Assessing ChatGPT 4.0's test performance and clinical diagnostic accuracy on USMLE STEP 2 CK and clinical case reports.

While there is data assessing the test performance of artificial intelligence (AI) chatbots, including the Generative Pre-trained Transformer 4.0 (GPT 4) chatbot (ChatGPT 4.0), there is scarce data on its diagnostic accuracy of clinical cases. We assessed the large language model (LLM), ChatGPT 4.0, on its ability to answer questions from the United States Medical Licensing Exam (USMLE) Step 2, as well as its ability to generate a differential diagnosis based on corresponding clinical vignettes from published case reports. A total of 109 Step 2 Clinical Knowledge (CK) practice questions were inputted into both ChatGPT 3.5 and ChatGPT 4.0, asking ChatGPT to pick the correct answer. Compared to its previous version, ChatGPT 3.5, we found improved accuracy of ChatGPT 4.0 when answering these questions, from 47.7 to 87.2% (p = 0.035) respectively. Utilizing the topics tested on Step 2 CK questions, we additionally found 63 corresponding published case report vignettes and asked ChatGPT 4.0 to come up with its top three differential diagnosis. ChatGPT 4.0 accurately created a shortlist of differential diagnoses in 74.6% of the 63 case reports (74.6%). We analyzed ChatGPT 4.0's confidence in its diagnosis by asking it to rank its top three differentials from most to least likely. Out of the 47 correct diagnoses, 33 were the first (70.2%) on the differential diagnosis list, 11 were second (23.4%), and three were third (6.4%). Our study shows the continued iterative improvement in ChatGPT's ability to answer standardized USMLE questions accurately and provides insights into ChatGPT's clinical diagnostic accuracy.

Liver and cardiovascular disease outcomes in metabolic syndrome and diabetic populations: Bi-directional opportunities to multiply preventive strategies.

The incidence and prevalence of metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are rising globally. MetS and T2DM are associated with significant morbidity and mortality, which is partly related to liver and cardiovascular disease. Insulin resistance is central to MetS and T2DM pathophysiology, and drives ectopic fat deposition in the liver, also known as metabolic dysfunction-associated steatotic liver disease (MASLD). MetS and T2DM are not only risk factors for developing MASLD but are also independently associated with disease progression to steatohepatitis, cirrhosis, and hepatocellular carcinoma. In addition to the risk of liver disease, MetS and T2DM are independent risk factors for cardiovascular disease (CVD), including coronary artery disease (CAD) and heart failure (HF). Importantly, there is a bidirectional relationship between liver and CVD due to shared disease pathophysiology in patients with MetS and T2DM. In this review, we have described studies exploring the relationship of MetS and T2DM with MASLD and CVD, independently. Following this we discuss studies evaluating the interplay between liver and cardiovascular risk as well as pragmatic risk mitigation strategies in this patient population.

Persistent Insulin Autoimmune Syndrome in a Caucasian Male in the Absence of Triggers.

Insulin autoimmune syndrome (IAS) or Hirata disease is a rare condition presenting as recurrent hypoglycemia, and associated with elevated insulin levels in the presence of insulin autoantibodies (IAAs) in patients who were never exposed to exogenous insulin and with no evidence of pancreatic abnormalities. IAS is much more frequent in East Asians, especially the Japanese population, compared to the lower incidence in Caucasians. However, it can be associated with other autoimmune diseases or drug use like methimazole and alpha-lipoic acid (ALA). We report a case of a 47-year-old Caucasian male presenting with a 12-month history of worsening episodes of fasting and post-prandial hypoglycemia associated with symptoms of dizziness, tremors, palpitations, and unconsciousness associated with hypoglycemia. Symptoms resolved with the administration of carbohydrate-containing foods, establishing Whipple's triad. At an outside facility, he had initial labs that showed elevated insulin levels (141 µU/ml) with normal glucose, C-peptide, and proinsulin levels, but there was no availability of an IAA lab assay. Given his symptoms, severity, and frequency of hypoglycemia, he was admitted to the hospital for a 72-hour fast, which showed the lowest glucose level of 64 mg/dl with inappropriately high insulin of 22.2 µU/ml, low C-peptide of 0.57 ng/ml, and undetectable proinsulin of <1.6 pmol/L, but with IAA being >50 U/ml (0.0-0.4 U/ml). He was treated with intensive dietary counseling with a low-carbohydrate diet and prednisone 20 mg twice daily initially. Additionally, he could not tolerate octreotide, diazoxide, and acarbose due to side effects. He is currently on prednisone 10 mg daily and nifedipine with no further hypoglycemic episodes, but still has a high IAA of >50 U/ml and serum insulin levels of 70-112 µU/ml. Our case highlights the importance of recognizing hypoglycemia and checking for IAA levels as first-line diagnostic tests, in the absence of which there could be a delay in diagnosis and leading to unnecessary lab and imaging testing. Our case is unique since it happened in a Caucasian without any prior exposure to a triggering factor and has not undergone self-remission yet, which happens in most of IAS cases.

