scores, patient symptoms, post procedure duplex ultrasound, closure level, and need for anticoagulation. Success was defined as GSV thrombosis on initial post procedure duplex ultrasound. Procedure associated extension of thrombus into the deep veins was defined using the American Venous Forum (AVF) endothermal heat induced thrombosis (EHIT) classification.Results104 venous ablation procedures were performed on 86 patients. Eleven (12.8%) patients received bilateral interventions, and six (7%) patients had asynchronous interventions on the same leg. The average age was 58.4 years (SD 12) and 93% were male. Pre-procedural symptoms included pain (102, 98.1%), varicose veins (87, 83.7%), edema (58, 55.8%), and active ulcers (19, 18.3%). A CEAP category of C2 was the most common indication (34.6%), followed by C3 (22.1%) and C6 (21.2%). Forty-five (43.2%) patients had deep system reflux, and 53% had concomitant phlebectomies. Average VCSS score was 7.5 (SD 3.5).We observed a GSV ablation rate of 92.7% (n = 89) in the 96 procedures which had post-procedure follow up, with no temporal evidence of a learning curve. On post procedure duplex of the 89 technically successful ablations, 77 (86.5%) patients had AVF EHIT level 1 closure, three (3.4%) had level 2 closure, eight (8.9%) had level 3 closure, and one had a level 4 closure. Fourteen (15.7%) patients were newly started on anticoagulation for an average of 33.2 days (SD 34.1). Of the 19 legs treated for active venous ulcers, 13 (68.4%) had improvement or resolution of their venous ulcers. No pulmonary embolic complications were reported.ConclusionsWe observed a successful GSV thrombosis rate of 92.7% using MOCA without evidence of a learning curve and comparable to that reported in the literature. The rate of thrombus extension into the deep veins was 14.6%, with no adverse effects associated with anticoagulation or clinically significant sequelae of AVF EHIT level 2 or greater. Comparisons with MOCA associated thrombus extension into deep veins in the literature are limited as post procedure screening duplex are not standard of care. However, we demonstrated that MOCA ablation of the GSV is a safe procedure that may be performed with good technical success.

A state-academic-community partnership formed in response to the mental health needs fueled by the COVID-19 pandemic and the disproportionate effects on marginalized communities. Taking a community-partnered approach and using a health equity lens, the partnership developed a website to guide users through digital mental health resources, prioritizing accessibility, engagement, and community needs.

ObjectiveTo document the recovery of vascular services in Europe following the first COVID-19 pandemic peak.MethodsAn online structured vascular service survey with repeated data entry between 23 March and 9 August 2020 was carried out. Unit level data were collected using repeated questionnaires addressing modifications to vascular services during the first peak (March - May 2020, "period 1"), and then again between May and June ("period 2") and June and July 2020 ("period 3"). The duration of each period was similar. From 2 June, as reductions in cases began to be reported, centres were first asked if they were in a region still affected by rising cases, or if they had passed the peak of the first wave. These centres were asked additional questions about adaptations made to their standard pathways to permit elective surgery to resume.ResultsThe impact of the pandemic continued to be felt well after countries' first peak was thought to have passed in 2020. Aneurysm screening had not returned to normal in 21.7% of centres. Carotid surgery was still offered on a case by case basis in 33.8% of centres, and only 52.9% of centres had returned to their normal aneurysm threshold for surgery. Half of centres (49.4%) believed their management of lower limb ischaemia continued to be negatively affected by the pandemic. Reduced operating theatre capacity continued in 45.5% of centres. Twenty per cent of responding centres documented a backlog of at least 20 aortic repairs. At least one negative swab and 14 days of isolation were the most common strategies used for permitting safe elective surgery to recommence.ConclusionCentres reported a broad return of services approaching pre-pandemic "normal" by July 2020. Many introduced protocols to manage peri-operative COVID-19 risk. Backlogs in cases were reported for all major vascular surgeries.

