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Cognitive decline in Cushing's syndrome: A systematic review

Katragadda, Anila; Kunadia, Jessica; Kirsch, Polly; Dorcely, Brenda; Shah, Shruti; Henig, Zachary; Job, Asha; Feelders, Richard A; Agrawal, Nidhi
The neurocognitive and psychiatric effects of Cushing's syndrome (CS) are well recognized and negatively impact quality of life. The aim of this systematic review is to compare neurocognitive disease, psychiatric symptoms, and structural brain changes in patients with Cushing's disease (CD)/CS and those with non-functioning pituitary adenoma (NFPA), both before and after surgical treatment, and in comparison to healthy controls. Possible predictors of persistent neurocognitive symptoms and reduced quality of life in patients with CS are highlighted. We reviewed the English literature published in Medline/Pubmed until 2021 to identify eligible studies. This systematic review was registered on Prospero and reported following the PRISMA statement guidelines. The initial literature search yielded 1772 articles, of which 1096 articles remained after removing duplicates. After excluding case reports, animal studies, narrative reviews, comparative reviews, and articles not in English, 86 papers underwent full-text review. Studies eligible for inclusion met the following criteria: (1) described patients with CD/CS, (2) reports of psychiatric symptoms, (3) written in English or with available English translation, and (4) published in a peer-reviewed journal. The full-text review process identified 40 eligible studies. The 40 studies included a total of 2603 participants with CD or CS, with 45.2% of the total participants having CD. The majority of studies were case-control studies and used validated questionnaires such as the Beck's Depression Index, Trail Making Test, Hospital Anxiety and Depression Scale, and Cushing Quality of Life for screening. Compared to NFPA controls, patients with CD who had greater baseline serum cortisol levels had worse cognitive function, even after surgical remission. This suggests a possible association between greater baseline cortisol levels in patients with CS and persistent cognitive impairment. A longer duration of uncontrolled CS was associated with worse cognitive function; however, there was no association found between the length of remission and memory. Overall brain volume was increased in patients in remission from CD compared to active disease. However, temporal and frontal lobe volumes did not recover to normal volumes. Patients with CS experience neurocognitive dysfunction, psychiatric disorders, and diminished quality of life, and symptoms may persist after curative surgery. We found several factors consistently associated with persistent cognitive and neuropsychiatric symptoms in patients with CS including higher pre-operatively baseline cortisol production, longer duration of disease, frontal and temporal lobe atrophy, and the presence of cognitive and neuropsychiatric symptoms at baseline. Larger prospective studies are required to validate these findings.
PMID: 39506264
ISSN: 1365-2826
CID: 5778202

A Longer Biliopancreatic Limb and Shorter Common Channel Enhance Weight Loss But May Have Harmful Effects in Mouse Models of Roux-en-Y Gastric Bypass

Lau, Raymond; Stevenson, Matthew; Tirumalasetty, Munichandra Babu; Lee, Jenny; Hall, Christopher; Miao, Qing; Brathwaite, Collin; Ragolia, Louis
BACKGROUND:RYGB consists of the Roux limb (RL), the biliopancreatic limb (BPL), and the common channel (CC). There is no consensus on the optimal limb lengths. METHODS:Using a mouse model of RYGB, 30 diet-induced obese mice were divided into two groups with varying BPL and CC lengths: a standard BPL with a long CC (RYGB S) and a long BPL with a short CC (RYGB L). Additionally, 9 age-matched, lean control mice (LC) were also included in this study. RESULTS:RYGB S had limb lengths of RL = 17%, BPL = 24%, and CC = 59%. RYGB L had limb lengths of RL = 17%, BPL = 32%, and CC = 51%. RYGB S and RYGB L had 67% and 40% survival, respectively. Mortality in RYGB L included more instances where the cause of death was not apparent. RYGB L demonstrated greater weight loss, lower energy expenditure, and lower heart mass as compared to RYGB S. Both RYGB groups had lower epidydimal fat mass, spleen mass, and bone mineral density compared to LC. RYGB L had a lower heart mass than RYGB S and LC. While the relative abundance of Eubacterium was lower in RYGB L than in RYGB S, no other gut microbiota differences were observed. CONCLUSIONS:A longer BPL with a shorter CC induces greater weight loss but may lead to adverse effects, including lower heart mass, reduced bone density, and deaths with unclear causes.
PMID: 39516446
ISSN: 1708-0428
CID: 5752272

