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.
Background and Objectives: The modified Glasgow Prognostic Score (mGPS)—a composite of serum C-reactive protein (CRP) and albumin—simultaneously reflects systemic inflammatory activity and nutritional reserve. Its specific prognostic role in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab in the second-line setting has not previously been examined in a large multicentre cohort. The aims of this study are to determine whether baseline mGPS independently predicts overall survival (OS) and progression-free survival (PFS) in this population and whether its discriminatory capacity compares favourably with the International Metastatic RCC Database Consortium (IMDC) risk score. Methods: This multicentre retrospective cohort study included 174 consecutive patients with histopathologically confirmed mRCC who progressed on first-line VEGF-targeted tyrosine kinase inhibitor (TKI) therapy and subsequently received nivolumab monotherapy at six oncology centres in Türkiye between January 2015 and December 2023. Baseline mGPS was calculated from serum albumin and CRP measured within four weeks before treatment initiation. Kaplan–Meier analysis with log-rank testing and Cox proportional-hazards regression were used for survival analyses; discriminatory capacity was quantified using Uno’s concordance (C) statistic. Results: The median follow-up was 24.2 months. The median OS was 44.5, 15.3, and 10.0 months for the mGPS 0, 1, and 2 groups, respectively (log-rank p < 0.0001); the median PFS was 6.7, 4.2, and 2.6 months (p = 0.022). On multivariable analysis, mGPS 2 independently predicted inferior OS (hazard ratio [HR] 3.61, 95% confidence interval [CI] 1.78–7.31; p < 0.001) and PFS (HR 1.87, 95% CI 1.17–2.97; p = 0.008). Uno’s C-statistic for OS was numerically higher for the combined mGPS + IMDC model (0.70) than for either the mGPS (0.66) or IMDC (0.63) alone; these differences were not formally tested and are presented descriptively. Conclusions: Baseline mGPS is a simple, inexpensive, and independent prognostic biomarker in mRCC patients treated with second-line nivolumab, providing discriminatory information that may be complementary alongside IMDC risk stratification. Prospective validation in randomised trials is warranted.
Background and Objectives: Caries experience, plaque accumulation, gingival inflammation, and periodontal screening findings may coexist as manifestations of a shared oral-health burden. We examined whether these routinely recorded indicators form distinct multivariable profiles or primarily represent ordered levels along a common burden continuum in children and adolescents. Materials and Methods: This secondary exploratory analysis included 638 participants from a multicenter cross-sectional clinical database: 407 aged 6–12 years and 231 aged 13–19 years. Permanent-dentition Decayed, Missing, and Filled Teeth score, Plaque Index, Gingival Index, and Community Periodontal Index were standardized and analyzed separately by age stratum. Unsupervised K-means clustering compared solutions containing two to five groups to summarize participant-level patterns without imposing predefined clinical categories. Hierarchical Ward classification assessed algorithmic concordance; principal component analysis and a composite standardized burden score assessed dimensionality. Sensitivity analyses excluded the periodontal index or treated it as ordinal with Gower-distance partitioning around medoids, and 1000 repeated 80% subsamples assessed sampling stability using the adjusted Rand index. Results: A single principal component explained 91.0% of variance at 6–12 years and 91.8% at 13–19 years, with all four indicators loading strongly on the same dimension. Ordered cluster membership correlated closely with the composite burden score (Spearman ρ = 0.942 and 0.939; both p < 0.001). The retained low-, intermediate-, and high-burden groupings were highly consistent when the periodontal index was excluded or treated as ordinal and under repeated subsampling. In adolescents, a two-group alternative preserved the low- and high-burden extremes while dividing the intermediate group, indicating that the number of groups changes descriptive granularity rather than revealing a separate phenotype. Conclusions: The principal new finding is that four commonly used oral-health indicators converge on one dominant participant-level burden dimension rather than defining distinct clinical phenotypes. This supports an integrated epidemiological description of cumulative oral-health burden while cautioning against interpreting data-driven groups as diagnostic or treatment categories. The numerical group distributions are sample-specific and require external and longitudinal validation before being transferred to other populations or clinical decision-making.
