Search Results (4,367)

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. Full article

Background: Veno-venous extra-corporeal membrane oxygenation (ECMO) cannulations are mostly performed while patients are heavily sedated and mechanically ventilated. For patients with acute respiratory distress syndrome (ARDS), cannulating for ECMO while awake and spontaneously breathing, as well as treating without sedation and mechanical ventilation, has potential advantages. This study aimed to compare clinical outcomes between patients cannulated for ECMO while awake and patients cannulated while sedated and mechanically ventilated. Methods: A retrospective multicenter study. Data were accessed from the Israeli ECMO registry of patients with COVID-19-induced ARDS treated at eight ECMO centers in Israel. The study group comprised 24 patients who were cannulated while awake and spontaneously breathing. A control group comprised 96 patients who were cannulated after sedation and mechanical ventilation, matched 1:4 by age, sex, and body mass index. The primary outcome was six-month survival. Secondary outcomes were: the duration of ECMO therapy, the duration of invasive mechanical ventilation-free ECMO therapy, and the duration of invasive mechanical ventilation. Results: The mean age was 52 + 11 years; 78% were males. Fifteen patients (63%) in the study group were eventually intubated. The mean durations on ECMO and in the intensive care unit did not differ between the groups. The study group had a higher six-month survival (75% vs. 49%, p = 0.02) and fewer infectious complications such as pneumonia or bacteremia (21% vs. 40%, p < 0.001) compared to the control group. After adjusting for PO₂/FiO₂ ratio and for the COVID-19 variant, the hazard ratio was 0.45 (C.I 0.19–1.06, p = 0.069). Conclusions: Awake VV-ECMO cannulation in COVID-19-induced ARDS is feasible in selected patients and was associated with higher survival in unadjusted analyses. However, after adjustment for key covariates, this association was attenuated and did not reach statistical significance. Full article

Newborn screening (NBS) for sickle cell disease (SCD) has been performed in the United States (US) for decades, significantly reducing infant morbidity and mortality. A landmark clinical trial demonstrated that early identification of SCD enabled timely and life-saving prophylactic penicillin; this led to recommendations for universal NBS across the US. Early use of hydroxyurea as a safe and effective treatment for SCD further improved clinical outcomes by preventing acute and chronic disease complications. These advances add to the importance of early diagnosis through NBS, providing an opportunity for early treatment intervention. In recent years, high-resource countries—including those in Europe, the UK, and Canada—have adopted NBS for SCD using diverse strategies. Simultaneously, pilot programs in lower-resource settings such as Africa, Brazil, and India have demonstrated local feasibility and impact through implementation efforts. An overarching equity gap for achieving global NBS for SCD is the variable access to simple, accurate, and affordable testing. Other challenges include timing of NBS testing, targeted populations, laboratory methods, and parental education with genetic counseling. Questions remain about the equitable enrollment of affected infants worldwide into comprehensive care to ensure early treatment. These challenges raise concerns about sustainability, underscore the need for long-term funding and a strategic plan, and highlight persistent inequities from the lack of global NBS standards. Full article

Background and Objectives: Acute and obstructive pyelonephritis (AOP) management, despite advancements in diagnostic imaging and antimicrobial therapy, is characterized by delayed recognition and increasing antimicrobial resistance. This review aimed to summarize current evidence regarding the clinical characteristics, microbiological spectrum, biomarkers, and imaging findings associated with AOP. Materials and Methods: A systematic review was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251162736). Literature searches were performed across the PubMed, Scopus, and Web of Science databases for articles published between January 2014 and 31 March 2025 using the term “acute obstructive pyelonephritis”. Inclusion criteria comprised original full-text English-language studies, published in the last 10 years and conducted in adults, reporting clinical, laboratory, microbiological, and imaging characteristics. Exclusion criteria are letters to the editor, expert opinions, case reports, conference or meeting abstracts, reviews, and redundant publications; having unclear or incomplete data; and being performed on cell cultures or on mammals. The quality of included studies was assessed using the Newcastle–Ottawa Scale. Results: Twenty-three studies met the inclusion criteria. AOP predominantly affected elderly patients with comorbidities, especially diabetes mellitus and urinary tract obstruction. Predictors of septic shock included thrombocytopenia, hypoalbuminemia, elevated procalcitonin (>1.12 µg/L), presepsin, and a neutrophil-to-lymphocyte ratio ≥ 8.7. Escherichia coli remained the leading pathogen (60–95%) with extended-spectrum β-lactamase (ESBL) rates between 20 and 70%, followed by Klebsiella pneumoniae. CT demonstrated 71–100% sensitivity for detecting obstructive complications, confirming its superiority over ultrasound, while MRI provided comparable diagnostic accuracy in selected cases. Source control through double-J stenting or percutaneous drainage significantly improved survival. Conclusions: AOP requires prompt recognition and early decompression to prevent sepsis-related mortality. Biomarkers such as procalcitonin, presepsin, and neutrophil to lymphocyte ratio enhance risk stratification, while CT remains the gold-standard imaging modality. The increasing prevalence of ESBL-producing pathogens underscores the need for antimicrobial stewardship and individualized therapeutic strategies guided by local resistance data. Full article

