Age-related macular degeneration (AMD) is increasingly linked to systemic cardiovascular and metabolic dysfunction as well as cerebral small vessel disease. Subretinal drusenoid deposits (SDD) and basal laminar deposits (BLamD) have emerged as structural biomarkers associated with AMD progression and systemic vascular compromise. This study aimed to investigate associations between hypertension, dyslipidemia, and cerebrovascular disease - transient ischemic attack, stroke, and myocardial infarction - and retinal structural alterations in AMD patients presenting SDD in order to assess the relationship with progression of disease. Thirty-eight eyes of 31 patients with AMD and SDD were examined in this retrospective longitudinal study. Retinal imaging, including near-infrared reflectance and spectral-domain optical coherence tomography (SDOCT), was used to characterize retinal alterations. Systemic cardiovascular and small vessel disease profiles were obtained from the clinical history. Morphometric changes in retinal layers were quantified through SDOCT and correlated with systemic metabolic and vascular parameters. During a mean follow-up of 2.1 ± 0.86 years, 44.7% of eyes progressed to advanced AMD: 23.6% to complete RPE and outer retinal atrophy (cRORA)/geographic atrophy, and 21% to macular neovascularization. High-risk vascular diseases were present in 32.3% of patients. BLamD significantly increased progression risk (P = 0.03), whereas conventional drusen did not (P = 0.79). Higher serum triglycerides correlated negatively with outer retinal layer changes (r = -0.66, P = 0.004) and perifoveal thinning (r = -0.75, P < 0.001), while HDL showed positive correlations. Hypertension was frequent (87.1%) but not independently predictive of progression. AMD patients with SDD exhibit significant associations between systemic cardio/cerebro-vascular disease and metabolic dysregulation and retinal structural degeneration. BLamD further increase progression risk, underscoring their relevance as imaging biomarkers of vascular and metabolic compromise.
Sepsis is a leading cause of morbidity and mortality among hospitalized patients and is associated with intensive use of β-lactam antibiotics. These drugs show time-dependent pharmacodynamics and high pharmacokinetic variability in this population, making it difficult to achieve therapeutic levels. Therapeutic drug monitoring (TDM) may optimise dosing, but its routine clinical implementation remains limited. To evaluate whether individualized β-lactam dosing guided by TDM reduces time to full clinical recovery compared with standard dosing in hospitalized patients with sepsis (ICU and ward). OPTIBETA is a pragmatic, randomized, controlled, open-label clinical trial with blinded outcome assessment to be conducted at a tertiary hospital in Spain. Adult patients (≥18 years) admitted to the intensive care unit or infectious diseases ward with sepsis will be included. Participants will be randomized 1:1 to either a TDM-guided dosing arm (dose adjustments according to PK/PD targets) or a standard dosing arm. Clinical, microbiological, and pharmacological outcomes will be collected. The primary endpoint is time to complete clinical cure. Secondary outcomes include overall survival, microbiological cure, ICU and hospital length of stay, adverse events, and achievement of PK/PD targets. The estimated sample size is 198 patients. We hypothesize that TDM-guided dosing will reduce time to clinical cure, improve overall outcomes, and decrease adverse events compared with standard dosing. OPTIBETA will provide high-quality evidence on the role of β-lactam TDM in hospitalized patients with sepsis and may support its inclusion in antimicrobial stewardship programs.
Sarcopenia, assessed via computed tomography (CT), is an emerging prognostic tool in critically ill, pulmonary, and geriatric patients. Laboratory inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and neutrophil-to-lymphocyte ratio (NLR) are routinely obtained in these populations. Whether CT-assessed sarcopenia combined with laboratory markers offers superior prognostic accuracy over either measure alone remains unclear. To systematically evaluate the prognostic value of CT-assessed sarcopenia, alone or combined with laboratory inflammatory/nutritional markers, for predicting mortality, mechanical ventilation duration, and ICU length of stay in critically ill, pulmonary, and geriatric patients. MEDLINE/PubMed, Scopus, Embase, and Cochrane Library were searched from inception to December 2024. Observational studies (prospective or retrospective cohorts, case-control) that reported CT-based sarcopenia assessment alongside at least one laboratory inflammatory marker and at least one clinical outcome were included. Two reviewers independently screened studies, extracted data, and assessed methodological quality using the Newcastle-Ottawa Scale (NOS). Random-effects meta-analysis was performed; heterogeneity was assessed using the I² statistic. Twenty-five studies encompassing 12,347 patients were identified. The pooled odds ratio for mortality in sarcopenic versus non-sarcopenic patients was 2.28 (95% CI: 1.83-2.83; I² = 22.1%) across critically ill ICU cohorts. In COVID-19 pulmonary populations, pooled OR for in-hospital mortality with low skeletal muscle mass was 5.84 (95% CI: 1.07-31.83). CT-derived muscle measurements correlated inversely with CRP (r = -0.315), fibrinogen (r = -0.392), D-dimers (r = -0.363), and WBC count (r = -0.287). Combined CT-sarcopenia and inflammatory marker models outperformed conventional scoring systems (APACHE II, SOFA, CURB-65, PSI). CT-assessed sarcopenia, when integrated with laboratory inflammatory markers, provides a robust, mechanistically grounded, and clinically accessible multimodal prognostic framework across critically ill, pulmonary, and geriatric populations.
