Citations

Abstract To examine the activity of ibrutinib in steroid-refractory chronic graft-versus-host disease (SR-cGVHD) after the US Food and Drug Administration approval, we conducted a multicenter retrospective study. Data were standardly collected (N = 270 from 19 centers). Involved organs included skin (75%), eye (61%), mouth (54%), joint/fascia (47%), gastrointestinal (GI) (26%), lung (27%), liver (19%), genital (7%), and others (4.4%). The National Institutes of Health (NIH) severity was mild in 5.7%, moderate 42%, and severe 53%. Thirty-nine percent had overlap subtype. Karnofsky performance status (KPS) was ≥80% in 72%. The median prednisone was 0.21 mg/kg (0-2.27). Ibrutinib was started at a median of 18.2 months after cGVHD onset and in earlier lines of therapy (second line, 26%; third, 30%; fourth, 21%; fifth, 9.6%; sixth, 10%; seventh or higher, 1.2%). Among evaluable patients, the 6-month NIH overall response rate (ORR; complete response [CR]/partial response [PR]) was 45% (PR 42%; CR 3%). The median duration of response was 15 months (range, 1-46). Liver involvement had association with 6-month ORR (multivariate [MVA] odds ratio, 5.49; 95% confidence interval [CI], 2.3-14.2; P < .001). The best overall response was 56%, with most (86%) achieving by 1 to 3 months. With a median follow-up for survivors of 30.5 months, failure-free survival (FFS) was 59% (53%-65%) at 6 months and 41% (36%-48%) at 12 months. On MVA, increased age (hazard ratio [HR], 1.01; 95% CI, 1.0-1.02; P = .033), higher baseline prednisone (HR, 1.92; 95% CI, 1.09-3.38; P = .032), and lung involvement (HR, 1.58; 95% CI, 1.1-2.28; P = .016) had worse FFS. Ibrutinib discontinuation was most commonly due to progressive cGVHD (44%) or toxicity (42%). These data support that ibrutinib has activity in SR-cGVHD, provide new insight into factors associated with response and FFS, and demonstrate the toxicity profile associated with discontinuation.

The purpose of sympathetic neuronal discharge and the recruitment of neuronal subpopulations for human circulatory homeostasis remains unknown. This study tested the hypothesis that sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y (NPY) bioavailability. Across baseline and an intravenous dexmedetomidine infusion (α2-adrenergic agonist) sympathetic action potential (AP) frequency and total sympathetic AP clusters were associated with NPY bioavailability. This is the first study to report that sympathetic neuronal discharge and recruitment patterns regulate NPY bioavailability to support circulatory homeostasis in humans.

With longer survival of patients with primary sclerosing cholangitis (PSC) undergoing liver transplantation (LT), the frequency and risk factors associated with vascular and biliary complications in the allograft and the impact on long-term outcomes are poorly understood. To assess frequency and risk factors for long-term outcomes in patients after LT for PSC, all recipients of LT for advanced stage PSC for a non-cholangiocarcinoma indication from 1984 to 2012, with follow-up through March 2022 (>10+ y follow-up), were identified. One-, 5-, and 10-year cumulative risks of complications were estimated using the Aalen-Johansen method, where death was considered a competing risk. Two hundred ninety-three patients (mean age, 47.3 ± 12 y) formed our study cohort. One hundred and thirty-four patients received LT before 1995, and 159 were transplanted after 1995. Over a median (IQR) follow-up of 15.0 (10.3–22.1) years, LT was complicated by hepatic artery thrombosis (N = 30), portal vein stenosis/thrombosis (N = 48), biliary leak (N = 47), biliary strictures (N = 87), recurrent PSC (N=107), and graft failure (N=70). The 1-, 5-, 10-, and 15-year cumulative incidence of recurrent PSC was 1.0%, 8.0%, 23.5%, and 34.3%, respectively. The type of donor and older donor age were associated with an increased risk of biliary strictures. Donor age >60 years was associated with an increased risk of recurrent PSC. Long-term patient and graft survival have not changed significantly for patients transplanted for PSC. Controlling transplant-related factors, such as donor age, prompt identification of vascular and biliary complications early, and long-term rigorous follow-up, is recommended to continue to improve on these outcomes.

Abstract Purpose: Gastroenteropancreatic neuroendocrine tumors (GEP-NET) are relatively indolent but can be more aggressive. The current recommendations for using serum chromogranin A (CgA) for patients with GEP-NET are equivocal. This study was designed to validate an automated CgA immunofluorescence assay for monitoring disease progression in patients with GEP-NET. Patients and Methods: A prospective, multicenter, blinded observational study was designed to validate an automated CgA immunofluorescence assay for monitoring disease progression in patients with GEP-NET. Tumor progression was evaluated with RECIST 1.1 by CT/MRI. An increase ≥50% above the prior CgA concentration to a value >100 ng/mL in the following CgA concentration was considered positive. Results: A total of 153 patients with GEP-NET were enrolled. Using the prespecified cut-off of CgA change for tumor progression, specificity was 93.4% (95% confidence interval, 90.4%–95.5%; P < 0.001), sensitivity 34.4% (25.6%–44.3%), positive predictive value 57.9% (45.0–69.8), negative predictive value 84.3% (80.5–87.6), and AUC 0.73 (0.67–0.79). Conclusions: Changes in serial measurements of serum CgA had a favorable specificity and negative predictive value, making this test a useful adjunct to routine radiographic monitoring.

