Background and Objectives: Acute chest syndrome (ACS) is the leading cause of sickle cell disease (SCD)-related mortality (~25% of deaths). A subset of patients develops severe respiratory compromise requiring intensive care unit (ICU) admission or mechanical ventilation (MV), a high-risk group with widely variable reported mortality. This review aimed to determine the mortality rates, ICU/hospital length of stay, and reported complications among adult SCD patients with ACS admitted to the ICU or placed on MV. Materials and Methods: This PRISMA 2020-compliant systematic review was prospectively registered on PROSPERO (CRD420261295111). Cochrane Library, PubMed, Web of Science, ScienceDirect, EBSCOhost, and Scopus were searched without date restriction. Due to substantial clinical and methodological heterogeneity, the pre-specified meta-analysis was replaced by a narrative synthesis. Methodological quality was assessed using the Newcastle–Ottawa Scale. Results: Eight studies were included (one multicenter prospective cohort, two national database studies, three single-center cohorts, and one before–after antimicrobial stewardship study). In-hospital mortality ranged from 0.95% to 3.8%; overall mortality including follow-up reached 12.9% in a dedicated ICU cohort, a distinct endpoint from in-hospital death. Mechanical ventilation was the strongest indicator of mortality, with odds ratios of 67.53 (MV < 96 h) and 8.73 (MV ≥ 96 h) in the largest national cohort. Tricuspid regurgitant jet velocity ≥3 m/second was associated with cor pulmonale, invasive ventilation, and all immediate hospital deaths in one severe cohort. Documented bacterial infection was uncommon (10–20% of episodes), despite frequent antibiotic use, and procalcitonin-guided discontinuation safely reduced antibiotic exposure. All eight included studies were rated high quality on the Newcastle–Ottawa Scale (score ≥ 7/9). Conclusions: Mechanical ventilation, pulmonary hypertension/cor pulmonale, and comorbidity burden are the most consistent markers of poor outcome in ACS. The findings support early recognition, severity-based respiratory support, and antimicrobial stewardship, but should be interpreted cautiously given the substitution of narrative synthesis for meta-analysis, heterogeneous populations, and the geographic concentration of the included studies.
Background and Objectives: Chronic critical illness (CCI) is a growing problem in modern intensive care, though its pathophysiology remains incompletely defined. While the ICS triad is thought to perpetuate organ dysfunction, the temporal interplay between its components has not been studied. The objective was to characterize the temporal dynamics of each component and to assess their synchrony in CCI patients. Materials and Methods: This retrospective cohort study analyzed data from the Russian Intensive Care Dataset (RICD v3.0). Adult ICU patients with at least one documented ICS episode (CRP > 20 mg/L, albumin < 30 g/L, lymphocytes < 0.8 × 109/L within 24 h) were included. Daily binary statuses were generated for each domain using an episode-persistence algorithm. Pairwise concordance was assessed using Cohen’s κ with bootstrap resampling and generalized estimating equation (GEE) models; domain burden, episode frequency, and status combinations were also evaluated. Results: A total of 820 CCI patients contributed 18,525 non-critical patient-days. CRP and albumin domains were persistently positive (median burden 100% both), while lymphocyte positivity was brief (median burden 34.2%) and recurrent (≥2 episodes in 45.1%). CRP and lymphocyte domains were discordant in 81.2% of days (κ = −0.024; OR 0.60; Holm-adjusted p = 0.005); lymphocyte and albumin domains in 77.0% (κ = −0.021; OR 0.49; Holm-adjusted p < 0.001). CRP and albumin were largely concordant (78.5%; κ = 0.299; OR 2.71; Holm-adjusted p < 0.001). Isolated lymphopenia was rare (0.6%), whereas complete compensation was seen in 7.7% of observations. Conclusions: These findings suggest that the ICS triad components follow distinct, temporally discordant trajectories after CCI onset, questioning the view of CCI as a unified state. While periods of complete compensation were observed, their relationship to clinical resolution of CCI requires further investigation.