Efficacy and safety of tirzepatide, GLP-1 receptor agonists, and other weight loss drugs in overweight and obesity: a network meta-analysis.

OBJECTIVE: This network meta-analysis evaluates the efficacy and safety of tirzepatide compared to glucagon-like peptide-1 receptor agonists (GLP-1 RA) and other weight loss drugs in the treatment of overweight and obesity. METHODS: MEDLINE, Embase, and Cochrane CENTRAL were searched for randomized controlled trials on tirzepatide, GLP-1 RA, and weight loss drugs approved by the US Food and Drug Administration. A network meta-analysis was performed, drawing direct and indirect comparisons between treatment groups. Network diagrams and surface under the cumulative ranking curve analysis were performed for primary (≥5%, ≥10%, ≥15%, absolute weight loss) and secondary outcomes and adverse effects. RESULTS: Thirty-one randomized controlled trials, involving more than 35,000 patients, were included in this study. Tirzepatide 15 mg ranked in the top three across weight-related parameters, glycemic profile (glycated hemoglobin), lipid parameters (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides), and blood pressure. Tirzepatide 15 mg had the highest efficacy compared with placebo for achieving ≥15% weight loss (risk ratio 10.24, 95% CI: 6.42-16.34). As compared to placebo, tirzepatide and GLP-1 RA across all doses had significant increases in gastrointestinal adverse effects. CONCLUSIONS: The superiority of tirzepatide and GLP-1 RA in inducing weight loss and their ability to target multiple metabolic parameters render them promising candidates in the treatment of patients with overweight and obesity.

Insulin Edema Associated With Glargine.

Insulin edema is a poorly understood complication of insulin therapy. It has been reported in patients with both type 1 and 2 diabetes mellitus and typically occurs in patients with newly diagnosed or poorly controlled diabetes mellitus either after initiation or intensification of insulin therapy. A 20-year-old man presented with anorexia, polydipsia, and weight loss. Serum glucose on admission was 824 mg/dL (45.8 mmol/L) and hemoglobin A1c was >14.0. Additional workup was notable for positive anti-IA2 antibodies and low C-peptide of 0.5 ng/mL (1.1-4.4 ng/mL). He was diagnosed with type 1 diabetes mellitus and was started on insulin therapy with glargine and lispro. Within 4 days after insulin initiation, he developed bilateral leg swelling and reported a 25-pound (11.3-kg) weight gain over the next 10 days. After excluding other systemic causes of edema such as heart failure, renal failure, and liver failure, a diagnosis of insulin edema was made. Insulin glargine was switched to insulin degludec. Complete resolution of edema occurred within 3 days of switching the insulins. Insulin edema is a diagnosis of exclusion. Insulin's role in renal sodium handling, vasodilation, and increased vascular permeability have been postulated as possible mechanisms. Clinicians should be aware of this rare complication.

Novel interactive text-messaging curriculum for endocrinology board review.

