Search Results (120)

Introduction: Ado-trastuzumab emtansine (T-DM1) is a targeted agent for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which combines the anti-tumor activity of trastuzumab with the cytotoxic effect of DM1, a microtubule inhibitor. Although T-DM1 has improved outcomes in patients with HER2-positive breast cancer, portal hypertension may occur during treatment in the absence of overt cirrhosis on liver biopsy. These clinical and pathological features are consistent with porto-sinusoidal vascular disorder (PSVD). This study aimed to summarize the reported clinical, biochemical, imaging, histological, therapeutic, and prognostic features of T-DM1-associated PSVD. Methods: PubMed and Web of Science were searched for published cases of T-DM1-associated PSVD. Given the evolving terminology of PSVD, related terms, including non-cirrhotic portal hypertension and nodular regenerative hyperplasia, were also included in the search strategy. If the patient has a recorded history of T-DM1 exposure and the liver biopsy results meet PSVD criteria, the case is included regardless of whether there is clinical, endoscopic, or imaging evidence of portal hypertension. Cases without liver biopsy or with features suggestive of overt cirrhosis were excluded. Patient-level data were extracted and descriptively summarized, including demographic characteristics, clinical manifestations, biochemical indicators, imaging examination results, liver biopsy results, treatment methods, and prognosis. Unreported data were considered missing values and were not imputed. Results: Seven eligible articles comprising eight patients were identified. All patients were female, with a mean age of 60.38 years and a median age of 62.50 years. The interval from T-DM1 initiation to PSVD diagnosis ranged from 6 to 30 months. When reported, the mean interval from treatment initiation to symptom onset was 18.3 months. Thrombocytopenia and splenomegaly were observed in 7 of 8 patients. Mild elevations in alanine aminotransferase and aspartate aminotransferase were observed in all patients. Liver biopsy showed thinned and disorganized hepatic plates accompanied by nodular regeneration of hepatocytes in six patients. Clinical improvement was observed after discontinuation or modification of T-DM1 in most cases. Conclusions: T-DM1-associated PSVD is a rare but clinically significant complication that may develop months after treatment initiation. It commonly presents with thrombocytopenia, splenomegaly, gastrointestinal bleeding, or mild liver biochemical abnormalities in the absence of overt cirrhosis. Early recognition of unexplained platelet decline, splenic enlargement, or portal hypertension-related findings during T-DM1 therapy may facilitate timely diagnosis and individualized management. Withdrawal or modification of the suspected drug may contribute to clinical improvement, although further studies are needed to clarify the mechanism and optimal management strategy. Full article

Obstructive jaundice is a common digestive disorder with multiple etiologies. Non-tuberculous mycobacterial (NTM) infection is an opportunistic disease that may present with localized pulmonary involvement or disseminated multi-organ manifestations. However, biliary involvement in disseminated NTM infection is rare, and its characteristics and progression remain poorly understood. We report a patient with progressive jaundice who was eventually considered to have probable biliary NTM infection after comprehensive evaluation, exclusion of alternative etiologies, and a favorable therapeutic response despite negative microbiological testing. Endoscopic retrograde cholangiopancreatography (ERCP) was performed to relieve biliary obstruction, but the patient developed recurrent and refractory ampullary bleeding requiring repeated endoscopic interventions. Clinical improvement was achieved following combined antimycobacterial therapy and immunomodulatory treatment. Biliary NTM infection is a rare cause of obstructive jaundice, and ERCP remains necessary for biliary decompression, while post-ERCP bleeding risk should be carefully monitored. Full article

Background. Acquired platelet dysfunction with eosinophilia (APDE) is a transient bleeding disorder initially thought to occur exclusively in Southeast Asia. There are no uniformly agreed diagnostic criteria, and its full clinical features have not been defined. Methods. A literature search was conducted through MEDLINE, EMBASE, and Google Scholar for publications on APDE in order to explore patient demography, epidemiology, diagnostic criteria, and laboratory findings of the disease. Results. Ten retrospective, observational studies, five case series, and 21 case reports were identified with a total of 431 patients. Diagnostic criteria varied, with a two-tier approach for the diagnosis of impaired platelet function. In recent years, cases of APDE have been reported extensively outside of the Malay peninsula. Male patients (243/390, 62.3%) predominated. Their ages ranged from 11 months to 30 years, with only 40 (9.3%) subjects aged 18 years or older. Eosinophilia was absent in 10 to 33% of subjects in a few observational studies. Thrombocytopenia was present in 42 (9.7%) subjects. Parasitic infestation was less common in the new millennium. Spontaneous recovery within six months was the trend, and serious complications were extremely rare. Conclusions. APDE is no longer restricted to Southeast Asia. A uniform set of diagnostic criteria is needed. Clinician awareness followed by reliable but easily available laboratory tests is essential to confirm diagnosis. It is proposed that rapid diagnosis can be accomplished by screening the blood smear for grey platelets by a trained examiner followed by confirmatory platelet aggregometry. National or international collaboration and prospective studies are required to delineate the core and variable clinical and laboratory features of APDE. Full article