Acute Rheumatic Fever

Chowdhury, Sadakat; Koziatek, Christian A.; Rajnik, Michael
Acute rheumatic fever (ARF) is an immune-mediated nonsuppurative complication of group A streptococcal (GAS) pharyngitis. Approximately 470,000 new cases of ARF occur annually, with a more significant disease burden in developing countries with higher rates of untreated or inadequately treated GAS infections. Globally, over 275,000 deaths yearly are attributed to rheumatic heart disease (RHD). The most significant contributors to the spread of GAS pharyngitis are household overcrowding, poor sanitation, and inadequate access to healthcare. The pathophysiology of ARF is characterized by an aberrant immune response to GAS infection triggered by molecular mimicry between GAS antigens and self-antigens. This immune response typically manifests 2 to 4 weeks after the initial GAS infection and may lead to the development of carditis, valvulitis, Sydenham chorea, subcutaneous nodules, erythema marginatum, and polyarthritis that is usually migratory. The severity and distribution of these manifestations vary significantly between individuals making the diagnosis of ARF challenging. Early recognition of ARF using the modified Jones criteria is essential in treating acute infection and preventing complications. A major long-term consequence is RHD, which carries significant morbidity and mortality.
PMID: 37603629
CID: 5563012

Intraoperative margin assessment with near real time pathology during partial gland ablation of prostate cancer: A feasibility study

Mannas, Miles P; Deng, Fang-Ming; Ion-Margineanu, Adrian; Freudiger, Christian; Jones, Derek; Hoskoppal, Deepthi; Melamed, Jonathan; Wysock, James; Orringer, Daniel A; Taneja, Samir S
BACKGROUND:In-field or in-margin recurrence after partial gland cryosurgical ablation (PGCA) of prostate cancer (PCa) remains a limitation of the paradigm. Stimulated Raman histology (SRH) is a novel microscopic technique allowing real time, label-free, high-resolution microscopic images of unprocessed, un-sectioned tissue which can be interpreted by humans or artificial intelligence (AI). We evaluated surgical team and AI interpretation of SRH for real-time pathologic feedback in the planning and treatment of PCa with PGCA. METHODS:About 12 participants underwent prostate mapping biopsies during PGCA of their PCa between January and June 2022. Prostate biopsies were immediately scanned in a SRH microscope at 20 microns depth using 2 Raman shifts to create SRH images which were interpreted by the surgical team intraoperatively to guide PGCA, and retrospectively assessed by AI. The cores were then processed, hematoxylin and eosin stained as per normal pathologic protocols and used for ground truth pathologic assessment. RESULTS:Surgical team interpretation of SRH intraoperatively revealed 98.1% accuracy, 100% sensitivity, 97.3% specificity for identification of PCa, while AI showed a 97.9% accuracy, 100% sensitivity and 97.5% specificity for identification of clinically significant PCa. 3 participants' PGCA treatments were modified after SRH visualized PCa adjacent to an expected MRI predicted tumor margin or at an untreated cryosurgical margin. CONCLUSION/CONCLUSIONS:SRH allows for accurate rapid identification of PCa in PB by a surgical team interpretation or AI. PCa tumor mapping and margin assessment during PGCA appears to be feasible and accurate. Further studies evaluating impact on clinical outcomes are warranted.
PMID: 39129081
ISSN: 1873-2496
CID: 5726492

Safety of psychotropic medications in pregnancy: an umbrella review

Fabiano, Nicholas; Wong, Stanley; Gupta, Arnav; Tran, Jason; Bhambra, Nishaant; Min, Kevin K; Dragioti, Elena; Barbui, Corrado; Fiedorowicz, Jess G; Gosling, Corentin J; Cortese, Samuele; Gandhi, Jasmine; Saraf, Gayatri; Shorr, Risa; Vigod, Simone N; Frey, Benicio N; Delorme, Richard; Solmi, Marco
Weighing risks and benefits of the use of psychotropic medications during pregnancy remains a challenge worldwide. We systematically assessed the strength of associations between psychotropic medication use in pregnant people with mental disorders and various adverse health outcomes in both pregnant people and foetuses. Systematic reviews with meta-analyses of observational studies investigating the association between exposure to psychotropic medication in pregnancy and any adverse health outcomes were included. Credibility was graded into convincing, highly suggestive, suggestive, weak or not significant. Quality of the meta-analyses and of individual studies were assessed with A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) the Newcastle-Ottawa Scale (NOS), respectively. We considered 21 meta-analyses encompassing 17,290,755 participants (AMSTAR 2 high = 1, low = 12, or critically low = 8). Evidence was suggestive for: (1) preterm birth in pregnant people with either any mental disorder (equivalent odds ratio 1.62 (95% confidence interval 1.24-2.12) or depression (1.65 [1.34-2.02]) receiving antidepressants during any trimester of pregnancy; (2) small for gestational age for pregnant people with depression receiving a SSRI during any trimester of pregnancy (1.50 [1.19-1.90]); and (3) major congenital malformation (1.24 [1.09-1.40]) or cardiac malformations (1.28 [1.11-1.47]) in babies for pregnant people with depression or anxiety receiving paroxetine during first trimester of pregnancy. Additional associations were supported by weak evidence, or were not statistically significant. This umbrella review found no convincing or highly suggestive level of evidence of adverse health outcomes associated with psychotropic medication use in pregnant people with mental disorders.
PMID: 39266712
ISSN: 1476-5578
CID: 5690682

