Citations

Background: Cutaneous collagenous vasculopathy (CCV) is a rare acquired microangiopathy that commonly affects middle-aged, fair-skinned individuals. It presents with telangiectatic lesions involving the lower extremities. Histologic analysis is mandatory for diagnosis. Objectives: To describe and characterize the patients diagnosed with CCV at the Mayo Clinic. Methods: A multicenter retrospective observational analysis was performed on patients with a clinical and histological diagnosis of CCV at the Mayo Clinic in Florida, Arizona, and Rochester from January 2000 to October 2023. Results: The study included 34 patients, 22 (64.7%) females. The median age at diagnosis was 52 years (range, 12-80 years). CCV lesions were found to affect the lower extremities in 29 (85.3%) patients, followed by the trunk in 14 (41.2%). Nineteen (55.9%) patients presented 1 concomitant medical condition, 8 (23.5%) 2 conditions, and 5 (14.7%) 3 or more medical conditions, such as arterial hypertension 10 (29.4%), type 2 diabetes mellitus 3 (8.8%), hyperlipidemia 3 (8.8%), cardiac disease 3 (8.8%), and hematologic malignancy 3 (8.8%). Thirty-one patients (91.2%) were taking medications, with 19 (55.9%) taking 3 or more. Pathology staining revealed periodic acid-Schiff positivity in 23 of 34 cases (67.6%), and collagen IV in 26 of 34 cases (47.1%). Treatments included pulsed dye laser 3 (8.8%) and topical sirolimus 1 (2.9%). Conclusions: CCV is an uncommon microangiopathy that affects pediatric, middle-aged, and elderly patients. It involves the lower extremities, trunk, and upper extremities. Patients often present with associated metabolic and cardiovascular conditions and are usually taking at least 1 medication. Treatment options are limited.

Background Assessment of gastric conduit perfusion during esophagectomy is crucial to determine its viability and identify the optimal site for anastomosis. Indocyanine green (ICG) fluorescence imaging is commonly used for this purpose, but it is contraindicated in patients with hypersensitivity to ICG, iodine, or shellfish. Oxygen saturation endoscopic imaging (OXEI) is a newer, non-pharmacologic technique for assessing perfusion. We report our experience with OXEI in 3 esophagectomy patients who had contraindications to ICG. Methods All 3 patients underwent robot-assisted esophagectomies. None of the conduits had ischemic areas identified by white light. Using a 5 mm laparoscopic specialized camera (ELUXEO Vision, FUJIFILM Healthcare Americas Corp., USA), OXEI was deployed for intracorporeal assessment of gastric conduit perfusion after pull-up into the chest. Postoperative outcomes including anastomotic leaks and complications were recorded. Results In two patients, OXEI revealed ischemic zones, which were resected to ensure optimal conduit viability. In the remaining patient, OXEI indicated robust vascularity throughout the conduit. All three patients experienced uneventful postoperative courses and were discharged within 10 days. There were no instances of anastomotic leaks or other major complications. Conclusion In our experience, OXEI is a viable method for intraoperative assessment of gastric conduit perfusion in patients with contraindications to ICG. Prospective studies are needed to validate its efficacy in preventing anastomotic complications and to compare it with other methods of perfusion assessment including gross visual and ICG dye in a larger patient population.

OBJECTIVES: We aimed to summarize the most significant and impactful publications describing the pharmacotherapeutic care of critically ill patients in 2023. DATA SOURCES: PubMed/MEDLINE and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update. STUDY SELECTION: Randomized controlled trials and prospective studies of adult critically ill patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2023, and December 31, 2023, were eligible for inclusion in this article. DATA EXTRACTION: Articles from a systematic search and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update were included. An a priori defined three-round modified Delphi process was employed to achieve consensus on the most impactful publications based on the following considerations: 1) overall contribution to scientific knowledge and 2) novelty to the literature. DATA SYNTHESIS: The systematic search and Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update returned a total of 1202 articles, of which 1164 were excluded. The remaining 38 articles underwent a three-round modified Delphi process. In each round, articles were independently scored based on overall contribution to scientific knowledge and novelty to the literature. Included articles are summarized and their impact discussed. Article topics included hydrocortisone for severe community-acquired pneumonia, inhaled amikacin for prevention of ventilator-associated pneumonia, methylene blue for septic shock, restrictive vs. liberal fluid management for sepsis-induced hypotension, andexanet alfa for major bleeding associated with factor Xa inhibitors, and early administration of four-factor prothrombin complex concentrate in patients with trauma at risk for massive transfusion. CONCLUSIONS: This review provides a summary and perspective on the potential impact of the most relevant articles in 2023 describing advances in the pharmacotherapeutic care of critically ill patients.

