Tolerance induction through early feeding to prevent food allergy in infants and children with sensitization against food allergens (TIFFANI): rationale, study design, and methods of a randomized controlled trial.

BACKGROUND: Children with sensitization against foods have to be orally food-challenged before eating these foods for the first time. However, the waiting time for an oral food challenge (OFC) in Germany is about 3-6 months. In contrast, there are hints that an early introduction of allergenic foods might be protective regarding the development of food allergy. The aim of this clinical trial is therefore to investigate, whether an introduction and regular consumption of small amounts of food allergens is safe and will result in an increase of tolerance in children with sensitization against food allergens with unknown clinical relevance. METHODS: In this randomized, placebo-controlled, double-blind, single-center trial, 138 children (8 months to 4 years of age) sensitized to the target allergen(s) hen's egg, cow's milk, peanuts, and/or hazelnuts with unknown clinical relevance will be randomized in a 1:1 ratio to either an active or a placebo group, daily receiving a rusk-like biscuit powder with or without the target allergen(s) for 3-6 months until an OFC will be performed in routine diagnostics. The primary endpoint is an IgE-mediated food allergy to the primary target allergen, after the interventional period. DISCUSSION: Children with sensitization against food allergens with unknown clinical relevance often have to avoid the corresponding foods for several months until an OFC is performed. Therefore, the "window of opportunity" for an early preventive introduction of allergenic foods might be missed. This trial will assess whether an introduction of small allergen amounts will favor tolerance development in these children. TRIAL REGISTRATION: German Clinical Trials Register DRKS00032769. Registered on 02 October 2023.

Estradiol and Dihydrotestosterone Levels in COVID-19 Patients.

OBJECTIVE: To determine differences in plasma sex hormone levels in male and female coronavirus disease 2019 (COVID-19) patients and healthy volunteers (HVs) because cell entry of severe acute respiratory syndrome coronavirus 2 occurs via the angiotensin-converting enzyme 2 receptor which is downregulated by 17ß-estradiol. PATIENTS AND METHODS: Citrated plasma samples were collected from 101 patients with COVID-19 upon presentation to the emergency department and from 40 HVs between November 1, 2020, and May 30, 2021. Plasma 17ß-estradiol and 5α-dihydrotestosterone (DHT) levels were measured using enzyme-linked immunosorbent assay (pg/mL). Data are presented as median and quartiles (IQR). Wilcoxon rank sum test with a P value less than .05 was considered significant. RESULTS: Patients with COVID-19 (median age, 49 years) included 51 males and 50 females (25 postmenopausal). Hospital admission was required for 58.8% of male patients (n = 30) and 48.0% of female patients (n = 24) (66.7% postmenopausal, n = 16) Healthy volunteers (median age, 41 years) included 20 males and 20 females (9 postmenopausal). Female patients with COVID-19 were found to have decreased 17ß-estradiol levels (18.5 [IQR, 10.5-32.3] pg/mL; 41.4 [IQR, 15.5-111.0] pg/mL, P=.025), and lower 17ß-estradiol to DHT ratios (0.073 [IQR, 0.052-0.159] pg/mL; 0.207 [IQR, 0.104-0.538] pg/mL, P=.015) than female HVs. Male patients with COVID-19 were found to have decreased DHT levels (302.8 [IQR, 249.9-470.8] pg/mL; 457.2 [IQR, 368.7-844.3] pg/mL, P=.005), compared with male HVs. Levels of DHT did not differ between female patients with COVID-19 and female HVs, whereas 17ß-estradiol levels did not differ between male patients with COVID-19 and male HVs. CONCLUSION: Sex hormone levels differ between patients with COVID-19 and HVs, with sex-specific patterns of hypogonadism in males and females. These alterations may be associated with disease development and severity.

An interdisciplinary approach to characterize peanut-allergic patients-First data from the FOOD@ consortium.

