Journal of Clinical Medicine最新文献

Background/Objectives: Targeted muscle reinnervation and regenerative peripheral nerve interface procedures have emerged as effective techniques for reducing post-amputation pain and preventing symptomatic neuroma formation. However, the optimal timing of these procedures remains debated. This study aims to compare complication and reoperation rates between acute and delayed advanced nerve interface procedures in lower-extremity amputees. Methods: A retrospective cohort study was conducted including 74 patients who underwent acute or delayed targeted muscle reinnervation and/or regenerative peripheral nerve interface procedures between 2019 and 2025 at a tertiary academic medical center. Procedures performed concurrently with amputation or during early-stage reconstruction were classified as acute, whereas procedures performed more than one month after amputation were classified as delayed interventions. The primary outcome was postoperative surgical complications occurring within one year. Mann-Whitney U and chi-square tests were used for group comparisons. Univariable and multivariable logistic regression analyses were performed to identify factors associated with surgical complications, adjusting for potential confounders. A p-value < 0.05 was considered statistically significant. Results: Of 80 limbs, 47 (58.8%) underwent acute and 33 (41.3%) underwent delayed procedures. One-year complication rates were 23.4% in the acute group, and 12.1% in the delayed group, with wound-related complications predominantly occurring in patients undergoing amputation for infection or vascular disease. Unexpected reoperation rates were 19.1% for acute and 12.1% for delayed interventions. On univariable and multivariable analyses, early procedures demonstrated higher odds of surgical complications. However, these associations did not reach statistical significance and were limited by baseline differences in patient comorbidity and etiology. Conclusions: Early advanced nerve interface procedures were performed in more medically complex patients and were associated with higher observed rates of surgical complications, whereas delayed procedures were associated with a higher incidence of recurrent symptomatic neuromas. These findings underscore the importance of patient selection, etiology of amputation, and surgical context, rather than timing alone, when determining the optimal approach to nerve interface reconstruction following lower-extremity amputation.

Background/Objectives: The COVID-19 pandemic severely impacted healthcare systems globally, with Italian healthcare professionals experiencing heightened stress, organizational challenges, and a significant psychological burden. This study investigates the frequency of depressive symptoms and health-related quality of life (H-QoL) among outpatient healthcare workers in Italy, comparing pre-pandemic (2017) and post-pandemic (2025) periods. Methods: A cross-sectional study was conducted in 2025, including 97 healthcare professionals from five outpatient departments at the University Hospital of Cagliari. Participants completed demographic surveys, the Short Form Health Survey (SF-12), and the Patient Health Questionnaire (PHQ-9) to assess H-QoL and depressive symptoms. Data were compared with previously published data from the same facility collected in 2017 and with pre-pandemic Italian community surveys. Results: Compared to 2017, there was a statistically significant increase in depressive episodes (38.1% vs. 33.2%, p = 0.01) and a higher proportion of individuals with low H-QoL (62.9% vs. 43.5%, p < 0.0001) in 2025. After age- and sex-standardization, both depressive symptoms and low H-QoL were significantly more prevalent among healthcare professionals in 2025 compared with the general population before the pandemic. Within the 2025 sample, non-medical healthcare workers showed a significantly higher prevalence of depressive symptoms than medical doctors, while female healthcare workers were more likely to report low H-QoL. Conclusions: Despite the pandemic's end, healthcare workers, especially those in outpatient settings, continue to face elevated psychological distress. Specific professional and gender-related vulnerabilities persist, and structural challenges, such as staff shortages and organizational issues, may exacerbate this burden. Sustained mental health support and targeted systemic interventions remain crucial to mitigate the long-term impact on the healthcare workforce.

Background/Objectives: Performing Hajj, the annual Islamic pilgrimage to Mecca and one of the world's largest mass gatherings, involves considerable physical exertion in high temperatures and presents unique challenges for people with type 1 diabetes (PWT1D). We examined the feasibility, safety, and user experience of automated insulin delivery (AID) systems during Hajj. Methods: This mixed-methods study evaluated six PWT1D who used an AID pump (2 MiniMed 780G, 2 Medtrum, 1 OmniPod 5, and 1 Open-source AID) while performing Hajj in 2024-2025. Pump and CGM-derived metrics were compared across pre-Hajj, during Hajj, and post-Hajj periods. A structured survey captured participants' experiences, challenges, and recommendations for AID use during Hajj. Results: The average percent time in range (TIR) remained stable from pre- to during Hajj (54.98 to 54.18, p > 0.05) and significantly increased post-Hajj (62.62, p < 0.05). The percent time above range (TAR > 180) and Glycemia Risk Index significantly decreased from pre- to post-Hajj (28.34 to 26.28 and 50.3 to 19.3, respectively, both p < 0.05). The percent time below range (TBR) remained low (<1%) across the three periods with no incidence of acute diabetes-related complications. Participants emphasized increased confidence and peace of mind with AID use and reported challenges related to heat exposure, prolonged walking, and lack of awareness regarding diabetes technology among HCPs. Conclusions: The use of AID during Hajj appeared to be safe and effective for PWT1D in our study, maintaining stable glycemic control under physically demanding conditions. As the first study to evaluate AID use during Hajj, our findings call for larger studies to explore the integration of diabetes technology into Hajj care protocols and highlight the need for structured pre-Hajj education for PWT1D and HCPs.

