Publications by Year: 2026

BACKGROUND: AI chatbots are proliferating in healthcare systems. It is essential to explore how physicians use these tools in order to understand their influence on clinical care and outcomes. Our goal was to understand how physicians conceive of and incorporate AI into clinical decision-making.

METHODS: We conducted semistructured interviews with generalist physicians from inpatient and outpatient settings in the USA. Prior to the interview, participants were asked to use an AI chatbot, ChatGPT-4, to complete three mock clinical cases. Physicians were interviewed regarding their perspectives on the AI chatbot. Interviews were analyzed using reflexive thematic analysis and conducted via video conference meeting, where they were recorded and transcribed.

RESULTS: We interviewed 22 physicians with 2-32 years of experience (median = 3 years). We identified a central organizing concept of "physician as filter" defining how physicians used the AI chatbot. This idea was composed of four themes. Theme 1: Physicians perceive clinical decision-making as a problem-solving activity, applying internally held knowledge to externally gathered information. Theme 2: AI chatbot systems are part of a continuum of information resources. Theme 3: Trust in the AI chatbot's outputs depends on the user's own clinical knowledge. Theme 4: Clinical decision-making is understood as the personalization of clinical knowledge and context.

CONCLUSIONS: AI chatbots may help physicians with formulating a clinical problem and generating a hypothesis by expanding their repertoire of possible cases. Despite the "wealth of information" provided by AI chatbots, physician trust in the outputs is limited, especially when AI chatbots do not provide references. Physician users described filtering chatbot outputs, using their own clinical knowledge and experience, to determine what information is relevant. In describing how providers perceive AI chatbots, we hope to guide further investigation of physician AI interaction and chatbot development that facilitates improved clinical reasoning.

BACKGROUND: Moyamoya syndrome (MMS) associated with sickle cell disease (SCD) is a severe vasculopathy that significantly increases stroke risk. While cerebral revascularization is increasingly considered in this population, concerns about perioperative safety and long-term outcomes have limited its use in clinical practice.

METHODS: We conducted a multicenter, retrospective cohort study of 553 patients with MMS who underwent surgical revascularization across 13 centers. Patients were grouped by SCD status (SCD-MMS vs. moyamoya disease (MMD)). Primary outcomes included perioperative stroke, perioperative complications, and functional status at discharge. Secondary outcomes included length of stay, and follow-up stroke.

RESULTS: Of 553 patients, 32 (5.8%) had SCD. There were no significant differences in overall perioperative stroke (OR 1.05, 95% CI 0.19 to 5.54), symptomatic perioperative stroke (OR 0.94, 95% CI 0.09 to 8.94), perioperative complications (OR 1.66, 95% CI 0.47 to 5.86), or follow-up stroke (OR 0.88, 95% CI 0.17 to 4.55). Functional outcomes at discharge were similarly favorable in both groups (mRS 0-1: OR 0.84, 95% CI 0.29 to 2.40). SCD was associated with a longer hospital stay (beta 2.78 days, 95% CI 0.60 to 4.96).

CONCLUSION: Surgical revascularization for MMS in patients with SCD does not confer additional procedural risk and yields outcomes comparable to those of patients without SCD. These findings support the role of bypass surgery as a viable treatment option in this high-risk population.

BACKGROUND: Early phase clinical trials (EP-CTs) investigate novel therapeutic approaches for patients with cancer, but little is known about patterns of supportive care service utilization and advance care planning (ACP) in this population. We sought to characterize these features in an EP-CT population and evaluate associations among receipt of supportive care services and ACP documentation.

METHODS: We retrospectively reviewed the electronic health record (EHR) of consecutive patients enrolled in EP-CTs at Massachusetts General Hospital from 01/01/17-12/30/19. We abstracted sociodemographics, performance status (Eastern Cooperative Oncology Group [ECOG] score), oncology history, trial details, as well as receipt and timing of six supportive care services (palliative care [PC], social work [SW], spiritual services [SS], parental support [PS], physical therapy [PT], and nutrition). We additionally abstracted receipt and timing of ACP documentation (defined as any EHR-documented conversation addressing illness understanding or values, preferences, or goals for future medical care, as identified using a structured keyword search). We then separately examined associations between receipt of any supportive care service and ACP documentation, number of supportive care services received and ACP documentation, and subtype of supportive care received and ACP documentation. These analyses used logistic regression models adjusted for age, sex, cancer type, and performance status.