Cutaneous viral infections result from the complex interaction between viruses and skin structures, influenced by viral tropism and the host immune response. They can generate lesions ranging from transient rashes to chronic or potentially tumorous formations. Cutaneous manifestations are often the first sign of infection and allow for early recognition. The aim of this review is to analyze the role of viruses in skin pathology, the mechanisms of infection, and the clinical impact. A narrative review of the recent literature was performed, including original articles, systematic reviews, and clinical guidelines on cutaneous viral infections. Data on pathogenic mechanisms, types of lesions, evolution, and therapeutic options were evaluated, covering the main viruses involved in dermatology: herpesviruses, papillomaviruses, poxviruses, and viruses associated with acute rashes. Cutaneous viral infections can be self-limited, recurrent, or chronic, and some can promote malignant transformation of skin cells. The variability of clinical manifestations reflects the virus–host interaction and influences diagnosis and management. Recent advances highlight the development of vaccines and targeted antiviral therapies, which improve prognosis and infection control. Viruses play a major role in the etiology of skin diseases, and their early recognition is essential for preventing complications. Understanding the mechanisms of infection and the cutaneous response contributes to the optimization of therapeutic and preventive strategies, strengthening the modern management of viral cutaneous pathology. Full article

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. Full article

Background and objectives: The increasing volume of total hip and knee arthroplasty created a significant postoperative surveillance burden. While plain radiographs are standard, the detection of aseptic loosening is subjective. This review evaluates the state of the art regarding AI in radiographic analysis for identifying aseptic loosening and mechanical failure in primary hip and knee prostheses. Methods: A systematic search in PubMed, Scopus, Web of Science, and Cochrane was conducted up to November 2025, following PRISMA guidelines. Peer-reviewed studies describing AI tools applied to radiographs for detecting aseptic loosening or implant failure were included. Studies focusing on infection or acute complications were excluded. Results: Ten studies published between 2020 and 2025 met the inclusion criteria. In internal testing, AI models demonstrated high diagnostic capability, with accuracies ranging from 83.9% to 97.5% and AUC values between 0.86 and 0.99. A performance drop was observed during external validation. Emerging trends include the integration of clinical variables and the use of sequential imaging. Conclusions: AI models show robust potential to match or outperform standard radiographic interpretation for detecting failure. Clinical deployment is limited by variable performance on external datasets. Future research must prioritize robust multi-institutional validation, explainability, and integration of longitudinal data. Full article

Background: Visceral Leishmaniasis (VL), a severe systemic parasitic disease caused by Leishmania species, can be complicated by secondary Hemophagocytic Lymphohistiocytosis (HLH). HLH is a life-threatening hyperinflammatory syndrome characterized by excessive immune activation that results in multiorgan dysfunction. The co-occurrence of VL and HLH in adults is a rare but critical diagnostic and therapeutic challenge, often leading to fatal outcomes if treatment is delayed. Case Presentation: We present two cases of adult males (60 and 72 years old) from Greece, an endemic area for L. infantum, who presented with prolonged fever, pancytopenia, hepatosplenomegaly, and impaired liver function. Both patients exhibited extremely elevated ferritin (all > 2000 ng/mL and one > 20,000 ng/mL) and hypertriglyceridemia, fulfilling key laboratory criteria for HLH. Diagnosis was confirmed by the visualization of Leishmania amastigotes in bone marrow aspirates, which also demonstrated features of hemophagocytosis. Case 1, critically ill with acute kidney injury and coagulopathy, required combined treatment with liposomal Amphotericin B and immunoglobulin therapy for HLH. Case 2, who showed rapid and “spectacular improvement” solely after receiving liposomal Amphotericin B, did not require HLH-specific immunosuppression. Conclusions: VL-associated HLH should be considered in adult patients presenting with complex systemic inflammation, fever, and cytopenias, particularly in endemic settings. Our cases illustrate that the prompt initiation of anti-leishmanial therapy with liposomal Amphotericin B can be sufficient to reverse the HLH syndrome by eliminating the infectious trigger. However, intensive immunomodulation may be necessary in patients presenting with critical multi-organ failure. Full article

