Ochsner Clinic Research Articles

Editorial introductions.

Editorial introductions.

William Forrest Johnston, MD, FACS, FASCRS.

William (Forrest) Johnston, MD, is a Colon and Rectal Surgeon and Assistant Program Director for the Colon and Rectal Surgery Fellowship at the Ochsner Clinic in New Orleans, LA. He was born in Winston-Salem, North Carolina, and moved to Galveston, Texas, at a young age. Living on a small island on the Gulf Coast, he enjoyed surfing and working for the Beach Patrol. He then went to Wake Forest University in North Carolina for under graduation, where he majored in Chemistry and Religion. Next, he went back to Texas to join Medical School at Baylor College of Medicine in Houston before moving to University of Virginia for his General Surgery residency. Initially he wanted to be a vascular surgeon and performed extensive research in that field. When he finished with the laboratory work, he changed his path to pursue colorectal surgery. He went on to complete Colorectal Surgery fellowship at the Lahey Clinic in Burlington, Massachusetts. Following his fellowship, he began his first faculty position at the Ochsner Clinic, where he has served since 2017.

Editorial introductions.

Editorial introductions.

Mentorship: Remembering My Mentor Guy Caldwell and His Mentor Michael Hoke

I had the great fortune to spend my 4 years of orthopedics training (1964-1968) at the Ochsner Clinic. My chiefs, Dr Morris and then Dr Dunn, were excellent surgeons and teachers. They were extremely kind to house staff and patients. I had the unique added privilege to spend part of my first year as

Editorial introductions.

Editorial introductions.

1225-P: Prevalence of Obesity and Bariatric Surgery Use in T1DM

With the increased prevalence of obesity, the phenotype of T1DM has changed. The prevalence of obesity in pts with T1DM is increasing, but there is limited data on how it compares to pts with T2DM. Bariatric surgery is effective for glycemic, weight and cardiometabolic risk surrogate amelioration in T2DM with obesity. However, the role of bariatric surgery in T1DM with obesity is largely unexplored. Retrospective chart review was done of patients with T1DM seen in Ochsner clinic system from January 2015 to January 2018. Obesity prevalence was quantified. Pts with bariatric surgery (BS) history were identified and their cardiometabolic surrogates pre and post BS were obtained. This was compared to pts with T2DM over the same time period. More in depth chart analysis of 300 pts from this cohort of T1DM pts was done to better characterize features of these pts 10, 282 pts with T1DM were identified over the observation period vs. 146,617 pts with T2DM. The prevalence of obesity in the T1DM cohort was 48.3% vs. 59.7% in the T2DM cohort while the prevalence of morbid obesity was 14.5% vs. 19% in the T1DM vs. T2DM groups. The number of pts who had bariatric surgery was 25 vs. 307 in the T1DM vs. T2DM groups. The percentage utilization of bariatric surgery as an intervention for obesity was very low in both cohorts (0.5 vs. 0.35 % in the T1DM vs. T2DM groups). Of the 300 pts with detailed chart review, actual diabetes subtypes were 163 (54%) T1DM, 43 (14.3%) as LADA, 1 (0.3%) as maturity-onset diabetes of the young, 2 (0.7%) as type 1.5 (essentially LADA), 8 (2.7%) as type 1+2 (T1DM with obesity and insulin resistance), 11 (3.7%) deceased, 71 (23.7%) as T2DM that had been miscoded as T1DM. For subsequent analyses, T1DM, LADA, type 1.5, and type 1+2 were included in the T1DM cohort. The weight and cardiometabolic surrogate changes in T1DM subjects were inconsistent and less marked than in T2DM subjects. Obesity prevalence in T1DM is close to that in T2DM and the use of bariatric surgery as an intervention remains very low both in T1DM and T2DM pts with obesity. Disclosure W. A. West: None. K. G. Romo: None. G. I. Uwaifo: None.

