Citations

This study aimed to determine if extended infusion (EI; over > 3 hr) beta-lactam therapy increased IV access requirements compared with traditional dosing (TD; over 30 min). Eighty-six adult ICU patients treated with TD anti-pseudomonal beta-lactams who underwent therapeutic drug monitoring (TDM) were included. Patients who transitioned from TD to EI after TDM (EI group) were matched 1:1 to patients who remained on TD. In the primary analysis, the median (interquartile range) total number of lumens in the 24 hours before TDM compared with the 48 hours after TDM were similar between groups (pre: TD 3 [2–5] vs. EI 4 [3–5]; p = 0.22 and post: TD 3 [2–4] vs. EI 4 [3–5]; p = 0.05). Delivery of beta-lactams via EI was not associated with a need for more IV access. Practical challenges such as access should not limit use of EI beta-lactams when indicated.

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening opportunistic infection increasingly recognized among non-HIV immunocompromised patients. In severe cases progressing to acute respiratory distress syndrome, venovenous extracorporeal membrane oxygenation (VV-ECMO) may serve as a rescue therapy. We conducted a retrospective multicenter review of 10 adult patients with proven or probable PCP who received VV-ECMO between 2017 and 2024. Seven of 10 patients survived to discharge, including all three HIV-positive patients and 4 of 7 non-HIV immunocompromised patients. The mean Respiratory ECMO Survival Prediction Score was –1.5, corresponding to a predicted survival of 33–57%. Multiorgan dysfunction was common, including renal failure requiring dialysis in 6 of 10 patients, need for neuromuscular blockade in 8 of 10, and pulmonary vasodilator use in 8 of 10. Despite high acuity and prolonged ECMO support, outcomes were favorable. These findings suggest that VV-ECMO may be a viable salvage therapy for select patients with severe PCP, including those without HIV.

INTRODUCTION: Chronic pancreatitis (CP) is a disease associated with chronic inflammation, fibrosis, and pain. There is a lack of tools available that facilitate early diagnosis, when intervention could prevent irreversible damage. Pilot data suggested prostaglandin E2 (PGE2) as a candidate biomarker for early CP. PGE2 activates signaling pathways that promote inflammation, pain, and fibrosis. METHODS: We assessed PGE2, metabolites, and downstream targets in pancreatic fluid collected endoscopically 0–10 (n = 110) and 10–20 (n = 111) minutes after intravenous secretin administration. PGE2 and metabolites were measured in plasma (n = 75) and urine (n = 71) from the same subjects. Subjects were enrolled in the PROCEED study and classified symptomatic controls, acute/recurrent acute pancreatitis (AP/RAP), or CP. RESULTS: A significant main effect was detected in 10–20 minutes pancreas fluid ( P = 0.027) and plasma ( P = 0.046); post hoc testing showed PGE2 was lower in the AP/RAP group compared with symptomatic controls. There was also trend toward lower PGE2 in urine ( P = 0.062). To elucidate the active downstream pathways, calcitonin gene-related peptide, substance P, and matrix metalloproteinases (MMPs) 1, 2, 3, 7, 9, and 13 were measured in pancreas fluid. A significant difference between the 3 groups was detected for both MMP7 and MMP9. MMP7 was elevated in individuals with CP vs AP/RAP ( P = 0.012) for samples collected early but both time points for MMP9 ( P = 0.027, P = 0.002). DISCUSSION: While PGE2 is detectable in pancreas fluid, these data suggest that it may not be sensitive enough to distinguish between AP/RAP and CP. However, MMPs may distinguish between stages of pancreatitis and require further testing as potential diagnostic biomarkers.

