Search Results (4,513)

Background: Direct oral anticoagulants (DOACs) have transformed antithrombotic therapy but carry significant bleeding risks requiring prompt reversal. Recent regulatory changes have altered the reversal landscape, notably with the withdrawal of andexanet alfa from the U.S. market. Anticoagulation stewardship programs (ASPs) are essential for navigating this evolving environment and optimizing safe use of anticoagulants. Methods: This narrative review synthesizes evidence from landmark clinical trials (RE-VERSE AD, ANNEXA-4, ANNEXA-I), contemporary guidelines, emerging literature on reversal agents, and critical regulatory updates including the 2025 U.S Food and Drug Administration (FDA) withdrawal of andexanet alfa. Results: Idarucizumab remains the only FDA-approved specific antidote for dabigatran. Following the withdrawal of andexanet alfa, prothrombin complex concentrates (PCCs), both 4-factor and activated are now the primary reversal options for Factor Xa inhibitors, with recent evidence demonstrating comparable hemostatic efficacy. Ciraparantag, a universal reversal agent, is currently in Phase III development. Effective ASPs must now adapt protocols to the post-andexanet era while ensuring timely access to alternative reversal strategies. Conclusions: The reversal landscape has undergone a fundamental transformation with the loss of andexanet alfa. Success in DOAC-associated bleeding management now depends on optimizing PCC-based strategies, integrating systematic stewardship approaches, and preparing for emerging universal antidotes. Institutions must urgently update algorithms, ensure PCC availability, and monitor outcomes in this new therapeutic environment. Full article

After vessel preparation, using different strategies such as balloon angioplasty, specialty balloons, atherectomy or intravascular lithotripsy, definitive treatment has emerged as a key feature in endovascular treatment strategies. Based on current guidelines, endovascular treatment is the most common treatment option in patients with claudication. In patients with chronic limb-threatening ischemia (CLTI), on the other hand, the best treatment modality, including bypass surgery and endovascular revascularization, needs to be selected by an interdisciplinary team, focusing on individual anatomic and patient-specific characteristics, on the availability of a vein graft and on cardiovascular and other comorbidities of the patients. With endovascular therapy, currently, a plethora of options are available for the treatment of femoropopliteal lesions, which are increasingly gaining in complexity. Therefore, a practical systematic case-based approach, entailing contemporary treatment options, like drug-coated balloon (DCB) angioplasty tools, self-expanding bare-metal stents (BMSs), drug-eluting stents (DESs), interwoven stents and covered stents, is crucial. Generally, most endovascular operators adhere to the ‘leave nothing behind’ concept, meaning that, after proper lesion preparation, lesions can be treated with DCBs, avoiding the implantation of permanent metallic implants. However, in the case of severe dissections or significant recoil, stent implantation becomes necessary to achieve adequate limb perfusion. The selection between long versus spot stenting and the different stent options depends on the current scientific evidence, guidelines and expert opinion statements. An interdisciplinary expert consensus was recently compiled on how these modalities should be used in specific lesions and patients in the femoropopliteal segment. Herein we present a practical case-based approach, which is based on this algorithm and aims at harmonization of endovascular treatment strategies in daily practice and ultimately at further improvements in limb and patient outcomes. Full article

Objectives: To map and synthesize the available evidence regarding the use of manual therapy, core stability training, and Pilates Method exercises in the rehabilitation of musculoskeletal conditions in adult dancers. Methods: A scoping review was conducted in accordance with the PRISMA-ScR guidelines. A systematic search across six electronic databases (PubMed, Scopus, Web of Science, SPORTDiscus, CINAHL, and PEDro) was performed. Study eligibility was strictly guided by the Population–Concept–Context (PCC) framework. Two independent reviewers screened the literature and extracted data. Results: A total of 16 studies met the inclusion criteria, encompassing randomized controlled trials, intervention studies, and case-level reports or series. Interventions primarily addressed chronic ankle instability, low back pain, and post-surgical rehabilitation. Results indicate that while individualized manual therapy and Pilates Method protocols are widely utilized in dance medicine, high-level evidence remains limited. Conclusions: Integrated rehabilitation approaches combining manual therapy with motor control exercises (such as the Pilates Method and core training) appear to have potential utility in supporting the safe return of dancers to performance. However, the current literature is heavily reliant on observational and case-driven evidence, highlighting the need for robust clinical trials to establish standardized, dance-specific rehabilitation guidelines. Full article