BackgroundLong standing, recalcitrant venous ulcers fail to heal despite standard compression therapy and wound care. Stenting of central veins has been reported to assist in venous ulcer healing. This study reports outcomes of deep venous stenting for central venous obstruction in patients with recalcitrant venous ulcers at a single comprehensive wound care center.MethodsA single center retrospective analysis was conducted of patients with CEAP (Clinical, Etiology, Anatomy, and Pathophysiology) 6 disease that had undergone deep venous stenting in addition to wound care and compression therapy. Intra-operative details, wound healing, and stent patency rates were recorded. Stent patency and intra-operative details were compared between the healed and unhealed groups.ResultsBetween 2010 and 2019, 15 patients met inclusion criteria (mean age: 63 years old, 12 males). Pre-operative mean wound area was 14.1 cm2 with mean wound duration of 30 months. 93% of patients healed the ulcers at mean healing time of 10.6 months. Wound recurrence rate was 57% with mean recurrence time of 14.8 months. Ten patients presented with an inferior vena cava (IVC) filter, 4 in the healed group and 6 in the unhealed group. The common iliac vein was stented in all patients. Extension into the IVC was required in 4, the common femoral vein in 11, and femoral vein in 2 patients. The average stent length was 190cm. During the follow-up period, primary patency rates in healed patients (mean follow-up time: 19.2 months) was 83% and 59% in the unhealed group (mean follow-up time: 36.6 months); secondary patency rates were 83% and 89%, respectively.ConclusionsIn patients with recalcitrant venous ulcers with central venous obstruction, deep venous stenting resulted in a high rate of healing. However, a prolonged 10 month healing time was observed and despite high stent patency, wound recurrence rate was high.

We examined in a rat model of Gulf War illness (GWI), the potential of (-)-epicatechin (Epi) to reverse skeletal muscle (SkM) atrophy and dysfunction, decrease mediators of inflammation and normalize metabolic perturbations. Male Wistar rats (n = 15) were provided orally with pyridostigmine bromide (PB) 1.3 mg/kg/day, permethrin (PM) 0.13 mg/kg/day (skin), DEET 40 mg/kg/day (skin) and were physically restrained for 5 min/day for 3 weeks. A one-week period ensued to fully develop the GWI-like profile followed by 2 weeks of either Epi treatment at 1 mg/kg/day by gavage (n = 8) or water (n = 7) for controls. A normal, control group (n = 15) was given vehicle and not restrained. At 6 weeks, animals were subjected to treadmill and limb strength testing followed by euthanasia. SkM and blood sampling was used for histological, biochemical and plasma pro-inflammatory cytokine and metabolomics assessments. GWI animals developed an intoxication profile characterized SkM atrophy and loss of function accompanied by increases in modulators of muscle atrophy, degradation markers and plasma pro-inflammatory cytokine levels. Treatment of GWI animals with Epi yielded either a significant partial or full normalization of the above stated indicators relative to normal controls. Plasma metabolomics revealed that metabolites linked to inflammation and SkM waste pathways were dysregulated in the GWI group whereas Epi, attenuated such changes. In conclusion, in a rat model of GWI, Epi partially reverses detrimental changes in SkM structure including modulators of atrophy, inflammation and select plasma metabolites yielding improved function.