AbstractBackgroundPhoton counting detectors (PCDs) for x‐ray computed tomography (CT) are the future of CT imaging. At present, semiconductor‐based PCDs such as cadmium telluride (CdTe), cadmium zinc telluride, and silicon have been either used or investigated for clinical PCD CT. Unfortunately, all of them have the same major challenges, namely high cost and limited spectral signal‐to‐noise ratio (SNR). Recent studies showed that some high‐quality scintillators, such as lanthanum bromide doped with cerium (LaBr3:Ce), are less expensive and almost as fast as CdTe.PurposeThe objective of this study is to assess the performance of a LaBr3:Ce PCD for clinical x‐ray CT.MethodsWe performed Monte Carlo simulations and compared the performance of 3 mm thick LaBr3:Ce and 2 mm thick CdTe for PCD CT with x‐rays at 120 kVp and 20–1000 mA. The two PCDs were operated with either a threshold–subtract (TS) counting scheme or a direct energy binning (DB) counting scheme. The performance was assessed in terms of the accuracy of registered spectra, counting capability, and count‐rate‐dependent spectral imaging‐task performance, for conventional CT imaging, water–bone material decomposition, and K‐edge imaging with tungsten as the K‐edge material. The performance for these imaging‐tasks was quantified by nCRLB, that is, the Cramér–Rao lower bound on the variance of basis line‐integral estimation, normalized by the corresponding value of CdTe at 20 mA.ResultsThe spectrum recorded by CdTe was distorted significantly due to charge sharing, whereas the spectra recorded by LaBr3:Ce better matched the incident spectrum. The dead time, estimated by fitting a paralyzable detector model to the count‐rate curves, was 20.7, 15.0, 37.2, and 13.0 ns for CdTe with TS, CdTe with DB, LaBr3:Ce with TS, and LaBr3:Ce with DB, respectively. Conventional CT imaging showed an adverse effect of reduced geometrical efficiency due to optical reflectors in LaBr3:Ce PCD. The nCRLBs (a lower value indicates a better SNR) for CdTe with TS, CdTe with DB, LaBr3:Ce with TS, LaBr3:Ce with DB, and the ideal PCD, were 1.00 ± 0.01, 1.00 ± 0.01, 1.18 ± 0.02, 1.18 ± 0.02, and 0.79 ± 0.01, respectively, at 20 mA. The nCRLBs for water–bone material decomposition, in the same order, were 1.00 ± 0.02, 1.00 ± 0.02, 0.85 ± 0.02, 0.85 ± 0.02, and 0.24 ± 0.02, respectively, at 20 mA; and 0.98 ± 0.02, 0.98 ± 0.02, 1.09 ± 0.02, 0.83 ± 0.02, and 0.24 ± 0.02, respectively, at 1000 mA. Finally, the nCRLBs for K‐edge imaging, the most demanding task among the five, were 1.00 ± 0.02, 1.00 ± 0.02, 0.55 ± 0.02, 0.55 ± 0.02, and 0.13 ± 0.02, respectively, at 20 mA; and 2.45 ± 0.02, 2.29 ± 0.02, 3.12 ± 0.02, 2.11 ± 0.02, and 0.13 ± 0.02, respectively, at 1,000 mA.ConclusionThe Monte Carlo simulations showed that, compared to CdTe with either TS or DB, LaBr3:Ce with DB provided more accurate spectra, comparable or better counting capability, and superior spectral imaging‐task performances, that is, water–bone material decomposition and K‐edge imaging. CdTe had a better performance than LaBr3:Ce for the conventional CT imaging task due to its higher geometrical efficiency. LaBr3:Ce PCD with DB scheme may be an excellent alternative option for CdTe PCD.

