Chronic and Neurotropic: A Paradigm-Challenging Case of Dengue Virus Encephalitis in a Patient With Advanced HIV Infection.

A 32-year-old female with advanced human immunodeficiency virus infection presented to an Australian hospital with subacute, worsening symptoms of encephalitis. Metagenomic sequencing and Dengue NS3 antigen staining of brain tissue confirmed active dengue virus (DENV) encephalitis. The most recent possible DENV exposure was months prior in West Africa, indicating chronicity.

Complete response to capmatinib in a patient with metastatic lung adenocarcinoma harboring CD47-MET fusion: a case report.

Comprehensive genomic profiling is highly recommended for treatment decision in nonsquamous, non-small cell lung cancer (NSCLC). However, rare genomic alterations are still being unveiled, with scarce data to guide therapy. Herein, we describe the treatment journey of a 56-year-old, never-smoker Caucasian woman with a metastatic NSCLC harboring a CD47-MET fusion, initially classified as a variant of unknown significance. She had undergone 3 lines of therapy over the course of 3 years, including chemotherapy, immunotherapy, and anti-angiogenic therapy. After reanalysis of her next-generation sequencing data in our service, the fusion was reclassified as likely oncogenic. The patient was started with fourth-line capmatinib, with a good tolerance so far and a complete metabolic response in the active sites of disease, currently ongoing for 18 months. In conclusion, we highlight the sensitivity of a novel MET fusion to capmatinib and emphasize the need for comprehensive panels in NSCLC and molecular tumor board discussions with specialized centers when rare findings arise.

An Unusual Case of Anti-Glomerular Basement Membrane Disease and Phospholipase A2 Receptor-Associated Membranous Nephropathy After Exposure to Hydrocarbons.

We present a rare case of a patient with toluene exposure manifesting as anti-glomerular basement membrane (GBM) disease on a background of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy. A 23-year-old man presented to the emergency department with hypertension, headache, hemoptysis, anemia, acute kidney injury, glomerular hematuria, and proteinuria. He endorsed repeated exposure to toluene-containing products while repairing dirt bikes. Serologies were positive for anti-GBM antibodies. Kidney biopsy showed crescentic glomerulonephritis with linear immunoglobulin G and granular PLA2R staining by immunofluorescence. He was initially treated with high-dose steroids, plasmapheresis, and hemodialysis for pulmonary-renal syndrome followed by oral cyclophosphamide and prednisone, which were discontinued after 3 months when follow-up biopsies confirmed little chance for renal recovery. He remained on dialysis 1 year later. This case exhibits a unique presentation of anti-GBM syndrome and underlying membranous nephropathy following repeated hydrocarbon exposure. Inhaled toxins promote recurrent localized inflammation, unmasking previously hidden epitopes. Early diagnosis and appropriate use of immunosuppressive and extracorporeal therapies are necessary to prevent morbidity and to improve survival in this rare condition.

Thamnostylum piriforme, a novel etiological agent of superficial mycosis.

Fungi are opportunistic eukaryotic entities often taking advantage of susceptibilities offered by a host due to its immunocompromised status, changed microbiome, or ruptured physical barriers and eventually cause infections. They either invade the skin superficially or are deep-seated. Superficial mycosis affects the skin, hair, and nails inhabiting the outermost layer, stratum corneum. In the present study, we report a case of superficial mycosis (onychomycosis in particular) in a 45-year-old immunocompetent man who was an ex-defense personnel and presently serving as a security guard at the University of Jammu, District Jammu, Jammu and Kashmir, India. The infection evolved 17 years ago and negatively affected the quality of life of the patient. For the identification of the causal agent, direct microscopy, cultural, micro-morphological, molecular characterization (ITS sequencing), and phylogenetic analysis were taken into account. A mucoralean fungal species, Thamnostylum piriforme, was isolated from the fingernails (left hand) of the investigated patient, which represents a new global report as the causal agent of superficial mycosis. In vitro antifungal susceptibility testing showed T. piriforme sensitivity to itraconazole, amphotericin B and ketoconazole while resistance to fluconazole. Careful selection of optimal therapy for fungal infection based primarily on correct identification and antifungal susceptibility testing could provide effective results during treatment against these opportunistic human fungal pathogens.

Delayed and significant hypercalcaemia due to teriparatide therapy: a case report and review.