Background and Objectives: Neurogenic rosacea is a clinically useful, but not yet standardized, sensory-weighted presentation within the rosacea spectrum. This narrative review evaluates its clinical features, differential diagnosis, proposed mechanisms, and reported therapeutic approaches while distinguishing direct human evidence from indirect and experimental findings. Materials and Methods: PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar were searched through 30 June 2026 using predefined combinations of terms related to rosacea, facial dysesthesia, neurogenic inflammation, sensory pathways, mast cells, and treatment. English-language clinical and experimental publications were selected by relevance; reference lists were also screened. Evidence was grouped as phenotype-specific human evidence, human evidence from rosacea populations or related conditions, case-based evidence, and animal or cellular evidence. Results: Direct evidence specific to neurogenic rosacea is limited mainly to small observational series and case reports. Human rosacea studies support neurovascular involvement, whereas many TRP-channel, protease, LL-37–MRGPRX2, and mast cell links remain indirect or experimental. No validated diagnostic criteria or phenotype-specific treatment algorithms exist. Conclusions: Neurogenic rosacea is best regarded as a clinically useful but not yet standardized sensory-weighted presentation within the rosacea spectrum, as current evidence does not establish it as an independent phenotype. The clinical features summarized in this review may support recognition of this presentation and its differentiation from relevant mimics, while diagnostic and treatment decisions should remain individualized. Prospective cohorts, validated sensory measures, biomarkers, and controlled phenotype-stratified trials are needed.
Background and Objectives: Type 2 diabetes mellitus (T2DM), visceral adiposity, and hypertension frequently coexist, but their independent associations with carotid intima–media thickness (cIMT) remain uncertain. We compared cardiometabolic profiles by diabetes status and evaluated adjusted associations with cIMT. Materials and Methods: This retrospective cross-sectional study included 147 adults admitted to Clinical CF Hospital Timișoara between 1 July 2025 and 30 June 2026. Bilateral cIMT was available in 141 patients. Group comparisons, Spearman correlation, and heteroscedasticity-robust multivariable linear regression were performed. Results: T2DM was present in 39 patients (26.5%), hypertension in 125 (85.0%), and obesity in 120 (81.6%). Compared with participants without diabetes, those with T2DM had higher homeostasis model assessment of insulin resistance (HOMA-IR; 4.11 vs. 3.08; p = 0.005) and fasting glucose (6.60 vs. 5.06 mmol/L; p < 0.001), but lower total cholesterol (205.2 vs. 225.9 mg/dL; p = 0.009) and non-high-density lipoprotein cholesterol (156.5 vs. 176.6 mg/dL; p = 0.006). These lower lipid values may reflect treatment or other residual confounding and should not be interpreted as an intrinsic T2DM phenotype. Mean cIMT was numerically higher in T2DM (0.619 vs. 0.592 mm; p = 0.284). Visceral fat area correlated with cIMT before adjustment (ρ = 0.237; p = 0.005), but not after adjustment. Age (β = 0.057 mm/decade; p < 0.001) and hypertension (β = 0.046 mm; p = 0.042) retained adjusted associations with cIMT. Conclusions: T2DM identified metabolic dysregulation, whereas age and hypertension showed the strongest adjusted associations with cIMT. Visceral adiposity showed an unadjusted but not independent association, supporting comprehensive cardiovascular risk assessment and rigorous blood pressure management.
Background and Objectives: Pulse oximetry is essential in ICUs but may be less accurate when peripheral perfusion is impaired. Norepinephrine, the primary vasopressor for shock, may exacerbate vasoconstriction and microcirculatory alterations, increasing discrepancy between pulse oximetry saturation (SpO2) and arterial oxygen saturation (SaO2). This study aimed to evaluate whether norepinephrine dose is associated with disagreement between SpO2 and SaO2, with particular attention to measurement variability and large discrepancies. Materials and Methods: We analyzed 1050 paired SpO2–SaO2 measurements from 196 adult ICU patients receiving norepinephrine. Dose was weight-adjusted (µg/kg/min). Based on the clinically relevant thresholds defined in the 2021 Surviving Sepsis Campaign guidelines for initiating vasopressin, doses were categorized as low (≤0.25 µg/kg/min), moderate (0.25–0.50 µg/kg/min), or high (≥0.50 µg/kg/min). A large discrepancy was defined as |SpO2 − SaO2| ≥ 5%. A generalized estimating equation (GEE) model was applied to account for repeated measurements within patients. Results: Overall mean bias was 0.91 ± 3.58%. In the primary GEE analysis accounting for repeated measurements within patients, norepinephrine dose was not significantly associated with large SpO2–SaO2 discrepancies when analyzed as a continuous variable (adjusted OR 0.964, 95% CI 0.916–1.014, p = 0.158). Categorical analyses showed a non-monotonic pattern, with only the comparison between the moderate- and high-dose groups reaching statistical significance and with wide confidence intervals limiting the precision of this finding. Unadjusted descriptive analyses suggested greater measurement variability across dose ranges, which was largely attributable to within-patient clustering. ROC analysis demonstrated limited discriminatory ability for norepinephrine dose alone (AUC 0.60). Conclusions: After accounting for repeated measurements and relevant clinical covariates, norepinephrine dose did not demonstrate a consistent dose-dependent association with large SpO2–SaO2 discrepancies. Although large SpO2–SaO2 discrepancies may occur in critically ill patients receiving norepinephrine, norepinephrine infusion rate alone should not be used as a surrogate marker of pulse oximetry reliability.