Longitudinal assessment of disparities in pancreatic cancer care: A retrospective analysis of the National Cancer Database

Grewal, Mahip; Kroon, Victor J; Kaslow, Sarah R; Sorrentino, Anthony M; Winner, Megan D; Allendorf, John D; Shah, Paresh C; Simeone, Diane M; Welling, Theodore H; Berman, Russell S; Cohen, Steven M; Wolfgang, Christopher L; Sacks, Greg D; Javed, Ammar A
BACKGROUND:The existence of sociodemographic disparities in pancreatic cancer has been well-studied but how these disparities have changed over time is unclear. The purpose of this study was to longitudinally assess patient management in the context of sociodemographic factors to identify persisting disparities in pancreatic cancer care. METHODS:Using the National Cancer Database, patients diagnosed with pancreatic ductal adenocarcinoma from 2010 to 2017 were identified. The primary outcomes were surgical resection and/or receipt of chemotherapy. Outcome measures included changes in associations between sociodemographic factors (i.e., sex, age, race, comorbidity index, SES, and insurance type) and treatment-related factors (i.e., clinical stage at diagnosis, surgical resection, and receipt of chemotherapy). For each year, associations were assessed via univariate and multivariate analyses. RESULTS:Of 75,801 studied patients, the majority were female (51%), White (83%), and had government insurance (65%). Older age (range of OR 2010-2017 [range-OR]:0.19-0.29), Black race (range-OR: 0.61-0.78), lower SES (range-OR: 0.52-0.94), and uninsured status (range-OR: 0.46-0.71) were associated with lower odds of surgical resection (all p < 0.005), with minimal fluctuations over the study period. Older age (range-OR: 0.11-0.84), lower SES (range-OR: 0.41-0.63), and uninsured status (range-OR: 0.38-0.61) were associated with largely stable lower odds of receiving chemotherapy (all p < 0.005). CONCLUSIONS:Throughout the study period, age, SES, and insurance type were associated with stable lower odds for both surgery and chemotherapy. Black patients exhibited stable lower odds of resection underscoring the continued importance of mitigating racial disparities in surgery. Investigation of mechanisms driving sociodemographic disparities are needed to promote equitable care.
PMID: 39653505
ISSN: 1432-2323
CID: 5762392

Outcomes with distal transradial access in patients with advanced chronic kidney disease

Mosarla, Ramya C; Ahmed, Hamza; Rao, Shaline D; Kadosh, Bernard S; Cruz, Jennifer A; Goldberg, Randal I; Saraon, Tajinderpal; Gelb, Bruce E; Mattoo, Aprajita; Rao, Sunil V; Bangalore, Sripal
Radial artery occlusion (RAO), a complication of transradial access, has an incidence of 4.0% to 9.1% in patients with advanced chronic kidney disease (CKD) and may preclude its use creation of arteriovenous fistula. Distal transradial access (dTRA) has lower rates of RAO compared with TRA, but prior studies excluded patients with advanced CKD. This was a single center study of patients with advanced CKD who underwent coronary procedures with dTRA from January 1, 2019 to May 12, 2022 who were retrospectively evaluated for radial artery patency in follow-up with reverse Barbeau testing or repeat access of the artery. Of 71 patients, 66% were on hemodialysis and the remainder had CKD 3 to 5. Access was ultrasound-guided, and all received adequate spasmolytic therapy and patent hemostasis. Proximal radial arteries were patent in 100% of the patients at follow-up. Our data suggest that dTRA is safe for patients with advanced CKD and preserves radial artery patency.
PMID: 39150435
ISSN: 1557-2501
CID: 5727012

