Variable Clinical Presentation Research Articles

Pseudolymphomatous Cutaneous Angiosarcoma Presenting With Persistent Firm Facial Edema in a Patient With Systemic Sclerosis.

Pseudolymphomatous cutaneous angiosarcoma (cAS) is a rare subtype characterized by a prominent lymphocytic infiltrate, posing diagnostic challenges due to its resemblance to lymphoid neoplastic processes. We present a novel case highlighting the clinical and histopathological features, notably its association with persistent firm facial edema in a patient with systemic sclerosis (SSc). A 47-year-old woman with a 21-year history of SSc presented with firm palpebral edema evolving to involve the entire face and cervical region over six months. Diagnostic imaging revealed inflammatory changes in orbital regions, supradiaphragmatic lymphadenopathies, and lytic lesions. Skin biopsy demonstrated a diffuse neoplasm with vascular channels and solid areas, accompanied by dense lymphocytic proliferation. Pseudolymphomatous cutaneous angiosarcoma, a rare malignant neoplasm, exhibits variable clinical presentations and rapid progression. Histologically, it manifests as irregularly shaped vascular channels lined by prominent endothelial cells. Immunohistochemistry, particularly markers such as v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG), aids in diagnosis. Notably, this case marks the first presentation of cAS with persistent facial edema in SSc, highlighting the association between SSc and cancer risk. This case underscores the diagnostic challenges posed by cAS and emphasizes the importance of early detection for optimal patient outcomes. Further understanding of its association with autoimmune disorders such as SSc is crucial for comprehensive management strategies.

Mucocutaneous Leishmaniasis Rhinology Complications: A Rare Presentation.

This case report presents a unique manifestation of Mucocutaneous Leishmaniasis (MCL) in a 56-year-old woman with chronic nasal symptoms. Initially diagnosed with chronic sinusitis and septal perforation, the patient's history of a childhood sandfly bite and subsequent episodes of Leishmaniasis, revealed after nasal surgery, provided crucial information for accurate diagnosis. A retrospective review was conducted on this patient's electronic medical record. The patient's life-long struggle with nasal obstruction, congestion, and a septal perforation initially masked the underlying MCL. Sinus surgery and persistent symptoms further complicated the diagnostic process. Only after postoperative complications, including grainy skin texture extending into the nasal passages, did the patient recall the sandfly bite, prompting reevaluation and diagnosis of MCL. The case highlights the challenges of diagnosing MCL due to its varied presentation and potential mimicry of other chronic nasal conditions. It emphasizes the importance of thorough patient history-taking, especially when symptoms are atypical or persistent. Additionally, the report underscores the potential for unexpected postoperative complications in MCL patients and the need for vigilance in recognizing and assessing them. This case contributes to the understanding of MCL's diverse clinical presentation and the importance of early diagnosis and multidisciplinary management for prompt intervention and improved outcomes.

Potential biomarkers used for risk estimation of pediatric sepsis-associated organ dysfunction and immune dysregulation.

Pediatric sepsis is a serious issue globally and is a significant cause of illness and death among infants and children. Refractory septic shock and multiple organ dysfunction syndrome are the primary causes of mortality in children with sepsis. However, there is incomplete understanding of mechanistic insight of sepsis associated organ dysfunction. Biomarkers present during the body's response to infection-related inflammation can be used for screening, diagnosis, risk stratification/prognostication, and/or guidance in treatment decision-making. Research on biomarkers in children with sepsis can provide information about the risk of poor outcomes and sepsis-related organ dysfunction. This review focuses on clinically used biomarkers associated with immune dysregulation and organ dysfunction in pediatric sepsis, which could be useful for developing precision medicine strategies in pediatric sepsis management in the future. IMPACT: Sepsis is a complex syndrome with diverse clinical presentations, where organ dysfunction is a key factor in morbidity and mortality. Early detection of organ complications is vital in sepsis management, and potential biomarkers offer promise for precision medicine in pediatric cases. Well-designed studies are needed to identify phase-specific biomarkers and improve outcomes through more precise management.