Background: Peanut allergy is a frequent cause of food allergy and potentially life-threatening. Within this interdisciplinary research approach, we aim to unravel the complex mechanisms of peanut allergy. As a first step were applied in an exploratory manner the analysis of peanut allergic versus non-allergic controls. Methods: Biosamples were studied regarding DNA methylation signatures, gut microbiome, adaptive and innate immune cell populations, soluble signaling molecules and allergen-reactive antibody specificities. We applied a scalable systems medicine computational workflow to the assembled data. Results: We identified combined cellular and soluble biomarker signatures that stratify donors into peanut-allergic and non-allergic with high specificity. DNA methylation profiling revealed various genes of interest and stool microbiota differences in bacteria abundances. Conclusion: By extending our findings to a larger set of patients (e.g., children vs. adults), we will establish predictors for food allergy and tolerance and translate these as for example, indicators for interventional studies.

Tolerance induction through early feeding to prevent food allergy in infants with eczema (TEFFA): rationale, study design, and methods of a randomized controlled trial.

BACKGROUND: Up to 8% of all children in industrialized countries suffer from food allergies, whereas children with atopic eczema are affected considerably more frequently. In addition, the type and starting time of weaning foods seem to influence the development of food allergies. However, data from interventional studies on weaning are controversial. The aim of this randomized-controlled clinical trial is to investigate, whether an early introduction of hen's egg (HE), cow's milk (CM), peanut (PN), and hazelnut (HN) in children with atopic eczema can reduce the risk for developing food allergies in the first year of life. METHODS: This is a protocol for a randomized, placebo controlled, double blind, single-center clinical trial. One hundred fifty infants with atopic eczema at 4-8 months of age will be randomized in a 2:1 manner into an active group that will receive rusk-like biscuit powder with HE, CM, PN, and HN (initially approximately 2 mg of each food protein) for 6-8 months or a placebo group, whose participants will receive the same rusk-like biscuit powder without HE, CM, PN, and HN on a daily basis. During the interventional period, the amount of allergens in the study product will be increased three times, each after 6 weeks. All study participants who are sensitized to HE, CM, PN, or HN at the end of the interventional period will undergo an oral food challenge to the respective food in a further visit. Primary endpoint is IgE-mediated food allergy to at least one of the four foods (HE, CM, PN or HN) after 6-8 months of intervention (i.e., at around 1 year of age). Secondary endpoints include multiple food allergies, severity of eczema, wheezing, and sensitization levels against food allergens. DISCUSSION: This clinical trial will assess whether an early introduction of allergenic foods into the diet of children with atopic eczema can prevent the development of food allergies. This trial will contribute to update food allergy prevention guidelines. TRIAL REGISTRATION: German Clinical Trials Register DRKS00016770 . Registered on 09 January 2020.

Tolerance induction through non-avoidance to prevent persistent food allergy (TINA) in children and adults with peanut or tree nut allergy: rationale, study design and methods of a randomized controlled trial and observational cohort study.

BACKGROUND: Peanuts (PN) and tree nuts (TN) are among the most frequent elicitors of food allergy and can lead to life-threatening reactions. The current advice for allergic patients is to strictly avoid the offending food independently of their individual threshold level, whereas sensitized patients without allergic symptoms should frequently consume the food to avoid (re-)development of food allergy. The aim of this trial is to investigate (I) whether the consumption of low allergen amounts below the individual threshold may support natural tolerance development and (II) to what extent regular allergen consumption in sensitized but tolerant subjects prevents the (re-)development of PN or TN allergy. METHODS: The TINA trial consisting of (part I) a randomized, controlled, open, parallel group, single-center, superiority trial (RCT), and (part II) a prospective observational exploratory cohort study. Children and adults (age 1-67 years) with suspected or known primary PN and/or TN allergy will undergo an oral food challenge (OFC) to determine their clinical reactivity and individual threshold. In the RCT, 120 PN or TN allergic patients who tolerate ≥100 mg of food protein will be randomized (1:1 ratio) to consumption of products with low amounts of PN or TN on a regular basis or strict avoidance for 1 year. The consumption group will start with 1/100 of their individual threshold, increasing the protein amount to 1/50 and 1/10 after 4 and 8 months, respectively. The primary endpoint is the clinical tolerance to PN or TN after 1 year assessed by OFC. In the cohort study, 120 subjects sensitized to PN and/or TN but tolerant are advised to regularly consume the food and observed for 1 year. The primary endpoint is the maintenance of clinical tolerance to PN and/or TN after 1 year assessed by challenging with the former tolerated cumulative dose. DISCUSSION: This clinical trial will help to determine the impact of allergen consumption versus avoidance on natural tolerance development and whether the current dietary advice for PN or TN allergic patients with higher threshold levels is still valid. TRIAL REGISTRATION: German Clinical Trials Register; ID: DRKS00016764 (RCT), DRKS00020467 (cohort study). Registered on 15 January 2020, http://www.drks.de .