Background and Objectives: In advanced high-grade serous tubo-ovarian carcinoma (HGSOC), the chemotherapy response score (CRS) assesses histopathologic response to neoadjuvant chemotherapy (NACT). CRS1 and CRS2 are commonly grouped for similar prognostic outcomes, but whether partial response carries prognostic value and which factors predict pathologic response remain unclear. This multicenter study evaluated predictors of pathologic response and the association of CRS with recurrence-free survival (RFS) and overall survival (OS) after NACT followed by interval debulking surgery (IDS). Materials and Methods: We retrospectively analyzed 157 patients with FIGO stage IIIC-IV HGSOC treated with NACT followed by IDS between 2015 and 2021. Pathologic response was defined as CRS2–3 versus CRS1; logistic regression identified predictors of response. Survival was assessed using Kaplan–Meier analysis, and Cox regression evaluated factors associated with RFS and OS. Secondary analyses evaluated the conventional CRS1–2 versus CRS3 classification, direct CRS3-versus-CRS2 contrasts, and ordinal trends for RFS and OS. Results: CRS1, CRS2, and CRS3 were observed in 33 (21.0%), 97 (61.8%), and 27 (17.2%) patients, respectively. Median RFS was 10.4, 16.4, and 24.1 months for CRS1, CRS2, and CRS3, respectively (p < 0.001). Median OS was 21.2, 39.1, and 47.0 months, respectively (p < 0.001). In multivariate Cox analysis, CRS2 and CRS3 were independently associated with better RFS (HR 0.36 and 0.24) and OS (HR 0.48 and 0.41) compared with CRS1. In the conventional CRS1–2 versus CRS3 model, CRS3 remained associated with lower recurrence risk after multivariate adjustment (HR 0.60; p = 0.042), but not OS (HR 0.74; p = 0.354). Direct CRS3-versus-CRS2 contrasts were nonsignificant for RFS and OS (p = 0.131 and p = 0.628), whereas ordinal trends toward lower hazards were significant for both endpoints (p = 0.001 and p = 0.041). A higher CA-125 decrease rate (OR 1.04) and more than three NACT cycles (OR 4.89) independently predicted pathologic response, whereas FIGO stage IV predicted a lower response (OR 0.15). Conclusions: Partial pathological response (CRS2) was independently associated with improved RFS and OS compared with no or minimal response (CRS1), suggesting that prognostic information is not confined to complete or near-complete pathological response. The conventional CRS1–2 versus CRS3 classification remained independently prognostic for RFS after multivariate adjustment but did not reach statistical significance for OS, while direct CRS3-versus-CRS2 contrasts were nonsignificant for both outcomes. Thus, separate evaluation of CRS2 may provide additional RFS stratification within CRS1–2. However, the incremental contribution of CRS3 beyond CRS2 could not be established in the present cohort and requires validation in larger cohorts.
Background and Objectives: Intraoperative sentinel lymph node (SLN) assessment is a pivotal step in early-stage breast cancer surgery. Frozen section (FS) analysis remains a widely utilised technique; however, its limitations, particularly in the detection of micrometastases, are well-documented. The process is both time-consuming and costly. The objective of this study was to investigate the potential of ex vivo shear-wave elastography (SWE) as a rapid and reproducible method for quantifying lymph node stiffness and predicting metastatic involvement. Materials and Methods: Between January 2022 and January 2024, 100 patients with biopsy-confirmed invasive breast cancer undergoing SLNB were enrolled in the study. A total of 384 excised axillary lymph nodes were subjected to ex vivo SWE immediately following excision, prior to the standard histopathological procedure. The mean stiffness (Emean) values were recorded, and the diagnostic performance was evaluated with the use of ROC analysis. Results: Of the 384 nodes examined, 45 (11.6%) were found to have metastases on final histopathology. It was demonstrated that Emean exhibited excellent discriminatory power, with an Area Under the Curve (AUC) value of 0.957. At the optimal cut-off of 28 kPa, the sensitivity and specificity levels were recorded as 91% and 87%, respectively. Conclusions: The findings of this study indicate that ex vivo SWE is a highly accurate and reproducible method for identifying metastatic sentinel lymph nodes. The technique has the potential to complement or selectively replace intraoperative FS, thereby reducing unnecessary tissue processing. The logical next step is multicentre validation.