INTRODUCTION: Transient hypercalcaemia due to teriparatide occurs in up to 11% of patients though delayed hypercalcaemia (> 24 h post injection) is rare. We report the case of a female who developed significant delayed hypercalcaemia after teriparatide treatment for osteoporosis and review other cases in the literature to date. CASE REPORT: A 72-year-old female on teriparatide for the treatment of osteoporosis was found to have hypercalcaemia (3.30 mmol/l) on routine testing approximately 3 months after starting therapy. Serum calcium pretreatment was normal at 2.39 mmol/l. She was admitted to the hospital for investigations which identified a serum 25-hydroxyvitamin D of 94 nmol/l, a low parathyroid hormone of 6.0 pg/ml, and normal test results for 1,25 dihydroxyvitamin D (115 pmol/l), parathyroid hormone-related peptide (< 1.4 pmol/ml), serum electrophoresis and angiotensin-converting enzyme (39 IU/l). CT abdomen, pelvis, and thorax revealed no evidence of malignancy and an isotope bone scan ruled out skeletal metastases. Serum calcium normalised (2.34 mmol/l) several days after stopping teriparatide and calcium supplements and administering intravenous fluid. On restarting teriparatide, delayed hypercalcaemia reoccurred and treatment was switched to denosumab. DISCUSSION: Delayed moderate to severe hypercalcaemia (serum calcium > 3.0 mmol/l) due to teriparatide is rare but may lead to therapy withdrawal. The underlying predisposing risk factors remain unclear and highlight the importance of a routine serum calcium assessment on therapy.

Paediatric pustulotic arthro-osteitis patient with an IL36RN variant, heterozygous c.115+6T>C, who was successfully treated with tonsillectomy: A case report and literature review.

Pustulotic arthro-osteitis (PAO) is an infrequent condition, with its manifestation in children being even rare. Some reports propose an association between genetic variants and the onset of PAO. Currently, no definitive treatment protocol exists for paediatric patients with PAO. In this study, we present the paediatric case of PAO with an IL36RN variant who was successfully treated with tonsillectomy.

Single-cell analysis of the cellular landscape of vulvar melanoma provides new insight for immunotherapy administration.

BACKGROUND: Vulvar and vaginal melanoma (VuM & VaM) is a rare gynecologic malignancy with high mortality but low effectiveness to checkpoint immunotherapy compared to cutaneous melanoma. This article aims to elucidate the role of the disordered immune microenvironment in cancer progression in VuM. METHODS: At first, this article applied single-cell RNA sequencing (scRNA-seq) to the VuM obtained from a 68-year-old female patient, and constructed a single-cell atlas of VuM consist of 12,243 single cells. Then this article explores the genomic complexity and core signal channel in VuM microenvironment. RESULTS: This article provides new insights about the pathogenesis of VuM based on single-cell resolution data. It was found that the activation of CD8+ T cell contributed to induce tumor angiogenesis and immune escape, and the activation of the antigen-presenting molecular function participated in melanoma metastasis. CONCLUSION: This article provided new insights into underlining VuM molecular regulation and potential signaling involved in immunotherapy, which would benefit the clinical practice and administration.

Plasmapheresis and IVIG for Treatment of Non-Tumor Anti-Tr/DNER Antibody-Associated Ataxia: A Case Report.

Autoimmune cerebellar ataxia (ACA) is a condition characterized by progressive ataxia resulting from an immune-mediated attack on cerebellar structures. The presence of anti-Tr/DNER antibodies, strongly associated with Hodgkin lymphoma, has been identified in ACA. However, cases with no underlying malignancy are rare. We report the case of a 49-year-old woman presenting with progressive ataxia, slurred speech, and dizziness over three months. The patient exhibited significant cerebellar symptoms, including dysarthria and limb ataxia, without signs of other systemic illnesses. Comprehensive investigations, including imaging, lumbar puncture, and autoantibody testing, were performed. The cerebrospinal fluid (CSF) sample revealed positivity for Tr/DNER antibodies, leading to a diagnosis of autoimmune cerebellar ataxia. The patient underwent nine sessions of plasmapheresis, followed by six doses of intravenous immunoglobulin (IVIG), resulting in significant clinical improvement. Despite extensive cancer screening, no underlying malignancy was detected, suggesting a non-tumor origin of anti-Tr/DNER antibodies. The patient's gait improved, ataxia resolved, and cerebellar tests normalized following treatment. The patient was further managed with rituximab treatment every six months. This case represents a presentation of anti-Tr/DNER-associated autoimmune cerebellar ataxia without malignancy. The successful treatment with plasmapheresis and IVIG suggests that these interventions may be effective in managing autoimmune cerebellar ataxia associated with anti-Tr/DNER antibodies. Further research is needed to understand the underlying mechanisms of this condition and to determine the optimal treatment strategies.