Congenital factor V (FV) deficiency is a rare autosomal recessive bleeding disorder caused by pathogenic variants in F5 gene and characterized by heterogeneous clinical manifestations. The aim of this study was to define the mutational spectrum of F5 in Russian patients with congenital FV deficiency. We analyzed 16 unrelated patients with different disease severity and 9 relatives from five families. All functionally relevant regions of F5 were examined by Sanger sequencing. Multiplex ligation-dependent probe amplification (MLPA) was used to detect large deletions and duplications. Whole-genome sequencing and functional cDNA analysis were performed in selected cases. This study represents the first description of the F5 mutational spectrum in a Russian cohort. We identified 12 novel variants and demonstrated the functional effect of two previously unreported variants located outside canonical splice-site dinucleotides, leading to aberrant splicing. Notably, the proportion of variants undetectable by routine diagnostic approaches was higher than that reported in other populations. No clear genotype–phenotype correlation was observed. Despite the limited sample size, our findings expand current knowledge of the molecular basis of congenital FV deficiency and may improve genetic diagnostics in Russia. Full article

Background: Pregnancy in women with liver cirrhosis is considered a rare clinical condition due to the decreased fertility commonly associated with chronic liver disease. Hormonal disturbances, anovulation and impaired hepatic function contribute to the lower conception rates observed in this population. However, when pregnancy occurs, it is associated with a significantly increased risk of maternal and fetal complications. Maternal risks include hepatic decompensation, variceal bleeding, ascites, coagulopathy and a higher rate of hypertensive disorders during pregnancy and related complications. Fetal complications involve prematurity, intrauterine growth restriction, and increased perinatal mortality. Methods: We present the clinical case of a woman with idiopathic liver cirrhosis who experienced four consecutive pregnancies with different clinical courses and outcomes. Results: The case highlights the complexity of managing pregnancy in patients with chronic liver disease and underscores the importance of individualized clinical assessment and multidisciplinary management. This report also reviews current management strategies and discusses key considerations for optimizing care in pregnant women with liver cirrhosis. Conclusions: Advances in multidisciplinary care and improved management strategies have contributed to better pregnancy outcomes in recent years. Careful monitoring during pregnancy, appropriate management of portal hypertension, and coordinated care between obstetricians, hepatologists, and neonatologists are essential to minimizing potential complications, ensuring favorable maternal and fetal outcomes. Full article

Hemophilia is no longer regarded solely as a male disorder; female carriers are increasingly attracting the attention of the scientific community due to the common, albeit overlooked, bleeding tendency associated with their condition. Moreover, women can, in rare cases, experience disease severity comparable to that of hemophilic males. The overall bleeding phenotype in females is complicated by gynecological and obstetric bleedings, which do not always correlate directly to their factor levels. As a patient population, they remain significantly underdiagnosed and inadequately treated due to a range of contributing factors. In genetic terms, a carrier exhibits no clinical or laboratory pathology. In that context, the term “hemophilia carrier” has historically led to the presumption of normal hemostasis, thereby impeding the provision of appropriate healthcare services to females in need. Females are not represented in clinical trials and even hemophilia centers lack sufficient experience and appropriate infrastructure to effectively manage and monitor females with hemophilia. Emerging data regarding the needs of this population should be enriched by larger studies, and previously established management practices should be reevaluated, potentially incorporating newer therapeutic options. Full article