Non-culprit coronary lesions are increasingly recognized as an important source of recurrent cardiovascular events in patients with ST-segment elevation myocardial infarction (STEMI). Intravascular ultrasound (IVUS) provides detailed assessment of plaque morphology; however, data in real-world STEMI populations, particularly in Vietnam, remain limited. To characterize morphological features and associated factors of non-culprit coronary lesions using IVUS in STEMI patients. This prospective observational study included 103 STEMI patients with multivessel disease undergoing primary percutaneous coronary intervention. A total of 118 non-culprit lesions were assessed by IVUS. High-risk plaque features were defined as the presence of at least two of the following: minimal lumen area (MLA) <4.0 mm², plaque burden ≥70%, spotty calcification, or lipid core. Clinical, lipid, and lesion-related factors associated with high-risk features were analyzed. High-risk plaque characteristics were common, with 66% of lesions exhibiting ≥2 high-risk features. Calcified plaques predominated (75.4%), with spotty calcification observed in 52.5% of lesions, while lipid core was less frequent (14.4%). MLA <4 mm² and plaque burden ≥70% were present in 68% and 53% of lesions, respectively. Diabetes mellitus (44.4% vs. 19.4%, p=0.015), dyslipidemia (79.4% vs. 54.2%, p=0.017), and higher non-HDL cholesterol levels (p=0.005) were significantly associated with ≥2 high-risk features. Lesions located in the left anterior descending artery were more likely to exhibit high-risk characteristics (48.1% vs. 25.6%, p=0.019). In multivariable analysis, diabetes (OR 4.40, p=0.011), non-HDL cholesterol (OR 3.40, p=0.002), and LAD location (OR 3.35, p=0.027) were independent predictors. Non-culprit lesions in STEMI patients frequently demonstrate multiple high-risk features on IVUS. Diabetes, non-HDL cholesterol, and LAD location are independently associated with high-risk plaque phenotypes. These findings support the role of IVUS in comprehensive risk stratification of non-culprit lesions in multivessel STEMI.
Outcomes after mechanical thrombectomy vary widely despite high rates of angiographic reperfusion. Pretreatment infarct core volume is a major determinant of recovery, yet the functional impact of a given core burden may differ by collateral physiology. Therefore, this study aimed to determine whether baseline angiographic collateral grade modifies the association between pretreatment infarct core volume and 90-day functional independence, defined as modified Rankin Scale score 0-2, among adults with anterior-circulation large-vessel occlusion undergoing attempted mechanical thrombectomy. This retrospective observational cohort included consecutive adults who underwent attempted mechanical thrombectomy at a comprehensive stroke centre. Infarct core volume was quantified on diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient confirmation, or on computed tomography perfusion when magnetic resonance imaging was not feasible, using semi-automated volumetry with artifact correction. Collaterals were graded on baseline angiography using the ASITN/SIR scale (0 to 4) by a reader blinded to core volume and outcomes. The primary endpoint was 90-day functional independence (modified Rankin Scale 0 to 2). Multivariable logistic regression in anterior-circulation strokes evaluated core volume (per 10 cc), collateral grade (per 1 grade), and a prespecified interaction term, adjusting for clinical and workflow covariates. Sixty-nine patients were included (mean age 67.4 ± 10.2 years), with successful reperfusion (final mTICI 2b or higher) in 91.3%. Functional independence occurred in 47.8% overall and 53.8% among anterior-circulation strokes (28/52). Any intracranial haemorrhage occurred in 31.9%, symptomatic intracranial haemorrhage in 13.0%, and 90-day mortality in 20.3%. In anterior-circulation modelling, larger core volume reduced the odds of independence (adjusted OR 0.79 per 10 cc, 95% CI 0.66 to 0.93), higher collateral grade increased the odds (adjusted OR 2.24 per grade, 95% CI 1.18 to 4.25), and the interaction term was significant (adjusted OR 1.12, 95% CI 1.01 to 1.28), with good discrimination (AUC 0.81). Collateral physiology modifies the association between established infarct core burden and 90-day recovery after thrombectomy in anterior-circulation large-vessel occlusion, supporting integrated tissue-plus-physiology prognostication.