Background: The ABIM certification exam is one of the measures to ensure that physicians have the clinical skills for good care delivery. The 5-year average pass rate for ABIM Endocrinology exam is 82%. The pass rate significantly decreased to a nadir of 74% in 2021 and 2022, lowest of all medicine subspecialties. Objectives: To assess the feasibility of text messaging curriculum for fellows and its utility in improving their test performance. Methods: In 2021, endocrinology fellows from 51 programs across the country were invited to participate in our curriculum. They completed a pre-test, joined a texting group via Remind application and received 1 multiple choice question daily (total n = 78). After 15 weeks, they completed a post-test and survey. Paired results from pre- and post-test were compared. Results: A total of 89 fellows from 27 programs responded. Of these, 82 fellows, predominantly females (n = 60; 73 %), filled out the pre-test. On an average, 42 fellows (SD = 12) responded to the questions daily and 57 % of them answered the questions within 24 h. Thirty fellows completed the post-test. The median number of correct responses on the pre-test was 5 (IQR 3-6), compared to 8 (IQR 6-9) in the post-test. There was a significant improvement (p-value < 0.0001) in fellows' performance in the post-test when compared with the pre-test following our intervention. Conclusions: Text-messaging based curriculum for exam preparation is feasible and can improve test performance. Fellows find receiving a daily high yield multiple choice question via text-message as a useful tool for exam preparation.

Vanishing Adrenal Glands: Bilateral Adrenal Hemorrhage With Adrenal Insufficiency in COVID-19 Infection.

Coronavirus disease 2019 (COVID-19) has been associated with thrombotic and endocrine complications, including adrenal insufficiency in the setting of adrenal hemorrhage. We present a patient diagnosed with antiphospholipid syndrome (APLS) in the setting of COVID-19 infection resulting in bilateral adrenal hemorrhage, subsequently leading to adrenal insufficiency. Acute adrenal hemorrhage is an underrecognized cause of decompensation, multisystem failure, and death in severe illness. Reports of adrenal insufficiency in the setting of COVID-19 infection revealed microscopic infarction, which can increase the risk of hemorrhage. Other mechanisms include severe hyperinflammatory response and cytokine storm leading to endothelial dysfunction, vascular injury, adrenal parenchymal damage, and hemorrhage. COVID-19 infection can be associated with coagulopathy and thromboembolic events and can lead to adrenal hemorrhage. Adrenal insufficiency is life-threatening and needs to be recognized promptly. There can be a latent phase between hemorrhagic events and adrenal failure; hence, close monitoring and timely intervention are important.

Pancreatitis in a 57-Year-Old Female Two Weeks After Initiation of Empagliflozin.

Background/Objective: Pancreatitis is a common diagnosis requiring hospital admission, associated with significant costs. Although pancreatitis is an established side-effect with other diabetes medications, such as Glucagon like Peptide-1 Receptor Agonists and Dipeptidyl Peptidase 4 inhibitors, the association with SGLT2 inhibitors is not established. We present a patient with empagliflozin associated drug-induced acute pancreatitis (DIAP) and a review of published case reports. Case Report: A 57-year-old woman with T2DM presented to the hospital with severe abdominal pain. Her vital signs on presentation were temperature 98.3 F, blood pressure 139/79 mm Hg, pulse 62/min, and respiratory rate 15/min, saturating 99% on room air. Labs were notable for white blood cell count 12.8 (4.5-10.8 10∗3 µl), lipase- 36 (7-60 U/L), calcium- 9.4 (8.5-10.5 mg/dL), and triglycerides- 150 (35-150 mg/dL). Computed tomography abdomen showed induration of the peripancreatic fat, suggesting pancreatitis. No alcohol use was reported. DIAP and idiopathic pancreatitis were considered possible etiologies. Medication history revealed that the patient was started on empagliflozin 2 weeks before this admission. Empagliflozin was discontinued and she was discharged on metformin and glipizide. Discussion: Sodium Glucose Transporter 2 inhibitors (SGLT2) inhibitors are increasingly used for treating type 2 diabetes mellitus and heart failure. The association of these medications with pancreatitis, its timeline, and the underlying mechanisms are yet to be understood. This case is intended to add to the existing limited literature on this side effect. Conclusions: With the increasing use of SGLT2 inhibitors, more cases of DIAP are being reported. Physicians need to consider SGLT2 inhibitors as a possible cause of pancreatitis after excluding other etiologies.