Background: Intravascular hemolysis is a common complication in patients undergoing extracorporeal membrane oxygenation (ECMO), with plasma free hemoglobin (pfHb) serving as a biomarker for detection. Without standardized protocols, laboratories face challenges in interpreting and reporting results. Hemolysis indices may enhance reporting accuracy. Methods: This retrospective observational study at University Hospital Center Zagreb included 61 lithium heparin plasma samples from ECMO patients. pfHb was measured using the Harboe method (fHb) and estimated from hemolysis indices on Abbott Alinity c analyzer (efHb). Total and conjugated bilirubin, hemolysis, icterus, and lipemia indices (HIL) were recorded. Method comparison used Passing-Bablok regression and Bland-Altman analysis. An algorithm for pfHb reporting accounting for HIL interferences was developed. Results: Significant differences were observed between methods, with Harboe yielding higher median fHb (261 mg/L) versus efHb (58 mg/L). Regression analysis showed constant negative bias of -91 mg/L (95% CI: -143 to -16) for efHb relative to fHb. Bland-Altman analysis demonstrated wide limits of agreement. Correlation between fHb and efHb was moderate (Spearman's rho = 0.618, p < 0.001). The delta between methods increased with higher bilirubin concentrations. An algorithm integrating HIL indices with the Harboe method was developed to guide result validation and reporting. Conclusions: Accurate hemolysis assessment in ECMO patients requires careful interpretation, appropriate method selection, and laboratory-clinician collaboration. The proposed algorithm improves the clinical utility of pfHb testing by accounting for analytical interferences and supporting informed decision-making.

Background/Objectives: Dynamic computer-assisted surgery (dCAS) has emerged as a promising tool, particularly in implantology, enabling real-time procedural adjustments through 3D image-based tracking. However, their application in other areas of oral surgery remains limited. This systematic review aims to evaluate the advantages, limitations, clinical implications, and complications associated with the use of dCAS in oral surgery (excluding implants or miniscrew insertion) beyond implant placement, in comparison to conventional freehand (FH) techniques. Methods: A systematic review was conducted in accordance with the PRISMA guidelines. A focused PICO question was developed, and a comprehensive literature search was performed in PubMed, Scopus, and the Cochrane Library between February and March 2025, and supplemented by manual screening. The risk of bias of the included studies was evaluated using the Cochrane Risk of Bias tool (RoB 2) for randomized controlled trials (RCTs) and the ROBINS-I tool for non-randomized controlled trials (NRCTs). Data were summarized in tables and analyzed through qualitative synthesis. Results: Ten studies evaluating dCAS in several oral surgical procedures, including complex tooth extractions and endodontic surgery, were included. A substantial improvement was observed in accuracy of endodontic procedures. Operator experience was a key factor in surgical outcomes. Regarding postoperative complications, no significant differences were observed, although the trend indicated an equal or lower risk in comparison with conventional FH techniques. Conclusions: dCAS may significantly improve accuracy and efficiency in endodontic surgery and reduce operative time in complex mandibular third molar (M3M) extractions. The complication rate is comparable to that of conventional FH techniques. However, current evidence remains limited, heterogeneous, and mainly experimental. Further studies are recommended to validate the benefits of dCAS in clinical settings.

KRAS alterations are a hallmark of pancreatic ductal adenocarcinoma (PDAC) found in >90% of tumors. This review examines the historical evolution of the understanding of RAS and its central role in PDAC biology. We summarize the various downstream effectors, feedback loops, and resistance mechanisms that play a pivotal role in PDAC oncogenesis. Our review explores the early development of covalent inhibitors of KRAS G12C and efforts at specific inhibition of other codons and newer approaches of targeted protein degradation. We subsequently summarize the development of panRAS inhibitors and allosteric and switch-region targeting before focusing on rational therapeutic blockade of crosstalk and upstream signaling, with attention to synthetic lethality approaches transitioning from preclinical to early-phase in-human clinical trials. This review elaborates on ongoing KRAS-specific siRNA research and evolving KRAS-directed immunotherapies. We conclude by outlining the current KRAS clinical trial landscape and future areas of investigation.

