Fiberoptic bronchoscopy involves various topical airway anesthesia protocols, which can impact patient comfort, procedural ease, and overall outcomes. This study aimed to compare pre-procedure lignocaine spray (PPL) and spray-as-you-go (SAYG) airway anesthesia in terms of patient discomfort and operator comfort during fiberoptic bronchoscopy.

A single-blind randomized controlled trial was conducted at the Pulmonology Department of Shaikh Zayed Hospital, Lahore, Pakistan, from March 2021 to March 2022. Fifty participants were randomly assigned to two groups (n = 25 each). Standard procedural sedation with midazolam and 2 mL of 4% lignocaine spray in the oropharynx was used to suppress the gag reflex. Additionally, 2% lignocaine spray was administered during the procedure according to body weight (3 mg/kg) via oral scope insertion. Cough severity, pain perception, and operator comfort were assessed using the Visual Analogue Scale, Faces Pain Rating Scale, and a 4-point Likert scale, respectively.

Demographic characteristics were comparable between the groups, with a minor age difference (PPL: 53.25 years vs. SAYG: 50.88 years, p = 0.017). No significant differences were observed in pain perception, cough scores, or procedure duration between the PPL and SAYG groups. Operator comfort scores showed a trend favoring PPL (60% rated as “comfortable” or “very comfortable” vs. 28% in SAYG), though the difference was not statistically significant (p = 0.108).

Both PPL and SAYG topical airway anesthesia methods demonstrated similar effectiveness in pain control, cough suppression, operator comfort, and procedure duration. There was a slight, non-significant preference for PPL in operator comfort. These findings suggest that either technique may be effectively used, with potential implications for procedural efficiency and patient outcomes.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is now considered to be among the most prevalent chronic liver diseases worldwide. Its comprehensive management encompasses multiple stages, including risk assessment, early detection, stratified intervention, and long-term follow-up. Among these, improving diagnostic accuracy and optimizing individualized therapeutic strategies remain key challenges in both research and clinical practice. In recent years, artificial intelligence and smart devices have developed rapidly and have gradually been applied in the medical field, offering novel tools and pathways for MASLD risk stratification, non-invasive diagnosis, therapeutic evaluation, and patient self-management. This review summarizes the current applications of artificial intelligence and smart devices in MASLD care, highlights their benefits and limitations, and discusses future directions to support precision diagnosis and treatment strategies.

Microsatellite-stable colorectal cancer, which accounts for roughly 80–85% of cases, remains largely refractory to immune checkpoint inhibitors compared with microsatellite instability-high tumors. This review synthesizes current evidence on tumor-intrinsic and microenvironmental mechanisms underlying immune checkpoint inhibitor resistance in microsatellite-stable colorectal cancer—including low neoantigen burden and impaired antigen presentation, activation of Wnt/β-catenin and MAPK signaling that exclude T cells, an immunosuppressive cellular milieu (regulatory T cells, myeloid-derived suppressor cells, M2-like tumor-associated macrophages, cancer-associated fibroblasts), metabolic reprogramming, and gut microbiome dysbiosis—and evaluates translational strategies aimed at overcoming these barriers. Preclinical and early-phase clinical data indicate that rational, mechanism-guided combinations (vascular normalization, myeloid reprogramming, metabolic inhibitors, antigen-priming approaches, and microbiome modulation) can enhance immune infiltration and produce benefits in biomarker-defined subgroups. Moving the field forward will require biomarker-driven, adaptive clinical trials with embedded translational endpoints to optimize patient selection and manage toxicity.

Bone marrow metastasis (BMM) from non-hematolymphoid malignancies with resultant cytopenia(s) can mimic primary hematolymphoid disorders. This study aimed to investigate the clinical and pathological characteristics of BMM from non-hematopoietic tumors.

