Search Results (337)

Acute kidney injury (AKI) is a serious clinical condition that is linked to markedly higher rates of morbidity and mortality in cirrhosis patients. Its diagnosis is challenging due to overlapping clinical and laboratory features among causes such as hepatorenal syndrome (HRS), acute tubular injury (ATI), and prerenal hypovolemia. In order to address the distinct pathophysiology and clinical context of cirrhosis, the definitions and classification of AKI have changed over time, moving from RIFLE and AKIN to KDIGO and ICA-AKI. Because cirrhosis patients have altered muscle mass and fluid retention, traditional markers like serum creatinine (sCr) and urine output have significant limitations. Neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and cystatin C (CysC) are some of the new biomarkers that have shown promise in early AKI detection and in differentiating structural from functional kidney injury. NGAL and KIM-1 are sensitive indicators of tubular damage with potential prognostic implications. IL-18 reflects inflammatory injury, and CysC offers a more reliable measure of glomerular filtration. Incorporating these markers may improve early diagnosis, risk stratification, and treatment decisions, representing a key direction for future research in managing AKI in cirrhosis. Full article

Background/Objectives: Anti-p200 pemphigoid is a rare and likely underdiagnosed autoimmune blistering disorder. Laminin γ1 and laminin β4 have been implicated as potential target antigens in its pathogenesis. Recently, a novel indirect immunofluorescence assay targeting anti-laminin β4 antibodies has been developed, demonstrating high sensitivity and specificity, and offering a valuable tool for improved diagnosis. Methods: Of the 451 patients, 21 were selected for further laboratory analysis based on medical records. Sera from 10 patients, which showed a positive direct immunofluorescence (DIF) result and negative results in multiplex enzyme-linked immunosorbent assays (ELISAs) and/or mosaic six-parameter indirect immunofluorescence (IIF) for various autoimmune bullous diseases, were tested for the presence of anti-laminin β4 antibodies. Additionally, sera from 11 patients with positive DIF and positive ELISA for antibodies against BP180 and/or BP230 were analyzed. Results: Among the 10 patients with positive DIF and negative ELISA and/or mosaic six-parameter IIF, 6 sera were positive for anti-laminin β4 antibodies. These patients presented with atypical clinical features. In contrast, all 11 sera from patients with both positive DIF and positive ELISA for BP180 and/or BP230 were negative for anti-laminin β4 antibodies. Conclusions: In patients with a positive DIF result but negative ELISA and/or mosaic six-parameter IIF findings, testing for anti-laminin β4 antibodies should be considered. Furthermore, in cases presenting with atypical clinical features—such as acral distribution of lesions, intense pruritus, or erythematous–edematous plaques—the possibility of anti-p200 pemphigoid should be included in the differential diagnosis. Full article

Medical education is the paradigm of 21st century education and the current changes involve the adoption of integrative and comprehensive patient-centered teaching and learning approaches. Thus, curricular developers from George Emil Palade University of Medicine, Pharmacy, Sciences, and Technology of Targu Mures (G.E. Palade UMPhST of Targu Mures) have recently designed and implemented an innovative medical curriculum, as well as two valuable assessment tools for both theoretical knowledge and practical skills. Thus, during the first three preclinical years, the students will benefit from an organ- and system-centered block teaching approach, while the clinical years will focus on enabling students to achieve the most important practical skills in clinical practice, based on a patient bedside teaching system. In terms of theoretical knowledge assessment, the UNiX center at G.E. Palade UMPhST of Targu Mures, a recently designed center endowed with the latest next-generation technology, enables individualized, secured multiple-choice question-based assessments of the student’s learning outcomes. Moreover, an intelligent assessment tool for practical skills was also recently implemented in our branch in Hamburg, the Objective Structured Clinical Examination (O.S.C.E). This system uses direct observations for testing the student’s practical skills regarding anamnesis, clinical exams, procedures/maneuvers, the interpretation of laboratory tests and paraclinical investigations, differential diagnosis, management plans, communication, and medical counselling. The integrative, comprehensive, patient-centered curriculum and the intelligent assessment system, implemented in G.E Palade UMPhST of Targu Mures, help define innovation in education and enable the students to benefit from a high-quality medical education. Full article