Background/Objectives: Solitary rectal ulcer syndrome (SRUS) is a rare benign disorder presenting with rectal bleeding, straining, and mucosal discharge. Its pathogenesis likely involves pelvic floor dysfunction, particularly dyssynergic defecation. Although studied in adults, pediatric data—specifically anorectal manometry (ARM) findings—remain limited. We aimed to evaluate dyssynergic defecation in pediatric SRUS using ARM and analyze associated clinical, endoscopic, histopathological, and treatment data. Methods: A retrospective study of 24 children with biopsy-proven SRUS diagnosed between 2016 and 2024 was conducted. Clinical symptoms, colonoscopic, histopathological, treatment, and outcome data were reviewed. ARM was performed in 20 patients unresponsive to conservative treatment to assess anal pressures, rectal sensation, rectoanal inhibitory reflex, and balloon expulsion. Results: The median age was 13 years, with male predominance. Rectal bleeding was the most common symptom (95.8%). Colonoscopy revealed predominantly solitary ulcerative lesions 5–10 cm from the anal verge. Dyssynergic defecation was detected in 60% of patients, and only 25% could expel the balloon. Resting anal pressures were lower than reference values. Treatments included diet, laxatives, and topical agents, with partial or complete clinical response in approximately 60% of patients after 12 months. Conclusions: Pediatric SRUS is strongly associated with dyssynergic defecation. More pediatric-specific manometric studies are needed to optimize diagnosis and guide targeted therapies. Full article

Inherited platelet disorders (IPDs) comprise a heterogeneous group of rare conditions that present particular challenges during pregnancy, with bleeding risk increasing during labor and the immediate postpartum period. These disorders require coordinated, multidisciplinary management to mitigate maternal and neonatal bleeding risk. Although data remains limited, individuals with IPD, including Bernard–Soulier syndrome, Glanzmann thrombasthenia, MYH9-related disorders, Hermansky–Pudlak syndrome, and platelet storage pool disorders, are at an increased risk for obstetrical bleeding, with the degree of risk varying by underlying diagnosis. In severe inherited platelet disorders such as Glanzmann thrombasthenia, peripartum hemorrhage is common, with up to half of the deliveries in some series requiring red cell or platelet transfusion. Because these conditions are congenital, the fetus may also be affected, placing neonates at risk for serious bleeding complications, including intracranial hemorrhage, although available data is limited. Despite the considerable morbidity and mortality risk associated with inherited platelet disorders, management strategies during pregnancy and delivery remain poorly defined. This stands in contrast to other bleeding disorders, such as factor deficiencies, for which multiple therapeutic approaches have been evaluated in the peripartum setting. In this review, we summarize the available evidence and current management strategies for individuals with inherited platelet disorders during pregnancy and delivery. Full article

Background/Objectives: Haemophilia-related bleedings primarily affect the musculoskeletal system, and functional tests are used in clinical management. Yet, fine motor skills of the upper extremities have not been evaluated in adult persons with haemophilia (PwH). The Moberg Pick-Up Test (MPUT) assesses fine motor skills but has only been psychometrically evaluated in other cohorts. This study aims to examine its psychometric properties in PwH. Methods: A total of 40 moderate or severe PwH A or B were included. The MPUT, consisting of three trials, was conducted twice by rater A and once by rater B. The best performance per hand of each MPUT was used. Subjective hand function (Duruöz Hand Index (DHI) and numeric rating scale (NRS)), elbow joint status (Haemophilia Joint Health Score (HJHS)), pain (NRS), and wrist range of motion (ROM) were utilised for convergent validity evaluation. Inter-rater and test–retest reliability were determined through intraclass correlation coefficients (ICCs) for raw and log10-transformed data. Results: Inter-rater and test–retest reliability demonstrated moderate-to-excellent ICCs for both data types (ICC range: 0.624–0.918). The DHI correlated moderately with the average MPUT score of both hands (r = 0.410; p = 0.016). Left-hand MPUT scores did not correlate with left elbow HJHS scores, whereas right-hand MPUT scores correlated with right elbow HJHS scores (r = 0.396, p = 0.018). Subjective left-hand function (NRS) correlated with the results of the MPUT (r = 0.433; p = 0.009). Conclusions: The MPUT is a reliable and partially valid tool and can be useful to assess fine motor skills in PwH. Full article