Background and Objectives: Intra-corporeal esophagojejunostomy after totally laparoscopic total gastrectomy (TLTG) remains one of the most technically demanding steps of minimally invasive gastric surgery. The management of the common entry hole in linear stapler-based reconstructions still relies on advanced intra-corporeal suturing. The sutureless L-shape esophagojejunostomy with endoscopic assistance (SLEJ) technique, previously described by our group, was developed to overcome this limitation by combining an L-shaped linear stapler configuration with intraoperative endoscopic quality control. Building upon our initial results on the perioperative feasibility of the technique, the present study aimed to evaluate its intermediate-term anastomotic, functional, and oncological outcomes. Materials and Methods: Patients who underwent TLTG with D2 lymph node dissection and SLEJ reconstruction for gastric cancer between July 2024 and January 2026 were evaluated. Eligibility criteria included a minimum postoperative follow-up of six months, clinical and endoscopic surveillance, and complete contrast-enhanced thoraco-abdominopelvic computed tomography records. Protocol-based upper gastrointestinal endoscopy was performed at six-month intervals irrespective of symptoms to objectively assess anastomotic lumen width, mucosal healing, reflux findings, and possible intraluminal recurrence. The primary endpoint was anastomosis complication-free survival (anastomotic stenosis, alkaline reflux/reflux esophagitis, marginal ulcer, bleeding due to ulceration, and intraluminal recurrence); secondary endpoints were disease-free survival (DFS), local recurrence and changes to nutritional status. Results: A total of 26 patients (18 men and 8 women; mean age 59.0 ± 7.8 years) were analyzed. Anastomotic stricture developed in two patients and was successfully managed with two sessions of endoscopic balloon dilation in both. Similarly, alkaline reflux was documented in two additional patients and resolved under medical treatment. None of the patients required surgical revision. The mean ACFS follow-up duration was 12.42 months with ACFS rates of 92.3% at six months and 81.1% from the twelfth month onward. No local anastomotic recurrence was detected during follow-up. Disease progression occurred in four patients (15.4%), presenting as distant organ metastasis (n = 2) or peritoneal carcinomatosis (n = 2). The mean DFS follow-up duration was 12.62 ± 6.18 months, and the twelve-month OS and DFS rates were 82.1% and 84.0%. Postoperative body weight decreased significantly compared with preoperative values (76.69 ± 15.59 kg vs. 63.23 ± 10.55 kg; p < 0.001). A significant decrease was observed in the mean SMI between the preoperative and follow-up assessments (p < 0.001). The mean preoperative SMI was 49.90 ± 9.04 cm2/m2, compared with 44.53 ± 7.98 cm2/m2 at follow-up. No statistically significant changes were observed between the preoperative and follow-up periods for serum albumin and PNI variables (p = 0.703 and p = 0.970). Conclusions: The present intermediate-term analysis suggests that the SLEJ technique is feasible and associated with acceptable intermediate-term anastomotic, functional, and oncological outcomes in this preliminary single-center cohort. By standardizing common entry-hole management without intra-corporeal suturing and incorporating intraoperative endoscopic quality control, the technique offers a feasible alternative to established linear stapler-based reconstructions.
Cervical lymph node status is the single most important prognostic determinant in head and neck squamous cell carcinoma (HNSCC), yet conventional gray-scale ultrasound relies on morphological criteria that only indirectly reflect the underlying biological process driving nodal progression: tumor angiogenesis. This narrative review focuses specifically on cervical lymph nodes and examines whether multiparametric ultrasound (B-mode, Doppler, elastography, and contrast-enhanced ultrasound [CEUS]) can serve as a non-invasive, repeatable surrogate for nodal angiogenic activity in HNSCC and outlines a practical framework for its use in the head and neck clinic; evidence on the primary tumor itself was outside this review’s scope. A narrative synthesis of the literature on angiogenesis biology in HNSCC and on multiparametric ultrasound of cervical lymph nodes was performed, drawing on systematic reviews, meta-analyses, and clinical pilot studies identified through PubMed-indexed sources. Vascular endothelial growth factor (VEGF)-driven neoangiogenesis is a recognized diagnostic, prognostic, and predictive biological axis in HNSCC. Ultrasound modalities that visualize or quantify microvascular architecture and perfusion—Doppler vascularity patterns, shear-wave elastography, and CEUS—track features that are biologically continuous with angiogenesis (disorganized, high-permeability neovessels; altered tissue stiffness from stromal remodeling). Combining CEUS with B-mode ultrasound improves diagnostic accuracy for inconclusive cervical lymph nodes compared with either modality alone, and pilot multiparametric protocols in HNSCC show reproducible irregular contrast enhancement and elastographic heterogeneity in metastatic nodes. Multiparametric ultrasound does not replace histology, but it offers a repeatable, radiation-free, low-cost window onto the vascular phenotype of HNSCC that complements morphological staging. Given the heterogeneity and methodological limitations of the available evidence, multiparametric ultrasound should currently be regarded as a promising imaging biomarker rather than an established non-invasive surrogate for angiogenesis. Larger prospective, HNSCC-specific cohorts using standardized acquisition protocols, with direct histological correlation, are needed before this approach can be adopted into routine diagnostic pathways.
