Teclistamab is the first-in-class B cell maturation × cluster of differentiation 3 T cell bispecific antibody approved in the United States for relapsed or refractory multiple myeloma (MM). During the first year following US Food and Drug Administration approval, many institutions initiated teclistamab step-up dosing (SUD) in hospital settings.

To describe patient characteristics, length of hospital stay (LOS) during SUD, and real-world incidence and management of cytokine release syndrome (CRS) among patients with MM who initiated teclistamab in US hospital settings.

This retrospective observational study used the Premier Healthcare Database and included patients (≥18 years) with confirmed MM who received at least 1 teclistamab administration in a hospital setting between November 1, 2022, and September 21, 2023. We descriptively analyzed characteristics across all patients included as well as SUD patterns, LOS (defined as the time between admission to discharge), and CRS in those who completed SUD. CRS was identified using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes and a symptom- and treatment-based algorithm (the Keating algorithm).

A total of 413 patients were included. The median age (range) of the patients was 69 (32-89) years, 47.5% of patients were aged at least 70 years, and 69.7% had Medicare insurance. Most patients were male (56.4%), White (63.4%), and non-Hispanic (86.0%); 24.2% were Black. Most patients were treated in urban hospitals (96.4%), with 86.7% in teaching hospitals and 90.8% in hospitals with at least 300 beds. At the index hospital encounter, 47.9% of patients presented with anemia, 40.0% with peripheral neuropathy, and 35.8% with renal impairment/failure. Among 302 patients who completed SUD as of the data cutoff, 91.4% completed SUD in a single inpatient admission with a mean LOS of 8.7 days, after omitting extreme outliers; most patients had a 2-day (36.1%) or 3-day (31.1%) interval between SUD doses. CRS, per ICD-10-CM codes, was observed in 31.8% of patients (24.2% grade 1, 4.6% grade 2, and 1.0% grade 3). Per the Keating algorithm, 28.5% of patients experienced CRS-related symptoms, including fever (15.2%) and hypotension (10.3%); most of the events were classified as mild. Most patients with a complete SUD period had documented dexamethasone (97.0%) and acetaminophen (93.7%), 78.5% received diphenhydramine, and 29.8% received tocilizumab at any time during the SUD period.

This large, national, real-world study of patients with MM treated with teclistamab confirmed that early initiators of teclistamab were older adults from diverse racial groups with substantial comorbidities. Despite these factors, most patients were able to safely complete SUD following label-described schedules with manageable CRS events.

Cardiotoxicity due to immune checkpoint inhibitors (ICIs) is not a common phenomenon but can lead to fatal outcomes in cancer patients. The clinical manifestations of this cardiotoxicity are also nonspecific and difficult to identify promptly. Hence, the study aimed to define the risk factors of ICI-related cardiotoxicity to enable early identification of high-risk groups and implement timely intervention for patients receiving ICI therapy.

A scoping review was conducted using the methodological framework of Arksey and O'Malley. We performed a systematic literature search of ten electronic databases, including PubMed, Web of Science Core Collection, Embase, ProQuest, Scopus, CINAHL, CNKI, SinoMed, Wanfang, and VIP, for relevant articles on this topic. The literature and the obtained data were screened and extracted independently by two reviewers. This review is reported in accordance with PRISMA-ScR guidelines.

We identified 29 published studies and 60 risk factors of ICI-related cardiotoxicity in this scoping review. In addition to 25 common risk factors of immune-related adverse events and 5 traditional cardiovascular disease-associated risk factors, we also found 30 specific risk factors of ICI-related cardiotoxicity, including cardiovascular medical history, renal disease, obstructive sleep apnea, abnormalities in laboratory parameters, and cardiovascular medications.

Based on this scoping review, we provided a comprehensive list of 3 areas that included 60 risk factors of ICI-related cardiotoxicity and discussed the potential underlying mechanisms. This review could enable clinicians to identify high-risk patients for the timely prevention and treatment of ICI-related cardiotoxicity and further improve their outcomes.