Helicobacter pylori infection affects nearly half of the global population and is a major cause of peptic ulcer disease and gastric cancer. Increasing antibiotic resistance, particularly to clarithromycin, has reduced the efficacy of standard triple therapy, necessitating evaluation of alternative regimens and adjunctive therapies. To compare the eradication rates and safety of clarithromycin- and levofloxacin-based triple therapy, with and without adjunctive lactoferrin. In this randomized, open-label, 2 × 2 factorial trial, 160 adult patients with confirmed H. pylori infection were allocated equally into four groups: clarithromycin-based triple therapy, levofloxacin-based triple therapy, and each regimen combined with lactoferrin. Treatments were administered for 14 days. Eradication was assessed using stool antigen testing four weeks after therapy. Analysis was performed according to the intention-to-treat principle. Eradication rates were 72.5% in both the clarithromycin and levofloxacin groups, compared with 90.0% and 97.5% in the corresponding lactoferrin-supplemented groups, respectively (p = 0.003). Lactoferrin significantly improved eradication rates (72.5% vs. 93.8%, p < 0.001). No significant difference was observed between antibiotic regimens alone (p = 0.673). Adverse events were mild and comparable across groups. Adjunctive lactoferrin significantly enhances H. pylori eradication rates when combined with standard triple therapy, regardless of antibiotic backbone. The evidence proves that lactoferrin should function as an effective adjunct in eradication regimens, particularly in settings of increasing antibiotic resistance.
Pancreaticobiliary lesions represent a wide clinical range ranging between harmless inflammatory diseases up to aggressive cancers. Accurate differentiation remains challenging and none of the modalities is predictive enough to predict malignancy. This study compared the combined diagnostic usefulness of the clinical, radiological, laboratory, and histopathological data to predict malignancy. Group I (n=26) and Group II (n=34) were formed of 60 patients with pancreaticobiliary lesions who were assessed in a tertiary care hospital in this retrospective analytical study. Proper statistical tests were used to compare clinical symptoms, radiological results of transabdominal ultrasonography, contrast-enhanced computed tomography (CT), magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasound (EUS), serum biomarkers and histopathology. Anorexia (88.5% vs 29.4%, p<0.001), weight loss (69.2% vs 26.5%, p=0.002), and jaundice (69.2% vs 38.2%, p=0.034) were significantly more prevalent in malignant cases. EUS demonstrated sensitivity of 96.2% and NPV of 95.2%. CBD diameter on MRCP (14.5±5.9 vs 11.3±2.7 mm, p=0.006), serum bilirubin (median 5.7 vs 1.2 mg/dL, p=0.006), and CA 19-9 (median 236.0 vs 34.0 U/mL, p=0.006) were significantly elevated in the malignant group. Multivariate analysis confirmed anorexia, weight loss, CA 19-9 elevation, jaundice, bilirubin, and CBD diameter as independent predictors of malignancy. Multidisciplinary treatment which combines clinical presentation, EUS, MRCP biliary measurements, serum biomarkers will greatly increase the prediction of malignancy in pancreaticobiliary lesions. These results help to develop a composite predictive scoring model that may be used in clinical practice.
Relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) remains a major therapeutic challenge, particularly among patients with high-risk molecular features or primary refractory disease. Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising treatment strategy; however, its comparative effectiveness versus salvage chemotherapy requires comprehensive evaluation. This systematic review and meta-analysis were conducted in accordance with PRISMA 2020 and MOOSE guidelines. Randomized controlled trials and high-quality comparative cohort studies evaluating CAR-T therapy versus salvage chemotherapy in adult patients with R/R DLBCL were included. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included complete metabolic response (CMR), toxicity profiles, and multidisciplinary correlates (radiologic, laboratory, and histopathologic). Random-effects models, meta-regression analyses, and GRADE assessment were applied. Eight studies (n = 2,150) were included. CAR-T therapy significantly improved PFS (HR 0.55, 95% CI 0.42-0.71; p < 0.001) and OS (HR 0.68, 95% CI 0.54-0.86; p = 0.001). CMR rates were higher in the CAR-T group (56.0%) compared with salvage chemotherapy (24.5%) (RR 2.28, 95% CI 1.82-2.86; p < 0.001). Elevated inflammatory markers and tumor burden were associated with increased risk of immune-related toxicities. Subgroup analyses demonstrated greater benefit in primary refractory and double-hit lymphoma. CAR-T therapy was associated with cytokine release syndrome (9% grade ≥3) and ICANS (12%), whereas salvage chemotherapy demonstrated higher rates of hematologic toxicity. CAR-T therapy provides superior survival and response outcomes compared with salvage chemotherapy in R/R DLBCL, particularly in high-risk populations. Integration of radiologic, laboratory, and molecular predictors may enhance patient selection and optimize toxicity management.
Chronic kidney disease (CKD) is a common complication of hypertension and diabetes mellitus. Hemodialysis (HD) is a renal replacement therapy that requires self-care and therapeutic adherence (TA), which if not performed increase the risk of associated complications. Therefore, it is essential to adopt self-care practices and implement modifications in lifestyle patterns (LP). To determine changes in LP and TA in patients with CKD undergoing HD following educational interventions (EIs). Quasi-experimental, longitudinal, non-randomized study. Sociodemographic and clinical-therapeutic variables were analyzed. Evaluation tools were applied to identify changes in LP and TA before and after a 6-month period of EIs. The EIs consisted of 7 individualized sessions provided in the HD unit. Measures of central tendency, chi-square test, and Student's t test were used for data analysis. The sample included 39 patients, with a mean age of 52.87 years; 53% were male. Initially, 100% of participants were classified as "at risk" in LP, and 0% had "full adherence" in TA. After the EIs, 43.6% of patients achieved a "protective" LP, and 38.5% reached "full adherence" in TA (p = 0.00). Patients who received 7 individualized educational sessions showed significant improvements in self-care practices as measured by LP, as well as notable improvement in TA. la enfermedad renal crónica (ERC) es una complicación común de la hipertensión arterial y la diabetes mellitus. La hemodiálisis (HD) es un tratamiento sustitutivo de la función renal que requiere de autocuidado y de adherencia terapéutica (AT), las cuales al no realizarse aumentan el riesgo de complicaciones asociadas. Por lo tanto, es necesaria la toma de prácticas de autocuidado y modificaciones del patrón de vida (PV). determinar los cambios en el PV y AT en pacientes con ERC en HD posterior a intervenciones educativas (IE). estudio cuasi-experimental, longitudinal, no aleatorizado. Se estudiaron variables sociodemográficas y clínico-terapéuticas. Se aplicaron pruebas de evaluación para identificar los cambios de PV y AT antes y después de 6 meses de IE. Las IE consistieron en 7 sesiones individualizadas en el servicio de HD. Se emplearon medidas de tendencia central, chi cuadrada y t de Student. la muestra fue de 39 pacientes, edad media de 52.87 años y el 53% fue del sexo masculino. En cuanto al PV, 100% estaban “en riesgo” y en relación con la AT, 0% estaba en “adherencia total”. Después de la IE, el 43.6% resultó en PV “protector” y el 38.5% logró “adherencia total” de AT (p < 0.001). aquellos pacientes que recibieron 7 sesiones individualizadas de IE demostraron mejoras significativas en relación con las prácticas de autocuidado evaluadas mediante el PV y también se demostró una mejora en la AT.