We conducted a retrospective cohort study of patients diagnosed with BMM by non-hematolymphoid malignancies at our institution over the past 10 years. Demographic and clinical characteristics, histopathological findings of bone marrow, types of metastatic tumors, and prognosis were analyzed.

A total of 54 cases were included. The four most common malignancies with BMM, regardless of gender, were prostatic adenocarcinoma (29.6%), breast carcinoma (25.9%), colorectal adenocarcinoma (5.5%), and lung carcinoma (5.5%). The main clinical and laboratory manifestations were anemia (90.7%), reticulocytosis (80.5%), thrombocytopenia (73.9%), bone pain (55.5%), disseminated intravascular coagulation (39.6%), leukoerythroblastosis (35.3%), and leukopenia (24%). The vast majority (96.3%) of metastatic tumors were identified by morphology alone; however, in approximately 2.7% of cases, immunohistochemistry was required due to subtle morphologic features. In 29.6% (16/54) of patients, BMM was identified prior to or concurrently with other metastatic sites. The median time interval between the initial diagnosis of non-hematolymphoid malignancies and BMM was 29 months. Although patients who received anti-tumor treatment after BMM diagnosis showed significantly improved prognosis (P < 0.01), no significant differences were observed between those treated with immunotherapy versus chemotherapy and/or radiotherapy (P = 0.145).

Prostate and breast carcinomas are the most common malignancies associated with BMM, with anemia, reticulocytosis, and thrombocytopenia being the most frequent clinical manifestations. While our data demonstrate that anti-neoplastic treatments, regardless of regimen, significantly improve overall survival after BMM, no significant survival differences were observed when prostate and breast carcinomas were compared with other types of BMM.

Chimeric antigen receptor (CAR)-T cell therapy faces significant challenges in treating solid tumors, including immune evasion, suppressive tumor microenvironments, and on-target/off-tumor toxicity, which limit its clinical efficacy. Although it has revolutionized treatment for hematological malignancies, these obstacles hinder its broader application in solid tumors. Nanotechnology offers innovative strategies to address these limitations through enhanced delivery, localization, and control. This review summarizes recent advances in nanotechnology-assisted CAR-T cell therapies for gynecologic cancers, with a particular focus on messenger RNA (mRNA)-based delivery systems, lipid nanoparticles, hydrogels, and external activation techniques such as photothermal and acoustogenetic modulation. The integration of nanotechnology, especially mRNA-based delivery systems, holds transformative potential for overcoming these barriers. mRNA enables transient, non-integrating expression of CARs, meaning the genetic modifications are temporary. This improves safety and allows flexible control over treatment intensity, while rational sequence optimization (e.g., codon usage, guanine-cytosine content, secondary structure) enhances mRNA stability and protein translation efficiency. Lipid nanoparticles, the leading delivery platform, can be engineered for cell-type specificity and tissue targeting through modulation of their components and surface functionalization. Recent innovations, including siloxane-modified lipid nanoparticles, injectable hydrogels, and photothermal or acoustogenetic activation strategies, enable precise spatiotemporal control of CAR-T cell function in vivo. In ovarian cancer, preclinical studies targeting nfP2X7 and employing multifunctional nanoparticles have demonstrated synergistic efficacy and tumor-specific delivery. This review highlights how nanotechnology platforms can be integrated with CAR-T cell therapies to enhance safety, precision, and therapeutic outcomes in ovarian cancer.

This review presents the Oncodarwinian Hypothesis, which proposes a new medical paradigm: that of cancer as a potential macro-immunoadaptive response (susceptible to fine-tuning or reprogramming/management via artificial intelligence-based 3D printed p53 superproteins). A traditional hypothesis-generation method was adopted; it entails observing a biophenomenon longitudinally (tumor-precursor out-of-control cell division), formulating and refining targeted research questions, and then, rooted in a prior interdisciplinary theoretical framework, outlining (per deductive reasoning) a testable answer or statement apt to predict outcomes. Two main theoretical findings emerge from this review: the plausibility of a wireless p53 superprotein molecular biochip (3D printed) and cancer cells’ dual-focus immunological nature. It will be necessary to approach the key issue and prognosis of (supposedly meaningless) uncontrolled cell division in a different light. Basically, the same diseasing cancer also constitutes a self-replicating immunoadaptive algorithm that needs to be deciphered. An interdisciplinary quest to unravel its “source code” involves genomic palaeontology and learning the natural selection programming language — for developing (personalized) artificial intelligence-assisted p53 superproteins.