Chagas disease (CD), caused by Trypanosoma cruzi, is a neglected tropical illness affecting 6–8 million people in Latin America. Reaching scholarly consensus on the host response to T. cruzi infection remains a significant challenge, primarily due to substantial heterogeneity in outcomes driven by both the choice of animal model and the infecting parasite’s discrete typing unit (DTU). This variability complicates the evaluation and comparison of new therapeutic compounds against existing drugs, namely benznidazole and nifurtimox. This study provides a comprehensive, kinetic, multifaceted characterization of the acute infection using the highly virulent T. cruzi Y strain (TcII) in outbred Swiss mice. Here, crucial infection parameters are presented, including the optimal infective dose, the parasitemia dynamics, tissue damage markers, hematological profiles, cytokine production (Th1/Th2/Th17/Th22), and molecular parasite identification in target organs (heart, colon, esophagus, spleen, and liver) across the span of the infection. The novelty of this study lies in the kinetic integration of these parameters within a defined model; rather than presenting isolated data points, we demonstrate how the biochemical, physiological, and clinical signs and immunological responses, with the resulting organ involvement, evolve and interact over time. To complete the report, a necropsy evaluation was performed at the end of the acute, fatal infection, and it is presented here. This study fulfills a long-standing recommendation from diverse drug discovery groups for the creation of a definitive reference model to standardize preclinical testing for anti-Chagasic agents. Full article

Background: Fungal infection of pancreatic fluid collections (PFCs) in severe acute pancreatitis (SAP) is under-recognized and associated with poor outcomes. Overlap with bacterial infections and the need for invasive sampling often delay diagnosis, leading to prolonged antibiotic use without the use of antifungal agents. Methods: We report three cases of SAP complicated by fungal infection of PFCs. Two patients, one with alcohol-related pancreatitis and the other with biliary pancreatitis, developed symptomatic encapsulated necrosis. Both were successfully managed with endoscopic drainage and targeted antifungal therapy against Candida albicans, achieving full resolution. The third patient, with necrotizing biliary pancreatitis, underwent multiple surgical and endoscopic interventions and developed an infection with a non-albicans Candida species. Reduced susceptibility requires individualized antifungal adjustment guided by susceptibility testing. Despite aggressive multimodal therapy, the patient progressed to multiorgan failure and died subsequently. Results: These cases emphasize the clinical impact of fungal infections in patients with SAP, particularly their association with severe disease, prolonged hospitalization, and prior antibiotic exposure. These findings highlight the prognostic value of early microbiological sampling, species-level identification, and prompt initiation of antifungal therapy. Infections caused by non-albicans species pose additional challenges due to their reduced sensitivity to standard antifungal agents. Conclusions: Fungal infection of PFCs is a clinically significant and frequently underestimated complication of SAP. Early recognition and species-directed antifungal therapy are critical for improving outcomes in high-risk patients. Full article