Stage III periodontitis is a severe inflammatory disease characterized by significant tissue destruction. While Non-Surgical Periodontal Therapy (NSPT) is the gold standard, evidence suggests it may only or partially address of systemic oxidative imbalance. This study aimed to investigate the interplay between habitual dietary antioxidants, NSPT, and oxidative/nitrosative status in Mexican patients, a population with unique dietary patterns that may fuel disease pathways. A preliminary quasi-experimental study was conducted with 24 adults (11 with periodontitis; 13 healthy controls). Clinical examinations were performed by a calibrated periodontist. Habitual diet was assessed at baseline using a validated SFFQ. Salivary and plasma levels of Total Antioxidant Capacity (TAC), protein carbonyls (CARBO), lipid peroxidation (LPO), and nitrate/nitrite were measured. The periodontitis group exhibited significantly higher energy and lower polyunsaturated fatty acid (PUFA) intake (p < 0.05). A pivotal finding was the metabolic hyper-reactivity in diseased patients (30 significant nutrient-biomarker correlations vs. 5 in controls). Following NSPT, clinical parameters and plasma TAC improved (p < 0.05); however, salivary MDA+4-HDA remained at 0.94 μM/L-above the healthy threshold of 0.77 μM/L, consistent with a non-significant reduction in the Plaque/Calculus Index(p = 0.059). Our findings suggest that NSPT alone is insufficient to fully restore physiological oxidative homeostasis. The persistence of altered oxidative markers, linked to residual biofilm and dietary imbalances, supports the integration of targeted nutritional strategies as a necessary adjunct to achieve complete biological recovery in Stage III periodontitis; further large-scale studies are warranted to validate these results.
Mesotherapy (intradermal therapy) is an injection technique involving the administration of small amounts of drugs into the superficial dermis, where micro-deposits are formed and gradually diffuse into underlying tissues. This distinctive local pharmacokinetic profile, together with potential neurobiological and microcirculatory effects related to needle microtrauma and the injected solution, may contribute to analgesic effects in localised pain conditions, particularly of musculoskeletal origin. Across European family medicine, and more broadly within international primary care systems, there is growing interest in therapeutic strategies that are effective, safe, minimally invasive and compatible with longitudinal, patient-centred care pathways. In this context, available clinical evidence, accumulated clinical experience and international consensus recommendations suggest that mesotherapy may provide potential clinical benefits in a range of localised musculoskeletal pain conditions, including acute and chronic low back pain, neck pain, knee osteoarthritis, tendinopathies, myofascial pain syndrome and post-traumatic pain. The use of low drug doses is associated with reduced systemic exposure and a predominantly local, generally mild adverse-event profile, a feature of particular relevance in elderly and polymedicated patients commonly managed in family medicine. International consensus documents support the safe and standardised use of mesotherapy in musculoskeletal medicine and recognise its role as an adjuvant technique in other medical fields. From a primary care perspective, this article examines the clinical and organisational rationale for introducing mesotherapy into family medicine care pathways, highlighting its potential role as a complementary option within a multimodal, patient-centred approach and, in selected cases, as an early local intervention for localised musculoskeletal pain. However, it should be acknowledged that the current evidence base is characterised by a limited number of high-quality, randomised controlled trials, and that the available data do not allow definitive conclusions regarding the clinical effectiveness, cost-effectiveness or system-level impact of mesotherapy across different healthcare settings. At present, the existing evidence supports hypothesis-generating interpretations, suggesting that mesotherapy may be useful and efficient in selected clinical contexts rather than conclusively established. Within these limitations, there is a reasonable likelihood that mesotherapy could be integrated into primary care pathways for specific subgroups of patients, particularly those with well-localised musculoskeletal pain, contraindications to systemic therapies, or a high risk of drug-related adverse events. Further prospective studies, adequately powered randomised controlled trials and real-world evaluations are required to better define its clinical positioning, long-term safety, cost-effectiveness and optimal models of integration within different primary care systems. This article provides a narrative review and a practice-oriented appraisal of the available evidence.
