A Game of Adaptability: Reflecting on the Highlights and Challenges of Applying for Surgical Residency During the COVID-19 Pandemic

Virtual recruitment of candidates applying into General Surgery residency during the COVID-19 pandemic presented a number of benefits and challenges. Notable benefits for candidates included financial and resource cost savings, the ability to conduct multiple interviews within short time frame, and the ability to meet more faculty members on virtual interview day. Challenges included technological difficulties, difficulty assessing culture and authenticity of in-program relationships, zoom fatigue, and inability to form relationships with co-applicants. After assessing our experiences with these benefits and challenges, the authors recommend that future recruitment cycles maintain virtual interview days with optional, nonevaluative open house days for revisit and second look opportunities

Supporting Data for the Characterization of PNA-DNA Four-Way Junctions

Holliday or DNA four-way junctions (4WJs) are cruciform/bent structures composed of four DNA duplexes. 4WJs are key intermediates in homologous genetic recombination and double-strand break repair. To investigate 4WJs in vitro, junctions are assembled using four asymmetric DNA strands. The presence of four asymmetric strands about the junction branch point eliminates branch migration, and effectively immobilizes the resulting 4WJ. The purpose of these experiments is to show that immobile 4WJs composed of DNA and peptide nucleic acids (PNAs) can be distinguished from contaminating labile nucleic acid structures. These data compare the electrophoretic mobility of hybrid PNA–DNA junctions vs. i) a classic immobile DNA 4WJ, J1 and ii) contaminating nucleic acid structures

Damage Control Thoracotomy: A Systematic Review of Techniques and Outcomes

Background : Damage control surgery is the practice of delaying definitive management of traumatic injuries by controlling hemorrhage in the operating room and restoring normal physiology in the intensive care unit prior to definitive therapy. Presently, damage control or “abbreviated” laparotomy is used extensively for abdominal trauma in an unstable patient. The application of a damage control approach in thoracic trauma is less established and there is a paucity of literature supporting or refuting this practice. We aimed to systematically review the current data on damage control thoracotomy (DCT), to identify gaps in the literature and techniques in temporary closure. Methods : An electronic literature search of Pubmed, MEDLINE, and the Cochrane Database of Collected Reviews from 1972-2018 was performed using the keywords “thoracic,” “damage control,” and “thoracotomy.” Studies were included if they reported the use of DCT following thoracic trauma and included survival as an outcome. Results : Of 723 studies, seven met inclusion criteria for a total of a 130 DCT operations. Gauze packing with temporary closure of the skin with suture was the most frequently reported form of closure. The overall survival rate for the seven studies was 67%. Survival rates ranged from 42-77%. Average injury severity score was 30, and 64% of injuries were penetrating in nature. The most common complications included infections (57%; pneumonia, empyema, wound infection, bacteremia), respiratory failure (21%), ARDS (8%), and renal failure (18%). Conclusion : DCT may be associated with improved survival in the critically injured patient population. Delaying definitive operation by temporarily closing the thorax in order to allow time to restore normal physiology may be considered as a strategy in the unstable thoracic trauma patient population. The impact an open chest has on respiratory physiology remains inconclusive as well as best mechanisms of temporary closure. Multi-center studies are required to elucidate these important questions

Skin sympathetic nerve activity and ventricular rate control during atrial fibrillation