Complete or partial loss of smell (anosmia), sometimes in association with distorted olfactory perceptions (parosmia), is a common neurological symptom affecting nearly 60% of patients suffering from post-acute neurological sequelae of COronaVIrus Disease of 2019 (COVID-19) syndrome, called long COVID. Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) may gain access from the nasal cavity to the brain (neurotropism), and the olfactory route has been proposed as a peripheral site of virus entry. COVID-19 is a risk factor for developing Alzheimer’s Disease (AD), an age-dependent and progressive neurodegenerative disorder characterized in affected patients by early olfaction dysfunction that precedes signs of cognitive decline associated with neurodegeneration in vulnerable brain regions of their limbic system. Here, we summarize the recent literature data supporting the causal correlation between the persistent olfactory deterioration following SARS-CoV-2 infection and the long-delayed manifestation of AD-like memory impairment. SARS-CoV-2 infection of the olfactory neuroepithelium is likely to trigger a pattern of detrimental events that, directly and/or indirectly, affect the anatomically interconnected hippocampal and cortical areas, thus resulting in tardive clinical dementia. We also delineate future advancement on pharmacological and rehabilitative treatments to improve the olfactory dysfunction in patients recovering even from the acute/mild phase of COVID-19. Collectively, the present review aims at highlighting the physiopathological nexus between COVID-19 anosmia and post-pandemic mental health to favor the development of best-targeted and more effective therapeutic strategies in the fight against the long-term neurological complications associated with SARS-CoV-2 infection. Full article

Obesity hypoventilation syndrome (OHS) is a severe and underrecognized respiratory disorder characterized by the coexistence of obesity, daytime hypercapnia, and sleep-disordered breathing. Although well described in adults, pediatric OHS remains poorly defined despite the rising prevalence of childhood obesity. Its pathophysiology is multifactorial, involving obesity-related mechanical constraints, impaired ventilatory control, altered chemosensitivity, and frequent overlap with obstructive sleep apnea. Clinical manifestations in children are often subtle and nonspecific, including snoring, sleep fragmentation, daytime sleepiness, and neurocognitive impairment, frequently leading to delayed diagnosis and, in some cases, acute cardiopulmonary decompensation. Management of pediatric OHS is challenging and largely extrapolated from adult data. Positive airway pressure therapy remains the cornerstone of treatment, while weight reduction is essential but difficult to achieve in pediatric populations. Pharmacological approaches such as medroxyprogesterone or acetazolamide remain experimental, with limited pediatric evidence. This review synthesizes current knowledge on pediatric OHS, focusing on epidemiology, pathophysiology, clinical presentation, diagnostic challenges, and therapeutic strategies. Increased awareness and earlier recognition are essential to prevent progression to chronic respiratory failure and long-term cardiovascular complications. Full article

Background and Objectives: Transcatheter aortic valve implantation (TAVI) has become the mainstay of treatment for symptomatic aortic stenosis (AS) in patients over 70 years of age. It is also indicated for younger patients with significant comorbidities, for valve-in-valve interventions, and in selected patients with severe aortic insufficiency. We aimed to evaluate procedural and clinical outcomes of transfemoral TAVI performed over the course of 12 years by the same operators using different bioprosthetic valves. Materials and Methods: Between 2012 and 2023, 375 patients underwent TAVI in our clinic, with six types of bioprosthetic valves (Edwards Sapien XT, Medtronic Valves [CoreValve and Evolut R], Portico, Myval, Acurate Neo, and Direct Flow Medical). A transfemoral approach was used in all patients. The procedural and clinical outcomes were defined according to Valve Academic Research Consortium-3 (VARC-3) criteria. Results: The mean age of the patients was 78.4 ± 7.3, and their median STS score was 4.2 (2.9–5.9). Of the 375 patients, 361 had severe AS, 4 had severe aortic insufficiency, 5 were valve-in-valve, and 5 were valve-in-TAVI. Seven patients required a second valve implantation: four due to embolization of the prosthetic valve and three due to deep implantation of the prosthetic valve. Based on the VARC-3 criteria, the rates of technical success and device success were 90.4% and 85.3%, respectively. Major vascular complications were observed in 18 (4.8%) patients. Also, 42 (11.2%) patients required permanent pacemaker implantation. The incidence of moderate or worse paravalvular leak was 2.9%. The peri-procedural, 30-day, 1-year, and 5-year mortality rates were 5.1%, 4.3%, 15.2%, and 45.6%, respectively. STS scores (HR:1.129, 95%CI: 1.068–1.192, p < 0.001) and post-TAVI acute kidney injury (HR:3.993, 95%CI:1.629–9.785, p = 0.002) were detected as independent predictors of mortality in Cox regression analysis. Conclusions: This registry demonstrated the evolution of TAVI procedures at a single center over 12 years. A high level of collaboration between experienced operators and innovations in devices seem to be the key features for achieving high procedural success and low complication rates. Full article