Background and Objectives: Non-fermenting Gram-negative bacilli (NFGNB) are frequently recovered from respiratory specimens in intensive care units (ICUs) and are increasingly carbapenem-resistant. We described their distribution and resistance profiles in adult ICUs over three years. Materials and Methods: Respiratory specimens submitted from adult ICUs of a foundation university hospital in Istanbul between 6 January 2023 and 27 December 2025 were analysed retrospectively using laboratory information system data. Identification and susceptibility testing used the BD Phoenix M50 system with year-specific EUCAST breakpoints (v13.0–v15.0); colistin MICs were determined by broth microdilution. The number of patients contributing more than one isolate was 268. Accordingly, the primary trend analysis was performed using generalised estimating equations (GEE) accounting for within-patient clustering. Chi-square and first-isolate analyses were used as secondary and sensitivity analyses. Results: A total of 1407 isolates were recovered from 654 of 1194 patients with a respiratory culture. Acinetobacter spp. predominated (56.9% of isolates; 54.3% of patients), followed by Pseudomonas spp. (29.4%) and Stenotrophomonas maltophilia (11.1%). Carbapenem resistance in Acinetobacter spp. was 96.7% (95% CI 95.3–97.8) for imipenem and 96.6% (95.1–97.7) for meropenem, without temporal trend. In P. aeruginosa, meropenem resistance rose from 44.7% to 71.4% (GEE odds ratio per year 1.45, 95% CI 1.09–1.92, p = 0.011), whereas imipenem resistance did not change significantly. Among the agents tested, colistin was found to be the most effective (22.4% resistance in Acinetobacter spp. and 13.1% in P. aeruginosa). Ceftazidime–avibactam resistance in P. aeruginosa was 24.3%. Of the S. maltophilia isolates, 85.8% were categorised as susceptible-increased exposure to trimethoprim–sulfamethoxazole. Conclusions: Carbapenem resistance is high and stable in Acinetobacter spp. but rising for meropenem in P. aeruginosa. These data do not distinguish colonisation from infection and cannot be linked to clinical outcomes. They should therefore be used to inform local empirical-treatment policy alongside clinical assessment, rather than as evidence of treatment failure.
Background and Objectives: Traditional open anterior cruciate ligament transection (ACLT) surgical models performed through arthrotomy may introduce capsular trauma and postoperative inflammatory responses that can interfere with the interpretation of post-traumatic osteoarthritis (OA). This study aimed to evaluate the feasibility of a minimally invasive, arthroscopic ACLT rabbit model performed entirely under arthroscopic visualization, without arthrotomy, using a 2.4-mm arthroscope and 2.5-mm shaver, and to provide preliminary structural, histological, synovial, and systemic biochemical characterization of the model for future therapeutic testing. Materials and Methods: Bilateral arthroscopic ACLT was performed in three skeletally mature New Zealand rabbits, followed by a supervised 12-week exercise protocol. Joint degeneration was evaluated macroscopically and histopathologically using the standardized Pritzker-Osteoarthritis Research Society International (OARSI) grading system. Collagen matrix remodeling was assessed via Picrosirius Red staining. Local intra-articular catabolism was quantified via Enzyme-Linked Immunosorbent Assay (ELISA) for matrix metallopeptidase 13 (MMP-13) and interleukin-1β (IL-1β) from synovial fluid. Systemic oxidative stress, including lipid peroxidation biomarkers, malondialdehyde (MDA), and nitric oxide (NO), was evaluated in serum. Results: The arthroscopic approach induced osteoarthritic changes, with severity varying across the cohort. Histopathology revealed vertical matrix fissures and disruption of the normal columnar chondrocyte organization, yielding a median comprehensive Pritzker-OARSI score of 6 (range 6–10), with horizontal degradation restricted to stage 2. Synovial fluid analysis demonstrated measurable concentrations of MMP-13 (188.77 ± 93.87 ng/mL) and IL-1β (174.93 ± 95.51 pg/mL). Furthermore, serum oxidative stress parameters at the 12-week endpoint included lipid peroxidation (MDA: 1.01 ± 0.03 nmol/mL) and NO levels (82.72 ± 0.32 µmol/L), presented descriptively in the absence of a comparator group. Conclusions: This study establishes the first multifaceted pathological baseline of a minimally invasive arthroscopic ACLT rabbit model before therapeutic intervention. The arthroscopic ACLT model produced structural cartilage degeneration alongside measurable intra-articular catabolic and systemic oxidative stress changes, establishing a baseline phenotype and a starting point for future therapeutic studies.