Frequency of Symptoms and Asymptomatic SARS-CoV-2 Infection in Louisiana, USA

Background: While many surveillance studies of seroprevalence to SARS-CoV-2 rely on remnant blood samples obtained as medical waste, representative, prospective collection allows for analysis of a representative cross-section of symptomatic and asymptomatic presentation of infection in the community. Louisiana, and particularly New Orleans, were hard-hit in the early phase of the pandemic, and an ongoing outbreak was occurring in Baton Rouge throughout July.Methods: A representative, cross-sectional sample of subjects from two cities in Louisiana were sent to testing sites to complete a verbal consent, survey, nasopharyngeal swab, and blood draw. Swabs were tested for active viral shedding (PCR) and blood was tested for immunoglobulin G (IgG) specific to SARS-CoV-2.Findings: Anosmia was extremely predictive for a positive test (40·6% of those with anosmia tested positive, OR: 13·6; CI 10·1, 18·3) and 47·3% of the sample experienced no symptoms at all. A lower quantity of virus was noted during the contagious phase of infection in asymptomatic compared to symptomatic individuals. Symptom presentation clustered into three groups; low/no symptoms (0·4±0·9 symptoms on average), highly symptomatic (7·5±1·9) or moderately symptomatic (4·0±1·5). The probability of reporting symptoms changed with age; those under age 60 had a >50% probability of reporting symptoms while those 60 years and older had Interpretation: Anosmia should be used as a screening criterion to differentiate from other illnesses, and, given the high ratio of asymptomatic individuals, mask mandates should be enforced. Asymptomatic individuals should be tested with cause.Funding: This study was funded by ReNOLA, Ochsner Health, the Baton Rouge Area Foundation, Louisiana COVID-19 Health Equity Task Force, and The Humana Foundation, the Blue Cross and Blue Shield of Louisiana Foundation, Healthy Blue, the Huey and Angelina Wilson Foundation, and the Irene W. and C.B. Pennington Foundation.Declaration of Interests: The authors have no other conflicts of interest to report.Ethics Approval Statement: This study was approved by the Ochsner Clinic Foundation Institutional Review Board #2020·163.

COVID-19 Patients Form Memory CD8+ T Cells that Recognize a Small Set of Shared Immunodominant Epitopes in SARS-CoV-2

Development of effective strategies to detect, treat, or prevent COVID-19 requires a robust understanding of natural immunity to SARS-CoV-2, including the cellular response mediated by T cells. We used an unbiased, genome-wide screening technology to comprehensively identify the specific epitopes in SARS-CoV-2 that are recognized by the memory CD8+ T cells of 25 COVID-19 convalescent patients. For each of six HLA types examined, patient T cells recognized 3–8 immunodominant epitopes that are broadly shared among patients, and single-cell sequencing revealed common structural features of TCRs recognizing these epitopes. We detected minimal cross-reactivity to the endemic coronaviruses that cause the common cold, arguing that pre-existing immunity to other coronaviruses does not significantly shape CD8+ T cell responses to SARS-CoV-2. Notably, only 3 of the 29 immunodominant epitopes we identified reside in the Spike protein, highlighting the need for second-generation vaccines that recapitulate natural CD8+ T cell immunity to SARS-CoV-2.Funding: This work was supported by TScan Therapeutics, a privately-owned biotechnology company.Ethical Approval: The study was conducted in accordance with the Declaration of Helsinki (1996), approved by the Atlantic Health System Institutional Review Board and the Ochsner Clinic Foundation Institutional Review Board and registered at clinicaltrials.gov (# NCT04397900).

Medical Student Mobilization During a Pandemic: The Ochsner Clinical School Response to COVID-19.

In March 2020, the World Health Organization (WHO) declared that a novel coronavirus (COVID-19) had reached pandemic status. The United States experienced a rapid increase in cases that prompted statewide shutdowns, and hospitals quickly became overwhelmed with critically ill patients. Patient

Answering the Call: Medical Students Reinforce Health System Frontlines Through Ochsner COVID-19 Hotline.