Objective To systematically evaluate the effects of total intravenous anesthesia and inhalational anesthesia on postoperative recovery in patients undergoing transsphenoidal pituitary tumor resection.Methods A comprehensive search was conducted in international biomedical databases including Ovid Medline,Embase,CINAHL(EBSCO),Cochrane Library,and Web of Science,from inception to July 4,2023.Additionally,ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing and completed trials.The randomized controlled trials(RCT)comparing total intravenous anesthesia and inhalational anesthesia in patients undergoing transsphenoidal surgery for pituitary tumors were included.The methodological quality of the included studies was evaluated by the Cochrane Collaboration tool.Relevant data were extracted and synthesized for analysis.Results A total of 327 records were identified,of which eight RCTs met the inclusion criteria.Four studies showed that the patients receiving desflurane or sevoflurane anesthesia experienced faster emergence from anesthesia than those receiving propofol.Two studies indicated that patients in the propofol group had lower levels of emergence agitation and a lower incidence of early postoperative nausea and vomiting.The results on postoperative cognitive function were inconsistent across studies.No differences were found between the groups in terms of postoperative complications or overall recovery quality during hospitalization.Conclusions Inhalational anesthesia appears to provide an advantage in promoting faster emergence following transsphenoidal pituitary surgery,whereas total intravenous anesthesia may contribute to smoother and more stable recovery.Further high-quality studies are needed to clarify the effects of different anesthetic techniques on both short- and long-term postoperative recovery.

Transarterial chemoembolization (TACE) is recommended for intermediate-stage hepatocellular carcinoma (HCC). However, several therapies have shown better efficacy than TACE, meaning that the optimal therapy is unclear. We addressed this uncertainty using network meta-analysis (NMA).

A literature review was performed up to March 15, 2024. Efficacy was evaluated using overall survival (OS) and progression-free survival (PFS). The hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted from the Kaplan-Meier curves. A random-effects NMA was conducted, and subgroup analysis was performed according to the tumor number, tumor size, viral etiology, and alpha fetoprotein (AFP) level. The efficacy of the different therapies was ranked based on the P-score.

A total of 38 studies, 10,972 patients, and 13 therapeutic regimens were eligible. Seven therapies showed OS benefit over TACE, including TACE plus microwave ablation (MWA) (HR = 0.24, 95%CI = 0.06-0.91), TACE plus liver resection (HR = 0.35, 95%CI = 0.22-0.57), liver resection plus RFA (HR =0.49,95%CI=0.35-0.70), TACE plus immune checkpoint inhibitors (ICIs) plus tyrosine kinase inhibitors (TKIs) (HR = 0.51, 95%CI = 0.27-0.95), liver resection (HR = 0.54, 95%CI = 0.45-0.65), and TACE plus radiofrequency ablation (RFA) (HR = 0.57, 95%CI = 0.36-0.93). However, no therapies improved the PFS better than TACE alone. Subgroup analysis indicated that liver resection plus TACE showed the best OS for patients with hepatitis B virus (HBV) infection.

Seven therapies showed better efficacy than TACE alone for particular patients with intermediate-stage HCC.

https://www.crd.york.ac.uk/, PROSPERO CRD42023459740.

The objective of this study is to compare the pathological complete response (pCR) and survival rates of different neoadjuvant chemoradiotherapy modalities (NACRT) for locally advanced rectal cancer, which is defined as rectal cancer with T3-4/N + and without distant metastasis. We searched PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), and the Chinese Society of Clinical Oncology (CSCO) for randomized controlled trials (RCTs) and late-breaking abstracts on NACRT in locally advanced rectal cancer (LARC) patients with microsatellite stable (MSS) from inception to December 2024. Eighteen articles including 11658 MSS LARC patients were included: nine articles compared concurrent oxaliplatin or irinotecan with standard chemoradiotherapy, six articles conducted total neoadjuvant chemotherapy (cTNT), and three articles integrated immunotherapy (iTNT) as the NACRT regimen. CapOX cTNT modality ranked first to achieve the best pCR. The consolidation of two cycles of CapOX/FOLFOX cTNT ranked first in achieving the best 5-year overall survival (OS) rate. The consolidation of six cycles of FOLFOX cTNT ranked first in achieving the best 5-year disease-free survival (DFS) rate. Evidence from this network meta-analysis suggests that cTNT regimens, including CapOX cTNT and mFOLFIRINOX cTNT as induction regimens, have significant benefits in achieving the best pCR rate in MSS LARC patients. According to our network analysis, iTNT was not as beneficial as cTNT in achieving the best pCR. Consolidation of cTNT has the advantage of achieving long-term survival. Adverse events (AEs) reported for most iTNT modalities appear manageable.