New Heuristics to Stratify Applicants: Predictors of General Surgery Residency Applicant Step 1 Scores.

OBJECTIVE: In 2022, United States Medical Licensing Examination (USMLE) Step 1 scores will become pass/fail. This may be problematic, as residency programs heavily rely on USMLE Step 1 scores as a metric when determining interview invitations. This study aimed to assess candidate application metrics associated with USMLE Step 1 scores to offer programs new cues for stratifying applicants. DESIGN: Retrospective cohort study analyzing interviewed applicants to one general surgery residency program in 2019 and 2020. Applicant data analyzed included USMLE Step 1 scores, number of publications, clerkship scores, letter of recommendation scores (out of 2, scored by 0.25 interval), interview overall score (out of 5, scored by integer level), and standardized question score (out of 10). Each year, applicant's answers to one standardized behavioral question during their interview were scored by interviewers. SETTING: Tertiary medical center, academic general surgery residency program. PARTICIPANTS: Interviewed applicants at one general surgery residency program whose applications contained complete demographic information (203 out of 247). RESULTS: Multiple Linear Regression revealed that higher surgical clerkship (ß = 0.19, p = 0.006) and higher standardized interview question (ß = 0.32, p < 0.001) scores were positively associated with applicant USMLE Step 1 score (F[7, 195] = 6.61, p < 0.001, R2 = 0.19). Letter of recommendation score, number of peer reviewed publications, gender, race, and applicant type (preliminary/categorical) were not associated with USMLE Step 1 scores. CONCLUSIONS: With USMLE Step 1 scores transitioning to pass/fail, surgical residency programs need new selection heuristics. Surgery clerkship scores and standardized behavioral questions answered by applicants prior to the interview could provide a holistic view of applicants and help programs better stratify candidates without USMLE Step 1 scores.

Small bowel obstruction managed without hospital admission: A safe way to reduce both cost and time in the hospital?

BACKGROUND: Small bowel obstruction management has evolved to incorporate the Gastrografin challenge. We expanded its use to the emergency department observation unit, potentially avoiding hospital admission for highly select small bowel obstruction patients. We hypothesized that the emergency department observation unit small bowel obstruction protocol would reduce admissions, costs, and the total time spent in the hospital without compromising outcomes. METHODS: We reviewed patients who presented with small bowel obstruction from January 2015 to December 2018. Patients deemed to require urgent surgical intervention were admitted directly and excluded. The emergency department observation unit small bowel obstruction guidelines were introduced in November 2016. Patients were divided into pre and postintervention groups based on this date. The postintervention group was further subclassified to examine the emergency department observation unit patients. Cost analysis for each patient was performed looking at number of charges, direct costs, indirect cost, and total costs during their admission. RESULTS: In total, 125 patients were included (mean age 69 ± 14.3 years). The preintervention group (n = 62) and postintervention group (n = 63) had no significant difference in demographics. The postintervention group had a 51% (36.7 hours, P < .001) reduction in median duration of stay and a total cost reduction of 49% (P < .001). The emergency department observation unit subgroup (n = 46) median length of stay was 23.6 hours. The readmission rate was 16% preintervention compared to 8% in the postintervention group (P = .18). CONCLUSION: Management of highly selected small bowel obstruction patients with the emergency department observation unit small bowel obstruction protocol was associated with decreased length of stay and total cost, without an increase in complications, surgical intervention, or readmissions.

NASA-TLX assessment of workload in resident physicians and faculty surgeons covering trauma, surgical intensive care unit, and emergency general surgery services.