Background and Objectives: Periprosthetic fracture is a complex and urgent condition in orthopedic surgery. It requires an individual approach to every patient, and treatment is associated with high risk of complications. Materials and methods: Fifty-six patients treated due to periprosthetic fracture (PPF) after total knee arthroplasty were retrospectively analyzed according to surgical protocol, treatment time, and complication rate. The results were compared to the available literature. Results: Almost all patients (91%) were treated surgically—revision total knee arthroplasty or osteosynthesis. A therapeutic success was achieved in 81% of all cases. Replacement of the femoral component with the semi-constrained type of implant was performed most frequently during revision total knee arthroplasty. In PPFs of the femur, destabilization of fixation was observed mainly in type II according to the Lewis–Rorabeck classification. Conclusions: Despite the complexity of the problem, treatment of periprosthetic knee fractures can be effective. Provided that the implant remains stable, osteosynthesis is a good treatment option for PPF of the femur. In revision total knee arthroplasty, implants with a higher level of restriction are usually used to ensure better knee joint stability.
Malignant distal biliary obstruction (MDBO) is most commonly managed by endoscopic retrograde cholangiopancreatography (ERCP) with self-expandable metal stent placement. When ERCP fails or is not feasible, endoscopic ultrasound-guided biliary drainage (EUS-BD) has increasingly replaced percutaneous transhepatic biliary drainage in expert centers. Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has emerged as an indirect route for biliary decompression when the cystic duct is patent. This comprehensive narrative review focuses on the anatomical rationale, patient selection, procedural technique, comparative positioning, clinical outcomes, adverse events, and unresolved issues of EUS-GBD in MDBO. The supporting evidence is predominantly observational. Published meta-analyses report technical success generally exceeding 90%, pooled clinical success of approximately 82–89%, and overall adverse event rates of approximately 10–14%; these estimates vary with study selection, outcome definitions, assessment time points, and predominantly observational study designs. Comparative studies suggest efficacy and safety similar to EUS-guided choledochoduodenostomy after failed ERCP in anatomically selected patients, although nonrandomized allocation and confounding by indication remain major limitations. A prospective study has demonstrated feasibility as primary palliation, but this strategy cannot yet be considered standard of care. Prophylactic EUS-GBD to prevent post-stenting cholecystitis represents a separate indication and should not be conflated with EUS-GBD for biliary decompression. The key determinant of physiological success is unobstructed communication between the gallbladder and the central biliary tree; therefore, cystic duct patency, tumor relationship to the cystic duct take-off, gallbladder distension, and the absence of extensive gallbladder involvement must be assessed before intervention. EUS-GBD is best positioned as a rescue option after failed ERCP when direct EUS-BD is technically impossible, unsafe, or unsuccessful. Prospective randomized trials, standardized outcome definitions, comparative cost-effectiveness analyses, and dedicated long-term stent management protocols are needed before broader adoption.