On Saturday evening, March 14, 2020, third- and fourth-year medical students at the Ochsner Clinical School (OCS) received an urgent email from their school administration: Due to the growing COVID-19 pandemic, there have been over 1,500 calls to the Ochsner Call Line with over a 3-hour wait time

Editorial introductions

Editorial introductions

Analysis of the prognostic utility of the cell cycle progression (CCP) score generated from needle biopsy in men treated with definitive therapy

BackgroundAccurate risk stratification can help guide appropriate treatment decisions in men with localized prostate cancer. Here, we evaluated the independent ability of the molecular cell cycle progression (CCP) score and the combined cell-cycle clinical risk (CCR) score to predict 10-year risk of progression to metastatic disease in a large, pooled analysis of men with definitively treated prostate cancer.MethodsThe pooled analysis included 1,062 patients from four institutions (Martini Clinic, Durham VA Medical Center, Intermountain Healthcare, Ochsner Clinic) treated definitively for localized prostate cancer by either radical prostatectomy or radiotherapy (brachytherapy or external beam radiotherapy ± hormone therapy). The CCP score was determined using the RNA expression of 46 genes from archival formalin-fixed paraffin-embedded biopsy tissue. The CCR score was calculated using a predefined linear combination of the CCP score and the Cancer of the Prostate Risk Assessment (CAPRA) score. The scores were evaluated for association with 10-year risk of metastatic disease following definitive therapy after adjusting for other clinical variables.ResultsThe CCP score was strongly associated with 10-year risk of metastatic disease in multivariable analysis [Hazard Ratio per unit score = 2.21; 95% confidence interval (CI) 1.64, 2.98; p = 1.9 × 10−6] after adjusting for CAPRA, treatment type, and cohort. CCR was also highly prognostic (Hazard Ratio per unit score = 4.00; 95% CI 2.95, 5.42; p = 6.3 × 10−21). There was no evidence of interaction between CCP or CCR and cohort (p = 0.79 and p = 0.86, respectively) or treatment type (p = 0.55 and p = 0.78, respectively). Observed patient CCR-based predicted risks for metastatic disease by 10 years ranged from 0.1 to 99.4%, (IQR 0.7%, 4.6%).ConclusionsBoth CCP and CCR scores provided independent prognostic information for predicting progression to metastatic disease after both surgery and radiation. These results further demonstrate their potential use as a risk stratification tool in patients with newly-diagnosed prostate cancer.

Commentary: The Tulane University-Ochsner Clinic Foundation Neurosurgery Program: 75 Years of History, Including the Program's Rebirth After Katrina.

Neurosurgery training in New Orleans began when Dr Dean Echols became the head of Neurosurgery for the Ochnser Clinic and Charity Hospital in 1944. The oldest in Louisiana, the Tulane-Ochsner program has trained 63 board-certified neurosurgeons since its founding, including 5 chairmen. The program has a colorful history linked to New Orleans. Its residents have enjoyed training at Charity Hospital, Tulane Hospital and Clinics, Veterans Affairs Medical Center, and the Ochsner Clinic Foundation.

Blood Transfusion in Gynecologic Surgery: Adherence to Guidelines in Academic and Community-Based Practice [19H

INTRODUCTION: Blood transfusions are commonly administered during gynecological surgery. Traditionally, multiple units of packed red blood cells (pRBC) were transfused simultaneously, with a goal hemoglobin level (Hb) of 10 g/dL. However, research shows that this is associated with worse patient outcomes. In 2015, Ochsner implemented restrictive transfusion guidelines to improve patient outcomes and reduce costs. This protocol recommends transfusing one unit pRBC at a time, with an Hb goal of 7 (8 g/dL in patients with acute coronary syndrome or who are symptomatic). A retrospective study was conducted to assess gynecologists' understanding and adherence to these guidelines in academic versus community practices. METHODS: IRB approval was obtained from the Ochsner Clinic Foundation. Gynecologists completed an anonymous survey assessing their knowledge of Ochsner's transfusion guidelines. To evaluate adherence to the guidelines, a retrospective chart review was conducted on gynecologic surgeries that utilized pRBC transfusion in 2017. RESULTS: Compared to 2016, awareness of Ochsner's transfusion guidelines amongst practitioners (81.36% vs 72.7%) was increased. Knowledge of the guideline parameters also improved. 175 charts were reviewed from community (n=91), academic (n=53), and oncologic (n=31) sites. Academic sites adhered to guidelines more often than community sites (49% vs 31.8%, P<.017). The most common departure from the guidelines was transfusing multiple units of pRBC at once. CONCLUSION: Although most practitioners were aware of Ochsner's transfusion protocol, they violated these guidelines in practice. Despite overall knowledge of the guidelines, there continues to be a lack of adherence amongst providers. Further studies are needed to identify and address reasons for non-adherence.

