Publications by Year: 2026

Human Immunodeficiency Virus type 1 (HIV-1) is responsible for the global HIV/AIDS epidemic and the establishment of an integrated HIV-1 reservoir remains the primary obstacle to cure. Upon therapy interruption, reactivation of the persistent HIV-1 reservoir propagates viral rebound and mediates continued immunological decline. While furthering understanding of the HIV-1 reservoir is essential for HIV-1 cure, commonly used sequencing strategies are often limited by the reliance on short-read sequencing across separate assays to determine integration sites and proviral integrity - something that does not always adequately resolve complex human genomic repeats or low complexity regions. Simultaneous identification of proviral integration sites and proviral integrity at the single molecule level would enable HIV-1 reservoir characterization with minimal imputation or bioinformatic reconstruction. Here we present HIV Single Molecule Real Time Capture (HIV SMRTcap), a novel molecular and computational pipeline that directly and simultaneously identifies HIV-1 integration sites, defines proviral integrity, and characterizes clonal expansion of HIV-1 provirus-containing cells with single molecule resolution. In combination with long-read, single-molecule, real-time (SMRT) sequencing and custom analytic pipelines, HIV SMRTcap enables a highly comprehensive characterization of HIV-1 reservoirs. Moreover, we demonstrate here that HIV SMRTcap performs robustly across the major global subtypes (HIV-1 subtype A, B, C, D and A/D recombinant viruses), and can use both cell- and tissue-derived inputs, including samples from antiretroviral therapy (ART) treated individuals with undetectable viral loads. Our results demonstrate that HIV SMRTcap serves as a comprehensive, robust method for unbiased HIV-1 reservoir characterization. Used alone, or in combination with single-cell based methods, HIV SMRTcap will enable novel exploration of viral reservoirs across subtypes and in tissue-specific compartments, providing critical information needed to inform HIV-1 cure.

Missing, inaccurate, or poorly documented data in healthcare is often treated as a technical problem to be statistically resolved via imputation, deletion, or modeling assumptions about randomness. However, such inaccuracies relate to far more complex socioeconomic and geopolitical issues, rather than "errors of data entry" to be ameliorated with statistical modeling techniques. We outline that what is really missing or inaccurate is the context in which the data is collected-and that only by understanding this context can we begin to prevent artificial intelligence's (AIs) amplification of misleading, decontextualized data. We critically examine how traditional modeling methods fail to account for the factors that influence what data gets recorded, and for whom. We show how AI systems trained on decontextualized data reinforce health inequities at scale. And, we review recent literature on context-aware approaches to understanding data, that incorporate metadata, social determinants of health, fairness constraints, and participatory governance to build more ethical and representative systems. Our analysis urges the AI and healthcare communities to move beyond the traditional emphasis on statistical convenience, toward socially grounded and interdisciplinary strategies for handling decontextualized data.

Three patients with locally advanced conjunctival squamous cell carcinoma originating in the inferior fornix were treated with immunotherapy: a 74-year-old male was treated with 4 cycles of cemiplimab, a 54-year-old female was treated with 3 cycles of pembrolizumab, and a 69-year-old female was treated with 2 cycles of pembrolizumab. Tumor progressed in all 3 patients on immunotherapy, requiring orbital exenteration for disease control. Tumor mutational burden was low in all 3 patients: 1.2, 8.1, and 7.1 mut/Mb. Review of the literature reveals 18 cases of invasive conjunctival squamous cell carcinoma treated with immunotherapy in addition to the 3 cases reported herein, with tumors of responders tending to have a higher tumor mutational burden than those of nonresponders. There is increasing evidence that conjunctival squamous cell carcinoma originating in the sun-protected inferior fornix/inferior palpebral conjunctiva has low tumor mutational burden and is less likely to respond to immunotherapy than squamous cell carcinoma of bulbar conjunctival origin.

PURPOSE: Cutaneous squamous cell carcinoma has a propensity for perineural invasion. Treating perineural spread has involved surgery and adjuvant chemoradiation, and more recently, immune checkpoint inhibitors. This study aims to evaluate motor and sensory functional outcomes in patients with cranial neuropathies from perineural spread of squamous cell carcinoma, particularly those undergoing immunotherapy.