A rare clinical condition associated with numerous diagnostic and treatment challenges, pregnancy-associated melanoma (PAM), is defined as melanoma diagnosed either during pregnancy or within the first year postpartum. The physiological changes in pregnancy (hormonal changes and immune modulation), along with the normal changes in the pregnant woman’s skin (skin color changes, etc.), may all hinder early detection of this disease and create concerns regarding the advancement of melanoma and the well-being of both the mother and her fetus. The purpose of this review article was to summarize the current literature on the incidence, biology, diagnostic methods and treatments of PAM, with an emphasis on comparison between the two forms of melanoma. More recent research indicates that pregnancy itself is not typically associated with decreased melanoma-specific survival rates. However, when worse results are reported, it appears that this may be more due to delays in initial diagnoses (diagnosis of cancer after delivery) or detection of cancer postpartum, as well as the increased number of stages of melanoma at which women were diagnosed at the time of their first evaluation compared to non-pregnant controls, rather than being a result of enhanced biologic aggressiveness in melanoma driven by pregnancy itself. The preclinical and translational models have suggested that pregnancy may influence melanoma biology through the mechanisms of hormonal signaling, immune system modulation and vascular remodeling; however, these mechanisms remain hypothesis-generating, and current clinical evidence does not indicate that changes in hormone levels during pregnancy negatively affect melanoma survival. Surgical excision is the mainstay of treatment and can be performed safely during pregnancy. In select patients, a sentinel lymph node biopsy may also be performed. Due to the risk of fetal harm, systemic therapy (targeted agents and/or immune checkpoint inhibitors) cannot be used for the treatment of PAM during pregnancy. Post-pregnancy treatment of PAM will follow standard melanoma treatment guidelines; however, the treatment options will need to take into consideration whether or not the patient is breastfeeding and if she desires to become pregnant again in the future. In summary, PAM will require a multidisciplinary, individualized approach to maximize oncologic outcomes while protecting the health of both the mother and her fetus. Awareness of this disease and timely diagnosis are critical to maximizing the prognosis. Full article

Background and Objectives: Osteonecrosis of the jaw (ONJ) occurring after infection with SARS-CoV-2 has emerged as an increasingly reported complication in the post-COVID-19 era. Post-COVID-19 osteonecrosis of the jaw (PC-ONJ) has been described in association with both COVID-19-associated mucormycosis (CAM) and non-fungal phenotypes. This narrative review aims to synthesize and critically analyze the available evidence regarding terminology and classification, epidemiology and risk factors, pathophysiological mechanisms, clinical and imaging characteristics, diagnostic challenges, and management strategies relevant to oral and maxillofacial surgery practice. Materials and Methods: An extensive literature search was conducted in the PubMed/MEDLINE, Scopus, Web of Science, ScienceDirect, and Google Scholar databases. The search targeted peer-reviewed publications published between 2020 and 2025, reflecting the post-pandemic emergence of this clinical spectrum. Original studies, systematic and narrative reviews, multicenter case series, consensus guidelines, and well-documented case reports were considered. Results: Available data, largely derived from case reports and small series, demonstrate a predominance of maxillary involvement and frequent association with diabetes mellitus and systemic corticosteroid therapy. Proposed mechanisms include COVID-19-associated endothelial dysfunction, microvascular thrombosis, immune dysregulation, metabolic imbalance, and treatment-related effects. Clinically, patients may present with persistent orofacial pain, tooth mobility, exposed or probeable bone, and frequent sinonasal extension, with symptoms sometimes preceding bone exposure. Diagnostic challenges arise from the overlap with medication-related osteonecrosis of the jaw (MRONJ), osteoradionecrosis (ORN), and chronic osteomyelitis. Imaging is essential for assessing disease extent but remains insufficient for etiologic differentiation, making histopathological examination and targeted microbiological investigations necessary, particularly to exclude invasive fungal infection. Conclusions: Management must be etiology-driven. CAM requires urgent antifungal therapy combined with surgical debridement, whereas non-fungal forms are generally managed with conservative surgery and appropriate antimicrobial stewardship. Standardized diagnostic criteria and prospective multicenter studies are needed to reduce nosological ambiguity and optimize clinical decision-making in this emerging post-viral condition. Full article

