Alveolar macrophages (AMs), as primary immune sentinels in the respiratory tract, are uniquely adapted to tissue-specific demands shaped by local factors and the physiological environment, maintaining airway homeostasis through the clearance of surfactants and particulates. While AMs exhibit remarkable plasticity shaped by dynamic microenvironmental cues, the traditional M1/M2 paradigm fails to adequately capture this complex heterogeneity, and the specific role of AMs in the pathogenesis of pulmonary diseases, as well as AM-centric therapies, remain to be fully elucidated. This review systematically synthesizes the current understanding of AM ontogeny, homeostatic regulation, and their signaling pathways in lung homeostasis and pathologies. Furthermore, we propose a refined conceptual framework categorizing AMs into five distinct functional subtypes to better capture their in vivo plasticity. Then, pathological shifts in the lung microenvironment that drive the pathogenesis of diverse pulmonary disorders, including asthma, chronic obstructive pulmonary disease, acute lung injury, and pulmonary fibrosis, and trigger dysregulated transcriptional and metabolic reprogramming in AMs, are comprehensively discussed. Finally, we explore emerging therapeutic avenues, including metabolic modulation, trained immunity, and autophagy-apoptosis balance restoration. By addressing challenges in precisely regulating AM function, this overview provides a concise yet comprehensive framework for advancing AM-centric therapies in respiratory medicine.

Endovascular therapy is the standard of care for eligible patients with acute ischemic stroke due to LVO. However, nearly half of patients remain functionally dependent even after successful reperfusion. Albumin is a biologically plausible adjunctive cerebroprotective therapy and has shown neuroprotective effects in preclinical studies, but the clinical benefit of albumin combined with EVT remains uncertain.

Albumin for patients with acute large vessel occlusive stroke undergoing endovascular therapy-2 (ARISE-2) is an investigator-initiated, prospective, multicenter, randomised, open-label, controlled trial with blinded endpoint assessment (PROBE design). Eligible participants will be randomly assigned in a 1:1 ratio to receive either EVT plus intravenous 25% albumin at 0.5 g/kg (maximum dose, 37.5 g) initiated within 60 min after randomisation and then repeated once daily on days 2-4, or EVT alone. The initial target sample size is 1192 participants (596 per group). A prespecified adaptive sample size re-estimation will be performed after approximately 50% of participants have completed the 90-day follow-up, allowing the total sample size to be increased, but not reduced, to a maximum of 1788 participants. This trial aims to evaluate the efficacy and safety of albumin administered in combination with EVT in patients with acute ischemic stroke caused by anterior circulation LVO.

The primary outcome is a favourable functional outcome at 90 days, defined as a mRS score of 0-2, or return to the premorbid mRS for participants with a prestroke mRS score of 3-4.

The ARISE-2 trial is designed to evaluate the efficacy and safety of moderate-dose albumin combined with EVT in participants with acute ischemic stroke caused by anterior circulation LVO. The trial will provide evidence on whether albumin can improve functional outcomes as an adjunctive cerebroprotective strategy in patients undergoing reperfusion therapy.

ClinicalTrials.gov: NCT07263308.

Antithrombotic therapy is central to stroke prevention after spontaneous cervical artery dissection (sCAD), but its efficacy may depend on the underlying vascular morphology. We examined the temporal course of vascular changes after sCAD.

Consecutive patients with first-time sCAD underwent prospective serial duplex sonography for up to 10 years. In this retrospective cohort analysis, pathology change was defined as recanalisation of an occluded artery or progression from stenosis to occlusion. New pathology resulting from dissection recurrence was considered if an occlusion occurred in the presence of pre-existing stenosis or vice versa.

