A case report of lactobacillus bacteremia in a patient on chronic parenteral nutrition.

BACKGROUND AND AIMS: Short bowel syndrome is a malabsorption disorder typically caused by the physical loss of a portion of the intestine, whereafter the body is unable to adequately absorb nutrients, fluids, and electrolytes. Many patients with short bowel syndrome are reliant on home parenteral nutrition through a tunneled or peripherally inserted central catheter to ensure sufficient hydration and nutrition. Central venous catheters are a nidus for bacteria, and patients are at risk for infections associated with high levels of morbidity and mortality. Lactobacillus is a ubiquitous microorganism that most frequently colonizes mucosal surfaces such as the gastrointestinal tract. Lactobacillus bacteremia is rare, with limited occurrence in current medical literature. METHODS: Our patient is a 60-year-old female with a past medical history significant for multiple abdominal surgeries resulting in short bowel syndrome, with subsequent dependence on home parenteral nutrition via peripherally inserted central catheter. She had type III chronic intestinal failure, category D2, and stage 1 moderate malnutrition. She was originally admitted to the hospital for a presumed pulmonary embolism and was found to have a deep vein thrombosis in the setting of her peripherally inserted central catheter. On admission her abdominal exam was unremarkable, she denied abdominal pain, and her only gastrointestinal complaint was chronic stable diarrhea. During the hospitalization she developed severe left lower quadrant abdominal pain and noted decreased frequency of her bowel movements. A computed tomography scan of her abdomen revealed chronic stable intestinal distension and was concerning for obstruction. Clinically she remained without symptoms of acute obstruction or ileus. During the admission she became febrile, with blood cultures from her peripherally inserted central catheter and peripheral IV growing out gram negative rods determined to be lactobacillus bacteremia. The infectious disease team recommended removal of her peripherally inserted central catheter given their concern for a line infection. RESULTS: The patient was treated with broad-spectrum antibiotics, did well clinically, and was ultimately discharged following reinsertion of her peripherally inserted central catheter after negative repeat blood cultures. Though she initially did well in the outpatient setting, she ultimately passed away ten months later after re-presenting to the hospital in septic shock, secondary to bowel ischemia and suspected fungemia of her peripherally inserted central catheter. CONCLUSIONS: In this case report, we describe an unusual case of a patient with short bowel syndrome on chronic parenteral nutrition who developed catheter-associated lactobacillus bacteremia - the first reported case in an adult patient on parenteral nutrition.

Testicular Relapse of Primary Diffuse Large B-cell Lymphoma of the Central Nervous System - a Rare Occurrence.

Among diffuse large b-cell lymphoma (DLBCL) subtypes, primary testicular lymphoma (PTL) has one of the highest risks of central nervous system (CNS) relapse. The converse, primary CNS lymphoma (PCNSL) relapse outside the CNS is rare. Molecular analysis has illustrated a genetic similarity between PTL and PCNSL. Here we present a case of a 64-year-old man with testicular relapse of PCNSL 20 months after a complete response to high dose methotrexate-based chemotherapy. His tumor demonstrated a molecular profile similar to both PCNSL and PTL on next generation sequencing, and molecular analysis confirmed common clonal origin of his CNS and testicular lesions. We review prior cases of testicular relapse of PCNSL, which lacked molecular investigations, and discuss the implications of the genomic findings in our patient, including future treatment options.

Diagnosis and Management of Functional Pouch Disorders: A Systematic Review.

BACKGROUND: Functional disorders impart significant morbidity in patients with inflammatory bowel disease who undergo restorative proctocolectomy. OBJECTIVE: This systematic review aimed to summarize the management strategies for various functional disorders of the pouch. DATA SOURCES: A database search of PubMed was conducted to identify relevant clinical studies assessing the management of various functional disorders in patients who underwent restorative proctocolectomy. STUDY SELECTION: Published clinical studies investigating a functional disorder of the pouch in patients who previously underwent a colectomy with ileal pouch-anal anastomosis. INTERVENTIONS: Restorative proctocolectomy was completed in patients with inflammatory bowel disease or other indications such as a diagnosis of familial adenomatous polyposis. MAIN OUTCOME MEASURES: The primary outcomes described in this review include the prevalence of functional disorders of the pouch in patients undergoing restorative proctocolectomy and the relevant management strategies. RESULTS: Ten clinical studies were identified using the predetermined search terms and screened for relevancy to patients with inflammatory bowel disease who previously underwent colectomy with ileal pouch-anal anastomosis. A qualitative summary was developed on the basis of data from these studies and from current guidelines developed for the management of inflammatory bowel disease. LIMITATIONS: This systematic review is limited by the small number and low quality of the clinical studies included as well as the nonquantitative summary of the findings. CONCLUSIONS: Functional disorders of the pouch are likely underdiagnosed. Although a source of significant morbidity, these diseases require additional clinical studies to better elucidate effective management strategies.