RESULTS: During our study period, 376 patients participated in EP-CTs (median age 63.0 years, 55.9% female, 97.3% stage 4, median ECOG 1, median follow-up: 223 days, median time from diagnosis to EP-CT: 844 days). Nearly all received at least one type of supportive care across their illness trajectory (88.0%), with varied rates by service type (PC: 54.8%, SW: 64.1%, SS: 39.1%, PS: 8.0%, PT: 54.0%, nutrition: 61.2%). Most also had some form of ACP (73.9%) documented between diagnosis and death. Multivariable regression models demonstrated that receipt of any of the six forms of supportive care was associated with higher likelihood of ACP documentation (odds ratio [OR]: 9.18, 95% confidence interval (CI): 4.49-18.78, p < 0.001). Similarly, we observed associations between number of supportive care services received when considered as a continuous covariate and ACP documentation (OR1 service:1.89, 95%CI:0.90-4.03, p = 0.090; OR2 services: 15.36, 95%CI 5.78-40.78, p < 0.001, OR3+ services: 35.78, 95%CI: 14.35-89.24, p < 0.001). These associations also persisted when considering PC independently (ORPC = 11.17, 95%CIPC = 5.76-21.67, p < 0.001) from other supportive care services (ORother = 5.41, 95%CIother: 2.64-11.09, p < 0.001).

CONCLUSIONS: In this large cohort of EP-CT participants, most patients received supportive care services and had documented ACP, suggesting trial-related engagement does not impede care delivery. Notably, receipt of supportive care services correlated with ACP documentation. These findings underscore the importance of addressing individual supportive care needs among EP-CT participants.

BACKGROUND: Clean intermittent catheterization (CIC) is an effective method of bladder emptying in children with neurogenic and non-neurogenic disorders that cause difficulty in urination. However, there is a lack of expert consensus on the standardized application of CIC in pediatric populations. This guideline intends to outline recommendations for standardizing CIC in children.

METHODS: A comprehensive literature review was performed by searching key academic databases, specifically PubMed, Embase, the Cochrane Library, and Web of Science. Eligible literature-including peer-reviewed clinical trials, cohort studies, case series, and expert consensus statements-was systematically identified, screened, and critically appraised. This guideline was developed according to the "WHO Handbook for Guideline Development (2nd edition)".

RESULTS: For children with symptoms of increased post-void residual (PVR) that may threaten the upper urinary tract, CIC is recommended regardless of the cause. Safe bladder capacity (SBC) and maximum bladder capacity measurement could guide optimal CIC frequency. When infants or young children require CIC, their caregivers should receive specialized training. The CIC procedure includes thorough hand and genital area cleansing, followed by careful catheter insertion to avoid contamination of surrounding tissues. Depending on the individual's ability to void, CIC will be either partial or complete. Partial CIC is recommended for individuals who are able to void partially. When implementing CIC, a collaborative model involving the patient, caregivers, and a multidisciplinary pediatric team specializing in lower urinary tract management should be adopted, and regular follow-up and efficacy assessments are required. Urodynamic study to determine the PVR and SBC in conjunction with a voiding/catheterization diary provides an objective basis for adjusting the frequency of catheterization and for determining whether to continue catheterization.

CONCLUSION: This guideline established a standardized protocol for children who require CIC to facilitate bladder emptying.

PURPOSE: The utility of combination treatment with gemcitabine and camonsertib, an ataxia telangiectasia and Rad3-related kinase inhibitor (ATRi), in mediating tumor cell death was assessed in preclinical models, prompting clinical investigation. The phase 1b TRESR study (NCT04497116) aimed to evaluate the safety, tolerability and preliminary efficacy of the combination in patients with advanced solid tumors harboring DNA damage repair (DDR) gene alterations.

METHODS: Cell lines and tumor xenografts were tested across a range of dose levels and schedules. Patients (N = 76) harboring tumors with DDR gene alterations received camonsertib (80-120 mg) and de-escalating gemcitabine (1000-100 mg/m²) in 21- or 28-day cycles on an intermittent dosing regimen. Safety, tolerability, and preliminary efficacy were assessed to identify an optimal dosing regimen.

RESULTS: In pre-clinical models, low-dose camonsertib (1/3 maximum tolerated dose [MTD]) and gemcitabine led to tumor regression and was well tolerated with minimal body weight loss observed. In patients, synergistic toxicities were observed, primarily myelosuppression, resulting in gemcitabine de-escalation. The introduction of a one week on / one week off (1/1w) schedule in combination with low-dose gemcitabine allowed for spontaneous neutrophil recovery, fewer dose modifications, and improved tolerability. Tumor responses were primarily observed in patients with gynecological cancers, with tumor control maintained for greater than one year in some patients.

CONCLUSION: Camonsertib and low-dose gemcitabine demonstrated preliminary clinical activity, but due to challenging tolerability further evaluation is warranted to identify the optimal dosing regimen and subset of patients who may benefit most from this combination.

BACKGROUND: Rectal cancer remains a significant clinical challenge with demand for conclusive biomarkers, essential in prognostication and therapy monitoring of neoadjuvant and adjuvant treatment strategies.

AIMS: The aim of the study was to evaluate AXL and cellular mesenchymal-epithelial transition factor (C-MET) biomarkers for cancer stem cells and to correlate them with clinicopathological characteristics and patient outcome data with respect to neoadjuvant chemoradiotherapy.

METHODS: Serum levels of soluble surface markers AXL and C-MET were retrospectively analyzed in 164 rectal cancer patients with additional immunofluorescent analyses of their primary tumor tissues.