Short-Term Efficacy of Cerebello-spinal tDCS and Body Weight-Supported Treadmill Training in the Hypertrophic Olivary Degeneration: a Rare Case Report.

The present case study reported a patient diagnosed with hypertrophic olivary degeneration, a rare condition characterized by a trans-neuronal degeneration and signal enhancement in T2-weighted images on magnetic resonance imaging, usually caused by cerebral hemorrhage, cerebral infarction, and trauma. Furthermore, the relevant literature review was performed. The existing pharmacological treatment has limited clinical benefits on the patient. Since spontaneous remission hardly occurs in the disease, there are no other effective treatments. In this case, the patient was a 55-year-old Chinese male who presented progressive gait difficulty for several months due to both-sided ataxia. Neurological examination revealed upper extremity and lower limb bilateral spasticity, ataxia, slurred speech, and dysmetria. Therefore, our study treated the patient through the inventive application of cerebello-spinal transcranial direct current stimulation and body weight-supported treadmill training. After a 4-week treatment, the patient could walk independently, without aid, speeding up by 7%, as well as the ataxia symptoms, and balance has improved significantly. It was demonstrated in this case report that the combination of cerebello-spinal tDCS and body weight-supported treadmill training can be an effective treatment for patients with Hypertrophic olivary degeneration.

Presentation of ichthyosis after substrate reduction therapy in Gaucher type 1.

We describe a case in which a type 1 Gaucher patient developed ichthyosis weeks after starting substrate reduction therapy (SRT) with eliglustat. There are no reports of ichthyosis in the literature in enzyme replacement or SRT for Gaucher disease. Ichthyosis is seen with type 2 and 3 Gaucher disease, but not type 1. This raises the question: Why would a patient develop ichthyosis after starting SRT?

Clinical course and therapeutic trial for a case of congenital secretory diarrhea due to novel GUCY2C variant.

Chronic diarrhea presents a significant challenge for managing nutritional and electrolyte deficiencies, especially in children, given the higher stakes of impacting growth and developmental consequence. Congenital secretory diarrhea (CSD) compounds this further, particularly in the case of the activating variants of the guanylate-cyclase 2C (GUCY2C) gene. GUCY2C encodes for the guanylate-cyclase 2C (GC-C) receptor that activates the downstream cystic fibrosis transmembrane receptor (CFTR) that primarily drives the severity of diarrhea with an unclear extent of influence on other intestinal channels. Thus far, management for CSD primarily consists of mitigating nutritional, electrolyte, and volume deficiencies with no known pathophysiology-driven treatments. For activating variants of GUCY2C, experimental compounds have shown efficacy in vitro for direct inhibition of GC-C but are not currently available for clinical use. However, Crofelemer, a CFTR inhibitory modulator with negligible systemic absorption, can theoretically help to treat this type of CSD. Herein, we describe and characterize the clinical course of a premature male infant with a de novo missense variant of GUCY2C not previously reported and highly consistent with CSD. With multi-disciplinary family-directed decision-making, a treatment for CSD was evaluated for the first time to our knowledge with Crofelemer.

Epilepsia Partialis Continua as a manifestation of aquaporin-4 autoimmunity.

A 52-year-old man experienced two seizures in January and June 2021. In October, the neurological examination did not reveal sensory/motor deficits. Brain magnetic resonance imaging (MRI) showed hyperintense lesions with contrast enhancement (CE) involving white matter bilaterally, brainstem, and cerebellum. Spine MRI showed hyperintense C2-C3 and C4-C6 lesions with CE. Anti-aquaporin-4 (AQP4) antibodies were detected, confirming the diagnosis of neuromyelitis optica spectrum disorder (NMOSD). The patient experienced a status epilepticus compatible with Epilepsia Partialis Continua treated with antiseizure medications. He was also treated with methylprednisolone, plasma exchange, and rituximab. Status epilepticus can be a rare manifestation of NMOSD, heightening the broad spectrum of AQP4 autoimmunity.

Growing up with Marshall syndrome: A case report from infancy to age 12.5 years.