ObjectiveTraumatic popliteal artery injuries are associated with the greatest risk of limb loss of all peripheral vascular injuries, with amputation rates of 10% to 15%. The purpose of the present study was to examine the outcomes of patients who had undergone operative repair for traumatic popliteal arterial injuries and identify the factors independently associated with limb loss.MethodsA multi-institutional retrospective review of all patients with traumatic popliteal artery injuries from 2007 to 2018 was performed. All the patients who had undergone operative repair of popliteal arterial injuries were included in the present analysis. The patients who had required a major lower extremity amputation (transtibial or transfemoral) were compared with those with successful limb salvage at the last follow-up. The significant predictors (P < .05) for amputation on univariate analysis were included in a multivariable analysis.ResultsA total of 302 patients from 11 institutions were included in the present analysis. The median age was 32 years (interquartile range, 21-40 years), and 79% were men. The median follow-up was 72 days (interquartile range, 20-366 days). The overall major amputation rate was 13%. Primary repair had been performed in 17% of patients, patch repair in 2%, and interposition or bypass in 81%. One patient had undergone endovascular repair with stenting. The overall 1-year primary patency was 89%. Of the patients who had lost primary patency, 46% ultimately required major amputation. Early loss (within 30 days postoperatively) of primary patency was five times more frequent for the patients who had subsequently required amputation. On multivariate regression, the significant perioperative factors independently associated with major amputation included the initial POPSAVEIT (popliteal scoring assessment for vascular extremity injury in trauma) score, loss of primary patency, absence of detectable immediate postoperative pedal Doppler signals, and lack of postoperative antiplatelet therapy. Concomitant popliteal vein injury, popliteal injury location (P1, P2, P3), injury severity score, and tibial vs popliteal distal bypass target were not independently associated with amputation.ConclusionsTraumatic popliteal artery injuries are associated with a significant rate of major amputation. The preoperative POPSAVEIT score remained independently associated with amputation after including the perioperative factors. The lack of postoperative pedal Doppler signals and loss of primary patency were highly associated with major amputation. The use of postoperative antiplatelet therapy was inversely associated with amputation, perhaps indicating a protective effect.

As the nation implements SARS-CoV-2 vaccination in adults at an unprecedented scale, it is now essential to focus on the prospect of SARS-CoV-2 vaccinations in pediatric populations. To date, no children younger than 12 years have been enrolled in clinical trials. Key challenges and knowledge gaps that must be addressed include (1) rationale for vaccines in children, (2) possible effects of immune maturation during childhood, (3) ethical concerns, (4) unique needs of children with developmental disorders and chronic conditions, (5) health inequities, and (6) vaccine hesitancy. Because COVID-19 is minimally symptomatic in the vast majority of children, a higher acceptable risk threshold is required when evaluating pediatric clinical trials. Profound differences in innate and adaptive immunity during childhood and adolescence are known to affect vaccine responsiveness for a variety of childhood diseases. COVID-19 and the accompanying social disruption, such as the school shutdowns, has been disproportionately damaging to minority and low-income children. In this commentary, we briefly address each of these key issues, specify research gaps, and suggest a broader learning health system approach to accelerate testing and clinical trial development for an ethical and effective strategy to implement a pediatric SARS-CoV-2 vaccine as rapidly and safely as possible. IMPACT: As the US begins an unprecedented implementation of SARS-CoV-2 vaccination, substantial knowledge gaps have yet to be addressed regarding vaccinations in the pediatric population. Maturational changes in the immune system during childhood have influenced the effectiveness of pediatric vaccines for other diseases and conditions, and could affect SARS-CoV-2 vaccine responsiveness in children. Given that COVID-19 disease is far milder in the majority of children than in adults, the risk-benefit of a pediatric SARS-CoV-2 vaccine must be carefully weighed. The needs of children with developmental disabilities and with chronic disease must be addressed. Minority and low-income children have been disproportionately adversely affected by the COVID-19 pandemic; care must be taken to address issues of health equity regarding pediatric SARS-CoV-2 vaccine trials and allocation. Research and strategies to address general vaccine hesitancy in communities must be addressed in the context of pediatric SARS-CoV-2 vaccines.

BackgroundUnderstanding SARS-CoV-2 infection in children is necessary to reopen schools safely.MethodsWe measured SARS-CoV-2 infection in 320 learners [10.5 ± 2.1 (sd); 7-17 y.o.] at four diverse schools with either remote or on-site learning. Schools A and B served low-income Hispanic learners; school C served many special-needs learners, and all provided predominantly remote instruction. School D served middle- and upper-income learners, with predominantly on-site instruction. Testing occurred in the fall (2020), and 6-8 weeks later during the fall-winter surge (notable for a tenfold increase in COVID-19 cases). Immune responses and mitigation fidelity were also measured.ResultsWe found SARS-CoV-2 infections in 17 learners only during the surge. School A (97% remote learners) had the highest infection (10/70, 14.3%, p