Addressing the stability control challenges of roadways with composite roofs in the No. 34 coal seam of Donghai Mine under high-strength mining conditions, this study employed integrated methodologies including laboratory experiments, numerical modeling, and field trials. It investigated the mechanical response characteristics of the composite roof and developed a synergistic control system, validated through industrial application. Key findings indicate significant differences in mechanical behavior and failure mechanisms between individual rock specimens and composite rock masses. A theoretical “elastic-plastic-fractured” zoning model for the composite roof was established based on the theory of surrounding rock deterioration, elucidating the mechanical mechanism where the cohesive strength of hard rock governs the load-bearing capacity of the outer shell, while the cohesive strength of soft rock controls plastic flow. The influence of in situ stress and support resistance on the evolution of the surrounding rock zone radii was quantitatively determined. The FLAC^3D strain-softening model accurately simulated the post-peak behavior of the surrounding rock. Analysis demonstrated specific inherent patterns in the magnitude, ratio, and orientation of principal stresses within the composite roof under mining influence. A high differential stress zone (σ₁/σ₃ = 6–7) formed within 20 m of the working face, accompanied by a deflection of the maximum principal stress direction by 53, triggering the expansion of a butterfly-shaped plastic zone. Based on these insights, we proposed and implemented a synergistic control system integrating high-pressure grouting, pre-stressed cables, and energy-absorbing bolts. Field tests demonstrated significant improvements: roof-to-floor convergence reduced by 48.4%, rib-to-rib convergence decreased by 39.3%, microseismic events declined by 61%, and the self-stabilization period of the surrounding rock shortened by 11%. Consequently, this research establishes a holistic “theoretical modeling-evolution diagnosis-synergistic control” solution chain, providing a validated theoretical foundation and engineering paradigm for composite roof support design. Full article

Diverticulosis is characterized by sac-like bulges of the mucosa through weakened portions of the intestinal wall, and is a common pathology observed in adult patient populations. The majority of diverticular disease and associated complications, such as inflammation of diverticula, form within the colon, with less frequent cases of diverticular disease observed in the small bowel. We present the case of a 48-year-old female who presented to the emergency department with a two-day history of abdominal pain, fever, and nausea. Upon admission, vital signs indicated fever and laboratory analysis demonstrated elevated white blood cell count. The patient’s workup included a computed tomography (CT) scan of the abdomen which revealed diffuse small bowel diverticulitis with surrounding inflammation, lymph node enlargement, and bowel wall thickening. CT scan of the abdomen with evidence of diverticula in the bowel wall is diagnostic of diverticulosis. Treatment could include bowel rest, clear liquid diet, broad-spectrum antibiotics, or surgical intervention. This case emphasizes the importance of CT imaging and consideration of broad differential diagnosis in patients presenting with abdominal pain due to the rare presentation of small bowel diverticulitis and aims to contribute to the current understanding and treatment of clinically significant diverticular pathologies. Full article

Background/Objectives: Acetazolamide is widely used for acute mountain sickness (AMS) prophylaxis. Whilst generally safe, acute kidney injury (AKI) is a rare but serious adverse event. We present a case of anuric AKI following minimal exposure to acetazolamide, contributing to the limited literature on its nephrotoxicity at prophylactic doses. Methods: A 54-year-old previously healthy male ingested 250 mg/day of oral acetazolamide for two days. He developed acute anuria and lumbar pain. Diagnostic evaluation included laboratory tests, imaging, microbiological cultures, autoimmune panels, and diuretic response. No signs of infection, urinary tract obstruction, or systemic disease were found. Results: The patient met KDIGO 2012 criteria for stage 3 AKI, with peak serum creatinine of 10.6 mg/dL and metabolic acidosis. Imaging confirmed non-obstructive nephrolithiasis. Conservative treatment failed; intermittent hemodialysis was initiated. Renal function recovered rapidly, with the normalization of serum creatinine and urinary output by day 4. Conclusions: This case represents the lowest cumulative dose of acetazolamide reported to cause stage 3 AKI. The findings support a pathophysiological mechanism involving sulfonamide-induced crystalluria and intratubular obstruction. Physicians should consider acetazolamide in the differential diagnosis of AKI, even with short-term prophylactic use. Full article