Psychological assessment of candidates for bariatric surgery

Nowadays, the number of bariatric surgery for treating morbid obesity is significant. There is strong evidence about the influence of mental state (depression, anxiety, eating disorder, etc.) on patient's cooperation with the medical team and the outcome, and on the short or long-term effectiveness of surgery. However, no protocol or recommendation exist for screening patients before bariatric procedures in Hungary. Thus, even if the surgeon or the hospital requires psychological expertise, neither doctors are familiar with the expectable results of such an expertise, nor psychologists know exactly what the most important areas are to talk through with patients. This article shortly reviews the mostly used bariatric surgery procedures and presents a protocol that was developed by the Ochsner Clinic, New Orleans in detail. Based on the protocol, the core parts of the psychological interview are the following: reasons for seeking surgery (I.), weight and diet history (II.), current eating behaviors (III.), understanding of the surgery and its associated lifestyle changes (IV.), social supports (V.), and history and psychiatric symptoms (current and past) (VI.). The original protocol was completed with newer, more recent studies, statements, and with examples by the authors. Orv Hetil. 2019; 160(12): 448-455.

The Ochsner Legacy

One of the iconic families in American surgery is the Ochsners. The youngest son of Swiss immigrants, Henry Ochsner (1877-1902) was the first to enter the medical profession. His promising internship at the Johns Hopkins Hospital ended when he died of cholera, a tragedy deeply felt by his mentor William Osler. On another branch of the family tree, Albert Ochsner (1858-1925) wrote authoritative textbooks on surgery and became president of the ACS and the American Surgical Association. His most significant achievement may have been his mentorship of his cousin's son Alton (1896-1981), guiding his medical education and training in surgery. The younger Ochsner succeeded Rudolph Matas as chair of surgery at Tulane University at the age of only 31 years. Under his leadership, Charity Hospital in New Orleans became a leading program for surgical training and Tulane earned a reputation for clinical excellence. Ochsner and four partners from the Tulane faculty created a multidisciplinary clinic to attract patients from a wider area, a facility that would become today's Ochsner Clinic. His son John (1927-2018) followed him in the profession and received specialty training in cardiovascular surgery under Michael DeBakey in Houston, a Tulane graduate and an Ochsner trainee. John Ochsner returned to the Ochsner Clinic to establish a major cardiothoracic and vascular surgery program. Further generations of the Ochsner family continued the family legacy in surgery and medicine, exemplified by M. Gage Ochsner (1954-2013), Alton's grandson and John's nephew, who became a leading traumatologist and surgical educator in Savannah.

Abstract B027: Antitumor effects of the programmed death receptor-1 and the programmed death-ligand 1 blockade in human colorectal carcinoma in a humanized orthotopic mouse model