Lupus nephritis (LN) is a severe immune-mediated renal disorder causing significant morbidity and mortality in patients with systemic lupus erythematosus (SLE). Traditional biomarkers (serum complement components C3 and C4 and anti-dsDNA antibodies) have limited sensitivity and specificity for detecting renal flares; thus, new markers are needed to improve relapse detection and therapeutic response monitoring. We conducted a cross-sectional study including 71 women with SLE and 20 age- and sex-matched controls. Clinical data were collected, global activity was evaluated using the SLEDAI, and renal activity was evaluated using the renal SLEDAI (rSLEDAI). Serum syndecan-1 (SDC-1) and anti-dsDNA were measured using ELISA, and 24 h proteinuria was quantified. According to the rSLEDAI, 38 patients (53.5%) had LN flare, with a mean SDC-1 level of 108.5 ± 69.3 ng/mL and anti-dsDNA level of 113.1 ± 148.8 IU/mL. SDC-1 was correlated with the rSLEDAI (r = 0.32; p = 0.006), prednisone dose (r = 0.37; p = 0.002), proteinuria (r = 0.33; p = 0.005), and anti-dsDNA (r = 0.33; p = 0.006), while anti-dsDNA was positively correlated with proteinuria (r = 0.39; p = 0.001 and SDC-1 (r = 0.33; p = 0.006) and negatively correlated with age (r = -0.33; p = 0.006). High SDC-1 (cutoff ≥ 89 ng/mL) had higher sensitivity for detecting renal flares than anti-dsDNA (66% vs. 45%). In the multivariable analysis, high SDC-1 levels had around a 3-fold higher risk of being associated with LN flares, independently of anti-dsDNA and complement component levels. These results support serum SDC-1 as a promising biomarker for identifying renal flares in SLE patients, and it should be combined with traditional biomarkers to increase its value as a clinical tool. Follow-up studies are required to determine its value for predicting long-term renal outcomes.
Left atrial reservoir strain (LASr) is an established marker of atrial dysfunction and elevated filling pressures in heart failure; however, its role in mediating downstream right ventricular (RV) mechanical impairment in advanced heart failure with reduced ejection fraction (HFrEF) remains incompletely defined. This study aimed to evaluate the association between LASr and RV myocardial mechanics using multichamber deformation imaging and to elucidate the mechanistic contribution of atrial dysfunction to RV impairment within the atrioventricular continuum. This cross-sectional observational study included 50 stabilized patients with Stage C and Stage D HFrEF. All participants underwent comprehensive transthoracic echocardiography incorporating conventional parameters, multichambered speckle-tracking strain analysis, and three-dimensional RV assessment. Associations between LASr and RV functional indices were assessed using Pearson correlation and multivariable regression analyses was applied to identify the key determinants of RV impairment. LASr was markedly reduced across the cohort and demonstrated a significant inverse association with RV free-wall strain and RV global longitudinal strain. Left atrial strain parameters and left atrial volume index did not differ significantly between Stage C and Stage D HFrEF, suggesting early plateauing of atrial mechanical dysfunction in advanced disease. In contrast, left ventricular global longitudinal strain worsened significantly with advancing heart failure stage. RV dysfunction was uniformly present across both stages and was more sensitively detected by strain-based indices than by conventional RV parameters. On multivariable regression analysis, LASr emerged as an independent determinant of RV mechanical dysfunction, along with chronic kidney disease. In advanced HFrEF, impaired left atrial reservoir function is closely linked to RV mechanical dysfunction, supporting atrioventricular interdependence. Multichambered deformation imaging provides important mechanistic insights beyond conventional LV-centric assessment and highlights the value of integrated atrial and RV strain evaluation in advanced heart failure.
N‑acetylcysteine (NAC), a thiol‑containing acetylated derivative of L‑cysteine, has emerged as a multifunctional therapeutic agent beyond its classic role as a mucolytic and as an antidote for acetaminophen toxicity. As a glutathione precursor and direct free‑radical scavenger, NAC exhibits dual antioxidant and anti‑inflammatory effects, modulating key pathways such as Nrf2 and NF‑κB and influencing cellular redox homeostasis. This comprehensive review synthesizes preclinical and clinical evidence for NAC's effects across multiple organ systems. In the respiratory system, NAC improves mucus clearance, reduces exacerbations in COPD, and shows variable benefits in idiopathic pulmonary fibrosis, with emerging precision‑medicine approaches exploring genotype‑guided therapy. In cardiovascular settings, NAC demonstrates endothelial‑protective properties, enhanced nitric oxide bioavailability, and potential to reduce perioperative oxidative injury, though large‑scale trials report mixed impacts on mortality and arrhythmia rates. Renal studies reveal protective effects against contrast‑induced nephropathy and perioperative acute kidney injury by attenuating oxidative and inflammatory markers. Within the central nervous system, NAC has shown neuroprotective properties in vitro and in vivo, including reduced oxidative stress, modulated glutamate transport, and partial mitigation of neurodegenerative processes, although clinical results remain inconsistent. Its safety profile is generally favorable, with mild gastrointestinal effects being the most common adverse events. Collectively, these findings highlight NAC as a promising adjunctive therapy with broad biological plausibility. However, variability in dosing, bioavailability, and patient selection underscores the need for further mechanistic research and well‑designed randomized trials to establish its long‑term clinical utility.