Preventive Care and Health Maintenance in Patients with Inflammatory Bowel Disease.

Health maintenance in patients with inflammatory bowel disease (IBD) is essential. In order to achieve clinical and endoscopic remission, many patients will require treatment with steroids, immunomodulators, biologics or small molecules, which place them at a higher risk of serious infections as well as certain malignancies. Some of these adverse events are preventable through vaccination and adherence to cancer screening guidelines, making preventive care and health maintenance in this patient population crucial. Gastroenterologists should take a proactive role in health care maintenance and collaborate with the patient's primary care provider. The aim of this article is to review and provide guidance on preventive care and health maintenance in patients with IBD, including vaccinations, cancer screening, bone health, nutrition, and mental health assessment as well as smoking cessation.

A Rare Case of Esophagitis Dissecans Superficialis Occurring with Barrett's Esophagus.

Esophagitis dissecans superficialis (EDS) is a rare but benign disease of the esophagus often identified endoscopically by sloughing of the superficial esophageal mucosa. We present an asymptomatic 66-year-old patient found to have EDS in the setting of Barrett's esophagus. The association of EDS with Barrett's esophagus has not been previously reported. He was initiated on proton pump inhibitor therapy with rapid and complete resolution of the endoscopic abnormality. This case illustrates the importance of identification of EDS as prognosis relies on prompt diagnosis and treatment.

Seroprevalence of SARS-CoV-2 among Internal Medicine Residents at a Major Academic Medicine Residency Program.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated disease (COVID-19) are a significant cause of morbidity and mortality across the United States. Internal medicine (IM) residents are a critical component of the healthcare workforce yet their seroprevalence of SARS-CoV-2 antibodies is largely unknown. The aim of this research was to ascertain the seroprevalences of SARS-CoV-2 among internal medicine residents during the first peak of COVID-19. METHODS: IM residents were enrolled in a surveillance program that included PCR and antibody testing for SARS-CoV-2 in June 2020. Residents also completed a short questionnaire to obtain sociodemographic information and characterize potential workplace exposure to COVID-19. RESULTS: A total of 101 IM residents participated in the study (out of N=162). Of the 101 samples, three (2.9%) tested positive for SARS-CoV-2 antibodies. No residents tested PCR positive for SARS-CoV-2. DISCUSSION: The implementation of COVID-19 patient cohorting and the incorporation of telemedicine to communicate with hospitalized patients into clinical practice early in the pandemic may have prevented the spread of the virus among the surveyed clinical trainees. CONCLUSION: Despite significant engagement with COVID-19 patients, IM residents demonstrated a low rate of SARS-CoV-2 seroprevalence.

Sulforaphane alters the acidification of the yeast vacuole.

Sulforaphane (SFN) is a compound [1-isothiocyanato-4-(methylsulfinyl)-butane] found in broccoli and other cruciferous vegetables that is currently of interest because of its potential as a chemopreventive and a chemotherapeutic drug. Recent studies in a diverse range of cellular and animal models have shown that SFN is involved in multiple intracellular pathways that regulate xenobiotic metabolism, inflammation, cell death, cell cycle progression, and epigenetic regulation. In order to better understand the mechanisms of action behind SFN-induced cell death, we undertook an unbiased genome wide screen with the yeast knockout (YKO) library to identify SFN sensitive (SFNS) mutants. The mutants were enriched with knockouts in genes linked to vacuolar function suggesting a link between this organelle and SFN's mechanism of action in yeast. Our subsequent work revealed that SFN increases the vacuolar pH of yeast cells and that varying the vacuolar pH can alter the sensitivity of yeast cells to the drug. In fact, several mutations that lower the vacuolar pH in yeast actually made the cells resistant to SFN (SFNR). Finally, we show that human lung cancer cells with more acidic compartments are also SFNR suggesting that SFN's mechanism of action identified in yeast may carry over to higher eukaryotic cells.

Optic neuritis, encephalitis and leptomeningeal enhancement in a patient with anti-MOG antibodies: A case study.

A subset of patients with neuromyelitis optica spectrum disorders are positive for myelin-oligodendrocyte glycoprotein (MOG) antibodies. These patients present with distinct clinical demyelinating syndrome often confused for multiple sclerosis. We describe the case of a patient who initially presented with 10-day history of right-sided retro-orbital headache worse with lateral gaze, photophobia, and subjective decreased visual acuity. After successful treatment on a steroid regimen, this patient represented two weeks following discharge with seizure and was found to have unilateral meningeal T2-FLAIR MRI hyperintensity with associated cortical swelling, a rare finding. CSF studies showed negative anti-AQP4 antibodies and positive anti-MOG antibodies. This case demonstrates that patients presenting with symptoms concerning for NMOSD who are AQP4-Ab-negative should be tested for anti-MOG antibodies for optimized disease management and important prognostic implications.

