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γδ T cells play an important role in disease control in acute myeloid leukemia (AML) and have become an emerging area of therapeutic interest. These cells represent a minor population of T lymphocytes with intrinsic abilities to recognize antigens in a major histocompatibility complex-independent manner and functionally straddle the innate and adaptive immunity interface. AML shows high expression of phosphoantigens and UL-16 binding proteins that activate the Vδ2 and Vδ1 subtypes of γδ T cells, respectively, leading to γδ T cell-mediated cytotoxicity. Insights from murine models and clinical data in humans show improved overall survival, leukemia-free survival, reduced risk of relapse, enhanced graft-versus-leukemia effect, and decreased graft-versus-host disease in patients with AML who have higher reconstitution of γδ T cells following allogeneic hematopoietic stem cell transplantation. Clinical trials leveraging γδ T cell biology have used unmodified and modified allogeneic cells as well as bispecific engagers and monoclonal antibodies. In this review, we discuss γδ T cells’ biology, roles in cancer and AML, and mechanisms of immune escape and antileukemia effect; we also discuss recent clinical advances related to γδ T cells in the field of AML therapeutics.

Acute respiratory distress syndrome (ARDS) is associated with high mortality rates in critically ill patients. Renopulmonary interplay remains crucial in contributing to the outcomes in patients with ARDS. While the role of acute kidney injury has been widely explored in these patients, there remains an unmet need in the literature about the impact of chronic kidney disease (CKD) in these patients. Is there a quantifiable association between CKD and in-hospital outcomes in patients with ARDS? We utilized a retrospective study design to compare descriptive statistics and outcomes in patients with ARDS with or without CKD. Pearson's chi-square test was used to compare categorical variables, while the Wilcoxon rank sum test was used for continuous variables. We also performed multivariate logistic regression analyses for each outcome and adjusted for demographics and comorbidities. Lastly, we conducted a sensitivity analysis using propensity score-matched outcomes between these groups. Among 479,450 patients with ARDS, 17.6% also had CKD, while 82.4% did not. Patients with ARDS and CKD were older (median age: 71 years vs. 60 years, < 0.001) and comprised a greater proportion of males (59.4% vs. 55.9%, < 0.001). CKD was associated with increased odds of in-hospital mortality (adjusted odds ratio [aOR] 1.29, < 0.001), acute heart failure (aOR 1.26, < 0.001), ventricular arrhythmias (aOR 1.16, < 0.001), cardiogenic shock (aOR 1.10, = 0.044), major adverse cardiovascular events (aOR 1.29, < 0.001), and length of stay ≥ 7 days (aOR 1.05, = 0.033). Our study provides insights into the magnitude of impact renal diseases may have on the outcomes of patients with ARDS. Further prospective studies are warranted to establish more substantial epidemiological evidence of this relationship to tailor the management of such patients.

Background: Malignant pleural effusion (MPE) affects approximately 150,000 patients in the United States each year and usually signifies advanced-stage cancer. The optimal treatment remains a challenge but indwelling pleural catheters (IPC) offer several advantages and may help achieve spontaneous pleurodesis (SP) in some patients. Objectives: We aim to investigate the predictors of SP among patients with MPE, particularly in a resource-limited community-based safety net hospital. Design: This is a retrospective cohort study done at a community-based safety net hospital. Methods: Adults diagnosed with or suspected of having MPE between January 2015 and December 2023 who underwent IPC placement were included. Data was collected retrospectively from December 2023 to June 2024. Data encompassed demographics, imaging, post-procedural complications, pleural fluid analysis, oncology treatment history, and utilization of medical thoracoscopy without chemical pleurodesis (MTWCP) for diagnosis. Results: A total of 173 patients underwent IPC insertion. Most of our patients were women (64.2%), and Latin American (65.9%), with a mean age of 55.3 years. The most common type of primary cancer was breast (28.9%) followed by lung (23.1%) and lymphoma (6.9%). Pleural fluid characteristics such as glucose, eosinophils, Lactate Dehydrogenase (LDH), and protein concentration were not significantly associated with SP. Most patients had low Eastern Cooperative Oncology Group scores of 0–2 (64.6%) and low LENT (Lactate Dehydrogenase (L), Eastern Cooperative Oncology Group (E) Performance Score, Neutrophil-to-Lymphocyte Ratio (N), and Tumor type (T) score) scores of 0–4 (59%). Lower scores (better functional status) were significantly associated with SP. Post-IPC chemotherapy and/or radiotherapy and immunotherapy were significantly associated with SP, adjusted odds ratio (OR) 7.295 (95% CI: 3.05–17.4, p = 0.001) and adjusted OR 6.261 (95% CI: 2.73–14.36, p = 0.001) respectively. MTWCP was also a predictor of SP with an adjusted OR of 4.031 (95% CI: 1.452–11.19, p = 0.007). Conclusion: Our study is the first to assess predictors of SP in a resource-limited safety net hospital representing under-represented and underserved patients. We identify several factors associated with higher rates of SP such as higher functional status, MTWCP, chemotherapy, immunotherapy, and radiation post-IPC placement. The study findings can help clinicians consider IPC placement and guide them regarding the duration and possible complications of IPC. MTWCP appears to improve the success of SP. Further studies are needed to assess these findings further. Plain language summary Factors associated with increased rates of lung and chest wall fusion in patients who had an indwelling pleural catheter inserted for a malignant pleural effusion • The lungs and chest wall are lined with thin membranes called pleura. The area between the lung and chest wall, i.e- the pleural space contains a small amount of fluid, approximately 1 teaspoon. Pleural effusion is an abnormal build-up of fluid within this space. • Malignant pleural effusions (MPE) defined as the spread of cancer cells within the pleural space may develop in 15% of patients with cancer. • MPE may cause symptoms such as shortness of breath, cough, and chest pain. • Indwelling pleural catheters are small, flexible tubes made from silicone that can be inserted into the chest cavity and allow drainage of MPE even while at home. • These indwelling pleural catheters may cause spontaneous pleurodesis (SP) which occurs when the two layers of the lining of the lung fuse together. • We studied various factors that may be associated with a faster onset of spontaneous pleurodesis. • We found that functional status, chemotherapy, immunotherapy and radiation post-IPC placement and placement of IPC after medical thoracoscopy (a procedure where a camera inserted into the pleural space for visualization and biopsies after fluid drainage) were associated with significantly higher rates of spontaneous pleurodesis.

