Bilateral Endogenous Endophthalmitis With Klebsiella pneumoniae Bacteremia Secondary to Hepatic Abscess.

Klebsiella endophthalmitis is a rare cause of endogenous endophthalmitis, with very few cases documented in the US. We present a male patient in his 60s with a history of latent tuberculosis who presented to the hospital with complaints of acute bilateral vision loss that began three days prior to admission. The workup revealed Klebsiella pneumoniae bacteremia, a large hepatic abscess, severe orbital swelling, and acute angle-closure glaucoma. The patient received intravitreal antibiotics, intravenous antibiotics, a hepatic drain, intraocular pressure-lowering medications, and steroids. Bacteremia was cleared with antibiotics and source control; however, vision loss did not improve. This case emphasizes the acuity and severity of Klebsiella endogenous endophthalmitis and outlines the need for immediate intervention with the onset of symptoms to prevent irreversible vision loss.

PCSK9 Inhibitors and Anthracyclines: The Future of Cardioprotection in Cardio-Oncology.

The field of cardio-oncology is an expanding frontier within cardiovascular medicine, and the need for evidence-based guidelines is apparent. One of the emerging focuses within cardio-oncology is the concomitant use of medications for cardioprotection in the setting of chemotherapy regimens that have known cardiovascular toxicity. While clinical trials focusing on cardioprotection during chemotherapy are sparse, an inaugural trial exploring the prophylactic potential of Sodium-Glucose Cotransporter-2 inhibitors (SGLT2is) for anthracycline (ANT)-induced cardiotoxicity has recently commenced. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, though less studied in this oncology demographic, have exhibited promise in preclinical studies for conferring cardiac protection during non-ischemic toxic insults. While primarily used to reduce low-density lipoprotein, PCSK9 inhibitors exhibit pleiotropic effects, including the attenuation of inflammation, reactive oxygen species, and endothelial dysfunction. In ANT-induced cardiotoxicity, these same processes are accelerated, resulting in premature termination of treatment, chronic cardiovascular sequelae, heart failure, and/or death. This review serves a dual purpose: firstly, to provide a concise overview of the mechanisms implicated in ANT-induced cardiotoxicity, and, finally, to summarize the existing preclinical data supporting the theoretical possibility of the cardioprotective effects of PCSK9 inhibition in ANT-induced cardiotoxicity.

Concurrent Stage III Unresectable Duodenal Adenocarcinoma and Metastatic Gastrointestinal Stromal Tumor Treated With Combination of Imatinib and mFOLFIRI.

Cases of concurrent duodenal adenocarcinoma and gastrointestinal stromal tumors (GISTs) are rare, and only a few have been reported. While some cases of other synchronous primary tumors with GIST have been reported, no shared mutations have been consistently found, creating challenges in selecting chemotherapy in cases of inoperable tumors. Here, we presented a case of a stage IIIA locally advanced/unresectable duodenal adenocarcinoma with concurrent metastatic small bowel GIST successfully being treated with combined imatinib and modified folinic acid, 5-fluorouracil, and irinotecan (mFOLFIRI) regimen.

Myeloid-Derived Suppressor Cells: Therapeutic Target for Gastrointestinal Cancers.

Gastrointestinal cancers represent one of the more challenging cancers to treat. Current strategies to cure and control gastrointestinal (GI) cancers like surgery, radiation, chemotherapy, and immunotherapy have met with limited success, and research has turned towards further characterizing the tumor microenvironment to develop novel therapeutics. Myeloid-derived suppressor cells (MDSCs) have emerged as crucial drivers of pathogenesis and progression within the tumor microenvironment in GI malignancies. Many MDSCs clinical targets have been defined in preclinical models, that potentially play an integral role in blocking recruitment and expansion, promoting MDSC differentiation into mature myeloid cells, depleting existing MDSCs, altering MDSC metabolic pathways, and directly inhibiting MDSC function. This review article analyzes the role of MDSCs in GI cancers as viable therapeutic targets for gastrointestinal malignancies and reviews the existing clinical trial landscape of recently completed and ongoing clinical studies testing novel therapeutics in GI cancers.

A Novel Receivership Model for Transition of Young Adults With Diabetes: Experience From a Single-center Academic Transition Program.

OBJECTIVE: The transition from pediatric to adult care for young adults with diabetes represents an important but often challenging time characterized by a shift from a family-centered care model of pediatrics to a patient-centered care model of adult medicine. We developed a structured transition program based on an adult receivership model at a large academic medical center to improve care coordination and patient satisfaction with the transition process. METHODS: From 2016 to 2020, we implemented a series of quality improvement efforts for young adults aged 18 to 23 years with diabetes by incorporating best practices from the American Diabetes Association guidelines on care for emerging adults. We measured transition orientation attendance, patient satisfaction, hemoglobin A1c (HbA1c) pre- and post-transfer, and care gaps to determine the impact of the program. RESULTS: In this study, 307 individuals with type 1 diabetes and 16 individuals with type 2 diabetes were taken care of by the adult endocrinology department at the University of Michigan between January 1, 2016 and October 31, 2020. We observed high attendance rates (86% among internal transfers) and favorable patient satisfaction scores for the transition orientation session. Despite the glycemic challenges posed during the transition, HbA1c modestly yet significantly improved 1-year after transfer (-0.4%, P < .01). CONCLUSION: We successfully established and maintained a young adult diabetes transition program using a quality improvement approach. Future work will focus on reducing care gaps at the time of transfer, assessing long-term retention rates, and enhancing care coordination for patients referred from outside the health network.

3D ultrastructural analysis of α-granule, dense granule, mitochondria, and canalicular system arrangement in resting human platelets.

BACKGROUND: State-of-the-art 3-dimensional (3D) electron microscopy approaches provide a new standard for the visualization of human platelet ultrastructure. Application of these approaches to platelets rapidly fixed prior to purification to minimize activation should provide new insights into resting platelet ultrastructure. OBJECTIVES: Our goal was to determine the 3D organization of α-granules, dense granules, mitochondria, and canalicular system in resting human platelets and map their spatial relationships. METHODS: We used serial block face-scanning electron microscopy images to render the 3D ultrastructure of α-granules, dense granules, mitochondria, canalicular system, and plasma membrane for 30 human platelets, 10 each from 3 donors. α-Granule compositional data were assessed by sequential, serial section cryo-immunogold electron microscopy and by immunofluorescence (structured illumination microscopy). RESULTS AND CONCLUSIONS: α-Granule number correlated linearly with platelet size, while dense granule and mitochondria number had little correlation with platelet size. For all subcellular compartments, individual organelle parameters varied considerably and organelle volume fraction had little correlation with platelet size. Three-dimensional data from 30 platelets indicated only limited spatial intermixing of the different organelle classes. Interestingly, almost 70% of α-granules came within ≤35 nm of each other, a distance associated in other cell systems with protein-mediated contact sites. Size and shape analysis of the 1488 α-granules analyzed revealed no more variation than that expected for a Gaussian distribution. Protein distribution data indicated that all α-granules likely contained the same major set of proteins, albeit at varying amounts and varying distribution within the granule matrix.