Marshall syndrome is an extremely rare genetic disorder usually diagnosed in infancy with a prevalence of <1 in 1 million. Based on the literature reviewed, this is the first case report to provide a longitudinal history of a child with Marshall syndrome (from birth to age 12.5 years). This longitudinal case report arose in part from desires of this child's parents to share the story of their early fears at her initial diagnosis and compare those to how well she has turned out.

Vaginal involvement as a rare extranodal manifestation in advanced-stage follicular lymphoma: a case report and literature review.

Apart from bone marrow involvement, extranodal involvement of follicular lymphoma (FL) is rare. Gynecologic FL is seldom reported, among which the vagina is the rarest involved site. No vaginal involvement in advanced-staged FL was reported before. Here, we report a case of FL with systemic involvement including the vagina.

Novel use of Siltuximab in a patient with VEXAS Syndrome.

VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is an increasingly recognized disorder that occurs due to somatic mutations of a ubiquitin-activating enzyme encoded by ubiquitin-like modifier activating enzyme 1 gene, UBA1. Clinical findings associated with VEXAS syndrome include recurrent fevers, polychondritis, periorbital edema, pleural effusions, myocarditis and/or pericarditis, hepatosplenomegaly, myelodysplastic syndrome, cytopenias, inflammatory arthritis, neutrophilic dermatosis, and deep venous thrombosis. Novel renal manifestations like interstitial nephritis are infrequent, and to our knowledge, acute renal failure due to C3 glomerulonephritis (C3GN) has not yet been reported. Overwhelming systemic inflammation can result in morbid end-organ damage and death. While there is no formal guideline or established protocol for its management, treatment of VEXAS syndrome with tocilizumab, an interleukin-6 (IL-6)-directed therapy, has been described in the literature. Here, we report a case of a 71-year-old male patient presenting with C3GN as an initial manifestation of VEXAS syndrome and explore the rationale for our approach to treatment with IL-6 blockade. Our patient was initially treated with two inpatient doses of tocilizumab with successful transition to siltuximab in the outpatient setting. He continues to benefit from ongoing siltuximab treatment for more than one year to date without any safety issues or relapse of VEXAS syndrome.

Adapted Milwaukee protocol for rabies treatment in a Brazilian indigenous child: case report.

BACKGROUND: This case report describes the treatment of a 12-year-old indigenous Brazilian girl from the Maxakali group with rabies using the adapted Milwaukee Protocol. CASE PRESENTATION: The patient suffered a superficial bat bite on her right elbow, reported on April 5, 2022. Despite receiving immunoglobulin, a vaccine, and antiviral medications such as amantadine and sapropterin, the patient succumbed to the disease 25 days after hospital admission. The report highlights the inherent challenges in treating rabies due to the virus's neurotropic nature and the difficulties in delivering antiviral drugs to the central nervous system. The case underscores the need for early antiviral intervention and calls for more studies to validate and improve treatment protocols for rabies in vulnerable populations, particularly those with genetic and immunological susceptibilities like the Maxakali indigenous group. CONCLUSION: The findings suggest that while the Milwaukee Protocol offers some hope, significant obstacles remain in achieving successful outcomes in rabies cases.

A diagnostic dilemma: cytomegalovirus colitis as an uncommon comorbidity in inflammatory bowel disease: a case report.

BACKGROUND: The role of cytomegalovirus infection as an opportunistic pathogen in exacerbating ulcerative colitis and its response to treatment remain a topic of ongoing debate. Clinicians encounter numerous challenges, including the criteria for differentiating between an acute ulcerative colitis flare and true cytomegalovirus colitis, the diagnostic tests for identifying cytomegalovirus colitis, and determining the appropriate timing for initiating antiviral therapy. CASE PRESENTATION: A 28-year-old Syrian female with a seven-year history of pancolitis presented with worsening bloody diarrhea, abdominal pain, and tenesmus despite ongoing treatment with azathioprine, mesalazine, and prednisolone. She experienced a new flare of acute severe ulcerative colitis despite recently completing two induction doses of infliximab (5 mg/kg) initiated four weeks prior for moderate-to-severe ulcerative colitis. She had no prior surgical history. Her symptoms included watery, bloody diarrhea occurring nine to ten times per day, abdominal pain, and tenesmus. Initial laboratory tests indicated anemia, leukocytosis, elevated C-reactive protein (CRP) and fecal calprotectin levels, and positive CMV IgG. Stool cultures, Clostridium difficile toxin, testing for Escherichia coli and Cryptosporidium, and microscopy for ova and parasites were all negative. Sigmoidoscopy revealed numerous prominent erythematous area with spontaneous bleeding. Biopsies demonstrated CMV inclusions confirmed by immunohistochemistry, although prior biopsies were negative. We tapered prednisolone and azathioprine and initiated ganciclovir at 5 mg/kg for ten days, followed by valganciclovir at 450 mg twice daily for three weeks. After one month, she showed marked improvement, with CRP and fecal calprotectin levels returning to normal. She scored one point on the partial Mayo score. The third induction dose of infliximab was administered on schedule, and azathioprine was resumed. CONCLUSION: Concurrent cytomegalovirus infection in patients with inflammatory bowel disease presents a significant clinical challenge due to its associated morbidity and mortality. Diagnosing and managing this condition is particularly difficult, especially regarding the initiation or continuation of immunosuppressive therapies.