Background: Pulmonary embolism (PE) increases right ventricular (RV) afterload, potentially leading to myocardial stress and electrocardiographic abnormalities. Although QTc prolongation has been suggested as a marker of RV dysfunction, its prevalence, clinical significance, and prognostic value in acute PE remain poorly defined. Objective: The objective of this study is to evaluate the prevalence and clinical implications of QTc prolongation in patients with intermediate–high and high-risk acute PE. Methods: We retrospectively analyzed 95 consecutive patients admitted with intermediate–high or high-risk PE between September 2021 and December 2023. QTc prolongation was defined as ≥470 ms in males and ≥480 ms in females. Clinical, imaging, and laboratory data were compared between patients with normal and prolonged QTc intervals. QTc was assessed at admission, after treatment, and prior to discharge. Results: QTc prolongation was observed in 28.4% of patients at presentation. This group had significantly higher lactate levels (2.3 vs. 1.8 mmol/L, p = 0.03) and a non-significant trend toward elevated troponin and lower oxygen saturation. No differences were observed in echocardiographic or CT-based RV dysfunction parameters. QTc values normalized by discharge irrespective of treatment modality. There was no association between QTc prolongation and in-hospital or long-term mortality. A trend toward more aspiration thrombectomy was noted in the prolonged QTc group (29.6% vs. 11.8%, p = 0.06). Conclusions: QTc prolongation is common in acute intermediate–high and high-risk PE and may reflect transient myocardial stress. While not predictive of clinical outcomes, it should be considered in the differential diagnosis of QTc prolongation in patients presenting with dyspnea and chest pain. Full article

Background and clinical significance: Acute reduction in vigilance is a frequent reason for emergency department admissions, especially among the elderly. While intracranial causes or infections with fluid depletion are often responsible, there remain cases where imaging, laboratory tests, and clinical examination fail to provide a clear diagnosis. Case presentation: A 91-year-old woman was presented to the emergency department with recurrent episodes of somnolence to deep coma. On admission, her vital signs were stable, and cerebral CT imaging revealed no intracranial pathology. Laboratory analyses, including blood gas measurements, were unremarkable. Empirical treatment for possible intoxications with benzodiazepines or opioids using flumazenil and naloxone had no effect. An Addison’s crisis was considered but excluded following methylprednisolone administration without improvement in consciousness. Eventually, an isolated elevation of serum ammonia was identified as the cause of the reduced vigilance. Further investigation linked the hyperammonemia to abnormal intestinal bacterial colonization, likely due to a prior ureteroenterostomy. There was no evidence of liver dysfunction, thus classifying the condition as non-hepatic hyperammonemia. Therapy was initiated with rifaximin, supported by aggressive laxative regimens. Ammonia levels and vital parameters were closely monitored. The patient’s condition improved gradually, with serum ammonia levels returning to normal and cognitive function fully restored. Conclusions: This case highlights an uncommon cause of coma due to non-hepatic hyperammonemia in the absence of liver disease, emphasizing the diagnostic challenge when standard evaluations are inconclusive. It underscores the need for broad differential thinking in emergency settings and the importance of considering rare metabolic disturbances as potential causes of altered mental status. Full article

Background and Aims: Ornidazole, a nitroimidazole antibiotic, is widely used for protozoal and anaerobic infections and is generally considered safe. However, ornidazole-induced liver injury (OILI) is an underrecognized yet potentially severe adverse reaction. This multicenter study aims to characterize the clinical features, histopathology, and outcomes of OILI to improve the awareness and management of this rare entity worldwide. Methods: We conducted a retrospective analysis of 101 patients with OILI from eight tertiary centers between 2006 and 2023. Cases were included based on liver enzyme elevations temporally linked to ornidazole and the exclusion of other causes. Causality was assessed using the Roussel Uclaf Causality Assessment Method (RUCAM) score. Clinical data, laboratory parameters, autoantibody profiles, histology, treatments, and outcomes were evaluated. Results: OILI was classified as highly probable in 42.6% of cases (n = 43), probable in 51.5% of cases (n = 52), and possible in 5.9% (n = 6) of cases. The predominant pattern was acute hepatocellular injury (83.2%) (n = 84). Autoimmune-like hepatitis occurred in 5% of cases (n = 5), with ANA positivity in 16.8% of cases (n = 17). Corticosteroids were used in 24.8% of cases (n = 25) and were associated with higher ANA positivity and a 20% (n = 5) relapse rate post-discontinuation. Recovery was achieved in 87.7% of cases (n = 88), while 7.9% of cases (n = 8) required liver transplantation and 4% (n = 4) died. Conclusions: Ornidazole can cause serious idiosyncratic liver injury, including autoimmune phenotypes, and should be considered in the differential diagnosis of acute hepatitis. Given the notable risk of liver failure and death, early recognition, drug discontinuation, and close monitoring are essential. In select cases, corticosteroids and plasmapheresis may be beneficial, though the evidence remains limited. Full article