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder characterized by reduced circulating levels and/or impaired function of alpha-1 antitrypsin (AAT), a key serine protease inhibitor, in which loss of effective antiprotease protection results in unchecked neutrophil elastase activity and progressive lung tissue destruction. Although AATD accounts for approximately 1% of chronic obstructive pulmonary disease (COPD) cases and up to 2% of emphysema, AATD-related COPD remains largely underdiagnosed, despite guideline recommendations for systematic evaluation in patients with COPD, particularly in high-risk clinical settings. Pathologically, AATD-related COPD is not limited to the typical early-onset, lower-lobe-predominant emphysema, also including upper-lobe or mixed emphysema patterns, airway-predominant disease, small airways dysfunction, and bronchiectasis. Clinically, AATD-related COPD is distinguished from smoking-related COPD by its earlier onset, physiological impairment that is often disproportionate to smoking exposure, and its potential presence of certain extrapulmonary manifestations. Diagnosis and monitoring are also challenged by the frequent discordance between airflow limitation and gas transfer impairment, as well as the early involvement of small airways, limiting reliance on spirometry alone. A multimodal assessment incorporating more sensitive functional techniques and CT densitometry may provide a more precise evaluation of disease burden, progression, and prognosis. Management generally follows standard COPD principles, with intravenous AAT augmentation therapy remaining currently the only established disease-modifying therapy for selected patients with severe deficiency. The advent of new pharmacological and gene-based therapies emphasizes the importance of developing personalized management strategies that integrate genotype and longitudinal disease behavior. This narrative review summarizes current evidence on AATD-associated COPD, focusing on its genetic basis and pathophysiological features, clinical and functional heterogeneity, current and emerging diagnostic and monitoring approaches, and disease-specific management considerations. Full article

Background/Objectives: Antimicrobial resistance (AMR) in companion animals is an emerging public health threat due to zoonotic potential and limited therapeutic options. Dogs with otitis externa may harbor multidrug-resistant (MDR) bacteria, including Escherichia coli (E. coli), Proteus mirabilis (P. mirabilis), and Enterobacter cloacae complex (E. cloacae complex), some producing extended-spectrum beta-lactamase (ESBL) or AmpC β-lactamases. This study aimed to assess the prevalence, AMR patterns, MDR occurrence, β-lactamase production, and co-infection profiles of these pathogens in canine otitis externa. Methods: Ear canal samples were collected from 592 dogs presenting clinical signs of otitis externa, with one sample per dog included in the analysis. Samples were collected from veterinary clinics in Timiș County, Romania, from 2022 to 2025. Samples were cultured on blood agar and MacConkey agar, followed by biochemical testing and MALDI-TOF mass spectrometry for bacterial identification. Antimicrobial susceptibility testing against 15 agents across six classes was performed using the VITEK^® 2 system. MDR and β-lactamase production (ESBL, AmpC) were determined according to CLSI 2018 veterinary guidelines. Co-isolation with bacterial and fungal species were recorded. Results: E. coli, P. mirabilis, and E. cloacae complex were isolated in 9.12%, 6.25%, and 1.2% of cases, respectively. E. coli exhibited the highest resistance to aminoglycosides (tobramycin 72.2%, gentamicin 61.1%) and full susceptibility to carbapenems. P. mirabilis showed the highest resistance to ampicillin (54%) and trimethoprim + sulfamethoxazole (46%), with complete susceptibility to carbapenems and fluoroquinolones. E. cloacae complex displayed universal resistance to cephalosporins but remained susceptible to non-cephalosporin β-lactams (piperacillin–tazobactam), carbapenems and aminoglycosides. MDR prevalence was 35.2% for E. coli, 18.9% for P. mirabilis, and 14.3% for the E. cloacae complex. ESBL production was detected in 13% of E. coli and 8.1% of P. mirabilis isolates, while all E. cloacae complex isolates were AmpC-positive. Co-isolations were common, primarily involving Staphylococcus pseudintermedius (S. pseudintermedius) and Malassezia pachydermatis (M. pachydermatis). Conclusions: MDR and β-lactamase-producing bacteria were identified in dogs with otitis externa, emphasizing the importance of routine antimicrobial susceptibility testing, targeted therapy based on local resistance profiles, and continuous AMR surveillance to prevent treatment failure and mitigate zoonotic risk. Full article