Background/Objectives: MYH9 gene variants cause MYH9-related disease (MYH9-RD), which is also known as Epstein syndrome, Fechtner syndrome, May–Hegglin anomaly, and Sebastian syndrome. MYH9-RD is characterized by sensorineural hearing loss, macrothrombocytopenia, thrombocytopenia, hematuria/proteinuria, glomerulonephritis, cataracts purpura, and mucosal bleeding. In addition, the MYH9 gene is also known to be causative of autosomal dominant non-syndromic hearing loss (DFNA17). MYH9-RD is a relatively rare disorder, and the detailed clinical features and mutational spectra remain unclear. Methods: In this study, we performed next-generation sequencing analysis for 15,684 hearing loss patients and identified MYH9-associated hearing loss patients. Detailed clinical information was collected for these patients and summarized. Results: In this study, we identified 24 patients from 18 families with MYH9-associated hearing loss. We clarified the details of hearing deterioration observed in patients based on collected serial audiogram data. Some cases showed rapid hearing deterioration that worsened by about 50 dB within 5 years. Hearing loss is more likely to progress in patients with myosin head domain variants than in patients with myosin tail domain variants, but hearing loss in each set of patients finally deteriorates to bilateral profound hearing loss. Conclusions: In this study, we were able to clarify the detailed characteristics of MYH9-RD- and DFNA17-related hearing loss in a relatively large number of patients, particularly in some cases that showed rapid and asymmetrical hearing deterioration progressing to bilateral profound hearing loss. Our data will be useful for providing more appropriate treatment and follow-up for MYH9-associated hearing loss. Full article

Background/Objectives: Autoimmune factor VIII deficiency (AiFVIIID) is a rare disorder that causes severe bleeding. Emicizumab has recently been found to be effective in treating AiFVIIID; however, monitoring with standard coagulation tests presents challenges. Methods: Clot waveform analysis (CWA), which involves CWA-activated partial thromboplastin time (APTT), the CWA-small amount of tissue factor activation assay (sTF/FIXa), and clotting time using a small amount of thrombin (sTT), was used to both diagnose AiFVIIID and monitor emicizumab. Results: CWA-sTT reflects the residual FVIII activity in patients with AiFVIIID. Several tests were employed, including APTT, FVIII activity, CWA, mixing tests with normal plasma, FVIII inhibitor assays, and anti-FVIII antibody activity for the diagnosis of AiFVIID in three cases. However, the sensitivity of APTT reagents to AiFVIID differed between thrombocheck-APTT and APTT-SP. Emicizumab treatment was effective for major bleeding, and anti-FVIII antibody activity could be measured using CWA-sTT. Conclusions: The sensitivity of APTT reagents to AiFVIID varies. CWA-sTT may provide utility in the diagnosis of AiFVIIID. Emicizumab is useful for the treatment of AiFVIID, and anti-FVIII antibody activity can be measured even in patients treated with emicizumab. Full article

Background: Acquired haemophilia A (AHA) is a rare autoimmune disorder characterized by the development of autoantibodies against Factor VIII activity, leading to a significant reduction in its functionality. Clinically, AHA presents with an unexpected prolongation of activated partial thromboplastin time (aPTT) and spontaneous bleeding episodes in patients without any personal or family history of haemorrhages. Bleeding manifestations can be severe at presentation, making early diagnosis and prompt treatment essential to reduce morbidity and mortality. Methods: We report on a single-centre cohort of 35 patients with AHA (examined from 1984 to 2024), analysing their demographics, underlying conditions, bleeding characteristics, treatment and outcome. Results: The median age of patients at diagnosis was 69 years (ranging from 18 to 92), 15 were males and 20 females. AHA was idiopathic in 37% of cases, severe bleeding was observed in 54% of patients treated with bypassing agents. Recombinant activated Factor VII (rFVIIa) was administered in 79% of cases and activated prothrombin complex concentrate (aPCC) in 10%, with no significant differences in haemostatic response and no thromboembolic complications. Occurrence of major bleeding showed no significant association with sex, age group, underlying condition, baseline Factor VIII activity or inhibitor titre at diagnosis. A total of 69% of patients were treated with corticosteroids alone, and 23% received a combination of corticosteroids and cyclophosphamide. Two patients died, six were lost to follow-up after partial remission, and one relapsed without bleeds after complete remission. Statistical analyses highlighted that the FVIII inhibitor titre > 20 BU was the only significant prognostic factor affecting time to complete remission. Conclusions: These observations emphasize the critical role of clinical suspicion and timely referral to experienced centres with adequate laboratory support for the effective management of AHA. Full article