In total, 159 patients (83 men; mean age 44.8 years) with first-time sCAD were followed-up starting 1.3 days (median) after symptom onset. Bilateral dissections occurred in 6 patients and recurrent dissections in 26 arteries, resulting in follow-up of 191 arteries (108 internal carotid, 83 vertebral). Recanalisation occurred in 40/80 occluded arteries (cumulative rate 70.4%), whereas progression to occlusion occurred in 9/109 stenosed arteries (10.0%). All changes except one (recanalisation) occurred within 4 months. Recurrent dissection occurred within 6 weeks in 20 patients (14.7%) and between 2 and 7 years in 7 patients (13.7%). Overall, 62 vascular changes or new pathologies were observed in 50 patients (31.4%), with 42 occurring within the first 6 weeks.

Under intensive surveillance, vessel morphology after sCAD is highly dynamic during the early phase, with frequent recanalisation and recurrent dissection. Structured early vascular follow-up may be important if evolving vessel morphology is to guide future individualised antithrombotic treatment strategies.

Given the widespread reliance on insulin among diabetic patients, ensuring its stability is an essential task not only for preserving its therapeutic efficacy but also for safeguarding patient health and safety. In addition, insulin storage practices were frequently misunderstood that may compromise drug potency. Moreover, there were discrepancies in the shelf lives of the different insulin products offered in Tunisia. Therefore, two analytical methods for the analysis of insulin using high-performance liquid chromatography coupled to ultraviolet detector (HPLC-UV) and zinc using atomic absorption spectroscopy (AAS) in Tunisian marketed pharmaceutical product-based insulin were employed. Then the stability of these products was assessed. The study showed good insulin stability at neutral pH exposed to daylight for at least 30 days at 25°C, whereas instability was revealed only in diluted solutions at pH 2. Our work highlights the necessity for a more comprehensive evaluation of insulin stability, particularly under conditions where consistent refrigeration is not feasible. Such an assessment is essential to inform practical storage guidelines and ensure therapeutic efficacy in resource-limited settings.

Isometric exercise (IE) has been introduced as an effective non-pharmacological strategy for blood pressure (BP) management; however, the influence of exercise intensity remains unclear during lower-limb IE. This study investigated the acute effects of volume-matched high-intensity (HIIE) and low-intensity IE (LIIE) on cardiovascular function in men with elevated BP. Seventeen men with prehypertension or stage I hypertension completed three randomized crossover conditions, including HIIE (60% of maximal voluntary contraction (MVC)), LIIE (30% of MVC), and a non-exercise control condition (CON). BP, heart rate variability (HRV), brachial-ankle pulse wave velocity (baPWV) were measured at baseline and three different time points during recovery, while flow-mediated dilation (FMD) was measured at baseline and 30-min post-exercise. No significant BP reduction was observed. However, HIIE induced greater autonomic disturbance with elevated heart rate and reduced HRV indices during recovery (p < 0.05). Right baPWV decreased following HIIE (p < 0.05) while FMD increased after both exercise conditions (p < 0.001). Our findings suggest that volume-matched HIIE induces greater acute autonomic and vascular responses than LIIE in men with elevated BP, despite no immediate changes in BP. HIIE may provide a stronger physiological stimulus associated with vascular adaptation.

Multifocal atherosclerosis (MFA) is one of the common diseases in elderly patients. Currently, there is no single approach to treating patients with MFA. The active implementation of endovascular surgery has significantly expanded the treatment options for comorbid elderly patients with MFA.

Of the study: to evaluate the effectiveness and safety of various methods of surgical revascularization in geriatric patients with multifocal atherosclerosis.

This single-center observational cohort study was conducted in the Department of Cardiovascular Surgery at the Research and Clinical Center of the Russian National Research Medical University named after N.I. Pirogov. The study included 44 elderly patients with arterial diseases of various localizations. Two groups of patients were identified depending on the chosen treatment method: a group of patients undergoing endovascular treatment (n=30), and a group after open surgical procedures (n=14). Endovascular interventions: balloon angioplasty and/or stenting (carotid, iliac-femoral, popliteal-tibial, etc.), aortic endoprosthetic replacement (EVAR/TEVAR), endovascular reconstructions of visceral/renal arteries. Open surgeries: carotid endarterectomy, aortic prosthetic replacement/grafting/shunting, peripheral shunting, thromboendarterectomy, etc. All operations were performed as part of the routine schedule from June 2024 to June 2025. The choice of revascularization method was made by a multidisciplinary team.