ABSTRACT Background and Aims Steroid supplementation remains controversial in septic shock, partly due to the heterogeneity of the populations studied. Cirrhotic patients with sepsis frequently develop relative adrenal insufficiency, showing poor response to vasopressors and poor prognosis. Early administration of low‐dose hydrocortisone might facilitate shock reversal and reduce mortality in this population. Methods Double‐blind, randomised, placebo‐controlled multicentre trial, enrolling adult cirrhotic patients with septic shock. Patients were assigned to receive i.v. hydrocortisone (100 mg followed by a continuous infusion of 200 mg/24 h) or placebo, for at least 3 days, followed by a tapering period of 3–7 days, depending on the time of shock resolution. Primary endpoint was 28‐day all‐cause mortality. Results After enrolment of 83 patients the trial was stopped early due to slow inclusions. Most patients required low‐to‐moderate doses of vasopressors. There was no difference in 28‐day mortality (35% vs. 39.5%; p = 0.84) between hydrocortisone and placebo groups. Shock resolution (85% vs. 72.1%; p = 0.25) and days to shock resolution [3 days (2.2–4; IQR) vs. 4 (2–7.5; IQR)] were also similar between groups. More patients receiving placebo died of refractory shock (47.6% vs. 8.7%). No significant differences between treatment arms were observed in shock relapse, new shock episodes or bacterial or fungal superinfections during hospital stay. Hypo‐ and hyperglycaemias were more frequent in the hydrocortisone arm. Severity of ACLF at inclusion and inadequacy of empirical antibiotic therapy (HR = 6.40; 95% CI: 3.21–12.79) independently predicted 28‐day mortality. Conclusions Supplemental hydrocortisone did not improve short‐term survival in cirrhotic patients with septic shock requiring low‐to‐moderate doses of vasopressors. Trial Registration S‐number University Hospitals Leuven, Belgium: S55168; EUDRACT: 2010–024273‐38; Clinicaltrials.gov id: NCT02602210

ABSTRACT Background Risk for medication error increases during care transitions. Error susceptibility increases in pediatrics due to age and weight‐based dosing. Governing bodies acknowledge errors endanger patients, and transplant pharmacotherapy experts are mandated by the Center for Medicare and Medicaid Services (CMS). Pharmacist‐led medication histories reduce errors; however, pharmacists' roles in the transitions of care between transplant centers are unaddressed by CMS. We assessed the impact of transplant pharmacist involvement in medication histories for pediatrics transitioning between transplant centers. Methods Pediatric patients pre‐ or post‐heart transplant transitioning to our center were proactively identified. Transplant pharmacists conducted medication histories by phone with caregivers and tracked discrepancies between existing medication lists and interview responses. Descriptive statistical analyses were completed. Results Of 27 patients identified, seven caregivers were uncontactable, one declined participation, and 19 underwent transplant pharmacist medication history. Medication list errors were detected in 100% of patients ( n = 19), with a median [IQR] of 5 [3–11] issues per patient. Of 122 issues, 72 (59%) were inaccurate or missing data, 17.2% ( n = 21) listed stopped drugs, 9.8% ( n = 12) revealed incorrect administration routes, 7.4% ( n = 9) were duplicate medications, and 6.6% ( n = 8) of errors were medications needing to be added. Corrections included updating 84 inaccuracies (68.8%); removing/adding drugs (30 [24.6%] and 8 [6.6%], respectively); and team communication. Conclusions Complex dosing strategies in pediatrics confer error vulnerability. Designing transition of care processes with transplant pharmacist involvement in medication histories can assist in ensuring medication list accuracy, thereby improving pediatric patient safety.

The Dublin ISUP Consensus Conference covered the proceedings on the best practice recommendations on nonurachal glandular lesions of the urinary bladder, bladder diverticular cancers, and molecular features of bladder and urachal glandular lesions. The conference proceedings on urachal neoplasms (except for their molecular features) are published elsewhere. The rationale for convening this conference was the lack of structured and consented pathologic recommendations in these rare lesions. Consensus by participants was reached on the following statements: (1) intestinal metaplasia with dysplasia is considered to be a precursor to primary bladder adenocarcinoma; (2) dysplasia arising from cystitis glandularis should be reported in terms of focality (focal or nonfocal) and grade (low or high); (3) the term “adenocarcinoma” should only be used for carcinomas showing pure (nonurothelial) morphology and should not be used interchangeably in urothelial carcinoma with “glandular differentiation” because of the pathobiological differences and management implications; (4) the different histologic subtypes of bladder adenocarcinoma should be specified in the report; (5) immunohistochemistry has an ancillary role in the work up of bladder adenocarcinoma versus gastrointestinal or Müllerian-type adenocarcinomas; (6) lymphovascular invasion should be included as a parameter when reporting bladder adenocarcinoma; (7) representative or targeted sampling will be sufficient for bladder diverticulum resection specimens; and (8) molecular analysis in genomic profiling should be performed only in advanced or metastatic bladder and urachal adenocarcinomas for targetable therapy. This report on glandular (nonurachal) lesions of the bladder from the Dublin ISUP consensus conference will serve as a best practice recommendation and as a guide for future research on these relatively rare lesions.