ObjectivePatients with functioning renal allografts may need ligation of pre-existing hemodialysis conduits. Chronic immunosuppression for renal allografts may adversely affect wound healing and perioperative complications following these procedures. We sought to analyze outcomes following elective ligation and resection of symptomatic arteriovenous (AV) access in immunosuppressed patients with renal allografts no longer requiring dialysis at a high-volume renal transplant hospital.MethodsWe retrospectively reviewed procedure codes for hemodialysis access resection and revision from 2014-2020 at a single academic tertiary care hospital. Patients who underwent complete or subtotal dialysis access resection with a functioning renal allograft were included for analysis of preoperative, operative, and postoperative outcomes. We performed descriptive statistics, and student's t-test using Microsoft Excel.ResultsThirty-four patients met inclusion criteria. The majority were male, 56%, and the most common causes of renal failure were hypertension and diabetes, respectively. Ligation and resection of proximal upper extremity access was performed in 68%. The mean operative time was 126 minutes with pain being the most common indication for intervention. Four patients required arterial reconstruction. Mean postoperative follow-up was 13 months. Arm pain and swelling resolved in 100% and 88% of patients following AV access resection, respectively. No impairment in mean postoperative glomerular filtration rates were noted. One patient required hemodialysis and died three months after fistula resection following complications from treatment of a newly diagnosed neuroendocrine tumor and subsequent fungemia, CONCLUSION: Elective operative resection of symptomatic AV access may be performed safely in immunosuppressed patients with functioning renal transplants. The risk of allograft impairment and/or failure as a result of AV access resection in our series was low. Elective ligation and resection can be achieved with low mortality, excellent symptomatic relief, and few wound complications despite chronic immunosuppression.

ObjectiveSpontaneous subclavian vein (SCV) thrombosis (Paget-Schroetter syndrome [PSS]) has been attributed to venous compression at the thoracic outlet and traditionally diagnosed using venography. Intravascular ultrasonography (IVUS) allows for a multidimensional view of vascular structures and might be more accurate in revealing venous compression. The goal of the present study was to compare venography and IVUS in patients presenting with PSS to assess the relative accuracy of each modality.MethodsPatients presenting for evaluation of PSS from 2013 to 2019 were evaluated for SCV compression using venography and IVUS. Venography and IVUS measurements of stenosis were performed of the index and contralateral limbs in both neutral and stress (arm overhead) positions. The IVUS data included the SCV diameters in the anteroposterior (AP) plane, craniocaudal (CC) plane, and cross-sectional area (CSA). Stenosis was reported as the percentage of reduction from a reference point (lateral margin of the first rib) for the venography and IVUS data.ResultsFor the 35 subjects, the average age was 35 years, 57% were women, 20% had presented with a documented pulmonary embolus, and 70% had initially been treated with thrombolysis. Venography demonstrated SCV occlusion in 3 patients (16%) with the index limb in the neutral position and in 18 patients (54%) with the limb in the stress position. The average stenosis in the index limbs was 41.5% (venography), and the average IVUS stenosis was 41.9% (CC), 61.8% (AP), and 74.5% (CSA; P < .05). A subset analysis revealed that in 10 of 35 patients (28%) in whom venography had identified no significant stenosis (average, 10%), IVUS had identified significant stenosis (33.5% CC, 54.3% AP, 68.7% CSA; P < .05).ConclusionsIVUS proved more sensitive than venography in detecting significant stenosis leading to SCV thrombosis. A reduction in the CSA was the most sensitive measure of stenosis. IVUS identified significant stenosis in patients in whom venography failed to do so. The greatest utility of IVUS is in the evaluation of patients with PSS in whom venography shows no evident compression.