BACKGROUND: Higher workload is associated with burnout and lower performance. Therefore, we aim to assess shift-related factors associated with higher workload on EGS, ICU, and trauma surgery services. METHODS: In this prospective cohort study, faculty surgeons and surgery residents completed a survey after each EGS, ICU, or trauma shift, including shift details and a modified NASA-TLX. RESULTS: Seventeen faculty and 12 residents completed 174 and 48 surveys after working scheduled 12-h and 24-h shifts, respectively (response rates: faculty - 62%, residents - 42%). NASA-TLX was significantly increased with a higher physician subjective fatigue level. Further, seeing more consults or performing more operations than average significantly increased workload. Finally, NASA-TLX was significantly higher for faculty when they felt their shift was more difficult than expected. CONCLUSIONS: Higher volume clinical responsibilities and higher subjective fatigue levels are independently associated with higher workload. Designing shift coverage to expand on busier days may decrease workload, impacting burnout and shift performance.

Urinary Retention Following Inguinal Herniorrhaphy: Role of Neuromuscular Blockade Reversal.

BACKGROUND: Nondepolarizing neuromuscular blockade is reversed with neostigmine/glycopyrrolate or sugammadex. Anticholinergic glycopyrrolate decreases bladder detrusor muscle contractility, potentially leading to postoperative urinary retention (POUR). POUR commonly complicates inguinal herniorrhaphy. In this study we assess association between reversal technique and POUR. METHODS: Records of adult patients undergoing unilateral inguinal herniorrhaphy with neuromuscular blockade from January 2013 to September 2020 were reviewed for POUR (unplanned postoperative insertion of urinary catheter). A propensity-adjusted analysis was performed to assess POUR in neostigmine/glycopyrrolate versus sugammadex using inverse probability of treatment weighting (IPTW) to adjust for potential confounding. RESULTS: We identified 181 patients who underwent herniorrhaphy with amnio-steroidal neuromuscular blockers, 75 (41.4%) who received sugammadex and 106 (58.6%) neostigmine/glycopyrrolate. Compared with sugammadex, neostigmine/glycopyrrolate group had longer surgical course [unweighted standardized difference (USTD)=0.38, P=0.004], received more intraoperative opioids (USTD=0.704, P<0.001), more often performed via laparoscopic approach (USTD=0.407, P=0.012), and less often with periprocedural urinary catheter insertion (USTD=0.452, P=0.003). POUR was observed in 2 (3%) of patients in the sugammadex group, and 16 (15%) in neostigmine/glycopyrrolate [unadjusted odds ratio (OR)=0.15; 95% confidence interval (CI): 0.03-0.69; P=0.015, and IPTW OR=0.13; 95% CI: 0.03-0.64; P=0.012]. Results remained similar with further analysis adjusted for opioid administration in the postanesthesia care unit (adjusted IPTW OR=0.18; 95% CI: 0.04-0.88; P=0.034). Of the POUR patients, 9 required unplanned overnight admission and 4 emergency room visit. CONCLUSION: These results suggest that neuromuscular blockade reversal with sugammadex is associated with lower rates of POUR following unilateral inguinal herniorrhaphy. Our results need to be reconfirmed in a randomized prospective study.

Exploring the utility of a novel point-of-care whole blood thrombin generation assay following trauma: A pilot study.

INTRODUCTION: Plasma thrombin generation kinetics as measured by the calibrated automated thrombogram (CAT) assay is a predictor of symptomatic venous thromboembolism after trauma. We hypothesized that data from a new prototype assay for measurement of thrombin generation kinetics in fresh whole blood (near patient testing of thrombin generation), will correlate with the standard CAT assay in the same patients, making it a potential tool in the future care of trauma patients. METHODS: Patients were enrolled from June 2018 to February 2020. Within 12 hours of injury, blood samples were collected simultaneously for both assays. Variables compared and correlated between assays were lag time, peak height, time to peak, and endogenous thrombin potential. Data are presented as median with interquartile range (IQR). Spearman and Pearson correlations were estimated and tested between both assays; a P value of <0.05 was considered to be significant. RESULTS: A total of 64 trauma patients had samples analyzed: injury severity score = 17 (IQR), 10-26], hospital length of stay = 7.5 (IQR), 2-18) days, age = 52 (IQR, 35-63) years, 71.9% male, and 42.2% of patients received a transfusion within 24 hours of injury. Thrombin generation parameters between plasma and whole blood were compared and found that all parameters of the two assays correlate in trauma patients. CONCLUSION: In this pilot study, we have found that a novel point-of-care whole blood thrombin generation assay yields results with modest but statistically significant correlations to those of a standard plasma thrombin generation assay. This finding supports studying this device in a larger, adequately powered study.