Background and Objectives: Cancer care is increasingly delivered through outpatient pathways, thereby progressively transferring part of the organisational and practical workload of care to patients and informal caregivers. Although peripherally inserted central catheters (PICCs) are widely used in oncology for safe vascular access, comparatively less attention has been devoted to the organisational and logistical burden of PICC management and to the related involvement of informal caregivers in ambulatory settings. Materials and Methods: A single-centre descriptive study was conducted among adult oncology outpatients undergoing PICC placement within an ambulatory oncology service. Health-related quality of life was assessed at baseline (T0) and at two-month follow-up (T1) using the SF-36 questionnaire. A structured exploratory 20-item survey was additionally administered at follow-up to investigate physical, psychological, and organisational/social burden associated with PICC management. Descriptive statistics and Wilcoxon signed-rank tests were used for analysis. Results: Forty patients were enrolled, and 37 completed the follow-up assessment. In exploratory analyses, statistically significant reductions were observed in the SF-36 domains of general health (p = 0.034) and vitality (p = 0.016), whereas no statistically significant changes were observed in the remaining domains. PICC-related complications were recorded in five participants (12.5%). The exploratory survey identified the highest burden scores within the organisational/social domain, particularly for travel requirements for weekly dressing changes, caregiver assistance with transportation, and travel-related costs. Conclusions: The findings provide preliminary evidence of practical and organisational demands within outpatient PICC management pathways that are not fully reflected by conventional device-related outcomes or generic HRQoL measures. Given the descriptive, single-centre design and exploratory burden assessment, these findings should be considered hypothesis-generating. Larger multicentre and longitudinal studies using validated measures are needed to confirm these observations and evaluate alternative models of PICC follow-up.
Background and Objectives: Delayed cerebral ischemia (DCI) is a major determinant of poor outcome after aneurysmal subarachnoid hemorrhage (aSAH), yet early risk prediction remains difficult, particularly in sedated or ventilated intensive care patients. We evaluated whether a large language model (LLM) could predict DCI from phase-based dynamic clinical data, compared with intensive care specialists. Materials and Methods: In this single-center, retrospective study, 216 consecutive patients with aSAH were assessed at three predefined phases of accumulating clinical data (day 1; days 1 + 3; days 1 + 3 + 5). For each patient–phase, an LLM (ChatGPT, GPT-5.5 Thinking) and two blinded intensive care specialists predicted DCI risk using only the data available up to that time point. DCI was adjudicated by a blinded three-member panel. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC), with non-inferiority defined a priori as Δ = 0.10. Calibration, decision-curve analysis, and reproducibility were also assessed. Results: Of 216 patients, 60 (27.8%) were DCI-positive and 15 were indeterminate; the primary sample comprised 201 patients. In the prespecified primary analysis, the LLM met the non-inferiority criterion relative to both specialists across all three phases (LLM AUC 0.703–0.747; specialists 0.712–0.764); however, in an equal-granularity sensitivity analysis, non-inferiority remained supported only in Phases 2 and 3 and was not demonstrated in Phase 1. Discrimination increased numerically as data accumulated (Phase 1 vs. 3, p = 0.072), an increase that was attenuated in a landmark-restricted analysis accounting for DCI-onset timing. The LLM showed the lowest false-reassurance rate (3.3–11.7%), reflecting a more cautious threshold rather than better discrimination. Confidence did not reliably indicate accuracy (~25% of high-confidence predictions were wrong); outputs were highly reproducible (Fleiss κ 0.887; intraclass correlation coefficient (ICC) 0.968). Conclusions: An LLM achieved DCI discrimination that was non-inferior to—but not better than—that of experienced specialists; its unreliable confidence scores support clinician-supervised rather than autonomous use.