ObjectiveTraumatic popliteal vascular injuries are associated with the highest risk of limb loss of all peripheral vascular injuries. A method to evaluate the predictors of amputation is needed because previous scores could not be validated. In the present study, we aimed to provide a simplified scoring system (POPSAVEIT [popliteal scoring assessment for vascular extremity injuries in trauma]) that could be used preoperatively to risk stratify patients with traumatic popliteal vascular injuries for amputation.MethodsA review of patients sustaining traumatic popliteal artery injuries was performed. Patients requiring amputation were compared with those with limb salvage at the last follow-up. Of these patients, 80% were randomly assigned to a training group for score generation and 20% to a testing group for validation. Significant predictors of amputation (P < .1) on univariate analysis were included in a multivariable analysis. Those with P < .05 on multivariable analysis were assigned points according to the relative value of their odds ratios (ORs). Receiver operating characteristic curves were generated to determine low- vs high-risk scores. An area under the curve of >0.65 was considered adequate for validation.ResultsA total of 355 patients were included, with an overall amputation rate of 16%. On multivariate regression analysis, the risk factors independently associated with amputation in the final model were as follows: systolic blood pressure

BackgroundUnderstanding SARS-CoV-2 infection in children is necessary to reopen schools safely.MethodsWe measured SARS-CoV-2 infection in 320 learners [10.5 ± 2.1 (sd); 7-17 y.o.] at four diverse schools with either remote or on-site learning. Schools A and B served low-income Hispanic learners; school C served many special-needs learners, and all provided predominantly remote instruction. School D served middle- and upper-income learners, with predominantly on-site instruction. Testing occurred in the fall (2020), and 6-8 weeks later during the fall-winter surge (notable for a tenfold increase in COVID-19 cases). Immune responses and mitigation fidelity were also measured.ResultsWe found SARS-CoV-2 infections in 17 learners only during the surge. School A (97% remote learners) had the highest infection (10/70, 14.3%, p

BackgroundFrailty has been increasingly recognized as an important risk factor for vascular procedures. To assess the impact of frailty on clinical outcomes and resource utilization in patients undergoing carotid revascularization using a national cohort.MethodsThe 2005-2017 National Inpatient Sample was used to identify patients who underwent carotid endarterectomy (CEA) or carotid stenting (CAS). Patients were classified as frail using diagnosis codes defined by the Johns Hopkins Adjusted Clinical Groups frailty indicator. Multivariable regression was used to evaluate associations between frailty and in-hospital mortality, postoperative stroke, myocardial infarction (MI), hospitalization costs, and length of stay (LOS).ResultsOf 1,426,343 patients undergoing carotid revascularization, 59,158 (4.2%) were identified as frail. Among frail patients, 79.4% underwent CEA and 20.6% underwent CAS. Compared to CEA, a greater proportion of patients undergoing CAS were frail (6.0% vs. 3.8%, P < 0.001). Compared to the nonfrail cohort, frail patients had higher rates of mortality (2.2% vs. 0.5%, P < 0.001), postoperative stroke (2.6% vs. 1.0%, P < 0.001), MI (2.2% vs. 0.8%, P < 0.001), and stroke/death (4.4% vs. 1.4%, P < 0.001). After adjustment, frailty was associated with increased odds of mortality (AOR = 1.59, 95% CI: 1.30-1.80, P < 0.001), stroke (AOR = 1.66, 95% CI: 1.38-1.83 P < 0.001), MI (AOR = 1.51, 95% CI: 1.29-1.72, P < 0.001), and stroke/death (AOR = 1.62, 95% CI: 1.45-1.81, P < 0.001). Furthermore, frailty was associated with increased hospitalization costs (β = +$5,980, 95% CI: $5,490-$6,470, P < 0.001) and LOS (β = +2.6 days, 95% CI: 2.4-2.8, P < 0.001).ConclusionsFrailty is associated with adverse outcomes and greater resource use for those undergoing carotid revascularization. Risk models should include an assessment of frailty to guide management and improve outcomes for these high-risk patients.

BackgroundEvidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2.MethodsWe performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation.ResultsData were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups.ConclusionsWe found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. (Funded by the European Union's Horizon 2020 Program and others; BATS ISRCTN number, ISRCTN69546370.).