FADD gene pathogenic variants causing recurrent febrile infection-related epilepsy syndrome: Case report and literature review.

FIRES and NORSE are clinical presentations of disease processes that, to date, remain unexplained without an established etiology in many cases. Neuroinflammation is thought to have paramount importance in the genesis of these conditions. We hereby report the clinical, EEG, brain MRI, and genetic findings of a nuclear family with recurrent febrile-related encephalopathy with refractory de novo Status Epilepticus. Whole-exome sequencing (WES) revealed a homozygous p.C105W pathogenic variant of FADD gene (FAS-associated protein with death domain, FADD), known to cause ultrarare forms of autosomal recessive immunodeficiency that could be associated with variable degrees of lymphoproliferation, cerebral atrophy, and cardiac abnormalities. The FADD-related conditions disrupt FAS-mediated apoptosis and can cause a clinical picture with the characteristics of FIRES. This observation is important because, on one hand, it increases the number of reported patients with FADD deficiency, showing that this disorder may present variable expressivity, and on the other hand, it demonstrates a genetic cause of FIRES involving a cell-mediated inflammation regulatory pathway. This finding supports early treatment with immunomodulatory therapy and could represent a new avenue of research in the field of new onset refractory status epilepticus and related conditions.

Successful treatment of severe primary mitral regurgitation due to rheumatic aetiology using a novel-designed transcatheter edge-to-edge repair system.

The transcatheter edge-to-edge mitral valve repair (TEER) has been recommended as a reliable treatment option for selected patients with severe degenerative and functional mitral regurgitation (MR). Although MR patients with rheumatic etiology were excluded from two significant trials (EVEREST II and COAPT) that established a role for the TEER in degenerative and functional MR. However, it has been reported that the TEER procedure could be safely and effectively performed in carefully selected rheumatic MR patients. Therefore, we share a case report of successfully treating severe rheumatic MR using a novel-designed TEER system (JensClipTM).

Interventional closure of an iatrogenic LAA-perforation by means of a PFO-occluder.

Atrial fibrillation (AF) is the most common rhythm disorder with a high risk for cardioembolic strokes. Interventional occlusion of the left atrial appendage (LAA) is an alternative to the widely established stroke prevention with oral anticoagulation. Complications through LAA closure (LAAC) are rare and usually occur periinterventional. We present a case of an 87-year-old patient who presents for elective LAAC. After placement of the LAA occluder (Amplatzer Amulet device 25 mm) in the LAA and partial resheathing, the patient developed a pericardial effusion (PE), became hemodynamically unstable and went into cardiac arrest with the need for cardiopulmonary resuscitation (CPR). After drainage of the PE, we closed the causative LAA-perforation using a persistent foramen ovale (PFO)-occluder device (Amplatzer Talisman, 25 mm). Thereby we were able to successfully seal the perforation and stabilize the patient. The patient was monitored at our intensive care unit for 2 days and left the hospital in good condition a few days after. Procedural complications during interventional LAAC are rare but can be serious. The most common complication, PE, requires percutaneous drainage and often cardiac surgery. We present a case in which a perforation and following PE with hemodynamic relevance and need for CPR was resolved with an interventional strategy through implantation of a PFO-occluder into the perforation. With this approach we were able to show that in the right setting even serious complications can be treated by interventional measures, thereby not only saving the patient's life, but also avoiding cardiac surgery.