Development and Validation of a Simplified Financial Toxicity Screening Tool for Use in Clinical Practice

Thom, Bridgette; Tin, Amy L; Chino, Fumiko; Vickers, Andrew J; Aviki, Emeline M
PURPOSE/OBJECTIVE:Cancer-related financial toxicity occurs frequently and is a key driver of inequities in access to care and disparities in treatment outcomes. Current practices to screen for financial toxicity are inconsistent because of the lack of a validated and clinically integrated screening tool. This analysis aimed to create and assess an abbreviated version of the validated Comprehensive Score for Financial Toxicity (COST) tool, a measure of financial toxicity used for research purposes, which could easily be added into often-lengthy clinical screening workflows. METHODS:At an urban comprehensive cancer center with suburban satellite locations, a financial toxicity screening quality improvement project was conducted from June 2022 to August 2023 as part of routine clinical care: 57,526 longitudinal COST surveys were completed by 38,249 patients with cancer. An iterative algorithm selected the items with highest correlation with the total score. Using a separate validation data set, positive and negative predictive values (PPV and NPV, respectively) of the abbreviated tool (two-item) were assessed against the full COST score, with varying risk thresholds. RESULTS:Inclusion of two COST questions (Q3: "I worry about the financial problems I will have in the future as a result of my illness or treatment"; Q6: "I am satisfied with my current financial situation") yielded a score that had a correlation of 0.922 with the full instrument score. For the two-item scale, PPV ranged from 74% to 91%, and NPV ranged from 91% to 98% when compared with the full COST tool. CONCLUSION/CONCLUSIONS:This analysis of a large data set finds that a simplified COST tool has high predictive value when compared with the full validated measure. An abbreviated COST measure of two questions is suitable for implementation into clinical screening workflows.
PMID: 39793553
ISSN: 2688-1535
CID: 5775432

Correction: A Longer Biliopancreatic Limb and Shorter Common Channel Enhance Weight Loss But May Have Harmful Effects in Mouse Models of Roux-en-Y Gastric Bypass

Lau, Raymond; Stevenson, Matthew; Tirumalasetty, Munichandra Babu; Lee, Jenny; Hall, Christopher; Miao, Qing; Brathwaite, Collin; Ragolia, Louis
PMID: 39612057
ISSN: 1708-0428
CID: 5780012

Can large language models address unmet patient information needs and reduce provider burnout in the management of thyroid disease?

Raghunathan, Rajam; Jacobs, Anna R; Sant, Vivek R; King, Lizabeth J; Rothberger, Gary; Prescott, Jason; Allendorf, John; Seib, Carolyn D; Patel, Kepal N; Suh, Insoo
BACKGROUND:Patient electronic messaging has increased clinician workload contributing to burnout. Large language models can respond to these patient queries, but no studies exist on large language model responses in thyroid disease. METHODS:This cross-sectional study randomly selected 33 of 52 patient questions found on Reddit/askdocs. Questions were found through a "thyroid + cancer" or "thyroid + disease" search and had verified-physician responses. Additional responses were generated using ChatGPT-3.5 and GPT-4. Questions and responses were anonymized and graded for accuracy, quality, and empathy using a 4-point Likert scale by blinded providers, including 4 surgeons, 1 endocrinologist, and 2 physician assistants (n = 7). Results were analyzed using a single-factor analysis of variance. RESULTS:For accuracy, the results averaged 2.71/4 (standard deviation 1.04), 3.49/4 (0.391), and 3.66/4 (0.286) for physicians, GPT-3.5, and GPT-4, respectively (P < .01), where 4 = completely true information, 3 = greater than 50% true information, and 2 = less than 50% true information. For quality, the results were 2.37/4 (standard deviation 0.661), 2.98/4 (0.352), and 3.81/4 (0.36) for physicians, GPT-3.5, and GPT-4, respectively (P < .01), where 4 = provided information beyond what was asked, 3 = completely answers the question, and 2 = partially answers the question. For empathy, the mean scores were 2.37/4 (standard deviation 0.661), 2.80/4 (0.582), and 3.14/4 (0.578) for physicians, GPT-3.5, and GPT-4, respectively (P < .01), where 4 = anticipates and infers patient feelings from the expressed question, 3 = mirrors the patient's feelings, and 2 = contains no dismissive comments. Responses by GPT were ranked first 95% of the time. CONCLUSIONS:Large language model responses to patient queries about thyroid disease have the potential to be more accurate, complete, empathetic, and consistent than physician responses.
PMID: 39424485
ISSN: 1532-7361
CID: 5718952