Abstract Background: The immune system plays an important role in tumor immune surveillance and progression. Immune checkpoint blockade is a new approach for cancer immunotherapy. The programmed death receptor-1 (PD-1) and the programmed death-ligand 1 (PD-L1) are immune checkpoint molecules and their expression results in negative regulation of T-cells primarily within the tumor microenvironment by preventing the killing of cancer cells by cytotoxic T-lymphocytes. Antibody blocking of the PD-1/PD-L1 signal exhibits promising therapeutic effects in non-small cell lung cancer and melanoma in patients. Due to its early success, more trials have been conducted to evaluate their efficacy for different tumors. We have developed a patient-derived orthotopic xenograft mouse model for colorectal carcinoma (CRC). Here, we investigate the potential efficacy of PD-1/PD-L1 blockade in our humanized orthotopic mouse models for human CRC. Methods: All studies were conducted under approved guidelines of the Institutional Animal Care and Use Committee and the Investigative Review Board of Ochsner Clinic Foundation. Humanized mice were established by intraperitoneal injection of donor human peripheral blood mononuclear cells (PBMCs) into recombinase activating gene 2 (Rag2) and common cytokine receptor gamma chain gene (IL2Rγ) double knockout (Rag2-/-/IL2Rγ-/-) Rag2 mice. Luciferase-tagged CRC cells were injected intra-rectally into Rag2 mice. One group of mice received a combination of anti-PD-1 and anti-PD-L1 antibodies (nivolumab, 200 µg/mouse and atezolizumab, 200 µg/mouse, intravenous injection) once a week for 3 weeks. Tumor growth was measured weekly by bioluminescent imaging (BLI). At necropsy, the CRC tumor weights were measured. Human CD45+ hematopoietic cells, CD4+ and CD8+ T-cells, and CD20+ B cells were detected in peritoneal lavage, blood, and tumor by flow cytometry. The presence of human immune cells (humanization) and tumor-infiltrating human lymphocytes was further confirmed by immunohistochemistry staining on paraffin-embedded tissue slides of mouse spleen and tumor, respectively. Results: Blood from mice receiving human PBMCs contained on average 31.4% CD45+ human cells (n=9) when tested by FACS analysis. Smaller tumor growth was observed in mice given PBMCs. This may be due to alloreactivity based on the recognition of MHC alloantigens in the transplanted tumor cells. However, mice further treated with the combination therapy of anti-PD-1 and anti-PD-L1 antibodies exhibited better antitumor response as well as less development of lung metastases compared to untreated controls. On average, tumor weight was reduced by 36% and lung metastases measured by ex-vivo BLI was reduced by 82% (n=5). In addition, circulating CD326+ tumor cells were reduced by 21% and CD3, CD4, CD8 and CD20 positive human lymphocytes were also reduced in the combination treatment group. Conclusion: Our study provides preclinical evidence of establishment of humanized Rag2 mice to be used as an orthotopic xenograft model for CRC; and treatment benefit for CRC through targeting immune checkpoint molecules PD-1 and PD-L1. The effect of immune checkpoint blockade in combination with conventional chemotherapy using CRC patient-derived specimens and PBMCs from MHC matched donors or autologous PBMCs will be further investigated. Citation Format: Li Li, Xin Zhang, Grace Maresh, Linh Hellmers, Avi Patel, Ravan Moret, Sarah Cohen, David Margolin. Antitumor effects of the programmed death receptor-1 and the programmed death-ligand 1 blockade in human colorectal carcinoma in a humanized orthotopic mouse model [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B027.

A Phase 2 Study of Actinium-225 (225Ac)-Lintuzumab in Older Patients with Untreated Acute Myeloid Leukemia (AML) - Interim Analysis of 1.5 µci/Kg/Dose

A Phase 2 Study of Actinium-225 (225Ac)-Lintuzumab in Older Patients with Untreated Acute Myeloid Leukemia (AML) - Interim Analysis of 1.5 µci/Kg/Dose

Comparison of the Prognostic Utility of the Cell Cycle Progression Score for Predicting Clinical Outcomes in African American and Non-African American Men with Localized Prostate Cancer