Deficiency of Adenosine Deaminase 2 (DADA2) with bilateral renal subcapsular hematoma: A case report and literature review

Introduction and Importance: Deficiency of adenosine deaminase 2 (DADA2) is a rare autosomal recessive genetic disorder caused by loss-of-function mutations in the adenosine deaminase 2 gene. This condition primarily manifests in pediatric cases before the age of 10 years, with sporadic cases reported in adults. Adenosine deaminase 2 (ADA2) is a critical enzyme involved in macrophage differentiation and immune homeostasis. The clinical manifestations of DADA2 vary widely and can affect multiple organ systems. Our case uniquely highlights an infrequent DADA2 manifestation. Case Presentation: An 18-year-old female presented with right flank pain, fever, and a history of joint pain, Raynaud’s phenomenon, livedo-like rash, and chronic abdominal pain. Physical examination revealed subcapsular hematoma in the right kidney. Further evaluation showed positive serologic tests for rheumatoid factor and anti-nuclear antibody (ANA). Genetic testing confirmed DADA2 homozygosity. The patient was discharged on the appropriate medications. Clinical Discussion: DADA2 is associated with vascular dysfunction and systemic vasculopathy. The clinical manifestations of DADA2 encompass a spectrum of organ involvement, including the skin, nervous system, gastrointestinal system, renal system, and the cardiovascular system. Early recognition and diagnosis are crucial for appropriate management. Conclusion: This case report highlights the diverse clinical presentations of ADA2 deficiency, specifically focusing on bilateral renal subcapsular hematoma. This finding emphasizes the importance of considering DADA2 as a differential diagnosis in patients presenting with unexplained renal manifestations. Increased awareness of the varied clinical presentations of DADA2 will contribute to earlier diagnosis, appropriate management, and improved outcomes in patients affected by this rare genetic disorder.

Intralobar pulmonary sequestration: a rare cause of hemoptysis: a case report

Overview and significance: Pulmonary sequestration (PS) is a rare congenital anomaly characterized by aberrant formation of nonfunctional lung tissue with anomalous systemic blood supply. Despite its rarity, PS presents significant diagnostic and management challenges, often necessitating a multidisciplinary approach for optimal patient outcomes. This case report provides insights into the clinical presentation, diagnostic modalities, and management strategies for PS. Case summary: The authors present a case of a 30-year-old male who complained of chronic cough and hemoptysis and was eventually diagnosed with intralobar PS by computed tomography (CT) imaging. The patient underwent a surgical procedure, specifically a lobectomy, to address the lung tissue. Clinical discussion: The diagnosis of intralobar PS is confirmed by CT imaging, showing features of abnormalities, including irregular cystic communication. A large area with abnormal systemic arterial supply and variable venous fluid. This patient presented with symptoms consistent with PS, including chronic cough and hemoptysis, highlighting the importance of timely diagnosis and intervention to prevent life-threatening complications. Conclusion: Lung sequestration has diagnostic challenges due to its variable clinical presentation and potential for misdiagnosis. However, advances in technology, such as CT angiography, make accurate diagnosis and precise surgical planning easier. Prompt intervention via lobectomy or transarterial embolization is important to reduce the risk of life-threatening complications associated with PS. These data highlight the importance of multidisciplinary collaboration between physicians, radiologists, and surgeons to effectively manage PS and improve patient outcomes.

Siblings with vitamin D-dependent rickets type 1A: Importance of genetic testing and a review of genotype-phenotype correlations.

Vitamin D-dependent rickets type 1A (VDDR1A) is a rare condition caused by biallelic pathogenic variants in CYP27B1, which encodes 25-hydroxyvitamin D3-1-α-hydroxylase. Inadequate activity of this enzyme results in deficient 1α-hydroxylation of inactive 25-hydroxyvitamin D to biologically active 1,25-dihydroxyvitamin D, with consequent adverse effects on calcium and phosphate metabolism. A female child was clinically diagnosed at 18 months old with hypophosphatemic rickets based on phenotype and biochemical testing, with neither parent affected. A subsequent affected male sibling led to the reconsideration of the diagnosis. Exome sequencing showed a homozygous CYP27B1 c.1040T>A (p.Ile347Asn) variant for both children. No variants were found in genes associated with hypophosphatemic rickets. A review of published cases of VDDR1A with homozygous CYP27B1 variants indicates variable clinical presentation, lack of genotype-phenotype correlation, and low serum phosphate at diagnosis in most cases. These findings emphasize the clinical importance of molecular testing as part of the diagnostic evaluation for cases of non-nutritional rickets.