Mitral valve prolapse (MVP) is generally associated with excellent long-term outcomes when MR is absent or mild. Nonetheless, a small proportion of patients exhibit a distinct arrhythmogenic susceptibility, characterized by complex ventricular ectopy, sustained ventricular arrhythmias (VAs), and in rare instances, sudden cardiac death (SCD). This subgroup-collectively referred to as arrhythmic MVP (AMVP)-has prompted renewed attention in identifying individuals at elevated risk. Among the structural alterations associated with MVP, mitral annular disjunction (MAD) has gained recognition as a major contributor to arrhythmic vulnerability, arising from the pathological separation of the posterior annulus from the adjacent ventricular muscle. Advances in multimodality imaging, including trans-thoracic echocardiography (TTE), cardiac magnetic resonance (CMR), and cardiac computed tomography (cCT), have significantly improved delineation of MAD and clarified its relationship to the broader MVP spectrum. Current evidence suggests that MVP, MAD, and AMVP should not be regarded as isolated conditions but as intersecting phenotypes within a shared pathological framework. In certain patients, especially those without established myocardial fibrosis, abnormal annular dynamics appear to constitute the primary arrhythmogenic driver and may diminish after surgical intervention. In others, persistent arrhythmias despite optimal repair reflect a fibrosis-based substrate. This review synthesizes contemporary insights into the anatomical, biomechanical, and electrophysiological interplay linking MVP, MAD, and ventricular arrhythmogenesis, emphasizing implications for imaging-based risk assessment and individualized surgical management strategies.

Background: Ultra-widefield (UWF) images are frequently used for fundus examinations during medical screening. Optos^® generates pseudo-color images using only red and green lasers, which may reduce the visibility of retinal interface lesions. In contrast, Clarus™ incorporates blue light, suggesting potential superiority in epiretinal membrane (ERM) detection. Methods: This retrospective study included 233 patients (408 eyes; 816 UWF images per device) who underwent simultaneous Optos^® and Clarus™ imaging plus optical coherence tomography (OCT) at our institution from March to April 2019. Ten blinded ophthalmologists assessed only the UWF images for ERM presence or absence. Diagnosis was confirmed by fundus examination and OCT. McNemar's test compared detection accuracy. Results: Clarus™ consistently outperformed Optos^®, with superior sensitivity [median 49% (range 42-70) vs. 14% (4-47); p = 0.002], correct judgment rate [85% (82-90) vs. 78% (44-88); p = 0.010], and lower unassessed rate [6% (2-13) vs. 13% (3-52); p = 0.002]. This superiority held across ERM stages, lens status, and ophthalmologist experience levels. Conclusions: This study demonstrated that Clarus™ significantly outperformed Optos^® in ERM detection accuracy. These results suggest that true-color UWF systems like Clarus™ may be more useful for macular screening in routine practice and health examinations.

Background: The macrogeometry and shape of dental implants strongly influence primary stability, which may at times result in excessively high insertion torque. This in vitro study aimed to evaluate whether increasing coronal thread density could reduce insertion torque without compromising primary stability. Methods: Two conical implants with identical macrogeometry and surface characteristics (Ø 4.2 × 11.5 mm) differed only in the thread pitch of the coronal 3 mm: a modified version (27% more coronal threads; Group 1) and a standard, commercially available version (Group 2). Thirty implants of each design were inserted into high-density (D1; 40 PCF; pounds per cubic foot) and low-density (D3; 20 PCF) polyurethane blocks (n = 120). Insertion torque (IT) and implant stability quotient (ISQ, measured by resonance frequency analysis) were recorded. Group comparisons used the Kruskal-Wallis test, and a generalized linear model (GLM) assessed the independent effects of IT and design on ISQ in D1 bone. Results: In D1 bone, Group 2 showed higher IT (median 74.0 vs. 63.5 N·cm; p < 0.001) and ISQ (mean 79.1 vs. 77.4; p ≤ 0.030). The GLM identified IT as a negative predictor of ISQ (β = -0.267 per 1 N·cm; p < 0.001), and Group 2 was associated with higher ISQ (+3.90; p < 0.001). In D3 bone, Group 2 again exhibited higher IT (median 37.5 vs. 33.0 N·cm; p < 0.001), while ISQ values were similar between designs (all p > 0.35). Conclusions: Increasing coronal thread density lowers insertion torque without reducing stability in softer bone and maintains sufficient ISQ for immediate loading in dense bone, making the design advantageous for varied bone qualities.

Background/Objectives: Real-world data on the therapeutic use of FLT3 inhibitors in Turkey remain limited. Therefore, we retrospectively evaluated outcomes from 13 academic centers nationwide, focusing on the multikinase inhibitor midostaurin in patients with newly diagnosed FLT3-mutated acute myeloid leukemia (AML). Methods: We collected comprehensive information regarding treatment efficacy, safety, and tolerability. Results: The overall response rate to intensive chemotherapy (3 + 7) plus midostaurin was 87.7%, with a complete remission rate of 84.2%, consistent with previously reported clinical trial results. Treatment discontinuation due to intolerance or toxicity was low (3.5%). One patient discontinued therapy because of septic shock during induction, and another due to a drug-drug interaction during consolidation. Median overall survival was 21.4 months. Allogeneic stem cell transplantation was performed in first remission in 52.6% of patients. Five patients (8.8%) were refractory to induction therapy, and relapse occurred in 21.1% (12 patients). Conclusions: These findings support the effectiveness and acceptable tolerability of midostaurin in routine clinical practice for FLT3-mutated AML.