Anterior cruciate ligament (ACL) reconstruction represents the current gold standard for restoring knee stability following ligament rupture, particularly in young and physically active individuals. The aim of this narrative review is to provide an updated overview of the biomechanical, biological, and clinical considerations underlying graft selection in ACL reconstruction, with particular emphasis on graft incorporation, fixation strategies, and postoperative outcomes. While surgical techniques and fixation devices have undergone substantial refinement, the optimal choice of graft remains a subject of ongoing debate. Traditionally, emphasis has been placed on the biomechanical characteristics of grafts, including tensile strength, stiffness, and resistance to cyclic loading. However, increasing attention has been directed toward biological factors that influence graft incorporation and clinical outcomes. The aim of this narrative review is to summarize the currently available literature regarding graft selection in ACL reconstruction by integrating biomechanical properties, biological graft incorporation, fixation strategies, and clinical outcomes. Particular emphasis is placed on the relationship between biomechanical performance and biological healing, as well as postoperative outcomes, in order to facilitate individualized graft selection in contemporary orthopedic practice.
Background and Objectives: Implant-based breast reconstruction following subcutaneous mastectomy is widely performed; however, the optimal strategy for implant support remains controversial. Absorbable synthetic meshes have emerged as lower-cost alternatives to acellular dermal matrix (ADM), yet their clinical and economic value remains incompletely defined. Materials and Methods: A systematic review was conducted in accordance with PRISMA guidelines using PubMed, Scopus, and Web of Science databases. Studies evaluating implant-based breast reconstruction with absorbable synthetic meshes, ADM, or without mesh were included. Outcomes of interest comprised postoperative complications, operative time, material costs, aesthetic outcomes, and patient-reported satisfaction. Methodological quality and risk of bias were assessed using design-appropriate appraisal tools. Results: Absorbable synthetic meshes were associated with low complication rates, including infection (3–8%), seroma (0–5%), hematoma (1–4%), skin necrosis (4–6%), and implant loss (3–6%). Compared with ADM, complication rates appeared comparable, while shorter operative times were reported in comparative studies. Material cost reductions of up to 90% were reported in comparative studies. Several studies reported favorable aesthetic outcomes and high patient satisfaction, although assessment methods were not standardized. Most included studies were retrospective or single-arm observational studies, with substantial clinical and methodological heterogeneity and an overall moderate risk of bias. Conclusions: Available evidence, derived predominantly from studies of polyglactin mesh, suggests that absorbable synthetic meshes may represent a feasible option for selected implant-based breast reconstructions, with potential advantages in terms of material costs and operative time. Evidence regarding polydioxanone mesh remains very limited, and the methodological limitations of the available studies preclude definitive conclusions.
Background and Objectives: Deciding which pigmented or non-pigmented skin lesions require surgical excision, as opposed to continued observation, is a common challenge in everyday dermatologic practice. Although dermoscopy is well established as a tool that improves melanoma detection accuracy compared with naked-eye examination, real-world evidence on how demographic profile, patient history, and dermoscopic impression jointly influence the surgical decision remains limited. This study examined the clinical and dermoscopic factors associated with a positive surgical decision (PSD) in a large single-centre screening cohort. Materials and Methods: This retrospective cross-sectional analysis included 643 consecutive patients (415 female (64.5%), 228 male (35.5%); mean age 51.3 ± 16.8 years) undergoing dermoscopic skin cancer screening. Data recorded included family history of melanoma (FHM), personal history of skin cancer (HSC), childhood sunburn (CS), clinically atypical lesions (CAL), suspicion of basal/squamous cell carcinoma (BCC/SCC), nevus count (NC, 0–4), and the surgical decision (PSD). Free-text dermoscopic descriptions were grouped into seven diagnostic categories. Group comparisons used the Mann–Whitney U, χ2, and Fisher’s exact tests; predictors of PSD were characterised using multivariable logistic regression (with Hosmer–Lemeshow and Nagelkerke R2 statistics), multiple correspondence analysis (MCA), Gower-distance k-medoids clustering, and receiver operating characteristic (ROC) analysis, including the area under the curve (AUC). Missing NC data (13.2%) were assessed using Little’s test for data missing completely at random (MCAR test). Results: A positive surgical decision was recorded in 133/643 patients (20.7%) and was significantly more common in men than women (25.9% vs. 17.9%; p = 0.017; corresponding to an odds ratio (OR) of 1.61). In multivariable analysis, suspicion of BCC/SCC (OR = 24.7, 95% confidence interval (CI): 9.26–66.0) and clinically atypical lesions (OR = 5.53, 95% CI 3.50–8.74) were the strongest independent predictors of PSD (Nagelkerke R2 = 0.31; Hosmer–Lemeshow p = 0.977), far outweighing family or personal history. A significant interaction between childhood sunburn and nevus count (OR = 1.39, 95% CI 1.16–1.66; p < 0.001) predicted clinical atypia. Missing NC data were consistent with a completely random pattern (Little’s χ2 = 2.80, df = 2, p = 0.247). Dermoscopic impression showed strong discriminative value for PSD: “no concern” had the highest negative predictive value (NPV = 0.927; AUC = 0.762), while “atypical lesion” combined high specificity (0.916) and positive predictive value (0.632; AUC = 0.736). On average, 4.8 patients were examined for every surgical referral generated (a screening-to-referral ratio, not a number needed to screen for a histologically confirmed cancer). Conclusions: Surgical decision-making in this cohort was driven almost exclusively by the dermoscopic impression—suspected BCC/SCC and clinical atypia—rather than by family or personal oncological history, while male sex was independently associated with a higher surgical rate. These findings support dermoscopy-led triage protocols and highlight the potential value of standardised risk stratification to optimise referral pathways in routine skin cancer screening.