BACKGROUND: Understanding SARS-CoV-2 infection in children is necessary to reopen schools safely. METHODS: We measured SARS-CoV-2 infection in 320 learners [10.5 ± 2.1(sd); 7-17 y.o.] at four diverse schools with either remote or on-site learning. Schools A and B served low-income Hispanic learners; school C served many special-needs learners; and all provided predominantly remote instruction. School D served middle- and upper-income learners, with predominantly on-site instruction. Testing occurred in the fall (2020), and 6-8 weeks later during the fall-winter surge (notable for a tenfold increase in COVID-19 cases). Immune responses and mitigation fidelity were also measured. RESULTS: We found SARS-CoV-2 infections in 17 learners only during the surge. School A (97% remote learners) had the highest infection (10/70, 14.3%, p

Background: Understanding SARS-CoV-2 infection in children is necessary to reopen schools safely. Methods: We measured SARS-CoV-2 infection in 320 learners [10.5 ± 2.1(sd); 7-17 y.o.] at four diverse schools with either remote or on-site learning. Schools A and B served low-income Hispanic learners; school C served many special-needs learners; and all provided predominantly remote instruction. School D served middle- and upper-income learners, with predominantly on-site instruction. Testing occurred in the fall (2020), and 6-8 weeks later during the fall-winter surge (notable for a tenfold increase in COVID-19 cases). Immune responses and mitigation fidelity were also measured. Results: We found SARS-CoV-2 infections in 17 learners only during the surge. School A (97% remote learners) had the highest infection (10/70, 14.3%, p

Viruses play an important role in the ecology and biogeochemistry of marine ecosystems. Beyond mortality and gene transfer, viruses can reprogram microbial metabolism during infection by expressing auxiliary metabolic genes (AMGs) involved in photosynthesis, central carbon metabolism, and nutrient cycling. While previous studies have focused on AMG diversity in the sunlit and dark ocean, less is known about the role of viruses in shaping metabolic networks along redox gradients associated with marine oxygen minimum zones (OMZs). Here, we analyzed relatively quantitative viral metagenomic datasets that profiled the oxygen gradient across Eastern Tropical South Pacific (ETSP) OMZ waters, assessing whether OMZ viruses might impact nitrogen (N) cycling via AMGs. Identified viral genomes encoded six N-cycle AMGs associated with denitrification, nitrification, assimilatory nitrate reduction, and nitrite transport. The majority of these AMGs (80%) were identified in T4-like Myoviridae phages, predicted to infect Cyanobacteria and Proteobacteria, or in unclassified archaeal viruses predicted to infect Thaumarchaeota. Four AMGs were exclusive to anoxic waters and had distributions that paralleled homologous microbial genes. Together, these findings suggest viruses modulate N-cycling processes within the ETSP OMZ and may contribute to nitrogen loss throughout the global oceans thus providing a baseline for their inclusion in the ecosystem and geochemical models.

Viruses play an important role in the ecology and biogeochemistry of marine ecosystems. Beyond mortality and gene transfer, viruses can reprogram microbial metabolism during infection by expressing auxiliary metabolic genes (AMGs) involved in photosynthesis, central carbon metabolism, and nutrient cycling. While previous studies have focused on AMG diversity in the sunlit and dark ocean, less is known about the role of viruses in shaping metabolic networks along redox gradients associated with marine oxygen minimum zones (OMZs). Here, we analyzed relatively quantitative viral metagenomic datasets that profiled the oxygen gradient across Eastern Tropical South Pacific (ETSP) OMZ waters, assessing whether OMZ viruses might impact nitrogen (N) cycling via AMGs. Identified viral genomes encoded six N-cycle AMGs associated with denitrification, nitrification, assimilatory nitrate reduction, and nitrite transport. The majority of these AMGs (80%) were identified in T4-like Myoviridae phages, predicted to infect Cyanobacteria and Proteobacteria, or in unclassified archaeal viruses predicted to infect Thaumarchaeota. Four AMGs were exclusive to anoxic waters and had distributions that paralleled homologous microbial genes. Together, these findings suggest viruses modulate N-cycling processes within the ETSP OMZ and may contribute to nitrogen loss throughout the global oceans thus providing a baseline for their inclusion in the ecosystem and geochemical models.