Amyand’s hernia: a case of right inguinoscrotal hernia with appendiceal content

Introduction: Amyand’s hernia, a rare condition where the appendix becomes lodged in the inguinal canal, poses diagnostic challenges due to its varied clinical presentations and lack of distinctive radiological features. This case underscores the importance of early detection and comprehensive diagnostic evaluation. Case Presentation: A 30-year-old male presented with a 2-year history of right inguinoscrotal swelling, culminating in agonizing symptoms and irreducible masses over the inguinoscrotal area. Despite the absence of significant medical history, diagnostic imaging confirmed a complete right inguinoscrotal hernia and bilateral hydrocele with internal echoes. Clinical Discussion: The case illustrates the difficulties in preoperative diagnosis of Amyand’s hernia, emphasizing the reliance on imaging modalities and clinical assessment. Successful surgical intervention involving appendectomy and hernioplasty highlights the necessity for prompt diagnosis and management. Conclusion: This case exemplifies the challenges and complexities associated with Amyand’s hernia, emphasizing the importance of early recognition and comprehensive surgical planning. Moving forward, increased clinical vigilance and awareness are essential to ensure optimal patient outcomes in cases of inguinoscrotal pathology.

Clinical aspects of oral cancer and potentially malignant disorders in South and Southeast Asia.

Oral cancer and Oral Potentially Malignant Disorders (OPMD) are major health problems in South and Southeast Asia. To describe and discuss the clinical aspects of Oral Cancer and OPMD in South and Southeast Asia. Literature review of concepts and data over the last four decades. Asian countries account for about two-thirds of new cases of oral cancer (OC) globally, with the highest burden in the South and Southeast Asian countries, including Pakistan and India. Habits, dietary patterns, socioeconomic status, and access to routine dental care play a crucial role in defining the demographics and clinical presentation of OC in these regions and significantly influence the morbidity and mortality of the disease. This region sees the use of different types of tobacco with or without areca nut (AN), such as pan masala, gutka, gul, snuff, mawa, and mishri. Tobacco use is high among men in Sri Lanka, Myanmar, Maldives, Bangladesh, Nepal, India and Bhutan. Areca nut is the fourth most common addictive substance globally and is frequently used in South and Southeast Asian countries, including Southeast China, Hainan Island, India, Taiwan, and the Pacific Islands, and immigrants from these regions in Africa, Europe, and North America. The use of these products results in mucosal alterations with varied clinical presentation of Oral Potentially Malignant Disorders (OPMDs) and OC. We discuss here the different types of OPMD and OC, the diagnostic aids and their relevance in clinical practice, and factors that influence their prognosis.

A novel locus in CSMD1 gene is associated with increased susceptibility to severe malaria in Malian children

BackgroundPlasmodium falciparum malaria is still a leading cause of child mortality in sub-Saharan Africa. The clinical manifestations of malaria range from asymptomatic infection to severe disease. The variation in clinical presentation is partly attributed to host genetic factors with estimated narrow-sense heritability of 23%. Here, we investigate the associations between candidate gene polymorphisms and the likelihood of severe malaria (SM) in a cohort of Malian children.MethodsBased on our previous genome-wide association studies (GWAS) analysis, candidate genes were selected for in-depth analysis using several criteria including gene-level GWAS scores, functional overlap with malaria pathogenesis, and evidence of association with protection or susceptibility to other infectious or inflammatory diseases. Single Nucleotide Polymorphisms (SNPs) residing within these genes were selected mainly based on p-values from previous severe malaria susceptibility GWAS studies and minor allele frequency (MAF) in West African populations.ResultsOf 182 candidate genes reported in our previous study, 11 genes and 22 SNPs residing in these genes were selected. The selected SNPs were genotyped using KASP technology in 477 DNA samples (87 SM and 390 controls). Logistic regression analysis revealed that a common intron variant, rs13340578 in CUB and Sushi Multi Domain (CSMD1) gene, is associated with increased odds of SM in recessive mode of inheritance (MAF = 0.42, OR = 1.8, 95% CI = [1.78, 1.84], p = 0.029). The SNP is in linkage disequilibrium (LD) with multiple variants with regulatory features.ConclusionTaken together, the current study showed that an intron variant rs13340578, residing in CSMD1 gene, is associated with increased susceptibility to malaria. This finding suggests that modified regulation of complement may contribute to malaria disease severity. Further studies are needed to identify the causal variants and the underlying molecular mechanisms.