<b>Introduction:</b> Vestibular schwannoma (VS) is the most common cerebellopontinetumor, causing sensorineural hearing loss, tinnitus, and vertigo. Chronic otitis mediawith cholesteatoma presents with recurrent ear discharge and hearing loss, typicallyrequiring surgical intervention. Although the coexistence of VS and cholesteatoma israre, it creates complex diagnostic and therapeutic challenges that necessitate individualized management approaches.<b>Aim:</b> : Considering the rare coexistence of VS and cholesteatoma, we aimed to analyze diagnostic patterns and therapeutic outcomes in our patient cohort.<b>Materials and methods:</b> We reviewed four patients with simultaneous VS and cholesteatoma. One patient presented with cholesteatoma in one ear and VS in the contralateral ear, and underwent middle ear cholesteatoma removal via an endaural approach, followed by translabyrinthine VS resection. The other three patients had ipsilateral lesions; two were managed with a transotic approach for the simultaneous removal of both lesions, while one underwent closed-cavity cholesteatoma surgery, with a cerebellopontine angle tumor subsequently detected and treated with gamma knife radiosurgery.<b>Results:</b> During a follow-up period of two to four years, no residual or recurrent cholesteatoma or tumor was observed in all patients except the one treated with gammaknife, who remained stable post-treatment.<b>Conclusions:</b> A tailored treatment strategy based on tumor stage, hearing status, patient age, and cholesteatoma characteristics resulted in favorable functional and anatomical outcomes. The coexistence of cholesteatoma and VS should be consideredin the differential diagnosis of hearing loss. Our findings underscore the importanceof a multidisciplinary approach in managing these rare concurrent conditions, ultimately optimizing hearing preservation and overall quality of life.

Identifying reliable prognostic markers is critical for improving chronic obstructive pulmonary disease (COPD) management. The advanced lung cancer inflammation index (ALI) is a novel marker reflecting inflammation and nutritional status. This study evaluated the association between ALI and all-cause and cause-specific mortality in COPD patients.

Data from 4616 adults with COPD in the National Health and Nutrition Examination Survey (1999-2018) were analyzed. Mortality outcomes were obtained from the National Death Index. Multivariable Cox proportional hazards models and restricted cubic splines assessed the association between the natural logarithm of ALI (lnALI) and mortality. Time-dependent receiver operating characteristic (ROC) curves evaluated the predictive performance of lnALI at 3, 5, and 10 years. Mediation analysis examined whether estimated glomerular filtration rate (eGFR) mediated these associations.

During a median 80-month follow-up, 1202 participants died: 349 from cardiovascular disease, 263 from cancer, and 194 from chronic lower respiratory diseases (CLRD). Higher lnALI was significantly associated with lower risks of all-cause, cardiovascular, and CLRD mortality. L-shaped associations were observed for all-cause and cardiovascular mortality, with inflection points at 4.04 and 3.64, respectively. The AUCs for predicting all-cause mortality were 0.670, 0.646, and 0.634; for cardiovascular mortality, 0.659, 0.653, and 0.629; and for CLRD mortality, 0.770, 0.751, and 0.739 at 3, 5, and 10 years. eGFR partially mediated the associations between lnALI and both all-cause and cardiovascular mortality.

Higher lnALI values were significantly associated with lower risks of all-cause, cardiovascular, and CLRD mortality in COPD patients.

Irreversible electroporation (IRE) has shown promise in improving survival outcomes and activating the immune response in patients with locally advanced pancreatic cancer (LAPC). Given these immune-enhancing effects, we hypothesized that combining IRE with immune checkpoint inhibitors may further improve treatment outcomes. This study aimed to evaluate the efficacy and safety of IRE combined with anti-PD-1 immunotherapy versus IRE alone in patients with LAPC.

In this retrospective study, LAPC patients treated either with IRE plus toripalimab (240 mg administered 7 days post-IRE) or with IRE alone were included. Propensity score matching (PSM) analyses were employed for analysis. Clinical outcomes including overall survival (OS), progression-free survival (PFS), and treatment-related adverse events were analyzed and compared between the groups.

A total of 108 patients from August 2015 and Match 2024 from SYSUCC cohort were identified with 76 undergoing IRE and 32 undergoing IRE and toripalimab in this study. After PSM, 96 patients consisting of 64 and 32 patients in the IRE and combination groups were enrolled. Clinical factors were all balanced between two groups. Patients receiving IRE combined with toripalimab showed significantly improved OS (35.03 months; 95% CI: 30.94-39.13 vs. 15.87 months; 95% CI: 8.99-22.74; P=0.014) and PFS (14.33months; 95% CI: 11.19-17.47 vs. 7.47 months; 95% CI: 3.86-11.08; P=0.022) compared to those receiving IRE alone. No treatment-related mortality was reported in either group and no statistically significant differences were observed in terms of complications and adverse events between two groups (all P>0.05).