Abstract SRD5A3-CDG is a congenital disorder of glycosylation (CDG) resulting from pathogenic variants in SRD5A3 and follows an autosomal recessive inheritance pattern. The enzyme encoded by SRD5A3, polyprenal reductase, plays a crucial role in synthesizing lipid precursors essential for N-linked glycosylation. Despite insights from functional studies into its enzymatic function, there remains a gap in understanding global changes in patient cells. We sought to identify N-glycoproteomic and proteomic signatures specific to SRD5A3-CDG, potentially aiding in biomarker discovery and advancing our understanding of disease mechanisms. Using tandem mass tag (TMT)-based relative quantitation, we analyzed fibroblasts derived from five patients along with control fibroblasts. N-glycoproteomics analysis by liquid chromatography–tandem mass spectrometry (LC–MS/MS) identified 3,047 glycopeptides with 544 unique N-glycosylation sites from 276 glycoproteins. Of these, 418 glycopeptides showed statistically significant changes with 379 glycopeptides decreased (P < 0.05) in SRD5A3-CDG patient-derived samples. These included high mannose, complex and hybrid glycan-bearing glycopeptides. High mannose glycopeptides from protocadherin Fat 4 and integrin alpha-11 and complex glycopeptides from CD55 were among the most significantly decreased glycopeptides. Proteomics analysis led to the identification of 5,933 proteins, of which 873 proteins showed statistically significant changes. Decreased proteins included cell surface glycoproteins, various mitochondrial protein populations and proteins involved in the N-glycosylation pathway. Lysosomal proteins such as N-acetylglucosamine-6-sulfatase and procathepsin-L also showed reduced levels of phosphorylated mannose-containing glycopeptides. Our findings point to disruptions in glycosylation pathways as well as energy metabolism and lysosomal functions in SRD5A3-CDG, providing clues to improved understanding and management of patients with this disorder.

Abstract Background: Epidemiological and laboratory-based studies have provided conflicting evidence for a role of ghrelin in colorectal cancer development. We conducted two-sample Mendelian randomization (MR) analyses to evaluate evidence for an association of circulating ghrelin and colorectal cancer risk overall and by sex, cancer subsite, and age at diagnosis. Methods: Genetic instruments proxying plasma total ghrelin levels were obtained from a recent genome-wide association study of 54,219 participants. Summary data for colorectal cancer risk were obtained from a recent meta-analysis of several genetic consortia (up to 73,673 cases and 86,854 controls). A two-sample MR approach and several sensitivity analyses were applied. Results: We found no evidence for an association of genetically predicted plasma total ghrelin levels and colorectal cancer risk (0.95, 95% confidence interval, 0.81–1.12; R2 of ghrelin genetic instruments: 4.6%), with similarly null results observed when stratified by sex, anatomical subsite, and for early-onset colorectal cancer. Conclusions: Our study suggests that plasma ghrelin levels are unlikely to have a causal relationship with overall, early-onset, and sex- and cancer subsite–stratified colorectal cancer risk. Impact: This large-scale analysis adds to the growing body of evidence that plasma total ghrelin levels are not associated with colorectal cancer risk.

We performed 6-yr follow-up testing on a world record-breaking master marathon runner. We determined that his performance declined since his record-breaking marathon in 2018 primarily due to a reduction in V̇o2max. His max heart rate (HR) changed minimally, but his peak O2 pulse decreased, suggesting that his maximal stroke volume and/or arteriovenous O2 difference decreased. These changes likely reflect primarily age-related effects in the absence of an overt pathological disease process.

The novel Coronavirus Disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, created a need for evidence-based guidelines for the evaluation, management, and follow-up after infection. Data have become rapidly available, creating a challenge for medical providers to stay abreast of the ever-evolving recommendations. This article, written collaboratively by pediatric cardiovascular experts, pediatricians, and sports medicine specialists, is focused on SARS-CoV- 2-related pediatric cardiac manifestations. It aims to provide a systematic review of high-yield literature related to all cardiovascular entities as a tool for primary pediatric clinicians to utilize as they consider the cardiac consequences of acute SARS-CoV-2 infection, MIS-C, vaccine-related myocarditis, return-to-play, and long COVID-19 syndrome.