The ADA 2026 Standards of Care in Diabetes introduces pivotal updates that refine diagnostic and therapeutic workflows. Expanding upon the 2025 guidelines, the 2026 edition broadens continuous-glucose-monitoring (CGM) eligibility to include all individuals on insulin or non-insulin therapies where CGM aids management. Significant new guidance addresses hyperglycemia management in oncology, identifying metformin as the preferred first-line intervention for drug-induced glycemic excursions. Additionally, type 1-diabetes (T1D) risk stratification is refined; a confirmed single IA-2 autoantibody now warrants monitoring levels similar to the Stage 2 disease. Furthermore, prerequisites for automated-insulin-delivery (AID) initiation have been removed to streamline technology access. For laboratory professionals, these revisions emphasize the critical role of advanced glycemic metrics and precise autoantibody profiling in complex clinical contexts. Full article

Background/Objectives: Damage Control Resuscitation (DCR) is a critical strategy in the management of severe trauma, focusing on the optimisation of the patient’s physiological condition. This study reviews current DCR strategies, emphasizing the mitigation of the “diamond of death”—hypothermia, acidosis, coagulopathy, and hypocalcemia—while addressing complex disturbances like respiratory distress syndrome (ARDS) and (acute kidney injury) AKI in high-ISS (Injury Severity Score) patients. Methods: A systematic review of 59 contemporary sources was conducted, encompassing clinical trials (e.g., CRASH-2), military-to-civilian protocol translations, and guidelines from the C and European Resuscitation Council. The analysis focused on pre-hospital interventions, in-hospital transfusion protocols, and the impact of transport logistics on survival. Results: Evidence highlights that aggressive crystalloid resuscitation (over 5 L) significantly increases mortality, favoring balanced blood component therapy (1:1:1 ratio) or Whole Blood guided by viscoelastic testing like rotational thromboelastometry (ROTEM) or thromboelastography (TEG). Pre-hospital success is driven by rapid hemorrhage control via tourniquets, early administration of Tranexamic Acid (TXA), no aggressive crystalloids, permissive hypotension, proactive calcium supplementation is recommended in early care. Furthermore, the integration of Helicopter Emergency Medical Services (HEMS) is independently associated with improved survival in multi-organ trauma by reducing time to definitive care and facilitating “en-route” damage control. Conclusions: The evolution of rescue strategies focused on mitigating the effects of the diamond of death, combined with the implementation of permissive hypotension and optimized HEMS logistics, constitutes the foundation of a modern model aimed at minimizing mortality in multi-organ trauma. Full article

Background/Objectives: Renal cell carcinoma (RCC) with venous tumor thrombus (VTT) extending into the inferior vena cava (IVC) occurs in 4–10% of patients and represents one of the most technically demanding scenarios in urologic surgery. Open radical nephrectomy with en bloc thrombectomy remains the gold standard for infradiaphragmatic disease (Mayo Levels 0–III), offering the only realistic prospect for long-term cure. This narrative review provides a technically oriented, evidence-based guide for surgical urologists managing these complex cases. Methods: PubMed/MEDLINE, Scopus, and Web of Science were searched (1970–March 2025) using terms related to RCC, venous tumor thrombus, IVC thrombectomy, and perioperative management. Priority was given to prospective studies, systematic reviews, large retrospective cohorts, and current guidelines (EAU 2025, NCCN v2.2024). Original intraoperative photographs supplement procedural descriptions. Results: We detail the complete perioperative pathway: VTT classification (Mayo/AJCC), multimodal imaging, patient optimization, and level-specific open surgical techniques—ranging from Satinsky clamping for Level 0–I thrombi to full piggyback liver mobilization with hepatic vascular exclusion for Level III disease. Contemporary perioperative mortality is <2% at high-volume centers (reported in single and multicenter retrospective series from high-volume institutions), with 5-year cancer-specific survival of approximately 50–60% in non-metastatic cases. Adjuvant pembrolizumab is now a standard of care following the KEYNOTE-564 trial. Neoadjuvant immune checkpoint inhibitor plus tyrosine kinase inhibitor combinations show promising VTT downstaging rates (44–100%), though their role remains investigational. Robotic-assisted thrombectomy demonstrates favorable perioperative outcomes for Level I–II thrombi at experienced centers. Conclusions: Open surgery remains the cornerstone of curative treatment for RCC with infradiaphragmatic VTT, requiring meticulous preoperative planning and multidisciplinary collaboration at high-volume centers. Integration of perioperative systemic therapies and robotic-assisted approaches holds promise for further improving outcomes in this challenging patient population. Full article