Background/Objectives: Aneurysmal subarachnoid hemorrhage (aSAH) involves a sudden onset of a perfusion-pressure injury from the initial insult combined with a secondary injury phase produced by delayed cerebral ischemia, cerebrospinal fluid circulation disturbances, and generalized instability of the patient’s physiological state. The situation may be further complicated when there has been rupture of the aneurysm at the site of the carotid–posterior communicating (PCom) artery junction that occurs in conjunction with a fetal configuration of the posterior cerebral artery (fPCA), thereby making definitive treatment dependent on preserving the critical nature of the branches of the posterior circulation since the aneurysm’s neck plane coincides with the dominant posterior circulation conduit. Case Presentation: A 65-year-old female patient who was obese (Grade III BMI = 42), had chronic bronchial asthma, and arterial hypertension experienced a “thunderclap” type of headache in the right retro-orbital area followed by a syncopal episode and developed acute confusion with agitation. Upon admission to the hospital, her Glasgow Coma Scale (GCS) was 13, her FOUR score was 15, her Montreal Cognitive Assessment (MoCA) score was 12/30, her Hunt–Hess grade was 3, WFNS grade 2, and Fisher grade 4 SAH with intraventricular extension. Digital subtraction angiography (DSA) and three-dimensional rotational angiography revealed a posteriorly directed right carotid communicating aneurysm that had a relatively compact neck (approximately 2.5 mm) and sac size of approximately 7.7 × 6.6 mm, with the fPCA originating at the neck plane. Microsurgical treatment was performed with junction-preserving reconstruction with skull base refinement, temporary occlusion of the internal carotid artery for a few minutes, placement of clips reconstructing the carotid–PCom interface, and micro-Doppler verification of patent vessel. Postoperatively, the blood pressure was kept within the range of 110–130 mmHg with nimodipine and closely monitored. The neurological recovery was sequential (GCS of 15 by POD 2; MoCA of 22 by POD 5). By POD 5 CT scan, the clip remained positioned in a stable fashion without evidence of infarct, hemorrhage, or hydrocephalus; at three months she was neurologically intact (mRS 0; Barthel 100; MoCA 28/30), and CTA confirmed persistent exclusion of the aneurysm and preservation of fPCA flow. Conclusions: In cases where the ruptured aneurysm is located at the carotid communicating junction with the PCom artery in a configuration of the posterior cerebral artery that is described as fetal, clip treatment should be viewed as a form of branch-preserving junction reconstruction of the carotid–PCom junction supported by adherence to controlled postoperative physiology and close ppostoperativesurveillance. Full article

Background: Cosmetic injection of botulinum neurotoxin type A (BoNT/A) into the submandibular glands is increasingly performed to enhance jawline contour. Although generally considered safe, unintended diffusion of the toxin can impair pharyngeal musculature and lead to dysphagia. Severe aspiration-prone dysphagia after esthetic submandibular gland injection has rarely been described. Case Presentation: A healthy 37-year-old woman developed acute oropharyngeal dysphagia the day after receiving cosmetic contouring injections with incobotulinumtoxinA (Xeomin^®), administered to both submandibular glands (20 units per gland, performed without ultrasound guidance). She presented to our rehabilitation medicine clinic 11 days later with severe difficulty swallowing solids and liquids. Her functional oral intake was severely restricted (Functional Oral Intake Scale [FOIS] score 3), and the Eating Assessment Tool-10 (EAT-10) score was 24. Videofluoroscopic swallowing study (VFSS) demonstrated markedly delayed pharyngeal swallow initiation, reduced palatal elevation, poor airway protection, consistent laryngeal penetration, and silent aspiration of thin liquids (Penetration–Aspiration Scale score 8). She underwent diet modification and structured dysphagia rehabilitation. At three months, repeat VFSS showed substantial improvement, with only occasional penetration of large-volume thin liquids, corresponding to FOIS 5 and EAT-10 score 8. By five months, VFSS confirmed complete resolution of penetration and aspiration with normalization of swallowing physiology, reflected by a FOIS score of 7 and EAT-10 score of 1. Conclusions: This case demonstrates that cosmetic incobotulinumtoxinA injection into the submandibular glands, particularly when performed without ultrasound guidance, can lead to significant oropharyngeal dysphagia. Clinicians performing esthetic lower-face procedures should be aware of this potential complication and ensure timely swallowing evaluation and rehabilitation when symptoms arise. Full article