Background and Objectives: Malignant double obstruction, defined as the coexistence of malignant biliary obstructio (MBO) and malignant gastric outlet obstruction (mGOO), frequently complicates advanced pancreatic and periampullary malignancies. Because biliary and duodenal obstructions are anatomically and functionally interconnected, treatment of one may influence the outcome of the other. This review aims to summarize current evidence on endoscopic management strategies and to propose an anatomy-driven approach integrating conventional and endoscopic ultrasound (EUS)-guided techniques. Materials and Methods: A narrative review of the current literature was performed, focusing on endoscopic approaches for malignant biliary and gastric outlet obstruction. Available evidence regarding endoscopic retrograde cholangiopancreatography (ERCP), EUS-guided biliary drainage (EUS-BD), enteral self-expandable metal stenting, and EUS-guided gastroenterostomy (EUS-GE) was critically analyzed, focusing on technical feasibility, clinical outcomes, adverse events, and therapeutic sequencing. Results: ERCP remains an effective option when papillary access is preserved; however, duodenal obstruction, especially when involving the papilla, represents a major limitation. EUS-BD has emerged as a reliable alternative after failed ERCP and may provide a primary drainage strategy in selected patients. In the setting of concomitant gastric outlet obstruction, EUS-guided hepaticogastrostomy may offer advantages over choledochoduodenostomy by avoiding the obstructed duodenal pathway. For malignant gastric outlet obstruction, enteral stenting provides rapid symptom relief, but is associated with limited long-term durability. EUS-GE has demonstrated high technical and clinical success rates, lower rates of recurrent obstruction compared with enteral stenting, and outcomes comparable to surgical gastrojejunostomy with reduced invasiveness. These findings support an integrated EUS-based approach for selected patients. Conclusions: Malignant double obstruction should be considered a single anatomofunctional entity rather than two independent conditions. An individualized, anatomy-driven strategy combining EUS-guided biliary drainage and EUS-GE may represent the future direction of endoscopic palliation, allowing durable internal bypass and facilitating oncological management. Further prospective studies are required to define optimal treatment sequencing and patient selection.
Background and Objectives: Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer, and its global incidence rate constantly rises. However, there are no current epidemiological data for many regions, including Małopolska in southern Poland. This study aimed to characterize the clinical and histological profile of patients with BCC and to identify factors associated with local recurrence and the presence of multiple tumors. Materials and Methods: We performed a single-center, retrospective observational study consistent with STROBE guidelines at the Department of Dermatology and Allergology, University Hospital in Cracow. The included patients were adults with at least one histologically confirmed BCC treated between 2015 and 2025. Demographic, clinical, histopathological, and follow-up data were collected at patient and lesion levels. The results were evaluated using univariable tests, multivariable logistic regression, Kaplan–Meier survival analysis, and generalized estimating equations. Results: We included 108 patients (median age at first diagnosis, 73 years; 52% male) with 418 BCCs; the median follow-up duration was 84 months. Superficial BCC was the most common subtype among lesions with available histological subtype information (56%). The head and neck region was the most frequent anatomical site in this group (51%). Multiple BCCs were present in 62% of patients. Longer follow-up was independently associated with the presence of multiple BCCs. A history of actinic keratoses showed a positive but statistically nonsignificant association with multiple BCCs. Recurrence was observed in 15 lesions (3.6%). Female sex and H-zone involvement showed higher odds of recurrence. Conclusions: In this elderly cohort, multiple BCC tumors may reflect longer follow-up and cumulative actinic damage. Recurrence was relatively infrequent but associated with clinically relevant features, including H-zone involvement and female sex. These findings support an individualized, multifactorial approach to treatment and follow-up, taking into account age, sex, lesion burden, anatomical location, and histological subtype.
Background and Objectives: This study examined whether positivity for any antineutrophil cytoplasmic antibody (ANCA) at diagnosis was associated with subsequent advanced systemic complications during follow-up in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Materials and Methods: We retrospectively reviewed the medical records of 271 patients with MPA or GPA enrolled in the ANCA-associated vasculitis cohort at a tertiary hospital. Any ANCA positivity was defined as the presence of any of the following: myeloperoxidase-ANCA, proteinase 3-ANCA, perinuclear ANCA, or cytoplasmic ANCA. Subsequent advanced systemic complications during follow-up, such as all-cause mortality and end-stage kidney disease (ESKD), were evaluated. Results: The median age of the 271 patients with MPA or GPA was 62.0 years, and 239 and 32 were identified as ANCA-positive and ANCA-negative vasculitis, respectively. During follow-up, 47 patients (17.3%) died, and 52 (19.2%) progressed to ESKD. In a cross-sectional comparative analysis, ESKD occurred significantly more frequently in ANCA-positive patients than in ANCA-negative patients. Among the five subsequent advanced systemic complications of MPA and GPA, ANCA-negative patients exhibited a significantly higher cumulative ESKD-free survival rate than ANCA-positive patients. However, in multivariable Cox proportional hazards analysis adjusted for age, sex, AAV subtype, and baseline serum creatinine, ANCA positivity was not independently associated with subsequent ESKD. Conclusions: Any ANCA positivity at diagnosis was associated with subsequent ESKD in unadjusted analyses but was not an independent predictor after adjustment for baseline renal function and other clinically relevant covariates.