Background: Urticaria, particularly chronic urticaria (CU), is a highly prevalent inflammatory skin disorder characterized by recurrent wheals and/or angioedema with a fluctuating and unpredictable course that significantly impairs quality of life and requires long-term monitoring. Despite established therapeutic guidelines, disease control remains suboptimal in a considerable proportion of patients. Telemedicine has emerged as a promising adjunctive strategy for chronic disease management. This review aims to critically evaluate the role, applications, benefits, and limitations of telemedicine and digital health interventions in urticaria management. Methods: A scoping review of the literature was conducted focusing on studies addressing telemedicine, digital patient-reported outcomes, mobile health applications, and remote monitoring strategies in urticaria. Evidence from pandemic and post-pandemic telemedicine models was also analyzed to identify transferable approaches. Results: Telemedicine demonstrates significant potential in urticaria management by enabling structured symptom monitoring, facilitating remote follow-up during therapeutic escalation (including biologic therapies), improving patient empowerment and adherence, and reducing healthcare utilization and indirect costs. Digital tools such as electronic diaries and validated PRO-based applications support continuous disease assessment. However, telemedicine cannot replace direct clinical examination, and limitations include diagnostic uncertainty, digital inequalities, data privacy concerns, and lack of large disease specific trials. Conclusions: Telemedicine represents a valuable complementary and integrative model for urticaria care, particularly suited for chronic disease monitoring. Hybrid care pathways combining remote and in-person management appear to be the most effective and sustainable strategy. Further high-quality urticaria-specific studies and standardized digital frameworks are required to optimize its clinical implementation. Full article

Objectives: Real-world data on surgical and multimodal management of upper tract urothelial carcinoma (UTUC) are limited. This study examined epidemiological trends, nephron-sparing surgery adoption, and the perioperative impact of lymphadenectomy (LND) and neoadjuvant chemotherapy (NAC). Methods: The German Nationwide Inpatient Data (GRAND) registry (2005–2023) identified UTUC patients undergoing radical nephroureterectomy (RNU), endoscopic laser destruction, or segmental ureteral resection (SUR) using OPS codes. Demographics, comorbidities, complications, and in-hospital mortality were extracted from ICD-10-GM data. Multivariable regression adjusted for baseline comorbidities assessed associations between treatment type, LND, NAC, and perioperative outcomes. Results: Among 53,427 UTUC patients, 77.3% underwent RNU, 13.8% endoscopic laser destruction, and 8.9% SUR. Endoscopic laser use rose from <10% (2005) to about 20% (2023). LND was performed in 13% of RNU cases, increasing from 1.1% to 19%. LND was associated with higher risks of transfusion (OR 1.47, 95% CI 1.37–1.57), acute kidney injury (OR 1.19, 95% CI 1.07–1.32), and ICU admission (OR 1.21, 95% CI 1.13–1.30), without affecting in-hospital mortality. NAC was given to 1.7% of patients, with a five-fold increase over time, and was associated with more transfusions (OR 1.28, 95% CI 1.07–1.52) and urinomas (OR 2.31, 95% CI 1.31–3.78), but not mortality. Conclusions: UTUC management is evolving, with growing use of endoscopic laser therapy and guideline-aligned lymphadenectomy during nephroureterectomy. Neoadjuvant chemotherapy remains underused despite acceptable perioperative safety, highlighting the need for increased awareness to optimize multimodal treatment. Full article