Neutrophil Extracellular Trap Formation and Syndecan-1 Shedding Are Increased After Trauma.

BACKGROUND: Damage-associated molecular patterns (DAMPs) stimulate endothelial syndecan-1 shedding and neutrophil extracellular traps (NET) formation. The role of NETs in trauma and trauma-induced hypercoagulability is unknown. We hypothesized that trauma patients with accelerated thrombin generation would have increased NETosis and syndecan-1 levels. METHODS: In this pilot study, we analyzed 50 citrated plasma samples from 30 trauma patients at 0 h (n = 22) and 6 h (n = 28) from time of injury (TOI) and 21 samples from healthy volunteers, for a total of 71 samples included in analysis. Thrombin generation was quantified using calibrated automated thrombogram (CAT) and reported as lag time (LT), peak height (PH), and time to peak (ttPeak). Nucleosome calibrated (H3NUC) and free histone standardized (H3Free) ELISAs were used to quantify NETs. Syndecan-1 levels were quantified by ELISA. Results are presented as median [interquartile range] and Spearman rank correlations. RESULTS: Plasma levels of H3NUC were increased in trauma patients as compared with healthy volunteers both at 0 h (89.8 ng/mL [35.4, 180.3]; 18.1 ng/mL [7.8, 37.4], P = 0.002) and at 6 h (86.5 ng/mL [19.2, 612.6]; 18.1 ng/mL [7.8, 37.4], P = 0.003) from TOI. H3Free levels were increased in trauma patients at 0 h (5.74 ng/mL [3.19, 8.76]; 1.61 ng/mL [0.66, 3.50], P = 0.002) and 6 h (5.52 ng/mL [1.46, 11.37]; 1.61 ng/mL [0.66, 3.50], P = 0.006). Syndecan-1 levels were greater in trauma patients (4.53 ng/mL [3.28, 6.28]; 2.40 ng/mL [1.66, 3.20], P < 0.001) only at 6 h from TOI. H3Free and syndecan-1 levels positively correlated both at 0 h (0.376, P = 0.013) and 6 h (0.583, P < 0.001) from TOI. H3NUC levels and syndecan-1 levels were positively correlated at 6 h from TOI (0.293, P = 0.041). TtPeak correlated inversely to H3 NUC (-0.358, P = 0.012) and syndecan-1 levels (-0.298, P = 0.038) at 6 h from TOI. CONCLUSIONS: Our pilot study demonstrates that trauma patients have increased NETosis, measured by H3NUC and H3Free levels, increased syndecan-1 shedding, and accelerated thrombin generation kinetics early after injury.

Diversity Matters: A 21-Year Review of Trends in Resident Recruitment into Surgical Specialties.

Background: Diversity within the healthcare workforce is essential to improve quality of care, although evaluation of diversity within surgical training remains limited. This study analyzed diversity in recruitment of residents into surgical subspecialties at a large academic medical institution and national trends. Methods: A 21-year cross-sectional study of medical school graduates accepted into all surgical subspecialty training programs was performed. The institutional cohort was divided into two groups (1997-2006, 2007-2017). Subspecialty acceptance rates were determined between 2011 and 2018. Data on candidate demographics including gender, race, ethnicity, citizenship, and origin of medical education at a single institution and nationally were extracted. Results: Two thousand found hundred seventy-two residents were included in this study. From 1997 to 2018, female acceptances increased from 21.1% to 29.7% (p < 0.01), non-White increased from 27.9% to 31.8% (p = 0.01), and international medical graduates decreased from 28.8% to 25.5% (p = 0.02). There was no significant change in accepted Hispanic and Non-US candidates. Female subspecialty rates for subspecialties increased nationally and was comparable to our cohort, except in general surgery. Hispanic subspecialty acceptance rates were less than 10% and Black/African American acceptance rates remained less than 5% across subspecialties nationally and at our institution. Conclusion: Diversity in surgical training has modestly progressed over the last two decades, but the degree of positive change has not been universal and highlights the critical need for improvement and action. Continued institution driven and collaborative strategies are essential to promote diversity in recruitment across all surgical specialties that has implications on our future workforce and surgical leadership.