For a long time, pain management has relied on relatively old opioids and broad-spectrum non-opioids, which display efficacy gaps and non-negligible safety risks. This review explores why voltage-gated sodium channels, particularly NaV1.7 and NaV1.8, emerged as prime targets for pain relief, and why early development efforts failed. NaV1.7 was initially considered a promising target due to its role in nociception and genetic evidence linking it to pain disorders. However, clinical trials of selective NaV1.7 inhibitors have repeatedly failed. We explore the reasons for these failures and discuss the clinical shortcomings of non-selective blockers and early NaV1.7 inhibitors. In contrast, NaV1.8 has emerged as a much stronger drug target, because it is mostly limited to peripheral nerves, directly drives continuous pain signaling, and shows less apparent functional redundancy in specific nociceptive axonal compartments. Nevertheless, compensatory mechanisms involving NaV1.7, NaV1.9, and other conductances remain context-, tissue-, and disease-dependent. Suzetrigine, a highly selective inhibitor of this channel, recently gained regulatory approval for acute pain, marking a major breakthrough in non-opioid options, even though its Phase 3 efficacy was comparable to hydrocodone/acetaminophen rather than superior to it. Its clinical success is built on high selectivity, excellent pharmacokinetics, and a smart trial design that focused specifically on standardized postoperative pain models. While suzetrigine shows that NaV1.8 can be successfully targeted, it represents a regulatory and mechanistic victory rather than a complete replacement for opioids in daily practice. Progress in this field will ultimately require precise targeting, better pharmacology, and trials that better match patient phenotypes.
Background and Objectives: Iron deficiency (ID) is common in heart failure with reduced ejection fraction (HFrEF) and is associated with adverse clinical outcomes. Although intravenous ferric carboxymaltose (FCM) improves functional status, its effects on ventricular electrophysiological indices remain incompletely characterized. This study evaluated short-term changes in the corrected index of cardiac electrophysiological balance (iCEBc) and conventional electrocardiographic repolarization parameters after FCM administration. Materials and Methods: This retrospective single-center pre–post study included 92 clinically stable patients with HFrEF and ID who received intravenous FCM. Standard 12-lead electrocardiograms and laboratory parameters were evaluated at baseline and 30 ± 5 days after treatment. The primary outcome was the within-patient change in iCEBc, while secondary outcomes included conventional ventricular repolarization indices. Results: Following FCM treatment, ferritin, transferrin saturation, and hemoglobin increased significantly (all p < 0.001). iCEBc decreased significantly (4.33 ± 1.04 vs. 4.04 ± 0.82, p = 0.016). Significant reductions were also observed in QTc, JTc, JT, Tp-e, Tp-e/QT, Tp-e/QTc, frontal QRS–T angle, and QT, whereas QRS duration remained unchanged. Changes in iron indices were not associated with changes in iCEBc. Conclusions: In this uncontrolled pre–post cohort, intravenous FCM was associated with favorable short-term changes in several electrocardiographic repolarization indices. However, because anemia correction occurred concurrently and no control group or clinical arrhythmic outcomes were available, these findings should be considered exploratory and hypothesis-generating rather than evidence of an antiarrhythmic effect.
Background and Objectives: Krebs von den Lungen-6 (KL-6) is a promising biomarker of interstitial lung disease (ILD), but data in immune-mediated ILD remain limited. We aimed to evaluate the clinical, functional, and radiological correlates of serum KL-6 levels in a real-world cohort of patients with immune-mediated ILD. Materials and Methods: We conducted a retrospective, cross-sectional, single-center study including adults with multidisciplinary follow-up for immune-mediated ILD and at least one serum KL-6 determination between January 2023 and September 2025. Clinical, laboratory, radiological, and pulmonary function data closest to the index KL-6 measurement were collected. KL-6 was analyzed as both a continuous variable and a categorical variable using a predefined cutoff of 500 U/mL. Correlation analyses and multivariable logistic regression were performed to identify factors independently associated with elevated KL-6 levels. Results: A total of 112 patients were included; 72.3% were women, with a median age of 70 years (IQR 63–77). The most frequent underlying diseases were systemic sclerosis (30.4%), rheumatoid arthritis (25.9%), and inflammatory myopathy (14.3%). Median KL-6 concentration was 770.5 U/mL (IQR 437.3–1148.5). Patients with FVC < 80% predicted and DLCO < 60% predicted had significantly higher KL-6 levels than those with better lung function (p = 0.001 and p = 0.004, respectively). KL-6 levels correlated inversely with DLCO (% predicted) (ρ = −0.388, p < 0.001) and FVC (% predicted) (ρ = −0.328, p < 0.001) but not with the presence of radiological fibrosis. In the multivariable analysis, lower DLCO (% predicted) (OR 0.919, 95% CI 0.884–0.955; p < 0.001) and older age (OR 1.063, 95% CI 1.014–1.115; p = 0.012) were independently associated with elevated KL-6 levels. Conclusions: Elevated serum KL-6 concentrations were associated with impaired gas transfer as measured by DLCO % predicted in this cross-sectional cohort. Longitudinal studies are required to determine whether KL-6 can predict functional decline, disease progression, or clinical outcomes.