Pharmacological approaches to the prevention of type 2 diabetes mellitus.

About 1 in 10 adults worldwide are estimated to have diabetes mellitus. They are at risk of developing life-threatening complications resulting in reduced quality of life, increased mortality and higher healthcare costs. The ability to prevent or delay type 2 diabetes mellitus (T2DM) by modifying some of its risk factors has been hypothesized for decades. The long and often gradual time-course of increasing dysglycemia prior to diabetes diagnosis suggests that interventions during that period could be effective in preventing T2DM. In addition to lifestyle modifications, certain drugs prevent or slow development of hyperglycemia. Recently, drugs used for obesity management were shown to prevent T2DM. In this review, we discuss various pharmacotherapeutic options for preventing T2DM.

Adverse Events Related to Tirzepatide.

Context: Tirzepatide is a dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) approved by the US Food and Drug Administration in May 2022 for patients with type 2 diabetes mellitus (T2DM). Objective: We aimed to determine the rates of individual adverse events (AEs) related to 3 studied doses of tirzepatide. Methods: We performed a systematic review with meta-analysis including 5 databases (PubMed, Embase, CINAHL, Scopus, and Web of Science) for all clinical trials reporting AEs related to tirzepatide. The safety data from individual studies were extracted and analyzed through meta-regression to assess rates of individual AEs. Study quality assessment was performed using the National Heart, Lung, and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: Ten trials (6836 participants) were included. Gastrointestinal (GI) AEs were the most commonly reported AEs and were dose dependent 39% (95% CI, 35%-43%), 46% (95% CI, 42%-49%), and 49% (95% CI, 38%-60%) for the 5, 10, and 15 mg dose, respectively. Among all GI AEs, nausea and diarrhea were most frequent at any dose of tirzepatide. Drug discontinuation due to AEs was highest with the 15 mg dose of tirzepatide (10%). Incidence of mild hypoglycemia (blood glucose < 70 mg/dL) was highest with tirzepatide 10 mg dose 22.6% (9.2%-39.8%). Rates of fatal AEs, severe hypoglycemia, acute pancreatitis, cholelithiasis, and cholecystitis were extremely low (≤ 1%) across all doses of tirzepatide. Conclusion: Tirzepatide is associated with a dose-dependent increase in incidence of GI AEs and AEs leading to drug discontinuation. Severe hypoglycemia, fatal AEs, acute pancreatitis, cholelithiasis, and cholecystitis are rare with this medication.

Enhancing Patient Literacy on Calcium Supplementation: A Quality Improvement Initiative.

OBJECTIVE: This study aims to assess patients' knowledge and identify barriers in interpreting calcium on supplement and nutrition labels and to determine whether education would be beneficial. METHODS: Patients with conditions requiring calcium supplementation were included in this study. Participants were first given a 9-question pre-education survey. They were then taught how to read calcium on labels using the educational cards developed. This was followed by a 7-question posteducation survey. Endocrinologists were surveyed to assess their experience in treating patients who required calcium supplementation. RESULTS: Before education, 31 (33%) and 37 (40%) of the participants felt that the supplement and nutrition labels, respectively, were confusing. After education, only 2 (2%) and 6 (6%) of the participants, respectively, still felt the same. There was a significant improvement in the interpretation of calcium citrate (Citracal) and calcium carbonate (TUMS) labels, with a trend of improvement in reading a milk label. Of the 47 endocrinologists surveyed, only 5 (11%) felt that their patients often or always knew the correct amount of calcium to be taken. Two-thirds 30 (64%) of the endocrinologists always or often explained to their patients how to interpret calcium labels. About half 23 (49%) of the endocrinologists always or often needed to take time to look up the calcium content of supplements. For most endocrinologists 29 (62%), this took at least 2 to 4 minutes. CONCLUSION: Our patients had trouble interpreting calcium labels, and the use of educational cards was effective in improving calcium literacy.

