Ectopia cordis coexisting with hypoplastic left heart structures.

Herein we present the fatal case of premature baby with coincidence of extreme form of ectopia cordis and hypoplastic left heart structures.

Rare intravascular large B-cell lymphoma (IVLBCL) can cause atypical intracerebral haemorrhage and mislead diagnostics.

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of non-Hodgkin's lymphoma. Common neurological symptoms are cognitive impairment and dementia. Only a few cases have been published reporting intracranial haemorrhage due to IVLBCL. We present a case of a female patient in her late 60s who presented with an atypical intracerebral haemorrhage as the first major complication of an IVLBCL. The patient's condition declined rapidly. She died several weeks later due to haemorrhagic shock. The definitive diagnosis was achieved postmortem. Due to aggressive disease progression, the diagnosis of IVLBCL is still challenging and can therefore lead to incorrect or delayed treatment, especially in cases of unusual manifestations like lobar intracranial haemorrhage.

Metastatic gastric adenocarcinoma discovered in the bone marrow.

Gastric cancer primarily metastasizes to the peritoneum, liver and lungs, with bone marrow involvement being a rare occurrence, found in less than 1% of cases. Disseminated carcinomatosis of the bone marrow (DCBM) is characterised by widespread infiltration of cancer cells into the bone marrow, leading to haematological disorders such as disseminated intravascular coagulation and thrombocytopenia. We present a unique case of a man in his late 50s with acute thrombocytopenia as the initial symptom, subsequently diagnosed with gastric cancer on bone marrow examination. Despite receiving chemotherapy, the patient's condition deteriorated rapidly, emphasising the challenging management and poor prognosis associated with DCBM. This case underscores the need for improved diagnostic strategies and therapeutic approaches to enhance patient outcomes in DCBM associated with gastric cancer.

Progressive multifocal leukoencephalopathy in systemic lupus erythematosus treated with pembrolizumab.

This case report discusses a patient with systemic lupus erythematosus (SLE) treated with low-dose azathioprine who developed progressive multifocal leukoencephalopathy (PML). PML is a rare, severe, demyelinating disease linked to John Cunningham polyomavirus (JCV) reactivation.Treated with pembrolizumab, an immune checkpoint inhibitor, the patient initially improved. However, after the fourth dose, her condition rapidly worsened resulting in treatment discontinuation and death. Similar cases highlight the complex interplay of factors in PML development in SLE patients, including immunosuppression and genetic factors. The use of pembrolizumab in PML and SLE necessitates careful consideration of potential complications.

Renal Cell Carcinoma with a Catastrophic Thrombus: A Case Report.

INTRODUCTION: Renal cell carcinoma (RCC) is a common malignancy known for its potential to invade the venous system, particularly the inferior vena cava (IVC), leading to tumor thrombus (TT) formation. While the presence of TT in RCC isn't unique, extension of TT above the diaphragm is rare. This case highlights the challenges encountered in diagnosing and managing RCC with extensive TT involvement. CASE REPORT: A 69-year-old man presents with 3-month history of dyspnea and increasing fatigue in the setting of 30 pounds weight loss. Laboratory studies showed anemia and acute kidney injury. CT abdomen and pelvis revealed 6.8cm solid mass within the left perinephric space, enlarged IVC with large thrombus. Kidney biopsy returned positive for clear cell renal carcinoma with metastasis to the liver. Several days into the hospitalization the patient began to experience increased abdominal pain. Repeat ultrasound showed tumor thrombus with extension within the intrahepatic IVC and hepatic veins and reversal of portal venous flow. During the imaging study, the patient suffered a cardiac arrest and expired. Postmortem examination revealed diffuse showering of tumor emboli within the pulmonary arteries, likely contributing to the patient's rapidly progressive respiratory failure, and subsequent cardiovascular collapse. CONCLUSION: This case illustrates the complexity of treating patients with extensive TT. In patients with RCC associated TT, the risk for thromboembolism is increased substantially, however the full benefit of anticoagulation remains controversial. Understanding the intricacies of TT involvement and its potential complications is crucial in guiding treatment decisions in patients with significant tumor thrombus burden.

A case of mortality in a re-introduced European bison associated with severe pneumonia caused by Dictyocaulus viviparus.