Characterizing cancer cachexia in the geriatric oncology population.

OBJECTIVES: Cancer cachexia, characterized by weight loss and sarcopenia, leads to a decline in physical function and is associated with poorer survival. Cancer cachexia remains poorly described in older adults with cancer. This study aims to characterize cancer cachexia in older adults by assessing its prevalence utilizing standard definitions and evaluating associations with components of the geriatric assessment (GA) and survival. MATERIALS AND METHODS: Patients with cancer older than 65 years of age who underwent a GA and had baseline CT imaging were eligible in this cross-sectional study. Cancer cachexia was defined by the international consensus definition reported in 2011. Sarcopenia was measured using cross-sectional imaging and utilizing sex-specific cut-offs. Associations between cachexia, sarcopenia, and weight loss with survival and GA domains were explored. RESULTS: Mean age of 100 subjects was 79.9 years (66-95) and 65% met criteria for cancer cachexia. Cachexia was associated with impairment in instrumental activities of daily living (IADL) (p = .017); no significant association was found between sarcopenia or weight loss and IADL impairment. Cachexia was significantly associated with poorer survival (median 1.0 vs 2.1 years, p = .011). CONCLUSIONS: Cancer cachexia as defined by the international consensus definition is prevalent in older adults with cancer and is associated with functional impairment and decreased survival. Larger prospective studies are needed to further describe cancer cachexia in this population.

Research priorities in cancer cachexia: The University of Rochester Cancer Center NCI Community Oncology Research Program Research Base Symposium on Cancer Cachexia and Sarcopenia.

PURPOSE OF REVIEW: Cancer cachexia remains understudied and there are no standard treatments available despite the publication of an international consensus definition and the completion of several large phase III intervention trials in the past 6 years. In September 2015, The University of Rochester Cancer Center NCORP Research Base led a Symposium on Cancer Cachexia and Sarcopenia with goals of reviewing the state of the science, identifying knowledge gaps, and formulating research priorities in cancer cachexia through active discussion and consensus. RECENT FINDINGS: Research priorities that emerged from the discussion included the implementation of morphometrics into clinical decision making, establishing specific diagnostic criteria for the stages of cachexia, expanding patient selection in intervention trials, identifying clinically meaningful trial endpoints, and the investigation of exercise as an intervention for cancer cachexia. SUMMARY: Standardizing how we define and measure cancer cachexia, targeting its complex biologic mechanisms, enrolling patients early in their disease course, and evaluating exercise, either alone or in combination, were proposed as initiatives that may ultimately result in the improved design of cancer cachexia therapeutic trials.

Prostate Cancer in Elderly Men: Screening, Active Surveillance, and Definitive Therapy.

Prostate cancer (PCa) is a common medical condition in the United States, with an estimated 16% of men receiving a diagnosis during their lifetime. Although it is the second leading cause of cancer-specific deaths among men, PCa will not be the cause of death for most men who are diagnosed with it. Although there are notable improvements recently, the relative dearth of high-quality data concerning PCa screening and treatment in older men calls for a thoughtful approach to evaluating such men for screening, diagnosis, and treatment options. This article offers guidance to an approach here.

Associations between a patient-reported outcome (PRO) measure of sarcopenia and falls, functional status, and physical performance in older patients with cancer.

OBJECTIVE: In older patients with cancer, we aimed to investigate associations between a patient-reported outcome measure for sarcopenia (SarcoPRO) and the Short Physical Performance Battery (SPPB), self-reported falls, and limitations in instrumental activities of daily living (IADLs). MATERIALS AND METHODS: Assessments were conducted as part of the initial evaluation of older, often frail, patients with cancer seen in the Specialized Oncology Care and Research in the Elderly (SOCARE) clinic. Univariate associations were evaluated using Spearman's correlation and Wilcoxon sign ranked tests. Logistic regressions were used to identify associations of clinical factors and SarcoPRO scores or SPPB scores with falls and IADL limitations. RESULTS: In total, 174 older patients with cancer were evaluated. A moderate correlation was found between the SarcoPRO and the SPPB (ρ=0.62). After adjusting for multiple clinical factors, neither the SarcoPRO nor the SPPB were associated with falls. In contrast, both higher SarcoPRO (i.e., worse) and lower SPPB (i.e., worse) scores were associated with limitations in IADLs (odds ratio for one unit change in predictor: SarcoPRO: 1.06, p<0.0001; SPPB: 0.71, p=0.003, respectively). Models using the SarcoPRO and SPPB explained similar amounts of variability in association with IADL limitations (AUC: 0.88 vs. 0.87, respectively). CONCLUSIONS: The SarcoPRO was moderately associated with the SPPB, an objective measure of physical performance, and was associated with limitations in IADLs. Thus, older patients with cancer who present with IADL limitations should be screened for sarcopenia. The SarcoPRO shows promise as a measure for screening as well as outcome assessment for research on sarcopenia.