Assessing and Optimizing Large Language Models on Spondyloarthritis Multi-Choice Question Answering: Protocol for Enhancement and Assessment.

Spondyloarthritis (SpA), a chronic inflammatory disorder, predominantly impacts the sacroiliac joints and spine, significantly escalating the risk of disability. SpA's complexity, as evidenced by its diverse clinical presentations and symptoms that often mimic other diseases, presents substantial challenges in its accurate diagnosis and differentiation. This complexity becomes even more pronounced in nonspecialist health care environments due to limited resources, resulting in delayed referrals, increased misdiagnosis rates, and exacerbated disability outcomes for patients with SpA. The emergence of large language models (LLMs) in medical diagnostics introduces a revolutionary potential to overcome these diagnostic hurdles. Despite recent advancements in artificial intelligence and LLMs demonstrating effectiveness in diagnosing and treating various diseases, their application in SpA remains underdeveloped. Currently, there is a notable absence of SpA-specific LLMs and an established benchmark for assessing the performance of such models in this particular field. Our objective is to develop a foundational medical model, creating a comprehensive evaluation benchmark tailored to the essential medical knowledge of SpA and its unique diagnostic and treatment protocols. The model, post-pretraining, will be subject to further enhancement through supervised fine-tuning. It is projected to significantly aid physicians in SpA diagnosis and treatment, especially in settings with limited access to specialized care. Furthermore, this initiative is poised to promote early and accurate SpA detection at the primary care level, thereby diminishing the risks associated with delayed or incorrect diagnoses. A rigorous benchmark, comprising 222 meticulously formulated multiple-choice questions on SpA, will be established and developed. These questions will be extensively revised to ensure their suitability for accurately evaluating LLMs' performance in real-world diagnostic and therapeutic scenarios. Our methodology involves selecting and refining top foundational models using public data sets. The best-performing model in our benchmark will undergo further training. Subsequently, more than 80,000 real-world inpatient and outpatient cases from hospitals will enhance LLM training, incorporating techniques such as supervised fine-tuning and low-rank adaptation. We will rigorously assess the models' generated responses for accuracy and evaluate their reasoning processes using the metrics of fluency, relevance, completeness, and medical proficiency. Development of the model is progressing, with significant enhancements anticipated by early 2024. The benchmark, along with the results of evaluations, is expected to be released in the second quarter of 2024. Our trained model aims to capitalize on the capabilities of LLMs in analyzing complex clinical data, thereby enabling precise detection, diagnosis, and treatment of SpA. This innovation is anticipated to play a vital role in diminishing the disabilities arising from delayed or incorrect SpA diagnoses. By promoting this model across diverse health care settings, we anticipate a significant improvement in SpA management, culminating in enhanced patient outcomes and a reduced overall burden of the disease. DERR1-10.2196/57001.

Canal cholesteatoma: an alarming sequela of congenital aural atresia

Congenital aural atresia is an external ear malformation that may have diverse clinical presentations ranging from conductive hearing loss to the formation of canal cholesteatoma. Canal cholesteatoma, once developed can aggressively erode the bony boundaries of the middle ear cleft and lead to dangerous complications. Here we present the clinical outlook and surgical management of a child with congenital aural atresia with extensive canal cholesteatoma and complications. A twelve-year-old girl with congenital aural atresia and microtia of the right ear presented with right sided infra-auricular abscess with overlying skin ulceration. She also had right sided grade 4 facial paralysis. Pure tone audiometry revealed severe conductive hearing loss on the right side. In contrast, a high-resolution computed tomography scan showed extensive soft tissue on the right side completely destroying the posterior bony canal wall, with erosion of the sigmoid plate and the mastoid tip. We performed a right sided modified radical mastoidectomy and canal atresia repair along with the removal of the necrotic and infected tissues. The little girl recovered uneventfully with improved facial nerve function and without any sign of cholesteatoma recidivism. In congenital aural atresia, early surgical intervention is the key to prevent the formation of canal cholesteatoma and subsequent complications.

Aggregatibacter actinomycetemcomitans infection in children: two case reports and a review of the literature.