BACKGROUND: Dictyocaulosis is a parasitic disease caused by pulmonary nematodes from genus Dictyocaulus affecting various ungulate hosts. It can cause verminous bronchopneumonia and for heavily infected individuals, fatal outcomes can occur. CASE PRESENTATION: The study describes the case of a male European bison which died three months after relocation from Slovakia to one of the reintroduction areas in Nucșoara village, Fagaraș Mountains, Romania. Necropsy revealed the presence of pulmonary nematodes in the respiratory tract. Morphology and molecular diagnosis was performed and Dictyocaulus viviparus was identified. CONCLUSION: Rigorous health monitoring is essential to assure the success of reintroduction programs, understanding and preventing infectious diseases and limiting their impact on population health.

[Concentration of gilteritinib in the cerebrospinal fluid of a patient with relapsed FLT3-ITD positive acute myeloid leukemia with optic nerve involvement].

A 72-year-old woman with relapsed FLT3-ITD-positive acute myeloid leukemia was treated with gilteritinib and achieved complete remission with incomplete hematological recovery. However, two months later, she developed optic nerve infiltration and lost vision in her right eye while maintaining hematological remission on gilteritinib. Intrathecal injection of cytotoxic drugs reduced the number of blasts in the cerebrospinal fluid (CSF), but her vision did not recover. At the onset of optic nerve infiltration, at a dose of 80 mg/day gilteritinib, the plasma trough and CSF levels of gilteritinib were 151.9 ng/ml and 1.9 ng/ml, respectively, with a central nervous system (CNS) penetration rate of 1.3%. Hematologic progressive disease (PD) was detected after 40 days, and the patient died one month later. Target sequencing at the time of hematologic PD revealed the FLT3 F691L mutation, which is known to confer resistance to gilteritinib. In this patient, pharmacokinetic (low CNS penetration of gilteritinib) and pharmacodynamic (acquisition of a drug resistance mutation) mechanisms were thought to be responsible for the CNS relapse and hematologic PD, respectively. We believe this is a valuable case to report considering the scarcity of data on CNS penetration of FLT3 inhibitors and their effects on CNS disease in the literature.

Small cell colorectal cancer: a rare tumour with an aggressive course.

A relatively healthy male patient in his 60s presented with chest pain and shortness of breath in addition to a history of significant weight loss over the preceding months. He was admitted to the hospital and investigated with a CT pulmonary angiogram, which did not demonstrate a pulmonary embolus, but he subsequently went on to have an ultrasound and CT scan because of abnormal findings. His CT demonstrated some thickening of the mid-transverse colon, and, in addition, large volume liver metastases described as innumerable and probably replacing most of the liver.Initially, his liver function tests were only mildly deranged at the presentation. Flexible sigmoidoscopy was performed, and a transverse colonic malignancy was identified and biopsied, which demonstrated an extrapulmonary small cell carcinoma (EPSCC). He was admitted for urgent chemotherapy for newly diagnosed metastatic small-cell colonic cancer; he developed tumour lysis syndrome following his first dose of chemotherapy. He continued to decline following this and died soon after his admission. Metastatic small-cell colonic cancer is a rare diagnosis which is challenging to manage due to the lack of trial evidence to drive treatment strategies. The management largely follows the pulmonary small cell cancer pathway. We, therefore, present a colonic EPSCC case outlining the diagnostic and treatment strategies for this disease.

Case Report: A Case Report on an 18-Year-Old Female with Cerebral Vasculitis in Systemic Lupus Erythematosus (SLE).

Cerebral vasculitis is a rare but severe complication of Systemic Lupus Erythematosus (SLE), presenting significant challenges in management due to its potential for devastating neurological consequences and poor prognosis. We present a case of an 18-year-old female with known SLE who presented with seizures, declining cognitive function, and unresponsiveness. Neurological examination, laboratory investigations, and radiological imaging supported the diagnosis of cerebral vasculitis secondary to SLE. Despite aggressive immunosuppressive therapy, the patient's neurological status continued to deteriorate, leading to respiratory failure and multiorgan dysfunction. Ultimately, the patient succumbed to multiorgan failure attributed to severe CNS vasculitis and its complications. This case underscores the importance of early recognition and aggressive management of cerebral vasculitis in SLE while highlighting the need for further research into more effective therapeutic strategies to improve patient outcomes.