Arrhythmogenic cardiomyopathies (ACMs) are a phenotypically and etiologically heterogeneous group of myocardial disorders characterized by fibrotic or fibro-fatty replacement of ventricular myocardium, electrical instability, and an elevated risk of sudden cardiac death. Initially identified as a right ventricular disease, ACMs are now recognized to include biventricular and left-dominant forms. Genetic causes account for a substantial proportion of cases and include desmosomal variants, non-desmosomal variants, and familial gene-elusive forms with no identifiable pathogenic mutation. Nongenetic etiologies, including post-inflammatory, autoimmune, and infiltrative mechanisms, may mimic the phenotype. In many patients, the disease remains idiopathic despite comprehensive evaluation. Cardiac magnetic resonance imaging has emerged as a key tool for identifying non-ischemic scar patterns and for distinguishing arrhythmogenic phenotypes from other cardiomyopathies. Emerging classifications propose the unifying concept of scarring cardiomyopathies based on shared structural substrates, although global consensus is evolving. Risk stratification remains challenging, particularly in patients without overt systolic dysfunction or identifiable genetic markers. Advances in tissue phenotyping, multi-omics, and artificial intelligence hold promise for improved prognostic assessment and individualized therapy.

Abstract Background Prior studies have examined small intestinal dysplasia and cancer in Crohn’s disease; however, there is limited information on ulcerative colitis (UC). We describe characteristics of small intestinal dysplasia and cancer in patients with UC. In this study, we aimed to identify common characteristics between patients with UC that were diagnosed with small intestinal malignancy. Methods Electronic medical records were reviewed for 3 tertiary referral centers to identify patients with a diagnosis of UC and small intestinal dysplasia or cancer between 2010 and 2023. Data collection included demographics, family history of gastrointestinal malignancy, UC diagnosis date, duration and location of disease, prior UC medical treatment or surgery, diagnosis of primary sclerosing cholangitis (PSC), PSC-related complications, and details of cancer or dysplasia. Descriptive statistics were performed. Results Thirty-five patients (60% male, mean age of diagnosis 39.3 ± 21.5 years old) were identified with UC and subsequent small intestinal dysplasia or cancer. Most had pancolitis (74.3%) or pancolitis with backwash ileitis (8.57%). Half underwent surgery for their UC, and half of these had the cancer or dysplasia found at the time of surgery. Ileal dysplasia was found in 2 patients (5.71%), duodenal adenocarcinoma in 2 (5.71%), ileal adenocarcinoma 2 (5.71%), duodenal carcinoid in 4 (11.4%), ileal carcinoid in 24 (68.6%), other duodenal neuroendocrine tumor in 1 (2.86%). Primary sclerosing cholangitis was diagnosed in 5 patients (14%), and 3 required liver transplants. Conclusions Small intestinal dysplasia and cancer are rare in this population. Most patients with small intestinal cancer or dysplasia were male, Caucasian, and had a history of extensive colitis. Ileal carcinoid had the highest incidence. Gastroenterologists should be aware of this finding in patients with UC.

Context.— A clinic was created for patients to review their explanted organs with a pathologist. Objective.— To prospectively investigate the benefits of this type of clinic as perceived by both transplant patients and their pathologists. Design.— In this prospective study, patients participated in a videotaped viewing of heart and/or lung explants by the patient and their guest(s) and pathologist (December 2017–August 2022). Patients received a 3D-printed replica of their explant. After viewing the explanted organ, patients and their guests participated in an interview to assess their experiences. Video-reflexive ethnography was used by pathologists for data collection and practice improvement. Results.— Of 143 patients who viewed their explanted organ, 21 patients consented to having the organ-viewing session taped and to participate in a postviewing interview. The study group was comprised of 12 men; the median age was 57.5 years (range, 29–67 years). Five pathologists took part in reflexive sessions. The clinics were viewed positively by patients, providing an opportunity to better understand their disease. Pathologists had a similarly positive experience and gained important insights to patient journeys. Proposals for improvement were brought forward from both patients and pathologists. Conclusions.— Video-reflexive ethnography provided the opportunity for patients and pathologists to reflect on patient-pathology clinic appointments. This work serves as a template to build out pathology-based clinics.