Background: The relationship between the ventricular rate (VR) during atrial fibrillation (AF) and skin sympathetic nerve activity (SKNA) remains unclear. Objective: The purpose of this study was to test the hypothesis that SKNA bursts accelerate VR during AF. Methods: We simultaneously recorded electrocardiogram and SKNA in 8 patients (median age 66.0 years [interquartile range {IQR} 59.0-77.0 years]; 4 men [50%]) with 30 paroxysmal AF episodes (all >10-minute long) and 12 patients (73.0 years [IQR 60.5-80.0 years]; 6 men [50%]) with persistent AF. The average amplitude of SKNA (aSKNA [μV]) during AF was analyzed in 1-minute windows and binned, showing 2 Gaussian distributions. We used the mean + 3SD of the first Gaussian distribution as the threshold that separates burst from baseline (nonburst) SKNA. All 1-minute aSKNA values above the threshold were detected, and the area between aSKNA and baseline of every 1 minute was calculated and added as burst area. Results: VR was higher during SKNA bursts than during the nonburst period (103 beats/min [IQR 83-113 beats/min] vs 88 beats/min [IQR 76-101 beats/min], respectively; P = .003). In the highest quartile of the burst area during persistent AF, the scatterplot of maximal aSKNA and VR during each SKNA burst shows higher aSKNA and VR. The overall estimate of the correlation between maximal VR and aSKNA during bursts show a positive correlation in the highest quartile of the burst area (0.64; 95% confidence interval 0.54-0.74; P < .0001). Conclusion: SKNA bursts are associated with VR acceleration. These SKNA bursts may be new therapeutic targets for rate control during AF

Alemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety findings.

OBJECTIVE: To evaluate 5-year efficacy and safety of alemtuzumab in patients with active relapsing-remitting multiple sclerosis and inadequate response to prior therapy. METHODS: In the 2-year Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II study (NCT00548405), alemtuzumab-treated patients received 2 courses (baseline and 12 months later). Patients could enter an extension (NCT00930553), with as-needed alemtuzumab retreatment for relapse or MRI activity. Annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale [EDSS] score increase [≥1.5 if baseline EDSS = 0]), 6-month confirmed disability improvement (CDI; ≥1-point EDSS decrease [baseline score ≥2.0]), no evidence of disease activity (NEDA), brain volume loss (BVL), and adverse events (AEs) were assessed. RESULTS: Most alemtuzumab-treated patients (92.9%) who completed CARE-MS II entered the extension; 59.8% received no alemtuzumab retreatment. ARR was low in each extension year (years 3-5: 0.22, 0.23, 0.18). Through 5 years, 75.1% of patients were free of 6-month CDW; 42.9% achieved 6-month CDI. In years 3, 4, and 5, proportions with NEDA were 52.9%, 54.2%, and 58.2%, respectively. Median yearly BVL remained low in the extension (years 1-5: -0.48%, -0.22%, -0.10%, -0.19%, -0.07%). AE exposure-adjusted incidence rates in the extension were lower than in the core study. Thyroid disorders peaked at year 3, declining thereafter. CONCLUSIONS: Alemtuzumab provides durable efficacy through 5 years in patients with an inadequate response to prior therapy in the absence of continuous treatment. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that alemtuzumab provides efficacy and slowing of brain atrophy through 5 years

Routine Venous Thromboembolism Prophylaxis May Be Inadequate in the Hypercoagulable State of Severe Coronavirus Disease 2019