Background and Clinical Significance: Splenic artery pseudoaneurysm (SAP) is a rare but life-threatening complication of chronic pancreatitis. Although endovascular embolization achieves high technical success, recurrence and delayed rupture may occur, particularly in patients with ongoing pancreatic inflammation or alcohol use disorder (AUD). Case Presentation: A 47-year-old woman with alcohol-associated chronic pancreatitis presented with hematochezia, melena, and syncope. CT angiography revealed a 3.6 cm SAP adjacent to a 4.2 cm pancreatic head pseudocyst, and she underwent successful coil embolization. Despite initial stability, she relapsed into heavy alcohol use, experienced recurrent pancreatitis flares, and developed progressive multisystem comorbidities. Surveillance imaging up to three months post-embolization showed pseudocyst fluctuations without early recanalization, but long-term follow-up lapsed. Eight months after embolization, she presented in hemorrhagic shock from recurrent SAP rupture and died despite massive transfusion and emergent splenic artery ligation. Conclusions: Fatal SAP rupture may occur months after technically successful embolization. Sentinel bleeding, AUD relapse, and progressive systemic decline are critical warning signs. Structured post-embolization imaging and multidisciplinary management are essential to improve long-term outcomes. Full article

Hemophilia A (HA) is an X-linked recessive bleeding disorder that predominantly affects males but rarely manifests clinically in females. We report an unusual case of a woman with HA carrying a de novo heterozygous F8 variant, skewed X chromosome inactivation (XCI), and mosaic monosomy X without the Turner syndrome phenotype. DNA was extracted from whole blood. After excluding F8 inversions and large rearrangements, Sanger sequencing of coding regions was performed. XCI was assessed by STR analysis of the AR gene. Haplotypes were identified by fragment analysis of three polymorphic sites. Karyotyping was performed using G-banding. A heterozygous missense variant in the F8 gene, c.6545G>A (p.Arg2182His), was detected with allelic imbalance. STR analysis confirmed ~93% skewed XCI. Karyotyping revealed mosaicism: 45,X [7]/46,XX [14]. Neither parent carried the c.6545G>A variant or karyotype aberrations. We suggest that 46,XX cells carried c.6545G/A with preferential inactivation of the normal X chromosome, whereas 45,X0 cells carried the mutant allele only. The limited proportion of active normal X chromosomes led to a mild rather than severe phenotype. This case highlights complex genetic mechanisms underlying HA in females and underscores the importance of comprehensive molecular and cytogenetic testing for accurate diagnosis, clinical management, and genetic counseling. Full article

Immune checkpoint inhibitors (ICIs), particularly PD-1/PD-L1 antibodies, have significantly improved outcomes in a variety of solid tumors, including urothelial carcinoma. However, their use is frequently associated with immune-related adverse events (irAEs) which frequently affect the skin and mucous membranes. Among these, plasma-cell-rich infiltrates are exceptionally rare. Circumorificial plasmacytosis (COP) is a rare, predominantly reactive condition typically involving mucosal transition zones, with histologic features characterized by dense, polyclonal plasma cell infiltrates and a benign clinical course. Only two case reports have described COP in association with ICI therapy and, to date, transformation or overlap with lymphoproliferative disorders such as marginal zone lymphoma has not been documented. We report the case of an 86-year-old male with urothelial carcinoma who developed a progressive, ulcerated, bleeding lesion of the lower lip during adjuvant nivolumab therapy. Histologic examination revealed a dense subepithelial infiltrate of mature plasma cells and lymphocytes. Direct and indirect immunofluorescence studies were negative, excluding autoimmune blistering disorders. Immunohistochemistry showed a predominance of CD138-positive plasma cells with a moderate kappa light-chain shift, CD19 expression, and absence of CD56, Cyclin-D1, and CD117, arguing against a plasma cell neoplasm. Molecular analysis via multiplex PCR revealed a clonal B-cell population with distinct IgH rearrangements, and some EBV-positive cells were also identified by EBER in situ hybridization. The histopathologic and molecular findings suggested a marginal zone lymphoma-like, plasmacytic proliferation arising in the setting of COP. This case illustrates a rare and diagnostically challenging constellation at the intersection of reactive and clonal B-cell proliferations in the context of ICI therapy. Although the lesion demonstrated features of clonality, the overall low B-cell content, indolent clinical course, and lack of systemic involvement support a reactive, immunodeficiency-associated lymphoproliferation rather than overt lymphoma. This case expands the known spectrum of mucocutaneous irAEs and highlights the need for careful clinicopathologic correlation, including immunophenotyping and molecular diagnostics. Awareness of such rare presentations is essential to avoid overdiagnosis and unnecessary systemic treatment in patients with otherwise indolent lesions. Full article