Soft tissue masses are predominantly benign, with a benign-to-malignant ratio exceeding 100:1, often located around joints. They may be contiguous or adjacent to joints or reflect systemic diseases or distant organ involvement. Clinically, they typically present as palpable swellings. Evaluation should consider duration, size, depth, and mobility. Also assess consistency, growth rate, symptoms, and history of trauma, infection, or malignancy. Laboratory tests are generally of limited diagnostic value. The primary clinical goal is to avoid unnecessary investigations or procedures for benign lesions while ensuring timely diagnosis and treatment of malignant ones. Imaging plays a central role: it confirms the presence of the lesion, assesses its location, size, and composition, differentiates between cystic and solid or benign and malignant features, and can sometimes provide a definitive diagnosis. Imaging is also crucial for biopsy planning, treatment strategy, identification of involved structures, and follow-up. Ultrasound (US) is the first-line imaging modality for palpable soft tissue masses due to its low cost, wide availability, and lack of ionizing radiation. If findings are inconclusive, magnetic resonance imaging (MRI) or computed tomography (CT) is recommended. This review aims to discuss the most common causes of periarticular soft tissue masses in the appendicular skeleton, focusing on clinical presentation and radiologic features. Full article

In children without Down syndrome who have acute megakaryoblastic leukemia (AMKL), inv(16)(p13q24)/CBFA2T3::GLIS2 is the most frequent genetic aberration. Pediatric CBFA2T3::GLIS2-positive AMKL is strongly associated with a poor prognosis and a high cumulative incidence of relapse. One of the key laboratory signs of CBFA2T3::GLIS2-positive AMKL is the RAM immunophenotype, which looks very similar to that of solid-tumor bone marrow (BM) infiltration. For this reason, in cases of isolated extramedullary involvement of CBFA2T3::GLIS2-positive AMKL, excluding solid tumors may be challenging. We report a case of a girl with isolated extramedullary CBFA2T3::GLIS2-positive AMKL relapse, which was misdiagnosed as secondary Ewing sarcoma. The morphological differential diagnosis between Ewing sarcoma and AMKL presented significant challenges owing to their overlapping histological features (small, round blue-cell morphology and similar growth patterns). The tumor cells’ immunophenotype completely mirrored that at the initial diagnosis of AMKL. Additional cytogenetic and molecular studies confirmed the presence of the CBFA2T3::GLIS2 fusion, but no Ewing sarcoma-specific EWSR1, FUS and CIC fusion transcripts were found. Thus, extramedullary CBFA2T3::GLIS2-positive AMKL relapse was confirmed. The presented case demonstrates the difficulties in differential diagnosis between AMKL relapse and the development of a secondary tumor. Full article

Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory condition marked by tumefactive lesions, IgG4+ plasma cell-rich infiltrates, storiform fibrosis, and obliterative phlebitis. Its multisystem involvement and overlap with malignancies, infections, and immune disorders complicate diagnosis despite recent classification advances. This study summarizes diagnostic challenges, highlights the role of histopathology as per the 2019 classification criteria established by the American College of Rheumatology and the European League Against Rheumatism (ACR/EULAR), and explores emerging tools to improve diagnostic accuracy. ACR/EULAR classification emphasizes three cardinal histopathological features (storiform fibrosis, obliterative phlebitis, or dense lymphoplasmacytic infiltrates) combined with an IgG4+/IgG+ plasma cell ratio >40% and organ-specific IgG4+ thresholds. While serum IgG4 levels are often elevated, their poor specificity necessitates confirmatory biopsy. Diagnostic limitations include sampling variability due to patchy fibrosis, interobserver discrepancies in immunohistochemical interpretation, and differentiation from mimics like lymphoma. Emerging solutions incorporate novel biomarkers (plasmablasts, anti-annexin A11) and advanced techniques (flow cytometry, digital pathology). Future research directions should focus on AI-assisted pattern recognition, multi-omics profiling, and organ-specific criteria refinement. While histopathology remains the diagnostic cornerstone, a multidisciplinary approach integrating clinical, radiological, and laboratory data is vital. Innovations in biomarkers promise improved diagnostic accuracy and personalized care, balancing novel advancements with foundational pathological evaluation. Full article