Summary of Background Data: Although pseudoangina is most commonly caused by cervical disc herniation, several cases have been described where thoracic herniation produced symptoms of pseudoangina. If thoracic herniation can produce angina-like pain, then it is important to consider whether pathology of the thoracolumbar spine, in general, can trigger false pain syndromes distinct from pseudoangina. Objective: We seek to provide the most comprehensive study regarding the diagnosis and treatment of spinal conditions causing false pain syndromes. Study Design: Systematic review of the current literature using PRISMA 2020 recommendations. Methods: We queried the literature and systematically selected relevant studies according to PRISMA guidelines. Results: Across 22 selected studies, the sample size was 30 patients, and a total of 26 met the criteria for statistical analysis. Seven (26.9%) of these patients presented with a chief complaint of pseudoangina resulting from thoracic disc herniation. 73.1% (19/26) of patients exhibited pain mimicking visceral origin. Overall, 13/19 (68.4%) patients exhibited thoracic spine disease only and 4/19 (21.1%) patients were affected at lumbar levels only, while 2 (10.5%) patients exhibited thoracolumbar herniation. Presentations included abdominal pain (11/19) mimicking appendicitis or pancreatitis, flank pain mimicking renal colic (8/19), and 2 cases of scrotal pain/orchalgia. Symptom durations ranged from acute (<24 h) to 7 years. Treatments were reported for 18/19 patients and all treated patients reported alleviated pain. Seven out of 18 patients were managed conservatively while 11/18 were treated surgically. Misdiagnosis resulted in unnecessary surgery (pancreaticojejunostomy) or other invasive procedures. Conclusions: In spinal disorders manifesting with atypical pain syndromes, delay in proper diagnosis and unnecessary treatments can, unfortunately, cause prolonged patient suffering and increased cost of health care. As a result, some have proposed that spinal screening should be incorporated into clinical examinations involving false pain syndromes.

Background: Delivering ethical care in global plastic surgery is challenging due to the unique complexities of resource-limited settings. Additionally, the rise of medical tourism has highlighted the importance of informed consent and awareness of the potential risks that are associated with seeking medical care in foreign countries. This article aims to consider core medical ethics principles and apply them in the context of delivering global plastic surgery. Methods: This article examines the application of the four core medical ethics principles in a framework set forth by Beauchamp and Childress, namely autonomy, beneficence, nonmaleficence, and justice, in the context of delivering plastic surgery in international settings. A literature review was performed, where all potential global plastic surgery articles were reviewed to better understand the application of the four core medical ethics framework in this context. Results: Increased communication between visiting surgeons and local healthcare providers; heightened education of surgeons traveling to low-to-middle-income countries regarding local medical practices, resource availability, and cultural norms before providing surgical education; and a greater emphasis on collecting and publishing data analyzing short- and long-term outcomes in low-to-middle-income countries are all likely to improve the success of international medical missions, ensuring that all patients receive medical treatment in a manner that upholds Beauchamp and Childress’ four core medical ethics principles. Conclusion: Providing plastic and reconstructive surgery abroad can be done ethically if the four main principles of medical ethics (respect for autonomy, beneficence, nonmaleficence, and justice) are used.

Introduction: Despite advances in obstetric care, postpartum hemorrhage (PPH) is a leading cause of maternal mortality worldwide. Prior reviews of studies published through 2016 suggest an association of antidepressant use during late pregnancy and increased risk of PPH. However, a causal link between prenatal antidepressants and PPH remains controversial. Objectives: This systematic literature review aimed to synthesize the empirical evidence on the association of antidepressant exposure in late pregnancy with the risk of PPH, including studies published before and after 2016. Methods: A systematic literature search was conducted using PubMed, OVID Medline, EMBASE, SCOPUS, PsycINFO, and CINAHL from inception to September 9, 2023. Original, peer-reviewed studies (published in English) that reported on the frequency or risk of PPH in women with evidence of antidepressant use during pregnancy and included at least one control group were included. Results: Twenty studies (eight published after 2016) met inclusion criteria, most of which focused on the risks of PPH associated with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). The main findings from the individual studies were mixed, but the majority documented statistically significant associations of PPH with late prenatal exposure, especially for exposures occurring within 30 days of delivery, compared with unexposed deliveries. Fourteen studies addressed underlying antidepressant indications or their correlates. Few studies focused on prenatal antidepressants and the risk of well-defined severe PPH or on antidepressant dose changes and general PPH risk. None examined competing risks of antidepressant discontinuation on mental health outcomes. Conclusions: Late pregnancy exposure to antidepressants may be a minor risk factor for PPH, but it is unclear to what extent reported associations are causal in nature, as opposed to correlational (effects related to nonpharmacological factors including maternal indication). For patients needing antidepressants during pregnancy, current evidence does not favor routinely discontinuing antidepressants specifically to reduce the risk of PPH.