METHODS: This was a multicenter case series and literature review.

RESULTS: Eighteen patients with cranial neuropathies from perineural spread had a mean age of 72.5 ± 9.7 years. Cranial nerves V and VII were most often involved. Treatments included radiotherapy (8/18; 44.4%), chemotherapy (7/18; 38.9%), and/or immunotherapy (11/18; 61.1%), with many receiving a combination of modalities (8/18; 44.4%). Of those receiving immunotherapy, 72.7% (8/11) demonstrated at least partial clinical and/or radiologic tumor response. Among those with functional outcomes documented, half had improvement in sensory/motor nerve function following immunotherapy (4/8; 50%). A literature review identified 55 articles describing 449 patients total with cranial neuropathies from squamous cell carcinoma perineural spread. Combinations of surgery, chemotherapy, and/or radiotherapy were employed, with immunotherapy used in 16 patients. From 5 patients on immunotherapy with documented functional outcomes, all demonstrated at least some improvement.

CONCLUSION: Immunotherapy plays an evolving role in managing advanced squamous cell carcinoma. Functional improvements in cranial neuropathy were demonstrated in 50% of patients receiving treatment with immunotherapy at a mean of 32.6 months of follow-up. This may hold important implications for the timing of surgical intervention, particularly in the case of cranial nerves V and VII palsies.

In this article, we summarize the progress made in lung cancer, mesothelioma, and thymic epithelial malignancy during the period 2005-2025. We enlisted multidisciplinary thoracic oncologic experts to tackle this task. The main focus of the article concerns how basic science with translational impact has improved the diagnosis, prognosis, and therapy of these cancers. During the past 20 years, we have come to the realization that "lung cancer" is a name that encompasses tumors with vast histologic, immune, and genomic differences that in turn influence prognosis and response to therapy. For example, programmed death-ligand 1 levels are being used as an immune signature which guides the use of immunotherapy. There is an 85% higher risk for developing lung cancer among first-degree relatives of patients with lung cancer. Accordingly, an increasing number of lung cancers are being identified in carriers of predisposing germline pathogenic inactivating mutations, suggesting that screening programs for early lung cancer detection may benefit family members. Underscoring the role of genetics, and the importance of germline testing, a different variant of mesothelioma has been identified developing in carriers of inactivating heterozygous germline mutations of BAP1 and of other tumor suppressor genes, including a new variant of mesothelioma caused by fusion genes. These variants of mesothelioma are characterized by specific histologic and molecular genetic alterations. These patients benefit from screening programs as they are at risk of multiple malignancies, their tumors are usually much less aggressive, and they are more responsive to therapy compared with sporadic, asbestos-induced mesotheliomas. Thus, the tailored therapeutic approach that is described here for lung cancer may extend to patients with mesothelioma, rather than the previous "one therapy fits all" approach. Progress in the rare thymic epithelial tumors has been less marked; however, recent insights into the biology of thymic tumors have resulted in the development of clinically relevant interventions.

OBJECTIVE: The purpose of this study was to evaluate the impact of left renal vein (LRV) division in patients undergoing open abdominal aortic aneurysm (AAA) repair.

METHODS: This systematic review and meta-analysis was registered in the PROSPERO register of systematic reviews (CRD42025640222) and conducted in accordance with Cochrane's guidelines for systematic review and meta-analysis. The PubMed, EMBASE, and Cochrane databases were searched systematically for studies comparing outcomes of patients who underwent open AAA repair with and without LRV division. Two authors screened the search results and collected data of interest independently, according to the PRISMA protocol. The primary outcome was 30-day mortality and secondary outcomes were short and long-term renal function. Risk ratios (RRs) and mean differences (MDs) with corresponding 95% confidence intervals (CI) were estimated using a random effects model. Significance was defined as a P value of <.05.