Background: Copper dyshomeostasis has been implicated in a subset of Alzheimer’s disease (AD) patients, characterized by elevated non-ceruloplasmin-bound copper (non-Cp Cu). However, traditional methods for estimating non-Cp Cu are indirect and analytically imprecise. This study introduces and validates a direct assay for exchangeable copper (ExcCu) by inductively coupled plasma-mass spectrometry (ICP-MS), compliant with Clinical and Laboratory Standards Institute (CLSI) guidelines. Methods: We performed analytical validation of the ExcCu assay following CLSI protocols (EP5, EP6, EP7, EP9, EP15, and EP28). ExcCu and other copper-related biomarkers were quantified in serum samples from 154 healthy controls, 82 AD patients, and 10 patients with Wilson disease (WD). Diagnostic performance was evaluated via receiver operating characteristic (ROC) curve analysis, and inter-method agreement was assessed using Bland–Altman plots. Results: The ExcCu assay demonstrated excellent linearity, precision (CV < 6%), and inter-laboratory reproducibility. Among AD patients, ExcCu levels were significantly elevated compared to controls (p < 0.001). ExcCu distinguished AD from controls with an AUC of 0.80 and a specificity of 95%. Compared to non-Cp Cu, ExcCu yielded no negative values and showed reduced bias. The relative exchangeable copper (REC) index was more effective in differentiating AD from WD (AUC = 0.88). Conclusions: The validated ExcCu assay overcomes the limitations of the traditional non-Cp Cu calculation, offering a reliable biomarker for copper-related AD subtypes. Its high specificity supports its use in patient stratification, potentially contributing to personalized approaches in AD diagnosis and therapy. Full article

Ataxia-telangiectasia is a rare autosomal recessive disorder that is difficult to diagnose due to its unpredictable presentation. It is characterized by cerebellar degeneration, telangiectasias, immunodeficiency, frequent pulmonary infections, and tumors. Immune system abnormalities manifest as disruptions in both cellular and humoral immunity. The most common findings include decreased levels of immunoglobulin classes (IgA, IgM, IgG, and IgG subclasses) and a reduced number of T and B lymphocytes. A four-year-old girl was initially evaluated and treated for skin lesions that presented as crusts spreading across her body. She was monitored by a pulmonologist due to frequent bronchial obstructions. Over time, she developed bilateral scleral telangiectasia, saccadic eye movements, and impaired convergence. Her gait was wide-based and unstable, with truncal ataxia and a positive Romberg sign. Laboratory tests revealed decreased immunoglobulin G levels, subclass IgG4 levels, elevated alpha-fetoprotein, and a reduced number of T and B lymphocytes. Brain magnetic resonance imaging showed cerebellar atrophy. Whole-exome sequencing identified heterozygous variants c.1564-165del, p.(Glu5221lefsTer43), and c.7630-2A>C in the serine/threonine-protein kinase ATM (ataxia-telangiectasia mutated) gene, confirming the diagnosis of ataxia-telangiectasia. Following diagnosis, treatment with intravenous immunoglobulin replacement was initiated along with infection prevention and management. The goal of this case report is to raise awareness of the atypical initial presentation that may lead to a diagnostic delay. We emphasize the importance of considering ataxia-telangiectasia in the differential diagnosis, even when classical neurological signs are not yet evident. Full article

Inherited platelet disorders (IPDs) are rare bleeding disorders characterized by impaired platelet function and/or reduced blood platelet count. Their diagnosis typically relies on complex laboratory methods, including flow cytometry, aggregometry, and molecular genetic analysis. In recent years, immunofluorescence microscopy has been established as an alternative diagnostic method for IPDs. Background/Objectives: This study aims to validate a quantitative approach enhancing reproducibility through automated image analysis for diagnosing IPDs using immunofluorescence microscopy, with Bernard–Soulier Syndrome (BSS) and Glanzmann thrombasthenia (GT) as model IPDs. Methods: Native blood smears from patients with suspected BSS or GT were stained using a standardized immunofluorescence protocol targeting platelet surface glycoproteins, granules, and cytoskeletal components. The slides were analyzed using an automated fluorescence microscope, and a rule-based subpopulation analysis was implemented to quantify fluorescence signals. The results were compared to those of a healthy control group, as well as data from flow cytometry and molecular genetic testing. Results: The automated analysis successfully differentiated BSS and GT patients from healthy controls based on distinct fluorescence signal patterns. In BSS samples, CD42b (GPIbα) expression was absent or severely reduced, while GT samples showed a deficiency of CD41/CD61 (GPIIb/IIIa). The platelet size distribution confirmed macrothrombocytopenia in BSS patients. Flow cytometry and molecular genetic testing corroborated these findings, supporting the diagnostic reliability of the automated immunofluorescence microscopy approach. Conclusions: This proof-of-principle study demonstrates that automated quantitative immunofluorescence microscopy is a viable alternative for diagnosing IPDs, offering a standardized, objective, and efficient method, particularly in settings where flow cytometry is not feasible. Full article