Background: Venetoclax-based combination therapies have provided treatment options for patients with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy. However, venetoclax resistance is common, and for such patients, the prognosis is dismal, and treatment approaches with different mechanisms of action are urgently needed. γδ T cells are a promising candidate owing to their good safety profile and cytotoxic effects in various types of cancers but are mostly unstudied in AML. Methods: Here we used flow cytometry to profile the subtype and memory phenotype of peripheral blood γδ T cells in AML patients and investigate the feasibility of using donor-derived Vγ9Vδ2 T cells to treat AML as both a single agent and in combination with venetoclax. Additionally, we used bioluminescence imaging to examine the effect of donor-derived Vγ9Vδ2 T cells on AML xenograft models alone and in combination with venetoclax. Results: We observed that Vδ2 T cells were less abundant and the TEMRA (terminally differentiated effector memory) phenotype was more prevalent as compared with that of healthy donors, suggesting that replenishing patients with Vδ2 T cells may be an effective treatment option. We found that donor-derived Vγ9Vδ2 T cells that Vγ9Vδ2 T cells efficiently induced apoptosis in AML cells from eight cell lines and three primary cultures in an effector-to-target cell ratio-dependent manner. Moreover, Vγ9Vδ2 T cells showed potent cytotoxicity against the venetoclax-resistant OCI-AML3 cell line and remained potent in the presence of venetoclax. Treatment with Vγ9Vδ2 T cells significantly extended survival in two AML xenograft models established with the aggressive Molm-13 and the venetoclax-resistant OCI-AML3 cell lines. An additive effect of venetoclax and Vγ9Vδ2 T cells was observed in the latter model. Conclusions: Overall, these findings suggest Vγ9Vδ2 T cells as a promising “off-the-shelf” immunotherapy approach for AML patients, especially for patients with venetoclax-resistant disease.

BackgroundCOVID-19-related pulmonary complications have been explored extensively in the recent past. There is also a significant amount of literature on the neurological manifestations of COVID-19. However, there exists an unmet need to assess the impact of COVID-19 on patients with cerebrovascular diseases and its role in affecting mortality in such patients.MethodsIn this cross-sectional study, we analyzed 401,318 hospitalized patients with cerebrovascular diseases using the discharge data from the National Inpatient Sample 2020 to assess the association of COVID-19 with multiple clinical conditions, along with additional factors, such as length of stay in the hospital, total charges incurred, region and type of hospital, and primary insurance/payer in the United States of America. We used a multivariable logistic regression model to predict factors relating to mortality in such patients.ResultsThe mortality during hospitalization in patients with cerebrovascular disease who were also diagnosed with COVID-19 was significantly higher than the patients without COVID-19 (22.50% vs 5.44%, p-value <0.0001). COVID-19 independently increased the odds of death significantly in patients with cerebrovascular diseases (adjusted OR = 4.81, p-value <0.0001). Other statistically and clinically significant factors that contributed to increased odds of mortality in such patients were comorbidities such as moderate/severe liver disease, myocardial infarction, congestive heart failure, and complications such as the development of a saddle pulmonary embolus.ConclusionCOVID-19 was associated with higher mortality in patients with cerebrovascular diseases. It also significantly increased the duration of hospital stay and odds of mortality in such patients.