Background and Objectives: The 2024 Korean medical–political conflict caused the mass resignation of trainee physicians, raising concerns about the quality of care for time-critical emergencies. This study aimed to assess the impact of workforce disruptions on the management and outcomes of adults presenting to the emergency department (ED) with septic shock. Materials and Methods: This retrospective single-center cohort study was conducted at a tertiary care ED and included adults with septic shock between September 2022 and August 2025. This study compared the pre-conflict period, operating under a resident-supported model, with the conflict period characterized by a specialist-led staffing model. The primary outcome was the all-cause in-hospital mortality. The secondary outcomes included process-related time intervals and clinical course measurements. Multivariate logistic regression was used to identify the independent predictors of mortality. Results: Altogether, 343 patients were included (159 pre-conflict, 184 conflict). During the conflict, ED crowding significantly decreased (average concurrent ED patients: 14.9 vs. 7.6, p < 0.001). Key diagnostic process metrics, including time to blood gas analysis, blood sampling, blood culture, computed tomography, and total ED length of stay, were significantly shortened. Time-critical therapeutic intervals, such as time to empirical antibiotics, remained unchanged. In-hospital mortality did not differ significantly between the pre- and conflict periods. Multivariate analysis demonstrated that the conflict period was not independently associated with mortality; only initial serum lactate levels and Acute Physiology and Chronic Health Evaluation II scores remained significant predictors. Conclusions: The 2024 Korean medical–political conflict was not associated with increased in-hospital mortality among patients with septic shock. Process-related metrics improved, while key therapeutic intervals and overall clinical outcomes remained stable. These findings may reflect reduced ED crowding, organizational adaptation, and continued adherence to established septic shock management practices. Reduced ED volume likely contributed substantially to improvements in diagnostic and throughput-related processes.
Background and Objectives: Topical diclofenac is recommended over oral non-steroidal anti-inflammatory drugs (NSAIDs) for osteoarthritis, particularly in older adults and those with comorbidities, on the assumption that low systemic absorption limits renal effects. Whether this presumed safety extends to patients already at increased risk of kidney injury has not been systematically evaluated. This review assessed the evidence on renal outcomes of topical diclofenac in adults. Materials and Methods: We conducted a systematic review (PROSPERO CRD420261393454) of studies reporting renal outcomes after topical diclofenac exposure. PubMed, Embase, Web of Science, and Scopus were searched from inception to 19 April 2026. Studies were stratified a priori into increased-renal-risk and general populations and synthesised separately, without pooling. Risk of bias was assessed with RoB 2, ROBINS-I, and JBI tools, certainty with GRADE, and synthesis followed the SWiM framework. Results: Eighteen studies, contributing data from more than 500,000 participants, were included; 14 underwent primary risk-of-bias appraisal (three at low, three at serious or high risk). In general populations, topical diclofenac produced little to no change in serum creatinine or creatinine clearance and smaller renal effects than oral diclofenac, providing high-certainty evidence of a favourable profile. In increased-renal-risk populations, one adjusted cohort reported higher acute kidney injury (AKI) risk among topical NSAID users, although exposure was predominantly to non-diclofenac agents; within the same cohort, topical NSAIDs carried lower risk than systemic NSAIDs. No study evaluated early renal injury biomarkers; certainty was moderate owing to indirectness. Conclusions: Relative to oral diclofenac, topical diclofenac shows a favourable renal safety profile, with high-certainty evidence in general populations. In adults at increased renal risk, moderate-certainty evidence derived from predominantly non-diclofenac exposure over short observation windows cannot exclude a modest excess of any-stage AKI; renal risk therefore appears reduced rather than absent. Diclofenac-specific studies in chronic kidney disease using sensitive biomarkers and longer follow-up are needed.