Mycobacterium abscessus Cutaneous Infection in the Immunosuppressed: A Case Report on an Atypical Pathogen.

Mycobacterium abscessus complex (MAbc) is a rapidly growing nontuberculous mycobacterium that represents an increasingly prevalent cause of skin infections. This report describes an atypical presentation of MAbc to heighten physician awareness of the pathogen. A 69-year-old woman with immunocompromised status presented with a 4-month history of a solitary, nonhealing ulcer on her right lower extremity after an insect bite. After no improvement following oral amoxicillin/clavulanate and topical mupirocin for the initial diagnosis of cellulitis, biopsy and culture of the lesion revealed MAbc. Microscopic examination revealed reactive cutaneous inflammation without evidence of malignancy. Acid-fast bacteria (AFB) stain was negative, and no granulomas were noted histologically. Clarithromycin and doxycycline were initiated while awaiting susceptibility testing results. Final culture showed MAbc sensitive to amikacin, cefoxitin, and clarithromycin. Unfortunately, before antibiotic therapy could be modified, the patient died. The presentation of a solitary lower-extremity ulcer is rare compared with current literature. This case occurred after a suspected insect bite rather than instrumentation. In addition, this case demonstrated negative AFB stain and absence of granulomas on histologic analysis. The patient's death did not allow for evaluation of treatment efficacy. Existing literature characterizing MAbc is sparse. Most cases present as multiple papules, nodules, and abscesses with positive AFB staining and granulomas; it is possible for deviations to exist depending on host immune status. Considering the highly drug-resistant nature of M abscessus, prompt diagnosis and treatment are crucial. For this to occur, clinicians must maintain high clinical suspicion for M abscessus infection in any chronic, nonhealing wound failing to respond to initial treatment.

Haemophagocytic lymphohistiocytosis secondary to disseminated histoplasmosis in a patient with leprosy.

Multidrug therapy has significantly reduced the global burden of Hansen's disease; however, complications from long-term treatment persist. A male resident of southern Kentucky, in his 30s and of Micronesian descent, presented with worsening abdominal pain associated with anorexia, fatigue, functional decline and occasional haemoptysis. He was compliant with multidrug therapy for leprosy. Laboratory investigations revealed pancytopenia. He was initially treated under a sepsis protocol and later switched to high-dose steroids due to a suspected immune reaction from missed corticosteroid doses. Despite aggressive treatment for refractory pancytopenia, the patient's condition deteriorated, and he passed away from cardiac arrest. Posthumous bone marrow biopsy revealed haemophagocytic lymphohistiocytosis secondary to disseminated histoplasmosis with bone marrow infiltration. This case highlights the importance of proactive fungal screening in immunocompromised leprosy patients, particularly in endemic regions, as early detection and timely intervention can prevent severe complications.

Acute mesenteric ischaemia: a rare complication mimicking necrotising enterocolitis in a premature infant.

Acute mesenteric ischaemia (AMI) is a life-threatening gastrointestinal complication uncommonly described in premature infants. The diagnosis of AMI is challenging and may be delayed due to the limitation of accurate diagnostic imaging and non-specific clinical signs. Furthermore, AMI can be misdiagnosed as necrotising enterocolitis (NEC) due to the overlapping clinical and radiological features. Though known to be associated with high mortality rates, early recognition and intervention can improve the survival rates in infants with AMI. We describe a case of a premature infant who presented with an acute abdomen and haemodynamic collapse, initially treated for NEC but later diagnosed with AMI intraoperatively. Due to the extensive bowel necrosis, surgical intervention was rendered futile and the infant finally succumbed to the disease.

Alveolar capillary dysplasia complicated by subglottic stenosis.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is an interstitial lung disease. In ACDMPV, respiratory impairment with severe pulmonary hypertension occurs from the early hours of life. Anomalies in the cardiovascular, gastrointestinal and genitourinary systems have been reported. However, little is known about upper airway abnormalities. We encountered a genetically diagnosed ACDMPV infant who presented with subglottic and bronchial stenosis. The prenatal diagnosis was hypoplastic left heart syndrome. Her respiratory condition worsened at 16 hours of life. We found subglottic stenosis when intubating. She died on day 7. Autopsy imaging with CT scan showed bilateral main bronchial stenosis. Chromosomal microarray revealed a 531 kb deletion in chromosome 16q24.1, including FOXF1.