Aneurysmal bone cyst (ABC) is a benign but locally aggressive osteolytic lesion that predominantly affects children and adolescents. Foot involvement is uncommon, with metatarsal lesions representing a rare subset. Reconstruction of the first metatarsal is particularly demanding due to its critical biomechanical role in forefoot load transmission and push-off during gait. A 17-year-old male presented with right forefoot pain after trauma and was found to have a pathological fracture through an expansile lytic lesion of the first metatarsal. Initial conservative management was followed by clinical deterioration. Imaging revealed a 30 × 47 × 30 mm multiloculated lesion with fluid-fluid levels. Biopsy confirmed aneurysmal bone cyst. The patient underwent en bloc resection and reconstruction using an ipsilateral fibular strut autograft. Fixation was achieved using a joint-preserving dual plate construct assisted by a distal mini-fragment plate. At 9 months, the patient demonstrated radiographic union, preservation of first-ray alignment, and no recurrence. Functional outcome improved significantly, with the AOFAS score increasing from 39% preoperatively to 90% postoperatively. Fibular strut graft reconstruction for metatarsal ABC is established in the literature. This case highlights a fixation refinement using mini-fragment-assisted dual plating to enhance distal fixation while preserving the first metatarsophalangeal joint. This technique may represent a viable option in selected cases.
Chiropractic vertebral manipulation is indicated in patients with acute and uncomplicated low back pain. Nowadays, many people seek care for low back pain from manual practitioners. However, within the overall legislative framework regulating in Italy professionals practicing in healthcare, chiropractors remain unevenly regulated. In fact, they are trained abroad and hold internationally recognized degrees that are not regulated under Italian healthcare professionals' legislation. Neither the educational profile, nor a Ministry technical expert committee, nor a national board for ongoing professional evaluation has been established, despite a law in 2007 aimed to regulate the profession and define the national register of doctors in chiropractic. Meanwhile, given their involvement in the healthcare sphere as part of multiprofessional teams, issues of liability arise, made more complex by the fact that chiropractors are not eligible for certain more favourable legal measures for liability assessment granted to healthcare professionals under Italian Law on healthcare safety and liability. Moreover, health-related information for obtaining informed consent cannot be managed independently by these practitioners, again due to their non-healthcare professional status. As a result, prescribing physicians must necessarily be involved in the overall care process. The interaction between healthcare and non-healthcare professionals presents complexities in the patient care and in the proper liability assessment. These aspects are also urgently needed for the definitive recognition and valorisation of the practitioners working in health sphere, which must include State oversight.
Few studies have assessed the distribution and temporal trends of healthcare expenditures related to inflammatory bowel disease (IBD). The aims of the study were to analyze the expenditure trends for IBD patients in Catalonia from 2011 to 2024, to identify key cost drivers, and to forecast future costs through 2036. All patients with a diagnosis of IBD included in the Catalan Health Surveillance System (CHSS) were eligible. CHSS compiles prospective data from public healthcare coverage of 8 million people in 2024. Healthcare utilization was analyzed, and expenditures were calculated using standard costs defined by the Catalan Department of Health. All expenditures were adjusted to 2024 euros using the Consumer Price Index to enable comparisons across years. Costs were estimated for IBD overall, Crohn's disease (CD) and ulcerative colitis (UC). An autoregressive integrated moving average model was used to forecast total costs up to 2036. IBD-related healthcare expenditure tripled from €67.4 M in 2011 to €201.6 M in 2024, while per-patient costs rose from €3,981 to €4,753. Biologic therapies were the main cost driver, especially in CD. Mean per-patient biologic costs decreased by 16.6% in CD but increased by 44.5% in UC. CD patients consistently incurred higher per capita costs. Forecasts indicate continued growth in total expenditure, reaching €319.0 M by 2036. Overall, IBD-related healthcare expenditures in Catalonia markedly increased from 2011 to 2024, driven mainly by the increase in IBD prevalence. Per-patient cost moderately increased. Per-patient cost containment was observed in pharmaceutical costs, probably due to a strict policy favoring the use of biosimilars. These findings may be of help for designing future healthcare policies.