Background: Guided endodontics (GE), introduced in 2016, is an innovative approach aimed at addressing the challenges faced in endodontic treatment, particularly in cases of pulp canal obliteration (PCO). Objectives: This narrative review aims to assess the efficacy and application of static guided endodontics to facilitate minimally invasive access to difficult-to-locate root canals during primary endodontic treatment of incisors and canines. Method: A search strategy of the literature was performed on PubMed until 18 November 2025. The review synthesizes findings from 28 studies, focusing on recent advancements, procedural planning, and clinical outcomes related to GE. Results: Key findings indicate that GE may improve the ability to locate and treat calcified canals, reduce complications associated with traditional methods. Radiographic assessments and clinical indicators demonstrate favorable short- to medium-term outcomes; however, there is an absence of standardized protocols for long-term follow-up. Conclusions: Recommendations for future research include the establishment of unified technical guidelines to enhance consistency and comparability of results across clinical settings. Overall, guided endodontics represents a promising advancement in improving the success of root canal therapy while preserving natural dentition. The primary goal of this article is to update the literature review on static guided endodontics in anterior teeth during primary endodontics. Full article

Background/Objectives: Nutritional therapy is an essential part of oncologic care, yet patients with brain tumors—especially those with glioblastoma—remain underserved by disease-specific dietary guidelines. This cross-sectional study compares energy and macronutrient intake, as well as body composition, between brain tumor patients, including a glioblastoma subgroup, and patients with gastrointestinal (GI) cancer. Methods: A total of 95 brain tumor patients and 109 GI cancer patients completed standardized three-day estimated food records and underwent bioelectrical impedance analysis and hand-grip strength measurements. Anthropometric parameters, as well as energy and macronutrient intake, were compared between groups. Results: Energy intake was lower in brain tumor patients compared with GI cancer patients (22.8 kcal/kg/day vs. 31.2 kcal/kg/day), as were protein (1.01 g/kg/day vs. 1.34 g/kg/day) and carbohydrates (182.8 g/day vs. 246.8 g/day; all p < 0.01). Despite the lower intake, brain tumor patients exhibited higher BMI scores, body fat percentages, and visceral fat levels (p < 0.05), while fat-free mass and skeletal muscle mass were comparable between groups. The phase angle was higher in brain tumor patients (p = 0.002), whereas the ECW/TBW ratio was lower (p = 0.003). In the glioblastoma subgroup, protein intake did not differ significantly compared with the GI cancer group. However, carbohydrate intake (190.9 g/day vs. 246.8 g/day; p = 0.01), as well as energy intake (25.7 kcal/kg/day vs. 31.2 kcal/kg/day; p = 0.05), remained significantly lower. Conclusions: Brain tumor patients were found to have energy intake levels below ESPEN recommendations for cancer patients (25–30 kcal/kg/day), and their protein intake was at the lower ESPEN threshold (1.0 g/kg/day), coupled with increased adipose tissue. The observed caloric deficit was accompanied by reduced carbohydrate intake, particularly in the glioblastoma subgroup. These findings highlight the need for individualized nutritional approaches in neuro-oncology. Until disease-specific recommendations are available, general dietary guidelines such as those by ESPEN offer a pragmatic interim orientation. Full article

Gestational Diabetes Mellitus (GDM) is the most common metabolic complication of pregnancy, affecting approximately 14% of pregnancies globally. Despite the frequent normalization of glycemic parameters immediately after delivery, GDM is an important precursor of subsequent chronic disease, increasing the risk of type 2 diabetes (T2DM). Current international guidelines suggest just a strictly observational approach during the immediate puerperium, recommending metabolic screening only between 6 and 12 weeks postpartum. This has contributed to the creation of a therapeutic “orphan window” where women receive no specific metabolic support, leaving their metabolic status unassessed and unmanaged. We postulate that the immediate postpartum period represents a critical window of “metabolic plasticity” where the abrupt cessation of placental hormones offers a unique opportunity to restore insulin sensitivity and promote “beta-cell rest” before the onset of irreversible dysfunction. Consequently, this narrative review and perspective examines the epidemiological urgency of the GDM-to-T2DM transition and provides a biological rationale for early pharmacological or nutraceutical intervention. Specifically, we discuss the limitations of metformin and present the hypothesis of myo-inositol combined with alpha-lactalbumin as a safe, lactation-compatible “bridging therapy” to preserve beta-cell function, improve compliance, and modify the natural history of diabetes in this high-risk population, highlighting that this theoretical proposal requires validation through future clinical trials. Full article