Ibrutinib as treatment for Bing-Neel syndrome reclassified as glioblastoma: a case report.

BACKGROUND: Glioblastoma is a highly malignant disease with limited treatment options. Ibrutinib, a covalent Bruton tyrosine kinase inhibitor, is an oral agent with manageable side effects used for hematological diseases including Waldenström macroglobulinemia. We present the case of a 69-year-old Caucasian male patient treated with ibrutinib for suspected Bing-Neel syndrome (BNS), which following a biopsy, was reclassified as glioblastoma. CASE PRESENTATION: In December 2018, a 69-year-old Caucasian male patient was diagnosed with Waldenström macroglobulinemia. As the patient was asymptomatic, without bone marrow failure or high M-component count, watchful waiting was initiated. Due to increasing neurological symptoms, the patient, based on magnetic resonance imaging, was diagnosed with Bing-Neel syndrome in May 2019. The patient received different treatments before starting ibrutinib monotherapy in August 2019 due to disease progression, both on magnetic resonance imaging and clinically. The patient remained clinically stable for 7 months. In March 2020, the patient developed headaches, and both magnetic resonance imaging and a biopsy revealed glioblastoma IDH-wildtype. Treatment was changed in line with the new diagnosis, but the patient died at the end of 2020. CONCLUSION: We present a case in which a patient with glioblastoma IDH-wildtype remained clinically stable for 7 months when treated with ibrutinib monotherapy, which is similar to what would be expected for the standard treatment for glioblastoma. To our knowledge, this is the first patient receiving ibrutinib for a glioblastoma IDH-wildtype with a meaningful clinical outcome. Our case may therefore support previous nonclinical findings, indicating a therapeutic value of ibrutinib in patients with glioblastoma and support for further investigation of ibrutinib as a possible treatment for glioblastoma.

Fatal infection caused by a genetically distinct elephant endotheliotropic herpesvirus type 5 in a captive Asian elephant in Germany.

BACKGROUND: Elephant endotheliotropic herpesvirus (EEHV) infection is the most common cause for lethal hemorrhagic disease in captive juvenile Asian elephants (Elephas maximus). Although EEHV1 is known as the most likely cause of fatal haemorrhagic disease in Asian elephants, EEHV5 was lately involved in lethal cases of haemorrhagic disease in captive elephants. CASE PRESENTATION: Here we report the first death of a four-year old Asian elephant diagnosed with EEHV5 in Germany. Molecular diagnosis yielded detection of EEHV5 DNA in all tested tissues. Histopathological examination revealed typical features of hemorrhagic disease in all examined organs. EEHV5 was sequenced from total DNA isolated from heart tissue by Illumina and Nanopore sequencing. Sequencing data showed 3,881 variants, distributed across the entire genome, compared to the published EEHV5 sequence. CONCLUSIONS: We have detected EEHV5 in a fatal disease case of a male Asian elephant. Whole genome sequencing revealed substantial differences of our DNA isolate compared to available EEHV5 sequences. This report of fatal haemorrhagic disease associated with EEHV5 infection should raise awareness for EEHV5 as an important elephant pathogen. Genome sequencing and downstream SNPs analysis will further encourage future research to understand genetic diversity, pathogenesis and virulence of EEHVs with respect to developing new diagnostic methods, prophylactic strategies, and implementation of surveillance and control measures.

Novel ABCC8 mutation in the genetic diagnosis of familial hyperinsulinaemic hypoglycaemia.