Learning Theories Versus Practice: How Do Internal Medicine Residents Study for Licensing Examinations?

OBJECTIVE:  The ability to recall relevant medical knowledge within clinical contexts is a critical aspect of effective and efficient patient diagnosis and management. The ever-growing and changing body of medical literature requires learners to develop effective life-long learning techniques. Learners can more successfully build their fund of knowledge and ability to retrieve it by using evidence-based learning strategies. Our objective was to evaluate the study habits of internal medicine (IM) residents at an academic institution to understand if they apply key learning strategies for the American Board of Internal Medicine (ABIM) exam preparation. We also briefly review various learning strategies that can be applied to IM residency curricula. METHODS: A web-based survey consisting of 16 multiple-response questions on study habits was filled out by the IM residents in 2019 at Tufts Medical Center. RESULTS: Of the 75 residents invited to participate in the study, 69 responded (response rate = 92%). Of the responders, n=25 (36.2%) were post-graduate year (PGY)-1, n=20 (29.0%) were PGY-2, and n=24 (34.8%) were PGY-3 residents. More than half the residents (n=40, 58%) had Step 2 Clinical Knowledge (CK) scores > 250. Residents self-reported applying spaced learning (67%), interleaving (64%), retrieval (64%), and elaboration practices (46%) for exam preparation. There was a significant association between the Step 2 CK score and elaboration (p=0.017) technique but not with spaced learning, interleaving, or retrieval. The majority of residents felt not at all prepared (n=42, 60.9%) for the ABIM exam. CONCLUSIONS: Despite two years of clinical training, 33% of the third-year residents felt inadequately prepared for the board certification exam. Incorporating evidence-based learning strategies into their daily curriculum may help them better prepare for the ABIM exam.

Let's Not Miss the Treatable Ones: Two Cases of Neonatal Sepsis Due to Malaria.

Congenital malaria is the direct infection of an infant with a malarial parasite from the mother either during pregnancy or at birth. Neonatal malaria occurs due to an infective mosquito bite after birth. Neonatal and congenital malaria (NCM) can occasionally present with life-threatening neonatal sepsis and rarely with neonatal jaundice. These conditions are typically managed by general pediatricians, especially in remote areas without access to specialized care. A high clinical index of suspicion is required to diagnose neonatal and congenital malaria, given that their presentation can mimic other more common neonatal conditions. We present two neonates with malaria, highlighting the importance of considering this treatable entity in the differential.

Monitoring Endocrine Complications of Immunotherapy: A Screening Tool.