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Objectives: The aim of this study was to determine the frequency of venous thromboembolism in critically ill coronavirus disease 2019 patients and associate a degree of inflammatory marker elevation to venous thromboembolism development. Design: An observational study that identified patients with severe coronavirus disease 2019 between March 12, 2020, and March 31, 2020. Data reported are those available through May 6, 2020. Setting: A multicenter study including three Indianapolis area academic hospitals. Patients: Two-hundred forty consecutive patients with confirmed severe acute respiratory syndrome coronavirus 2 infection were admitted to one of three hospitals. One-hundred nine critically ill coronavirus disease 2019 patients admitted to the ICU were included in the analysis. Interventions: All patients received routine subcutaneous chemical venous thromboembolism prophylaxis. Measurements and main results: The primary outcome of this study was to determine the frequency of venous thromboembolism and the degree of inflammatory and coagulation marker elevation associated with venous thromboembolism development. Descriptive statistics outlined the frequency of venous thromboembolism at any time during severe coronavirus disease 2019. Clinical course and laboratory metrics were compared between patients that developed venous thromboembolism and patients that did not develop venous thromboembolism. Hypercoagulable thromboelastography was defined as two or more hypercoagulable parameters. Main results: One-hundred nine patients developed severe coronavirus disease 2019 requiring ICU care. The mean (± SD) age was 61 ± 16 years and 57% were male. Seventy-five patients (69%) were discharged home, 7 patients (6%) remain in the hospital, and 27 patients (25%) died. Venous thromboembolism was diagnosed in 31 patients (28%) 8 ± 7 days after hospital admission, including two patients diagnosed with venous thromboembolism at presentation to the hospital. Elevated admission D-dimer and peak D-dimer were associated with venous thromboembolism development (p < 0.05). D-dimer greater than 2,600 ng/mL predicted venous thromboembolism with an area under the receiver operating characteristic curve of 0.760 (95% CI, 0.661-0.858; p < 0.0001), sensitivity of 89.7%, and specificity of 59.5%. Twelve patients (11%) had thromboelastography performed and 58% of these patients had a hypercoagulable study. The calculated coagulation index was hypercoagulable in 50% of patients with thromboelastography. Conclusions: These data show that coronavirus disease 2019 results in a hypercoagulable state. Routine chemical venous thromboembolism prophylaxis may be inadequate in preventing venous thromboembolism in severe coronavirus disease 2019.Dr. Kreutz’s institution received funding from Idorsia, and he received funding from Haemonetics. The remaining authors have disclosed that they do not have any potential conflicts of interest

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effects and tolerability of exercise therapy modality on cardiorespiratory fitness in lung cancer: A randomized controlled trial

Background: Poor cardiorespiratory fitness (CRF) is a cardinal feature of post-treatment primary lung cancer. The most effective exercise therapy regimen to improve CRF has not been determined. Methods: In this parallel-group factorial randomized controlled trial, lung cancer survivors with poor CRF (below age–sex sedentary values) were randomly allocated to receive 48 consecutive supervised sessions thrice weekly of (i) aerobic training (AT)—cycle ergometry at 55% to >95% of peak oxygen consumption (VO2peak); (ii) resistance training (RT)—lower and upper extremity exercises at 50–85% of maximal strength; (iii) combination training (CT)—AT plus RT; or (iv) stretching attention control (AC) for 16 weeks. The primary endpoint was change in CRF (VO2peak, mL O2·kg−1·min−1). Secondary endpoints were body composition, muscle strength, patient-reported outcomes, tolerability (relative dose intensity of exercise), and safety. Analysis of covariance determined change in primary and secondary endpoints from baseline to post-intervention (Week 17) with adjustment for baseline values of the endpoint and other relevant clinical covariates. Results: Ninety patients (65 ± 9 years; 66% female) were randomized (AT, n = 24; RT, n = 23; CT, n = 20; and AC, n = 23) of the planned n = 160. No serious adverse events were observed. For the overall cohort, the lost-to-follow-up rate was 10%. Mean attendance was ≥75% in all groups. In intention-to-treat analysis, VO2peak increased 1.1 mL O2·kg−1·min−1 [95% confidence interval (CI): 0.0, 2.2, P = 0.04] and 1.4 mL O2·kg−1·min−1 (95% CI: 0.2, 2.5, P = 0.02) in AT and CT, respectively, compared with AC. There was no difference in VO2peak change between RT and AC (−0.1 mL O2·kg−1·min−1, 95% CI: −1.2, 1.0, P = 0.88). Favourable improvements in maximal strength and body composition were observed in RT and CT groups compared with AT and AC groups (Ps < 0.05). No between-group changes were observed for any patient-reported outcomes. Relative dose intensity of exercise was lower in RT and CT compared with AT (Ps < 0.05). Conclusions: In the context of a smaller than planned sample size, AT and CT significantly improved VO2peak in lung cancer survivors; however, the tolerability-to-benefit ratio was superior for AT and hence may be the preferred modality to target impaired CRF in post-treatment lung cancer survivors