ObjectiveEicosanoids modulate inflammation via complex networks involving different pathways and downstream mediators, including oxylipins. Although altered eicosanoids are linked to rheumatoid arthritis (RA), suggesting that metabolization is enhanced, the role of oxylipins in disease stratification remains unexplored. This study was undertaken to characterize oxylipin networks during the earliest stages of RA and evaluate their associations with clinical features and treatment outcomes.MethodsIn total, 60 patients with early RA (according to the American College of Rheumatology/European League Against Rheumatism 2010 criteria), 11 individuals with clinically suspect arthralgia (CSA), and 28 healthy control subjects were recruited. Serum samples were collected at the time of onset. In the early RA group, 50 patients who had not been exposed to disease-modifying antirheumatic drug (DMARD) or glucocorticoid treatment at the time of recruitment were prospectively followed up at 6 and 12 months after having received conventional synthetic DMARDs. A total of 75 oxylipins, mostly derived from arachidonic, eicosapentanoic, and linoleic acids, were identified in the serum by liquid chromatography tandem mass spectrometry.ResultsUnivariate analyses demonstrated differences in expression patterns of 14 oxylipins across the RA, CSA, and healthy control groups, with each exhibiting a different trajectory. Network analyses revealed a strong grouping pattern of oxylipins in RA patients, whereas in individuals with CSA, a fuzzy network of oxylipins with higher degree and closeness was found. Partial least-squares discriminant analyses yielded variable important projection scores of >1 for 22 oxylipins, which allowed the identification of 2 clusters. Cluster usage differed among the groups (P = 0.003), and showed associations with disease severity and low rates of remission at 6 and 12 months in RA patients who were initially treatment-naive. Pathway enrichment analyses revealed different precursors and pathways between the groups, highlighting the relevance of the arachidonic acid pathway in individuals with CSA and the lipooxygenase pathway in patients with early RA. In applying distinct oxylipin signatures, subsets of seropositive and seronegative RA could be identified.ConclusionOxylipin networks differ across stages during the earliest phases of RA. These distinct oxylipin networks could potentially elucidate pathways with clinical relevance for disease progression, clinical heterogeneity, and treatment response.

As the nation implements SARS-CoV-2 vaccination in adults at an unprecedented scale, it is now essential to focus on the prospect of SARS-CoV-2 vaccinations in pediatric populations. To date, no children younger than 12 years have been enrolled in clinical trials. Key challenges and knowledge gaps that must be addressed include (1) rationale for vaccines in children, (2) possible effects of immune maturation during childhood, (3) ethical concerns, (4) unique needs of children with developmental disorders and chronic conditions, (5) health inequities, and (6) vaccine hesitancy. Because COVID-19 is minimally symptomatic in the vast majority of children, a higher acceptable risk threshold is required when evaluating pediatric clinical trials. Profound differences in innate and adaptive immunity during childhood and adolescence are known to affect vaccine responsiveness for a variety of childhood diseases. COVID-19 and the accompanying social disruption, such as the school shutdowns, has been disproportionately damaging to minority and low-income children. In this commentary, we briefly address each of these key issues, specify research gaps, and suggest a broader learning health system approach to accelerate testing and clinical trial development for an ethical and effective strategy to implement a pediatric SARS-CoV-2 vaccine as rapidly and safely as possible. IMPACT: As the US begins an unprecedented implementation of SARS-CoV-2 vaccination, substantial knowledge gaps have yet to be addressed regarding vaccinations in the pediatric population. Maturational changes in the immune system during childhood have influenced the effectiveness of pediatric vaccines for other diseases and conditions, and could affect SARS-CoV-2 vaccine responsiveness in children. Given that COVID-19 disease is far milder in the majority of children than in adults, the risk-benefit of a pediatric SARS-CoV-2 vaccine must be carefully weighed. The needs of children with developmental disabilities and with chronic disease must be addressed. Minority and low-income children have been disproportionately adversely affected by the COVID-19 pandemic; care must be taken to address issues of health equity regarding pediatric SARS-CoV-2 vaccine trials and allocation. Research and strategies to address general vaccine hesitancy in communities must be addressed in the context of pediatric SARS-CoV-2 vaccines.

Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for AFM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population.