RESULTS: Kaplan-Meier analysis confirmed the prognostic significance of Union for International Cancer Control stages, but with no significant correlation between investigated markers with patient age, gender, or tumor stage. In contrast, tumor tissues demonstrated stage-dependently increased marker expression. While AXL was detected at low levels, C-MET exhibited a bimodal distribution, with elevated levels seen in most patients, particularly post-neoadjuvant therapy and non-significantly in the subgroup with poorer response to neoadjuvant therapy (p=0.074).

CONCLUSIONS: AXL serum levels in the rectal cancer cohort were significantly different from healthy subjects but did not correlate with tumor stage or survival during and after neoadjuvant/adjuvant therapy. Soluble C-MET levels in the blood, influenced by neoadjuvant chemoradiotherapy, may serve as a predictive marker for treatment response.

BACKGROUND: Venous thromboembolism (VTE) is a frequent complication in malignancy. Low-molecular-weight heparins and direct oral anticoagulants have replaced vitamin K antagonists (VKAs) as the standard of care for cancer-associated VTE. Nonetheless, clinical trials have not established a survival benefit of these agents compared with VKA.

OBJECTIVES: We conducted a systematic review and meta-analysis to compare survival in cancer patients receiving VKA vs other anticoagulants.

METHODS: We searched Embase, Web of Science, PubMed, ClinicalTrials.gov, and Cochrane from inception until April 10, 2025, focusing on the use of VKA and non-VKA in cancer patients. Primary outcome was mortality and secondary outcomes included thromboembolism and bleeding.

RESULTS: Of 11,198 studies screened, 14 studies (70,025 patients) were included. VKA were associated with lower mortality than non-VKA in observational studies (odds ratio [OR], 0.84; 95% CI, 0.78-0.91; I 2 = 81%; n = 6 studies) but not in randomized controlled trials (OR, 0.99; 95% CI, 0.86-1.13; I 2 = 0%; n = 8 studies). In subgroup analysis, follow-up period of >6 months (OR, 0.85; 95% CI, 0.79-0.92; I 2 = 75%), solid malignancies (OR, 0.81; 95% CI, 0.75-0.88; I 2 = 78%), and indication of VTE only (OR, 0.89; 95% CI, 0.83-0.96; I 2 = 42%) demonstrated improved survival with VKA.

CONCLUSION: The use of VKA was associated with lower mortality than non-VKA anticoagulation in patients with cancer in observational studies but not in randomized trials. The analysis was limited by high heterogeneity, which must be considered when interpreting results.

PURPOSE: Resilience is crucial in mitigating the risk of stress-related health issues. Although many people can adapt to adverse stress or trauma, stress exposure can increase the risk of health issues, including obesity, cardiovascular disease, and digestive illnesses. Some individuals may even develop debilitating conditions, such as post-traumatic stress disorder (PTSD). People with PTSD often struggle to adapt, sometimes turning to alcohol to cope, which can lead to alcohol use disorder (AUD), characterized by excessive alcohol-seeking and dependence. Understanding the biological underpinnings of resilience, therefore, is a key to preventing both PTSD and AUD. Recent research has uncovered the neurobiological traits that protect against the development of stress-induced alcohol dependence. Studies have shown that proactive coping and a lack of stress-related symptoms are associated with resilience. Preclinical studies, especially in rodents, have provided deeper insights into how stress impacts alcohol-seeking behaviors. Research has shown that resilience involves adaptive changes at the molecular, cellular, neural circuit, and systems levels. This review aims to integrate this research to better understand what makes people vulnerable to stress and alcohol consumption, highlighting aspects frequently overlooked in clinical models.

SEARCH METHODS: This review employed systematic search strategies to achieve a comprehensive and structured assessment of the existing body of literature using the academic databases PubMed, Google Scholar, and Web of Science. Targeted keywords included "stress," "PTSD," "trauma," "alcohol," "AUD," "resilience," "vulnerability," "susceptibility," "sex difference," and "animal models"; Boolean operators (AND, OR, NOT) were used to refine the results. Exclusion criteria included research published before 1990, research that was not peer reviewed, and publications in languages other than English. Additional studies were identified by reviewing the references cited in key articles as well as by identifying subsequent studies that referenced these pivotal works. The search was carried out from April to June 2025 focusing on, but not limited to, experiments involving rodent models.

SEARCH RESULTS: The search yielded a total of 347 articles. After screening, 283 articles were removed, either because they met the predefined exclusion criteria or because they were duplicates. This process resulted in 64 articles, forming the core of this comprehensive review.

DISCUSSION AND CONCLUSIONS: This review summarizes an overview of recent progress in studies of PTSD and AUD, primarily focusing on the effect of resilience on post-stress alcohol intake in animal models. The findings highlight several biomarkers that may help identify individuals at risk for PTSD, AUD, or their co-occurrence, acknowledging that no single identifier can predict post-trauma outcomes. The identification of these markers is an ongoing process, yet it will be crucial for early diagnosis and risk assessment moving forward.