The combination of IRE and anti-PD-1 immunotherapy was associated with improved survival outcomes and acceptable safety profiles compared to IRE alone in patients with LAPC. Further investigation through prospective trials is warranted.

The conventional tumor-node-metastasis (TNM) classification system remains limited in accurately forecasting prognosis and guiding adjuvant chemotherapy decisions for patients with colorectal cancer (CRC). To address this gap, we introduced and validated a novel pathomics signature (PS_CRC) derived from hematoxylin and eosin-stained whole slide images, leveraging a deep learning framework.

This retrospective study analyzed 883 slides from two independent cohorts. An interpretable multi-instance learning model was developed to construct PS_CRC, with SHapley Additive exPlanations (SHAP) and gradient-weighted class activation mapping (Grad-CAM) for the improvement of model interpretability and the identification of critical histopathological features, respectively. The transcriptomic data was provided by The Cancer Genome Atlas (TCGA) and integrated to investigate the biological mechanisms underpinning PS_CRC.

The results demonstrated that PS_CRC was proven to be an independent prognostic indicator for both overall and disease-free survival. It significantly enhanced the prognostic performance alongside TNM staging, as shown by improvements in net reclassification and integrated discrimination indices. Furthermore, patients in stages II and III with low PS_CRC levels were more likely to benefit from chemotherapy. Morphologically, PS_CRC reflected features such as tumor infiltration, adipocyte presence, fibrotic stroma, and immune cell engagement. Transcriptome analysis further revealed links between PS_CRC and pathways involved in tumor progression and immune evasion.

Our findings suggested that the application of deep learning to histopathological images could be an efficient method to improve the prognostic accuracy and evaluate the treatment responses in CRC. The PS_CRC offers a promising aid for clinical decision-making by shedding light on key pathogenic processes. Nevertheless, further validation through prospective studies remains essential.

Relapsed/refractory (r/r) large B-cell lymphoma (LBCL) remains a difficult-to-treat disease with limited treatment options and high unmet clinical need, necessitating the development of new therapies with greater potency and broader applicability. While autologous chimeric antigen receptor (CAR)-T cell therapies have transformed the treatment landscape, 60-65% of patients receiving these therapies eventually relapse, underscoring the need for improved approaches. Allogeneic CAR-T and CAR-NK cell therapies have recently emerged as promising alternatives, offering the potential to shorten manufacturing times, reduce costs, and expand access to a broader patient population. This systematic review and meta-analysis compiles the currently available clinical trial data on the efficacy and safety of these novel therapies in adult patients with r/r LBCL.

A systematic search of MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials was conducted for studies published up to January 12, 2025, involving allogeneic CAR-T and CAR-NK cell therapies in R/R LBCL. The primary outcomes assessed were the best overall response rate (bORR) and best complete response rate (bCRR) at any time point. Secondary outcomes included rates of grade 1-2 and grade 3+ cytokine release syndrome (CRS), grade 1-2 and grade 3+ immune effector cell-associated neurotoxicity syndrome (ICANS), grade 1-2 and grade 3+ infections and incidence of graft-versus-host disease (GvHD).

Nineteen studies met the inclusion and exclusion criteria, encompassing 334 patients (155 CAR-NK; 179 CAR-T) evaluable for safety and 235 patients evaluable for response (77 CAR-NK; 158 CAR-T). The pooled estimates for the best overall response rate (bORR) and the best complete response rate (bCRR) were 52.5% [95% CI, 41.0-63.9] and 32.8% [95% CI, 24.2-42.0], respectively. Safety analysis revealed very low incidences of grade 3+ CRS (0.04% [95% CI 0.00-0.49]) or grade 3+ ICANS (0.64% [95% CI 0.01-2.23]) and only one occurrence of a GvH-like reaction across 334 infused patients enrolled in the included studies, highlighting the remarkable safety profile of CAR-engineered "off-the-shelf" allogeneic approaches. The estimated overall incidence of low-grade CRS was 30% [95% CI, 14-48], while the estimated overall incidence of low-grade ICANS was 1% [95% CI, 0%-4%], markedly lower than current-generation autologous CAR-T cell products. The incidence of low-grade and severe infections was 25% [95% CI 14-36%) (n=252) and 7% [95% CI 2-14%] (n=291), respectively.

Together, allogeneic CAR-T and CAR-NK cell therapies demonstrate encouraging efficacy in heavily pretreated patients with r/r LBCL. Coupled with their favorable safety profiles and the potential for off-the-shelf availability, allogeneic cell therapies hold great promise to broaden the reach of live cell-based treatments, delivering impactful results to a wider patient population in the coming years.