Familial hyperinsulinaemic hypoglycaemia-1 arises from mutations within the genes of pancreatic beta cells, resulting in unregulated insulin secretion from pancreatic beta cells. A 4.06 kg female neonate, born to a second-degree consanguineously married couple, presented with repeated asymptomatic hypoglycaemia. There was a significant history of a previous sibling's death from nesidioblastosis. Despite treatment with intravenous glucose, diazoxide, hydrochlorothiazide and octreotide, she continued to experience hypoglycaemic episodes. Despite efforts to manage sepsis, including antibiotics, antifungals and intravenous immunoglobulin/granulocyte-macrophage colony-stimulated factor, her condition worsened. She succumbed on day 34. This case underscores the complexities of managing congenital hyperinsulinaemic hypoglycaemia, especially in the context of concurrent infections and the need for multidisciplinary care. Early genetic diagnosis proved invaluable in facilitating timely and effective treatment. Furthermore, the genetic results enabled us to counsel the parents regarding the recurrence risk in subsequent pregnancies and the necessity for antenatal diagnosis.

Role of therapeutic plasmapheresis in acute liver failure in paediatric patients: A case series.

Paediatric acute liver failure (PALF) is a rare yet severe condition that is associated with high mortality. Apart from liver transplant, no specific therapy exists, particularly in developing countries. Evidence suggests that removal of damage-associated molecular patterns, cytokines, toxins, and other metabolites that accumulate due to impaired liver function can enhance natural recovery. Plasmapheresis can be used to remove these products; however, there is limited evidence to support this approach. This case series discusses three critically ill patients with acute liver failure who underwent plasmapheresis. The patients included a seven-year-old boy (Case 1), a 17-year-old boy (Case 2), and a 16-monthold boy (Case 3). Two patients showed significant improvement in bilirubin level, coagulation profile, inotropes requirement, and Glasgow coma scale score. Unfortunately, one patient with PALF, complicated with multi-organ dysfunction, died due to refractory shock on the fourth day of hospitalisation. Our findings illustrate that early use of therapeutic plasmapheresis in PALF can lead to improvement in clinical outcome. It may serve as a bridging therapy for liver transplant and for the spontaneous regeneration of the patient's liver.

Catastrophic antiphospholipid syndrome: a case report and literature review.

Catatrophic antiphospholipid syndrome (CAPS), a rare variant of antiphospholipid syndrome (APS), is associated with rapid multiorgan failure. While APS is associated with single medium-to-large blood vessel occlusions, CAPS is most often associated with several, concurrent vascular occlusions of small vessels, commonly of the kidneys, heart, skin and brain. We present a case of a 21-year-old female patient with a history of immune thrombocytopenia purpura and APS, who eventually developed concurrent cerebral venous sinus thrombosis, diffuse alveolar haemorrhage, renal thrombotic microangiopathy, and a necrotic, vasculitic wound on her forearm. Despite hospitalisation and treatment, her condition worsened and the patient eventually died after succumbing to suspected CAPS.

An autopsy case of an adult woman with Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation, and Neuroendocrine Tumors (ROHHAD(NET)) syndrome developing nonalcoholic steatohepatitis and hepatocellular carcinoma: A case report.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is an important etiology of hepatocellular carcinoma (HCC), and there is no established therapy for this syndrome. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neural crest tumor (ROHHAD(NET)) is an extremely rare syndrome considered to be life-threatening, with death occurring around 10 years of age. We present the oldest known autopsy case of this syndrome that developed HCC. This case provided important information on not only improving the course of this syndrome, but also understanding the natural history and therapeutic modalities of NASH and HCC. METHODS: The patient was diagnosed with ROHHAD(NET) syndrome in childhood, and liver cirrhosis due to NASH was diagnosed at age 17. HCC was detected at age 20, and embolization and irradiation were performed. At age 21, she died from accidental acute pancreatitis and subsequent liver failure and pulmonary hemorrhage. RESULTS: Rapid onset of obesity, hypoventilation, and hypothalamic disturbance appeared in childhood and was diagnosed as this syndrome. At age 17, liver cirrhosis due to NASH was diagnosed by liver biopsy, and at age 20, HCC was diagnosed by imaging. Transarterial chemoembolization and irradiation were performed, and the HCC was well controlled for a year. CONCLUSION: At age 21, she died from accidental acute pancreatitis, subsequent liver failure and pulmonary hemorrhage. Autopsy revealed that the HCC was mostly necrotized. This case was valuable not only for other ROHHAD(NET) syndrome cases, but also in improving our understanding of the natural history of NASH and HCC.