International Medical Graduates are Comparable to American Medical Graduates as General Surgery Interns.

BACKGROUND: International medical graduates (IMGs) are often relegated to preliminary positions in general surgery (GS) owing to uncertainties about the candidate's performance in the American healthcare setting. We aimed to determine the comparative performance of IMGs and American medical graduates (AMGs) at baseline and assess these trends over the course of their GS internship. METHODS: Evaluations of all IMG preliminary and AMG categorical interns from 2013 to 2017 at our GS residency program were obtained from three faculty members to score overall performance, technical skills, interpersonal communication, and medical knowledge on a 10-point Likert scale. Scores on the American Board of Surgery In-Training Exam, an in-house preparation test, United States Medical Licensing Exam, and performance during the biannual multistation objective assessments were compared between the two resident groups. RESULTS: Seventy-two interns (28 [39%] AMG categorical and 44 [61%] IMG preliminary) met inclusion criteria. The AMG group had significantly higher median Step 1 and Step 2 scores compared with our IMG group (243 versus 231, P = 0.002, and 250 versus 246, P = 0.03, respectively).Although in-house preparation test scores were higher among IMGs (median [interquartile range] of 36 [33-40] among AMGs and 38 [34-45] among IMGs; P = 0.002), there were no statistically significant differences between the American Board of Surgery In-Training Exam scores of the two groups. The median scores for the four faculty evaluation components were similar between the AMG (7, 8, 7, 7) and IMG resident groups (7, 7, 7, 7; P = nonsignificant). IMGs scored significantly higher in both biannual multistation objective assessments than AMGs (median [interquartile range] July: 59 [47-91] versus 55 [37-62], P = 0.005; January: 103 [86-116] versus 91 [87-104], P = 0.03). CONCLUSIONS: It is reassuring to confirm that no matter where they are from, great candidates can perform well as surgical interns in a GS training program.

Biomarkers of thromboinflammation correlate to COVID-19 infection and admission status in emergency department patients.

Background: COVID-19-associated coagulopathy is incompletely understood. Objectives: To characterize thrombin generation, Von Willebrand Factor (VWF), neutrophil extracellular traps (NETs), and their role in COVID-19 risk stratification in the emergency department (ED). Patients/methods: Plasma samples from 67 ED COVID-19 patients were compared to 38 healthy volunteers (HVs). Thrombin generation (calibrated automated thrombogram, CAT) was expressed as lag time (LT, min), peak height (PH, min), and time to peak (ttPeak, min). Citrullinated nucleosomes and histones were quantified with ELISA, VWF antigen and activity (IU/dL) through latex immunoassay, Factor VIII (IU/dL) through one-stage optical clot detection, and VWF multimers with Western blot densitometry. Wilcoxon testing and multivariable logistic regression were performed. Results presented as median [Q1, Q3]; p < 0.05 significant. Results: COVID-19 patients had longer LT (4.00 [3.26, 4.67]; 2.95 [2.67, 3.10], p < 0.001) and ttPeak (7.33 [6.33, 8.04]; 6.45 [6.00, 7.50], p = 0.004), greater VWF antigen (212 [158, 275]; 110 [91, 128], p < 0.001) and Factor VIII levels (148 [106, 190]; 106 [86, 129], p < 0.001), with decreased high molecular weight multimers (Normalized multimer ratio 0.807 [0.759, 0.869]; 0.891 [0.858, 0.966], p < 0.001), than HVs. COVID-19 patients requiring admission from the ED had longer LT and ttPeak with greater VWF antigen and Factor VIII levels than those not admitted. Two and three variable models of CAT parameters and VWF correlated with COVID-19 and admission status (C-statistics 0.677 to 0.922). Conclusions: Thrombin generation kinetics and VWF levels, independent of NETs, may have a role in predicting admission need for COVID-19 patients.

T Cell Impairment Is Predictive for a Severe Clinical Course in NEMO Deficiency.