Background and Objectives: Accurate identification of the internal opening is a key determinant of success in perianal fistula surgery, as missed openings are strongly associated with persistent infection and recurrence. Although magnetic resonance imaging provides detailed preoperative mapping, intraoperative confirmation relies largely on surgical judgment. This study evaluated the technical feasibility and early observed outcomes of flexible rectoscopy-guided identification of the internal opening during loose seton placement in patients with transsphincteric perianal fistula whose internal opening could not be localized by routine assessment or pelvic MRI. Materials and Methods: This single-center retrospective descriptive feasibility series included 44 adult patients with cryptoglandular transsphincteric perianal fistula who underwent loose seton placement. All included patients had an internal opening that could not be localized by routine preoperative assessment or pelvic MRI. Intraoperative flexible rectoscopy was used to identify the internal opening in relation to the dentate line. The primary endpoint was successful intraoperative visualization of the internal opening. Operative time, healing time, early follow-up outcomes, Wexner continence score and patient satisfaction were descriptively recorded. Results: The mean age was 41.00 ± 12.06 years and the mean BMI was 29.86 ± 3.65 kg/m2. The internal opening was successfully visualized using flexible rectoscopy in all 44 patients (100%). Mean operative time was 6.66 ± 1.49 min and mean healing time was 59.45 ± 9.96 days. During the available 3–7-month early follow-up, no complications were documented, while recurrence occurred in one patient (2.3%) at the fourth postoperative month. The exact binomial 95% confidence interval for the observed recurrence rate was 0.06–12.02%. The median postoperative Wexner score was 0 (IQR 0–0; range 0–1). Conclusions: Flexible rectoscopy enabled intraoperative identification of the internal opening in all patients in this descriptive series and may represent a feasible adjunct when routine assessment and pelvic MRI fail to localize the opening. The absence of a comparator and the relatively short follow-up prevent conclusions regarding comparative accuracy, safety or recurrence reduction. Larger prospective comparative studies with long-term follow-up are required.
Background and Objectives: This study aimed to determine the incidence of peritonitis developing within the first six months of therapy in peritoneal dialysis (PD) patients aged 65 years and older, and to evaluate the risk factors associated with one-year mortality. Materials and Methods: A total of 227 PD patients aged ≥65 years across nine centers were evaluated in this retrospective, multicentre cohort study. Demographic characteristics, comorbidities, laboratory parameters, and clinical outcomes were analyzed using electronic health records. Early peritonitis was defined as an episode occurring within the first six months following PD initiation. Univariate and multivariable logistic regression analyses were performed to identify predictors of one-year mortality. Results: Early peritonitis developed in 70 patients (30.8%), and the overall one-year mortality rate was 15.9% (n = 36). In univariate analysis, one-year mortality was significantly associated with underlying coronary heart disease (58.3% vs. 36.1%, p = 0.012) and heart failure (50.0% vs. 31.9%, p = 0.037). The number of peritonitis episodes within the first six months was not significantly associated with 1-year mortality (p = 0.108). In the multivariable logistic regression model, peritonitis within the first six months was identified as an independent predictor of mortality, increasing the risk of death (OR: 11.438; 95% CI: 1.352–96.749; p = 0.025). Coronary heart disease, heart failure, and peak CRP during the peritonitis attack did not reach statistical significance in this model (all p > 0.05), though this model should be interpreted cautiously given the limited number of events (17) relative to the number of predictors (4). Conclusions: Peritonitis developing during the early phase of therapy is independently associated with an increased risk of one-year mortality in elderly PD patients. Mortality in this population appears to be influenced by early infectious complications alongside underlying cardiovascular comorbidity burden. These findings highlight the clinical importance of close surveillance, early infection prophylaxis, and vigilant therapeutic strategies during the initial months of peritoneal dialysis.