Bladder cancer in the elderly patient: challenges and solutions.

Bladder cancer (BC) is an age-associated malignancy with increased prevalence in the elderly population. Elderly patients are a vulnerable population at increased risk for treatment-related toxicity secondary to medical comorbidities and geriatric syndromes. As a result, this population has been historically undertreated and suffers worse disease-specific outcomes than younger patients with BC. Recognition of this disparity has led to efforts to individualize treatment decisions based on functional status rather than chronologic age in an effort to optimize the use of curative therapies for the fit elderly and modify treatments to reduce the risk of toxicity and disease-related morbidity in vulnerable or frail patients. The comprehensive geriatric assessment is a decision framework that helps to balance underlying health considerations and risks of therapy with aggressiveness of the cancer. Development of systemic therapies with increased efficacy against BC and reduced toxicity are eagerly awaited, as are techniques and interventions to reduce the morbidity from surgery and radiation for patients with BC.

A second target of benzamide riboside: dihydrofolate reductase.

Dihydrofolate reductase (DHFR) is an essential enzyme involved in de novo purine and thymidine biosynthesis. For several decades, selective inhibition of DHFR has proven to be a potent therapeutic approach in the treatment of various cancers including acute lymphoblastic leukemia, non-Hodgkin's lymphoma, osteogenic sarcoma, carcinoma of the breast, and head and neck cancer. Therapeutic success with DHFR inhibitor methotrexate (MTX) has been compromised in the clinic, which limits the success of MTX treatment by both acquired and intrinsic resistance mechanisms. We report that benzamide riboside (BR), via anabolism to benzamide adenine dinucleotide (BAD) known to potently inhibit inosine monophosphate dehydrogenase (IMPDH), also inhibits cell growth through a mechanism involving downregulation of DHFR protein. Evidence to support this second site of action of BR includes the finding that CCRF-CEM/R human T-cell lymphoblasic leukemia cells, resistant to MTX as a consequence of gene amplification and overexpression of DHFR, are more resistant to BR than are parental cells. Studies of the mechanism by which BR lowers DHFR showed that BR, through its metabolite BAD, reduced NADP and NADPH cellular levels by inhibiting nicotinamide adenine dinucleotide kinase (NADK). As consequence of the lack of NADPH, DHFR was shown to be destabilized. We suggest that, inhibition of NADK is a new approach to downregulate DHFR and to inhibit cell growth.

Tissue-specific signatures of activating PIK3CA and RAS mutations in carcinosarcomas of gynecologic origin.

OBJECTIVES: Gynecologic carcinosarcoma is an aggressive malignancy that requires more effective treatment approaches. However, therapeutic implications regarding the specific gynecologic site of origin and the admixture of carcinomatous and sarcomatous elements that define this tumor remain uncertain. Therefore, broad genotyping was performed to identify tissue-specific somatic mutational profiles that may help direct targeted therapies in this complex neoplasia. METHODS: Genotyping was conducted on primary gynecologic carcinosarcomas arising from various disease sites (uterus, ovary, fallopian tube, vagina) and within isolated histological subcomponents. Nucleic acids extracted from diagnostic tissue were used in a genotyping platform that simultaneously queried >120 common mutations across 14 cancer genes. Mutational status was correlated with clinical variables using logistic regression and Kaplan-Meier survival estimates. RESULTS: Cancer gene mutations were identified in 46% of the 52 patient cohort and include TP53 (23%), PIK3CA (19%), KRAS (15%), CTNNB1 (4%) and NRAS (2%). Mutation in a single gene was observed in 31% of patient samples, while synchronous mutations involving 2 and 3 genes were noted in 13% and 2% of samples, respectively. Comparative evaluation of the carcinomatous and sarcomatous elements within a tumor demonstrated a similar mutation signature. Mutations in PIK3CA, KRAS and NRAS were exclusive to tumors of uterine origin and age-adjusted Cox proportional hazards modeling associated advanced age, stage and TP53 mutations with decreased survival in the uterine subset. CONCLUSION: While carcinosarcomas across gynecologic disease sites are histologically similar, therapeutically relevant mutations in the mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways predominated in carcinosarcomas arising in the uterus.