Cardiac pacemaker implantation is a primary therapy for various arrhythmic disorders; however, safety concerns persist in India. This study aimed to evaluate two-year safety outcomes of cardiac pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy devices in a tertiary care setting.

In this prospective cohort study, data collection was conducted over a one-year enrolment period (February 2023 to January 2024), encompassing patient demographics, pacemaker implantation details, indications, and comorbidities. Patients were prospectively followed for a total of two years from enrolment—during the data collection period and for an additional year, to record device-associated adverse events. Ethical approval was obtained (IECJNMC/1662), and data were analyzed using SPSS.

Among 183 patients, 95% received cardiac pacemakers, 3% cardiac resynchronization therapy devices, and 2% implantable cardioverter-defibrillators. The data comprised 58% males (mean age, 63 years). The adverse event rate was 5.5% (10/183), distributed as 3.8% device infection, 1.09% lead dislodgement, and 0.54% generator dysfunction, with no statistical difference between males and females (P > 0.05). Different age groups, various indications, and several comorbidities showed no significant disparities (P > 0.05) between males and females. The Cox model showed no significant effect of several predictors on the occurrence of adverse events (P > 0.05). The Kaplan–Meier survival curve revealed a higher incidence of adverse events in the first six months, followed by stabilization. Adverse events were appropriately documented and reported to the Indian Pharmacopoeia Commission.

The observed adverse event rate of 5.5% supports previous Indian and international data; however, the smaller sample size and short follow-up duration warrant further investigation for more specific outcomes.

Cell cycle checkpoint-related genes (CCCRGs) are implicated in the development and progression of hepatocellular carcinoma (HCC). However, their precise roles and underlying mechanisms remain insufficiently characterized and require further investigation. This study aimed to explore the prognostic significance of CCCRGs in HCC, and to investigate the mechanism by which they promote the progression of HCC.

HCC datasets from The Cancer Genome Atlas and International Cancer Genome Consortium were analyzed to identify hub genes. A prognostic model was constructed and validated using Kaplan–Meier analysis, nomogram, calibration curves, decision curve analysis, and receiver operating characteristic analysis. Immune infiltration patterns were assessed using single sample gene set enrichment analysis, while pathway activities were evaluated via gene set variation analysis. Single-cell RNA sequencing data from GSE149614 were analyzed with Seurat and CellChat to investigate cell–cell communication. Patient-derived HCC specimens were examined through immunohistological evaluation, HCC cell lines were used for in vitro functional assays, and in vivo tumor growth was assessed through animal experiments.

CCCRGs showed significant associations with prognosis, malignant biological behavior, and immune responses in HCC. Centromere protein (CENP) I was identified as a critical hub gene that markedly promoted HCC proliferation, metastasis, and epithelial–mesenchymal transition, while inhibiting apoptosis. Mechanistically, CENPI suppressed YAP phosphorylation, enhancing its nuclear translocation and thereby driving malignant progression. Additionally, CENPI impaired immune effector cell infiltration, likely by disrupting tumor antigen presentation and chemokine-mediated CD8+ T cell chemotaxis, thereby promoting immune escape.

This study underscores the prognostic significance of CCCRGs in HCC and identifies CENPI as a key driver of tumor progression through the Hippo pathway. Furthermore, it reveals CENPI’s role in promoting immune escape, suggesting novel therapeutic targets for HCC treatment.