PURPOSE: NEMO-deficient patients present with variable degrees of immunodeficiency. Accordingly, treatment ranges from antibiotic prophylaxis and/or IgG-substitution to allogenic hematopoietic stem cell transplantation (HSCT). The correct estimation of the immunodeficiency is essential to avoid over- as well as under-treatment. We compare the immunological phenotype of a NEMO-deficient patient with a newly-described splice site mutation that causes truncation of the NEMO zinc-finger (ZF) domain and a severe clinical course with the immunological phenotype of three NEMO-deficient patients with missense mutations and milder clinical courses and all previously published patients. METHODS: Lymphocyte subsets, proliferation, and intracellular NEMO-expression were assessed by FACS. NF-κB signal transduction was determined by measuring IκBα-degradation and the production of cytokines upon stimulation with TNF-α, IL-1ß, and TLR-agonists in immortalized fibroblasts and whole blood, respectively. RESULTS: The patient with truncated ZF-domain of NEMO showed low levels of IgM and IgG, reduced class-switched memory B cells, almost complete skewing towards naïve CD45RA+ T cells, impaired T cell proliferation as well as cytokine production upon stimulation with TNF-α, IL-1ß, and TLR-agonists. He suffered from severe infections (sepsis, pneumonia, osteomyelitis) during infancy. In contrast, three patients with missense mutations in IKBKG presented neither skewing of T cells towards naïvety nor impaired T cell proliferation. They are stable on prophylactic IgG-substitution or even off any prophylactic treatment. CONCLUSION: The loss of the ZF-domain and the impaired T cell proliferation accompanied by almost complete persistence of naïve T cells despite severe infections are suggestive for a profound immunodeficiency. Allogenic HSCT should be considered early for these patients before chronic sequelae occur.

What Do Former Residents Say About Their Nondesignated Preliminary Year? A Survey of Prelims' Experiences in a General Surgery Residency Program.

OBJECTIVE: The nondesignated preliminary (NDP) position in general surgery (GS) offers a 1-year surgical training opportunity for medical school graduates prior to obtaining categorical residency positions. Given that there is little long-term follow-up on the experiences of NDP residents, we sought to determine how NDPs felt about their intern year in GS. DESIGN: A cross-sectional survey of all NDP GS interns from 1993 to 2018. SETTING: Academic, tertiary care center with a large GS residency program (Mayo Clinic, Rochester, MN). PARTICIPANTS: NDP GS interns (n = 151). RESULTS: Two-hundred and four surveys were emailed and 151 (62%) former NDP residents responded. Exposure to diverse pathology (85%), opportunity to work with experts (85%) and operative experience (72%) were the top 3 positive experiences from the NDP year. The uncertainty of being an NDP resident (78%) and experience compared to categorical counterparts (32%) were cited as the top 2 negative experiences. While 73% (n = 110) considered their NDP year to have laid a "strong" foundation for their future career, most respondents felt that the year was stressful and suggested improving mentoring and support for preliminary residents. Eighty-two percent (n = 124) of respondents stated that, they would be willing to redo their preliminary year. Fifty-four percent (n = 82) of respondents stated that they might have preferred a categorical position at a smaller institution versus a preliminary year. Forty percent of respondents (n = 60) reported fewer interviews and 24% (n = 36) reported a similar number of interviews offered when applying to the Match as a PGY1 prelim resident. CONCLUSIONS: Pursuing the NDP year is difficult, given the uncertainty that looms and the immense pressure to perform well. While the vast majority of our NDPs obtained categorical residency spots following their 1 year of training, feedback from this survey using 25 years of experience suggests that we can and should do more to mentor, support, and assist these residents.

NASA-TLX Assessment of Surgeon Workload Variation Across Specialties.

OBJECTIVE: With advancements in surgical equipment and procedures, human-system interactions in operating rooms affect surgeon workload and performance. Workload was measured across surgical specialties using surveys to identify potential predictors of high workload for future performance improvement. SUMMARY BACKGROUND DATA: Surgical instrumentation and technique advancements have implications for surgeon workload and human-systems interactions. To understand and improve the interaction of components in the work system, NASA-Task Load Index can measure workload across various fields. Baseline workload measurements provide a broad overview of the field and identify areas most in need of improvement. METHODS: Surgeons were administered a modified NASA-Task Load Index survey (0 = low, 20 = high) following each procedure. Patient and procedural factors were retrieved retrospectively. RESULTS: Thirty-four surgeons (41% female) completed 662 surgery surveys (M = 14.85, SD = 7.94), of which 506 (76%) have associated patient and procedural data. Mental demand (M = 7.7, SD = 5.56), physical demand (M = 7.0, SD = 5.66), and effort (M = 7.8, SD = 5.77) were the highest rated workload subscales. Surgeons reported difficulty levels higher than expected for 22% of procedures, during which workload was significantly higher (P < 0.05) and procedural durations were significantly longer (P > 0.001). Surgeons reported poorer perceived performance during cases with unexpectedly high difficulty (P < 0.001). CONCLUSIONS: When procedural difficulty is greater than expected, there are negative implications for mental and physical demand that result in poorer perceived performance. Investigations are underway to identify patient and surgical variables associated with unexpected difficulty and high workload. Future efforts will focus on re-engineering the surgical planning process and procedural environment to optimize workload and performance for improved surgical care.