Introduction The advent of immunotherapy has revolutionized cancer therapy in recent years. Immunotherapy using monoclonal antibodies against checkpoint molecules, including programmed death (PD)-1, PD ligand (PD-L)1, and cytotoxic T-lymphocyte antigen 4 (CTLA)-4, has become a cornerstone in cancer therapy. However, due to the physiologic role of checkpoint molecules in preventing autoimmunity, immune-related adverse events (irAEs) have emerged as frequent complications. As the use of immunotherapy increases, a better understanding of irAEs and screening tools for timely diagnosis and management are needed. Materials and methods We surveyed oncology providers at our institution with 10 questions assessing their knowledge, and comfort levels in diagnosing and managing endocrine irAEs. We created an endocrine clinic referral order specifically for oncology-related endocrinopathies and created a screening tool for diagnosing these endocrinopathies. We met with our oncology providers in three different hour-long sessions. A post-intervention survey was sent out six months after our initial meeting to assess changes in the participants' knowledge and comfort levels. We also reviewed the electronic medical records system for the number of new referrals to endocrinology clinic. Results A total of 27 (N) participants responded to the initial survey and 14 (n) responded to the subsequent survey six months later. Based on the initial survey, only a minority (26%) of respondents were comfortable diagnosing and managing (15%) immunotherapy-related adrenal dysfunction whereas more respondents were comfortable diagnosing (55%) and managing (56%) thyroid dysfunction. The majority (67%) of the respondents knew which immunotherapies commonly are implicated in hypophysitis but only 42% of them were aware of the next steps of its management. We noted a significant increase in self-reported comfort levels in diagnosing (p < 0.05) and managing (p < 0.05) adrenal disorders post-intervention. There was also a trend of improvement in participants' comfort levels regarding diagnosing and managing thyroid dysfunction, management of hypophysitis, and immunotherapies implicated in thyroid dysfunction but the changes did not reach statistical significance. There was no significant change in their knowledge regarding immunotherapies implicated in hypophysitis and natural history of thyroid dysfunction in this setting. In the six months following our intervention, 30% (n=21) of the patients referred to the endocrine clinic were for immune-related endocrinopathies compared to 19% (n=7) of patients over a similar duration before the intervention. Data on the time between referral and endocrinology appointment was available for 16 out of the 21 patients and the mean (±SD) time to endocrine clinic appointment was 2.66 (±1.95) weeks. Nine (43%) of the 21 referred patients were seen in endocrinology clinic within two weeks. Conclusions Although immune-related endocrinopathies are rarely fatal, they have a significant impact on patients' quality of life. Endocrinopathies are typically manageable with prompt recognition and treatment. But the subtle and non-specific manifestations make the diagnostic process a challenge. Standardized and practical screening tools can help in diagnosing these adverse events promptly, seeking specialized care if needed and may also aid in reducing healthcare-related costs.

Predictors of Mortality in Hypercalcemia of Advanced Chronic Liver Disease.

OBJECTIVE: Hypercalcemia is sometimes observed in patients with cirrhosis, but very little is known about the epidemiology in patients with hypercalcemia of chronic liver disease (HCLD) or how its presence may modulate the overall mortality risk. We assessed the associations between the clinical and laboratory characteristics of patients with HCLD with 90-day mortality. METHODS: A systematic search of the medical records at our institution over a 10-year period was performed to retrospectively identify subjects with HCLD during inpatient admission. Univariate and multivariable regression analyses were performed to detect the risk factors for all-cause 90-day mortality. RESULTS: Thirty-eight subjects with HCLD were identified using stringent inclusion and exclusion criteria to exclude individuals with other secondary causes of hypercalcemia. A total of 35 subjects had 90-day vital status available, which revealed 40% mortality. The model for end-stage liver disease sodium score and duration of inpatient hypercalcemia were positively associated with mortality with respective odds ratios of 1.23 (95% CI, 1.06-3.23) and 1.24 (95% CI, 1.04-1.49) in a univariate regression model and 1.30 (95% CI, 1.04-1.62) and 1.33 (95% CI, 1.04-1.71) in a multivariable regression model. The admission and peak serum calcium levels were not associated with mortality. Only 6 subjects received bisphosphonates or calcitonin during their admission, limiting our ability to assess the impact of treatment on outcomes. CONCLUSION: In patients admitted to the hospital with HCLD, the duration of hypercalcemia was positively associated with 90-day mortality, providing a potential interventional target to reduce mortality in this high-risk population. Studies to validate the utility of treating hypercalcemia are required.

Undiagnosed Hoffa fracture of medial femoral condyle presenting as chronic pain in a post-polio limb.

Isolated coronal fracture of medial femoral condyle with intact lateral femoral condyle is extremely rare. A high index of suspicion is necessary for early diagnosis especially in cases of undisplaced fractures. Here we report a case of medial Hoffa fracture in a post-polio limb presenting as chronic pain. Management of such fractures in limbs affected by late sequelae of poliomyelitis is particularly problematic in view of osteoporosis and osseous hypoplasia. The fracture was approached through medial parapatellar arthrotomy and fixation was done with cannulated cancellous screws in anteroposterior direction. Union was achieved at 16 weeks.