An analysis of in-hospital complications was performed in 44 patients; no fatal cases were recorded during hospitalization. Postoperative delirium developed in 3 patients (2 in the endovascular treatment group and 1 in the open surgery group, p>0.05). Despite the less favorable initial geriatric and functional profile of patients undergoing endovascular surgery, early postoperative outcomes are comparable to the results in the group of patients who underwent open vascular surgery. To definitively assess the comparative effectiveness of treatment methods, larger-scale studies are needed, with careful adjustment for confounding factors, standardized collection of functional and patient-oriented outcomes, and analysis of long-term treatment results.

Thus, with comparable risks of complications in elderly patients in the vascular surgery department with MFA and atherosclerotic lesions in various arterial territories, endovascular surgery allows for the operation of more "fragile" patients.

To evaluate prognostic value of reversible and persistent intraoperative changes in somatosensory evoked potentials, motor evoked potentials and H-reflex for postoperative motor neurological deficit after open thoracoabdominal aortic replacement.

A single-center prospective observational study included 59 patients who underwent open thoracoabdominal aortic replacement under intraoperative neurophysiological monitoring. Somatosensory evoked potentials were recorded in 58 patients (98.3%), motor evoked potentials in 54 (91.5%), and H-reflex in 24 (40.7%) patients. The primary endpoint was new postoperative motor neurological deficit. Diagnostic performance of any signal decrease and no recovery by the end of surgery was assessed. An exploratory analysis of surgical factors associated with persistent absent recovery of motor evoked potentials and/or H-reflex was also performed.

Postoperative spinal cord ischemia was detected in 4/59 patients (6.8%): 3 cases of monoparesis (5.1%) and 1 case of paraplegia (1.7%). Any evoked potential decrease had high sensitivity but low specificity. No recovery of somatosensory evoked potentials among patients with their decrease had 25.0% sensitivity and 95.1% specificity. No recovery of motor evoked potentials had 75.0% sensitivity and 71.4% specificity, no recovery of H-reflex - 100.0% sensitivity and 53.3% specificity. The combined criterion of no recovery of motor evoked potentials and/or H-reflex demonstrated 100.0% sensitivity, 70.6% specificity and 100.0% negative predictive value. In exploratory analysis of surgical factors, significant difference was found in the number of intraoperatively sutured thoracic intercostal arteries: 4 [3; 5] in the absent recovery group versus 6 [4; 8] in the recovery group (p=0.048).

Persistent abnormalities remaining by the end of surgery have the greatest prognostic value rather than any intraoperative signal decrease. No recovery of motor evoked potentials and/or the H-reflex may be considered a clinically relevant risk factor for postoperative motor deficit.

Cardiovascular implantable electronic devices (CIEDs) are increasingly utilized for arrhythmia management, but device-related infections remain a significant complication. Rapidly growing non-tuberculous mycobacteria (RGM), including Mycobacterium smegmatis, are rare causes of CIED infections, typically reported in immunocompromised patients or in association with indwelling catheters. These infections pose diagnostic and therapeutic challenges due to non-specific clinical presentations and intrinsic antimicrobial resistance. We report an immunocompetent elderly patient who developed complete heart block requiring pacemaker implantation. The patient subsequently experienced device-related complications, including lead dislodgement and multiple revisions, followed by development of a pacemaker pocket site infection. Blood cultures grew M. smegmatis, and imaging revealed a significant fluid collection at the pocket site. The patient was managed with complete device removal, placement of a leadless pacemaker, and targeted multidrug antimicrobial therapy guided by susceptibility testing. The patient responded favorably, with resolution of bacteremia and pocket site infection. This case highlights the importance of considering M. smegmatis as a potential pathogen in CIED infections, even in immunocompetent hosts. Successful management requires prompt recognition, source control through device removal, accurate microbiologic diagnosis, and prolonged, susceptibility-guided antimicrobial therapy. Clinicians should maintain a high index of suspicion for RGM infections in patients with indwelling device infections, particularly when initial empiric therapy fails. Although rare, M. smegmatis CIED infections can occur in immunocompetent patients and are associated with device manipulation or revisions. This report underscores the need for vigilance, multidisciplinary management, and prolonged follow-up in such complex infections.