BackgroundBetter prostate cancer risk stratification is necessary to inform medical management, especially for African American (AA) men, for whom outcomes are particularly uncertain. ObjectiveTo evaluate the utility of both a cell cycle progression (CCP) score and a clinical cell-cycle risk (CCR) score to predict clinical outcomes in a large cohort of men with prostate cancer highly enriched in an AA patient population. Design, setting, and participantsPatients were diagnosed with clinically localized adenocarcinoma of the prostate and treated at The Ochsner Clinic (New Orleans, LA, USA) from January 2006 to December 2011. CCP scores were derived from archival formalin-fixed, paraffin-embedded biopsy tissue. CCR scores were calculated as the combination of molecular (CCP score) and clinical (Cancer of the Prostate Risk Assessment [CAPRA] score) components. InterventionActive treatment (radical prostatectomy, radiation therapy alone, or radiation and hormone therapy) or watchful waiting. Outcome measurements and statistical analysisThe primary outcome was progression to metastatic disease. Association with outcomes was evaluated via Cox proportional hazards survival analysis and likelihood ratio tests. Results and limitationsThe final cohort included 767 men, of whom 281 (36.6%) were AA. After accounting for ancestry, treatment, and CAPRA in multivariable analysis, the CCP score remained a significant predictor of metastatic disease (hazard ratio [HR] 2.04; p<0.001), and there was no interaction with ancestry (p=0.20) or treatment (p=0.09). The CCR score was highly prognostic (HR 3.86; p<0.001), and as with the CCP score, there was no interaction with ancestry (p=0.24) or treatment (p=0.32). Limitations include the retrospective study design and the use of self-reported ancestry information. ConclusionsA CCR score provided significant prognostic information regardless of ancestry. The findings demonstrate that AA men in this study cohort appear to have similar prostate cancer outcomes to non-AA patients after accounting for all available molecular and clinicopathologic variables. Patient summaryIn this study we evaluated the ability of a combined molecular and clinical score to predict the progression of localized prostate cancer. We found that the combined molecular and clinical score predicted progression to metastasis regardless of patient ancestry or treatment. This suggests that the combined molecular and clinical score may be a valuable tool for determining the risk of metastasis in men with newly diagnosed prostate cancer in order to make appropriate treatment decisions.

Group A Streptococcus.

1. Monika L. Dietrich, MD* 2. Russell W. Steele, MD†,‡ 1. *Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA 2. †Department of Pediatrics, Ochsner Health Center for Children, New Orleans, LA 3. ‡University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA * Abbreviations: ANF: : acute necrotizing fasciitis ARF: : acute rheumatic fever GAS: : group A Streptococcus IVIG: : intravenous immunoglobulin MRSA: : methicillin-resistant Staphylococcus aureus MSSA: : methicillin-susceptible S aureus PANDAS: : pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections PSGN: : poststreptococcal glomerulonephritis STSS: : streptococcal toxic shock syndrome 1. Clinical prediction rules for group A Streptococcus pharyngitis are unreliable in children, and unless viral etiology is strongly suspected, throat swab with a rapid antigen detection test should be performed. 2. Avoid “proof of cure” cultures when treating pharyngitis. 3. Clindamycin is important in invasive group A Streptococcus infection for toxin mediation but should not be used alone secondary to possible resistance. After completing this article, readers should be able to: 1. Understand the epidemiology, transmission, and major virulence factors of group A Streptococcus (GAS) infections. 2. Plan the appropriate diagnostic evaluation of suspected GAS infection. 3. Recognize the clinical features of, and major complications associated with, invasive and noninvasive GAS infections. 4. Plan appropriate management for a patient with a GAS infection. In 1933, Rebecca Lancefield changed our understanding of β-hemolytic streptococci by developing a system of serologic classification based on the carbohydrate composition of cell wall antigens. Of these organisms, the most significant in human pathogenicity is group A Streptococcus (GAS), otherwise known as Streptococcus pyogenes . (1) GAS is responsible for an impressively wide variety of clinical manifestations, from noninvasive infections, such as pharyngitis, scarlet fever, erysipelas, and cellulitis, to invasive disease, including sepsis, streptococcal toxic shock syndrome (STSS), and necrotizing fasciitis (Table 1). It has also been linked to multiple nonsuppurative complications including acute rheumatic fever (ARF), poststreptococcal glomerulonephritis (PSGN), and the controversial pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Globally, an estimated 18 million people are suffering from a serious GAS-related illness, with about 1.78 million new cases annually. Hundreds of millions of people develop less serious GAS infection every year, placing a massive burden on healthcare systems. The …