Endoscopic procedures are the cornerstone of intervention in gastroenterology—from evaluating common illnesses to non-surgically managing complex diseases. Expectedly, these procedures are linked to greenhouse gas (GHG) emissions globally and contribute significantly to the global climate change crisis. Professional gastroenterology societies globally raise awareness of this evolving crisis and suggest specific measures to appropriately measure the burden contributed by endoscopy units and mitigate the environmental impact of this common clinical practice. To the unsuspecting eye, the solution to this crisis is relatively simple: decrease the utilization of endoscopic procedures. However, the dependence of modern medicine on these procedures, both diagnostically and therapeutically, makes it significantly more challenging to reduce their utilization. Instead, a structured approach to systematically consider the specific indications for each procedure, minimize waste generation, promote recycling of waste products, and limit the number of repeat endoscopies until clinically necessary may be more pragmatic to reduce GHG emissions globally. In this narrative review, we discuss the perspectives of global gastroenterology societies on sustainable or “green” endoscopy and summarize their recommendations to aid the day-to-day gastroenterologist in making their contribution to environmental sustainability while providing optimal care to their patients.

Background: Colonoscopy remains the gold standard for colorectal cancer screening. Deep learning systems with real-time computer-aided polyp detection (CADe) demonstrate high accuracy in controlled research settings and preliminary randomized controlled trials (RCTs) report favorable outcomes in clinical settings. This study aims to evaluate the efficacy of AI-assisted colonoscopy compared to standard colonoscopy focusing on Polyp Detection Rate (PDR) and Adenoma Detection Rate (ADR), and to explore their implications for clinical practice. Methods: A systematic search was conducted using multiple indexing databases for RCTs comparing AI-assisted to standard colonoscopy. Random-effect models were utilized to calculate pooled odds ratios (ORs) with 95% confidence intervals. The risk of bias was assessed using the Cochrane Risk of Bias Tool, and heterogeneity was quantified using I statistics. Results: From 22,762 studies, 12 RCTs (n = 11,267) met the inclusion criteria. AI-assisted colonoscopy significantly improved PDR (OR 1.31, 95% CI 1.08–1.59, p = 0.005), despite heterogeneity among studies (I2 = 79%). While ADR showed improvement with AI-assisted colonoscopy (OR 1.24, 95% CI, 0.98–1.58, p = 0.08), the result was not statistically significant and had high heterogeneity (I2 = 81%). Conclusions: AI-assisted colonoscopy significantly enhances PDR, highlighting its potential role in colorectal cancer screening programs. However, while an improvement in the ADR was observed, the results were not statistically significant and showed considerable variability. These findings highlight the promise of AI in improving diagnostic accuracy but also point to the need for further research to better understand its impact on meaningful clinical outcomes.

Perforated peptic ulcer (PPU) represents a surgical emergency with substantial morbidity and mortality. Despite declining overall peptic ulcer disease (PUD) incidence, contemporary population-based data comparing outcomes between perforated and non-perforated PUD remain limited, particularly during the COVID-19 pandemic. This study aimed to characterize the clinical and economic burden of PPU and identify independent predictors of adverse outcomes. We conducted a retrospective cohort study using the National Inpatient Sample (2016-2021), identifying 2,561,379 weighted hospitalizations for PUD. Hospitalizations were stratified by the presence ( = 207,970, 8.1%) or absence ( = 2,353,409, 91.9%) of perforation. The primary outcome was in-hospital mortality; secondary outcomes included sepsis, septic shock, acute kidney injury (AKI), prolonged length of stay (≥7 days), and high healthcare costs (≥$12,000). We performed 1:1 propensity score matching and multivariable logistic regression to assess independent predictors of adverse outcomes in the PPU cohort. After propensity matching, PPU demonstrated significantly higher mortality than non-perforated PUD (7.2% vs. 3.0%, < 0.001), along with increased rates of sepsis (21.8% vs. 8.2%, < 0.001), septic shock (12.9% vs. 3.5%, < 0.001), and AKI (29.5% vs. 22.8%, < 0.001). Nearly half (45.6%) of PPU admissions exceeded 7 days, and 69.2% incurred costs ≥$12,000. Among PPU hospitalizations, multivariable analysis identified age ≥ 65 years (aOR 5.79, 95% CI 4.60-7.28), liver cirrhosis (aOR 1.93, 95% CI 1.62-2.30), chronic heart failure (aOR 1.73, 95% CI 1.56-1.92), and concurrent COVID-19 infection (aOR 4.35, 95% CI 3.46-5.47) as independent predictors of mortality. Chronic kidney disease strongly predicted AKI (aOR 2.81, 95% CI 2.64-2.98). Mortality increased from 6.9% (2016) to 8.0% (2021) in PPU hospitalizations ( < 0.001 for trend), with higher rates observed during the 2020 to 2021 period that coincided with the COVID-19 pandemic. Perforation complicates approximately 8% of hospitalized PUD cases but accounts for disproportionate mortality, sepsis, organ failure, and healthcare costs. Older age, cirrhosis, heart failure, and chronic kidney disease identify high-risk PPU patients requiring intensive monitoring and aggressive management. These findings support risk-stratified approaches focused on timely diagnosis, source control, and sepsis management to reduce the clinical and economic burden of PPU.