A simulation-based selection process for trying to identify medical students who will become outstanding general surgery residents.

BACKGROUND: Selecting the right applicants for general surgery training is critical and difficult. We refined our selection process by using a pre-interview preparation package and simulation-based assessments. METHODS: Sixty applicants invited for categorical general-surgery residency interview were mailed an educational package which included a link to instructional videos, surgical instruments and low-cost models for suturing, open knot tying, and adrenal anatomy knowledge. During the interview day, applicants participated in a 48-min simulation-based assessment consisting of same tasks included in the package. Performance scores were used to assist in ranking applicants. The matched 2018class was compared to our previous intern classes on several objective assessments (Surgical-Olympics and ABSITE score). RESULTS: Students scored >50tile moved high in our final rank-list. The 2018 class scored significantly higher in 10 of 15 Surgical-Olympic stations compared to our 2015-17class with no significant difference on ABSITE score. CONCLUSIONS: By mailing out a pre-interview welcome package and adding a simulation based assessment to our General Surgery categorical interview process, we believe early objective data suggests we positively influenced our 2018 NRMP match.

Reconstructive operations for enteric and colonic fistulas: Low mortality and recurrence in a single-surgeon series with long follow-up.

BACKGROUND: The aim of the study was to evaluate the outcomes of 100 consecutive patients undergoing reconstructive operation for enteric and colonic fistulas. These fistulas cause dramatic morbidity and profoundly diminish quality of life. Fistula takedown has been associated with high rates of recurrence. METHODS: Consecutive patients undergoing definitive fistula reconstruction by a single surgeon were reviewed retrospectively. Major adverse outcomes included bowel leak, fistula recurrence, death, total parenteral nutrition dependence, and incidence of new stomas. RESULTS: Among the 100 patients, median follow-up was 2.7 years. A total of 11 patients had postoperative leaks that evolved to 5 fistula recurrences. Of these patients 3 underwent successful secondary or tertiary takedown. The 30-day mortality rate was 1%, and the combined postoperative and fistula-related mortality rate at follow-up was 3%. New postoperative total parenteral nutrition dependence occurred in 2 patients (2%), and 9 (9%) had placement of a new stoma. Leaks were more frequent for patients who had a history of open abdomen than for patients who did not. CONCLUSIONS: With minimal patient selection and a methodic approach to evaluation and management, we achieved a 96% fistula-free survival rate. Few patients acquired new total parenteral nutrition dependence or a new stoma. These results compare favorably with outcomes published elsewhere.

Salvage of rib stabilization hardware with antibiotic beads.

BACKGROUND: Surgical stabilization of rib fractures (SSRF) can be used to improve pulmonary mechanics; however, hardware infection is a morbid complication. Antibiotic impregnated beads have been used to suppress infection in orthopedic practices. We aimed to determine the efficacy of antibiotic beads for infected and at-risk SSRF hardware. METHODS: This is a single institution retrospective review of adults (18 years or older) that received SSRF between 2009 and 2017. Infected and at-risk hardware were managed with antibiotic beads. The primary outcome was bony union of rib fractures. RESULTS: There were 285 SSRF patients. Infection rate was 3.5%. Antibiotic beads were placed in 17 patients - 9 for infected hardware and 8 for prophylaxis. Increased body mass index (p = 0.04) and hemorrhagic shock at admission (p = 0.03) were risk factors for infection. There was 100% bony union post-operatively. CONCLUSION: SSRF hardware infection is morbid. Antibiotic beads can salvage SSRF hardware until bony union.