Immune-cell dynamics within the tumor microenvironment (TME) determine whether immune cells can reach, recognize, and sustain antitumor function against malignant cells under suppressive pressure. These dynamics are shaped by hypoxia, nutrient stress, cytokine and chemokine signaling, stromal architecture, vascular access, and multicellular crosstalk, and are further regulated by transcriptional and epigenetic programs. In this review, we organize TME immunity around four major barriers to effective therapy: failed immune access, defective antigen visibility and priming, failure to sustain effector function, and suppressive tissue remodeling. We use FOSL2/Fra-2, a component of activator protein-1 (AP-1) transcription factor complexes, as an example of how local signals can produce distinct regulatory effects in malignant, immune, and stromal compartments. FOSL2-associated programs have been linked to differentiation, plasticity, myeloid and stromal remodeling, stress adaptation, and selected immune-regulatory processes; however, the strength and direction of these associations vary by lineage, tumor type, model system, and level of functional evidence. We distinguish perturbation-supported mechanisms from correlative state signatures and identify the need for spatial validation, functional perturbation, and biomarker validation. This perspective supports biomarker-guided TME-directed therapy matched to the dominant immune barrier.

Background Lung cancer remains the leading cause of cancer-related mortality worldwide. Although obesity is an established risk factor for multiple malignancies, numerous studies have reported an "obesity paradox," wherein patients with obesity demonstrate improved survival compared with normal-weight or underweight individuals. Whether this survival advantage reflects a true protective biological mechanism or methodological artifacts such as reverse causation driven by cancer cachexia and selection bias remains controversial, particularly within the acute inpatient setting. We evaluated the independent association between documented obesity and in-hospital mortality among lung cancer hospitalizations. Methods We performed a retrospective cross-sectional analysis of the US National Inpatient Sample (2020-2022). Adult hospitalizations (age ≥18 years) with a diagnosis of lung cancer were identified and dichotomized by the presence or absence of an International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) obesity code; the unit of analysis was the hospitalization rather than the individual patient, and the exposure was documented obesity coding rather than measured adiposity. Baseline demographics, comorbidities, and in-hospital complications were compared using the chi-squared test (categorical variables) and the Mann-Whitney U test (continuous variables). The primary outcome was in-hospital mortality; multivariable logistic regression adjusted for demographic, clinical, and hospital-level covariates. Results Of 61,963 unweighted lung cancer hospitalizations, 7,065 (11.4%) carried an obesity code. Obese patients were younger (median: 68 vs. 70 years) and more often female (4,090/7,065 (57.9%) vs. 28,011/54,898 (51%)). They had a higher prevalence of hypertension, diabetes, dyslipidemia, and obstructive sleep apnea (1,703 (24.1%) vs. 2,910 (5.3%)) but a lower weighted Elixhauser score (median: 10 vs. 16). In-hospital mortality was lower in the obese group (278 (3.9%) vs. 3,746 (6.8%); p<0.001). After adjustment, an obesity code was independently associated with 33% lower odds of in-hospital death (adjusted odds ratio (aOR): 0.67; 95% CI: 0.58-0.77; p<0.001). Conclusions Documented obesity coding was independently associated with lower in-hospital mortality among lung cancer hospitalizations. However, the low sensitivity of administrative obesity coding, a binary exposure that cannot separate normal-weight from cachectic patients, and the susceptibility of hospitalized cohorts to collider and reverse-causation bias mean this association should not be interpreted as a protective effect of adiposity. The paradox is most parsimoniously explained by confounding by illness severity rather than a therapeutic target, and the finding should be interpreted as an association involving documented obesity coding rather than an effect of adiposity itself.