The aim of this study was to detail the morphology of the pronator quadratus muscle (PQM) and to study its morphometry. The objectives were to perform side-based, sex-based analyses. A total of 70 upper extremities (35 right and 35 left) from adult embalmed cadavers were included in this study. The quadrilateral-shaped pronator quadratus was pointed at its medio-superior angle, medio-inferior angle, latero-superior angle and latero-inferior angle. These points were used to measure the lateral length, medial length, proximal width and distal width via a digital Vernier caliper (Mitutoyo, Japan). The midpoints of the elbow and wrist joints were considered for measuring the distance of the muscle from these joints. The outline of the muscle in this study was square shaped in 33 (47.1%), rectangular in 9 (12.8%), rhomboid in 8 (11.4%), trapezoidal in 16 (22.8%) and truncated in 4 (5.7%) specimens. PQM had aponeurotic fibers at the ulnar attachment in 47 patients (67.1%), at the radial attachment in 11 patients (15.8%) and from both bones of the forearm in 12 patients (17.1%). The mean lateral and medial lengths of the PQM were 4.64 ± 0.94 cm and 5.66 ± 1 cm, respectively. The mean proximal and distal widths were 4.09 ± 1 cm and 3.74 ± 0.67 cm, respectively. The muscle was located 19.53±24.29 cm away from the elbow and 2.61±7.27 cm from the wrist joint. The mean distance of the AIN from its origin to entry into the PQM was 12.69 ± 1.52 cm. The lateral length of the PQM in males was considerably greater than that in females (p <0.05). The dimensions compared between the right and left sides were not statistically significant (p > 0.05). This study of our sample population provides in‑depth morphometric data on PQM, which can be used to assist in orthopedic and reconstructive surgical procedures such as tendon transfers, flap surgeries and nerve repairs.
Progression independent of relapse activity (PIRA) and smouldering multiple sclerosis (MS) represent major unmet challenges in contemporary MS care. Disability may accumulate independently of clinical relapses, driven in part by chronic compartmentalised inflammation behind a relatively intact blood-brain barrier and incompletely captured by conventional monitoring tools. This narrative review synthesises evidence across four complementary biomarker domains for detecting smouldering MS and PIRA: advanced MRI (paramagnetic rim lesions [PRLs], slowly expanding lesions, deep grey matter atrophy, quantitative susceptibility mapping); fluid biomarkers (serum glial fibrillary acidic protein [sGFAP], serum neurofilament light chain [sNfL]); retinal optical coherence tomography (ganglion cell-inner plexiform layer thinning); and digital health metrics (wearable accelerometry, digital Symbol Digit Modalities Test). In a single prospective cohort, combined elevation of sGFAP and sNfL conferred a 4.71-fold increased hazard for PIRA (HR 4.71; 95% CI 2.05-9.77); independent data suggest sGFAP may carry selectivity for progression beyond sNfL, although this remains to be confirmed. No single domain sufficiently characterises smouldering pathology. We therefore propose a hypothesis-generating Multimodal PIRA Score (MPS) as a conceptual validation scaffold intended to structure-rather than inform-prospective multicentre evaluation against a long-horizon disability endpoint. Harmonisation of acquisition protocols, reference ranges, and digital phenotyping algorithms remains a prerequisite.
The aim of the study was to evaluate the effectiveness of laparoscopic and open hernioplasty in patients with inguinal hernias in terms of postoperative complications, recovery duration, and overall quality of life. The study was conducted in 2024 at the Regional Hospital in Osh (Kyrgyzstan). A total of 224 patients participated: 86 underwent open hernioplasty (Group 2) and 138 underwent laparoscopic surgery (Group 1). The methodology included the analysis of medical records, standardised questionnaires, assessment of pain using the visual analogue scale, hospitalisation duration, complication rates, and time to return to normal daily life. The results showed that patients who underwent laparoscopy experienced significant advantages. The average pain level in the first 48 hours after surgery was 3.2±1.1 points, compared to 5.4±1.6 in the open surgery group. The average hospital stay was 2.3 days in the laparoscopic group and 4.6 days in the open group. The complication rate (infections, seromas, haematomas) was 8% versus 18%. Full recovery and return to daily activity took 14 days after laparoscopy, compared to 28 days after open surgery. The recurrence rate within 6 months was 2% in the first group versus 7% in the second. Patients who underwent laparoscopic surgery also reported a higher level of satisfaction with the quality of life. The results could be used in clinical practice to support informed decision-making when choosing the surgical approach, with the aim of improving treatment outcomes and enhancing postoperative adaptation.