RESULTS: A total of 190 studies were screened for inclusion, of which nine studies (8 cohort studies and 1 case-control study) met the inclusion criteria. These studies included a total of 1324 patients, 350 of whom underwent LRV division and 974 patients who did not. Meta-analysis revealed no significant difference in 30-day mortality (28/205 vs 123/512; RR, 0.90; 95% CI, 0.63-1.29; P = .42; I2 =0%), acute kidney injury (RR, 1.74; 95% CI, 0.39-7.83; P = .33; I2 = 69%), need for dialysis (4/178 vs 10/473; RR, 1.61; 95% CI, 0.54-4.84), discharge estimated glomerular filtration rate (MD, -0.32; 95% CI, -2.57 to 1.92; P = .60; I2 = 0%), and discharge serum creatinine (MD, -0.01; 95% CI, -0.02 to 0.01; P = .29; I2 = 0%). LRV division was associated with an increase in postoperative serum creatinine (MD, 0.08; 95% CI, 0.04-0.11; P = .009; I2 = 0%) compared with patients with the LRV left intact.

CONCLUSIONS: Among patients undergoing AAA open surgical repair, our results demonstrate that LRV division is not associated with an increase in 30-day mortality or worse renal function.

T cells play a central role in host protection against respiratory pathogens, but a maladaptive T cell response can lead to pulmonary diseases. Previous studies have examined T cells from the lungs captured via bronchoalveolar lavage (BAL), endobronchial brushings, or biopsies. However, whether these different approaches are capturing distinct T cell phenotypes and/or clonotypes remains unclear. Here, using single cell RNA- and T cell receptor (TCR)-sequencing, we report unique phenotypes and clonotypes of T cells isolated via BAL versus endobronchial brushings in healthy controls (HCs) and allergic asthmatics (AAs). The most significant difference in T cell subset abundance between AAs and HCs was the enrichment of CD4 T helper type 2 (TH2) cells when comparing endobronchial brush samples (OR = 20.8, P = 0.004), but not when examining BAL (OR = 1.8, P = 0.38), indicating differences in the T cell subsets captured from the BAL versus airway mucosa. In further support of this observation, comparing the BAL and brush T cells across all subjects revealed an up-regulation of resident-memory T (TRM) cell markers (i.e. ITGAE, CD69) in brush T cells in both CD4 and CD8 lineages. In contrast, BAL CD8 and CD4 T cells exhibited an enriched type I and II interferon signature compared to brush T cells. We validated these findings by generating an independent cohort from publicly available single cell RNA-sequencing data of BAL and brush T cells. Lastly, leveraging the paired samples from our derivation cohort, we performed TCR repertoire analysis, revealing that brush T cells contained expanded TCR clones that were in low abundance or absent in the BAL. Expanded T cell clones from the brush expressed high levels of TRM cell markers, suggesting the airway mucosa is enriched for TRM cells with unique TCR specificity. In sum, sampling T cells via BAL versus airway brushings yielded distinct T cell phenotypes and clonotypes with important implications for future research in lung immunology.

BACKGROUND: Adults with congenital heart disease (CHD) are at high risk of premature death, making advance care planning (ACP) crucial for aligning care with individual values and goals. Previous ACP research has focused primarily on the United States and Canada, highlighting the need for a global perspective. We aimed to describe the ACP practices, needs, and preferences of adults with CHD around the globe and to investigate associations with patient-related factors.

METHODS: This cross-sectional study, part of the APPROACH-IS II project, assessed ACP preferences, needs, and practices by means of patient-reported surveys. Overall, 8281 patients with CHD (median age 32 years; 54% women; 15% mild, 58% moderate, 27% complex CHD) from 53 centres in 32 countries, spanning 6 continents, were included.

RESULTS: More than one-half of participants (55%) reported speaking to their physician about how their health might be in the future and 9% had preferences being documented in a plan. According to 66% of patients, the best time to initiate ACP is early in the disease trajectory. Most patients indicated being relatively comfortable talking to their physician about their future health and about death. ACP varied widely across different countries, with the United States and Canada at the top of the class for most variables.

CONCLUSIONS: When looking at global ACP practices, needs, and preferences, much room for improvement of ACP provision could be noticed. Also, a notable variation in ACP was observed worldwide.

CLINICAL TRIAL REGISTRATION: NCT04902768.