From the Desk of the Residency Program Director

It has been a historic year for the Nation, City of Philadelphia and teh Jefferson Internal Medicine Residency Program. We have eperienced many health care crises starting with the closure of the historic Philadelphia hospital, Hahnemann. We welcomed residents form this program as part of the Jefferson Family and integrated many patients into our practices

Nephrotic Syndrome: Is HIV Associated Nephropathy on Your Differential?

Case Description A 30-year old African American female with no significant past medical history initially presented to our emergency department with three days of sore throat, dysphagia, fever, fatigue, nausea and vomiting. She denied ear pain, rhinorrhea, shortness of breath or any sick contacts. Her social history was negative for tobacco, alcohol and illicit drug use. She works as a security officer, lives with her family and is sexually active only with her husband. On initial examination she was febrile to 101.9° F, with a heart rate of 100 beats per minute, blood pressure of 143/99 mmHg, respiratory rate of 18 breaths per minute and an oxygen saturation of 99% on room air. Her only pertinent physical examination findings were a mildly erythematous oropharynx without exudates, mildly swollen uvula and right tonsil, bilateral tender swollen sub-mandibular lymph nodes and reduced breath sounds on auscultation of the right lower lung base.She was routinely tested for HIV, ruled out for group A strep, and discharged home with the diagnosis of viral pharyngitis on supportive care. Following the identification of a presumptive positive rapid HIV screening test with evidence of HIV-1 p24 antigen and a reactive HIV-1 antibody on the multispot HIV 1 / 2 antibody test she was called to return to the ED for counseling regarding a positive HIV test. She reported continuation of her prior symptoms with worsening dysphagia, as well as new complaints of bilateral lower extremity edema to the knees. Initial laboratory testing revealed an elevated serum creatinine (Cr) of 2.2mg/dL (0.7-1.3 mg/dL) up from \u3c1.0mg/dL one-year prior, with an estimated Creatinine clearance (CrCl) of 43.4 ml/min using the modified Cockcroft-Gault equation. She was admitted for further workup. A trial of IV fluid hydration overnight worsened her symptoms and additional labs demonstrated hypoalbuminemia, 4+ proteinuria with 1+ blood, and a urine protein/creatinine ratio of 17mg/ mg (\u3c0.2 mg/mg), consistent with nephrotic syndrome. Her CD4 count was 115 cells/mm3 (500-1500 cells/ mm3) with an HIV viral load of 117,148 copies/ml. Based off negative labs for syphilis, hepatitis panel, ANA, complement C3/C4, and diabetes, findings were felt to be consistent with HIV Associated Nephropathy (HIVAN). The patient underwent renal biopsy to confirm the diagnosis and was started on abacavir, darunavir, dolutegravir, lamivudine and ritonavir. Pathology results were consistent with HIVAN with tubulointerstitial nephritis and collapsing glomerulonephropathy and electron microscopy showed diffuse epithelial cell injury with effacement of foot processes and segmental collapse of glomerular capillary loops. Her serum Cr peaked at 2.78 on day 7 of her admission. Her serum Cr and urea-nitrogen steadily improved after just one week of HAART therapy leading to a 42% reduction in serum Cr (Figure 1). Additionally, due to her un-resolving dysphagia the patient underwent esophagogastroduodenoscopy, which was unremarkable. However, she subsequently had esophageal manometry, which was consistent with diffuse esophageal spasm for which she was started on diltiazem

Untargeted LC-HRMS-based metabolomics to identify novel biomarkers of metastatic colorectal cancer

Colorectal cancer is one of the main causes of cancer death worldwide, and novel biomarkers are urgently needed for its early diagnosis and treatment. The utilization of metabolomics to identify and quantify metabolites in body fluids may allow the detection of changes in their concentrations that could serve as diagnostic markers for colorectal cancer and may also represent new therapeutic targets. Metabolomics generates a pathophysiological ‘fingerprint’ that is unique to each individual. The purpose of our study was to identify a differential metabolomic signature for metastatic colorectal cancer. Serum samples from 60 healthy controls and 65 patients with metastatic colorectal cancer were studied by liquid chromatography coupled to high-resolution mass spectrometry in an untargeted metabolomic approach. Multivariate analysis revealed a separation between patients with metastatic colorectal cancer and healthy controls, who significantly differed in serum concentrations of one endocannabinoid, two glycerophospholipids, and two sphingolipids. These findings demonstrate that metabolomics using liquid-chromatography coupled to high-resolution mass spectrometry offers a potent diagnostic tool for metastatic colorectal cancer.This study was supported by a grant (n° 15CC056/DTS17/00081- ISCIII-FEDER) from the Fundación para la Investigación Biosanitaria de Andalucía Oriental (FIBAO) and Roche Pharma S.L. Authors from the Fundación MEDINA acknowledge the receipt of financial support from this public-private partnership of Merck Sharp & Dohme de España S.A. with the University of Granada and Andalusian Regional Government (PIN-0474-2016)

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

From the Desk of the Residency Program Director

It has been another wonderful year in the Jefferson Internal Medicine Residency Program. Our program continues to train the best and brightest residents in the country. This publication is just one example of the passion, dedication and creativity our residents continue to provide to the Jefferson Community. The residents are not just outstanding clinicians but excel in all aspects of medicine including: research, humanities and medical education

From the Desk of the Residency Program Director

The past year has been the most trying many of us have faced as physicians. Despite the challenges, I leave this academic year with hope and gratitude for the future of medicine. The exceptional altruism and dedication portrayed by our colleagues both within and outside the Department of Medicine made this year possible. I\u27ve been overwhelmed by the collegiality and dedication of all our colleagues, but specifically our residents. Despite the challenges, they have risen to every encounter with grace and poise working alongside faculty to support the Jefferson mission: We Improve Lives. In the midst of the chaos, our residents have still completed research, quality improvement projects and contributed to the humanities. This publication is just one example of the passion, dedication and creativity our residents continue to provide to the Jefferson Community. As we hope to enter a post pandemic world in the coming academic year, rest assured we have trained the strongest, most dedicated, compassionate physicians yet. This journal, now in its 22th edition, continues to exemplify the perseverance, inquisitiveness and talent of our Internal Medicine residents. Congratulations to the Editors and all of the residents who contributed to another amazing edition of the Forum. I hope you will enjoy reading it

From the Desk of the Residency Director

It has been another wonderful year in the Jefferson Internal Medicine Residency Program. Our program continues to train the best and brightest residents in the country. During the three years we are fortunate to have them at our program. It is my distinct pleasure to watch them grow into confident, dedicated, compassionate clinicians. The residents are not just outstanding clinicians but excel in all aspects of medicine including research, humanities and medical education

From the Desk of the Residency Program Director

It has been another wonderful year in the Jefferson Internal Medicine Residency Program. Our program continues to train the best and brightest residents in the country. This publication is just one example of the passion, dedication and creativity our residents continue to provide to the Jefferson Community. The residents are not just outstanding clinicians but excel in all aspects of medicine including: research, humanities and medical education