Background and Objectives: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterised by recurrent nodules, abscesses, sinus tract formation, and tissue remodelling. Increasing evidence suggests that oxidative stress contributes to HS pathogenesis; however, the role of the Nrf2–Keap1–Sestrin-2 axis and its interaction with matrix remodelling pathways remains poorly understood. This study aimed to evaluate serum levels of Nrf2, Keap1, Sestrin-2, asprosin, MMP-1, and TIMP-1 in patients with HS and to investigate their potential roles in disease pathophysiology. Materials and Methods: A total of 26 patients with hidradenitis suppurativa and 20 healthy volunteers were enrolled in the study. Serum biomarkers were measured in patients with HS and healthy controls. In addition to conventional statistical analyses, multivariate analyses, including PCA, PLS-DA, VIP scoring, correlation mapping, ROC analysis, heatmap visualisation, and biplot assessment, were performed to characterise biomarker interactions and discriminatory performance. Results: HS patients exhibited significantly increased serum asprosin, Keap1, and MMP-1 levels, whereas Nrf2, Sestrin-2, and TIMP-1 levels were significantly reduced compared with controls. Multivariate analyses demonstrated clear separation between patient and control groups within the cohort, indicating a distinct biochemical signature associated with HS. VIP analysis identified Nrf2, Sestrin-2, and TIMP-1 as the most influential variables contributing to group discrimination. Within the HS group, none of the pairwise biomarker correlations remained statistically significant after Benjamini–Hochberg false discovery rate (FDR) correction. ROC analysis showed diagnostic performance for Nrf2 and Sestrin-2. Conclusions: These findings suggest that alterations in serum markers related to the Nrf2–Keap1–Sestrin-2 axis and the MMP-1/TIMP-1 balance are associated with oxidative stress, inflammation, and tissue remodelling in HS. Nrf2 and Sestrin-2 may represent candidate biomarkers; however, given the modest sample size and single-centre design, their discriminatory performance should be considered exploratory and requires confirmation in larger independent cohorts.
Background and Objectives: Olfactory dysfunction is an early non-cognitive feature of Alzheimer’s disease (AD). The volumetric behavior of olfactory and related frontal structures and their link to eating disturbances remains unclear; we therefore compared olfactory bulb (OB) and gyrus rectus (GR) volumes between patients with AD and controls and examined their relationship with eating disturbances and their diagnostic value. Materials and Methods: In this single-center, retrospective, case–control study, 135 patients with AD and 49 age-matched controls underwent 3-Tesla MRI. Right, left, and total OB and GR volumes were measured. Groups were compared using the Mann–Whitney U test; age- and sex-adjusted logistic regression and receiver operating characteristic (ROC) analyses were performed; and OB and GR volumes were compared according to eating disturbance status in patients with AD, with adjustment for age and sex. p-Values were corrected for multiple comparisons using the Benjamini–Hochberg false discovery rate procedure. Results: All OB and GR volumes were significantly lower in patients with AD compared to controls (all p < 0.001), with the total OB volume nearly half that of the controls. Among patients with AD, all OB volumes were significantly lower in those with eating disturbances (all p < 0.001) and remained independently associated after adjustment for age and sex, whereas none of the GR volumes was significantly associated with eating disturbance status after adjustment. In adjusted models, every volumetric measure was independently associated with AD (all p < 0.001). The total OB volume showed the best diagnostic performance (AUC 0.940; sensitivity 0.82; specificity 0.98), while GR volumes performed less well (AUC 0.78–0.84). Conclusions: AD is associated with marked OB and GR atrophy. OB volume was associated with eating disturbances and discriminated AD from controls with high accuracy, supporting OB volumetry as an accessible candidate imaging marker that warrants prospective validation.