Aggregatibacter actinomycetemcomitans (Aa), a Gram-negative coccobacillus commonly associated with endocarditis, poses a rare diagnostic challenge in pediatric cases. The presentation of two pediatric cases-myositis and chest mass-highlights novel aspects, including unusual symptom presentations in children which can be mistaken for malignancy. The limited sensitivity of standard blood tests complicates diagnosis, leading to delayed diagnosis and treatment. Representative samples must be taken, especially if blood cultures are negative. Despite advances in detection methods, diagnosing Aa infection remains difficult due to its rarity in children and variable clinical presentation. In conclusion, a comprehensive understanding of Aa infection in children is essential for early and effective diagnostic and therapeutic management.

#2991 Two cases of chronic lymphocytic leukemia associated immunotactoid glomerulopathy: variable clinical presentation, close hematological collaboration

Abstract Background and Aims Immunotactoid glomerulopathy (ITG) is a very rare disease, observable in less than 0.1% of native kidney biopsy samples. It is most often associated with hematological diseases. We confirmed ITG in two cases among our 850 kidney biopsy patients in the past 9 years. In both patients, chronic lymphocytic leukemia (CLL) was the underlying cause. Method Case 1, a 56-year-old man was admitted due to severely increased proteinuria (2 g/day) with preserved renal function, while case 2, a 57-year-old-man was referred with rapidly decreasing eGFR (20 ml/min/1.73m2) with nephrotic syndrome (serum albumin level was 24 g/l). In case 1, no previous history of hematological disease was known, in case 2, CLL - that did not require treatment - was diagnosed half a year before admission. He still had no kidney involvement even 3 months after the CLL diagnosis. We performed kidney biopsy. Light microscopy revealed mesangial proliferative-atypical membranous pattern in case 1, and membranoproliferative pattern in case 2. Immunofluorescence microscopy showed IgG1-lambda deposition, electron microscopy confirmed the organised deposits, microtubular structures with a diameter of 44 nanometers in both cases. Neither monoclonal gammopathy nor systemic immune disease was confirmed. In case 2, low titer ANA positivity, low C3 and high anti-C1q antibody titer was detected, lupus nephritis was ruled out. Previously, lymphocyte count was slightly increased in case 1, CLL was confirmed after kidney biopsy. The immunoglobulin heavy chain variable region gene somatic hypermutation status was borderline in case 1, while in the other case it was unmutated. Fluorescein in situ hybridisation revealed trisomy 12 in both cases. In case 1, chemotherapy was not used due to Rai stage 0, and with appropriate antihypertensive treatment, we could preserve kidney function, and proteinuria was persistently low (below 1 g/day). In case 2, due to Rai stage 1, and progressive renal and lymph node involvement, immunochemotherapy was started (obinutuzumab-venetoclax). Three months later eGFR stabilized at 27 ml/min/1.73 m2, proteinuria decreased below 1 g/day, the C3 level normalized. Conclusion ITG can develop in the early stages of CLL, but it can also indicate CLL progression. The light microscopy histological pattern and, in parallel, the clinical appearance can be of varying severity. Immunochemotherapy resulting reduction of CLL tumor burden and cessation of complement damage, both play a role of improving renal status. Our cases also draw attention to the need for close collaboration with hematologists.

#1271 Risk of primary infections in patients with IgA nephropathy: a Swedish population-based cohort study

Abstract Background and Aims IgA nephropathy (IgAN) is the most common global kidney disease with a highly variable clinical presentation. Diagnosis IgAN requires a biopsy, and the immunohistologic examination is dominated by depositions of aberrant IgA1 antibodies. Since IgA antibodies are mainly produced by the mucosal associated lymphoid tissue the relationship between the mucosal immune system and IgAN has long been considered. The current theories on the origin of the disease involve genetic and environmental factors, with mucosal infections potentially playing a role. In some IgAN patients gastrointestinal and/or upper respiratory infections can aggravate the disease with episodic macrohematuria and/or increased proteinuria. Coincidently, these infections are also more common among patients with selective IgA deficiency. The aim of this study was to investigate whether the presence of IgAN confers an increased risk of infections in general to the IgAN patient. Method IgAN was defined by a computerized biopsy record from 1997 to 2011 in Sweden. Each IgAN patient was matched with up to five reference individuals based on age, sex, calendar year, and county of residence. Exclusions included those with organ transplants, HIV, immunodeficiency, or end-stage kidney disease before study entry, and follow-up data were censored for subsequent occurrences. Linear and Cox regressions, adjusted for age, sex, and education, were performed to analyze total infections and antimicrobial treatments in both patient and reference groups. Sibling analyses were also performed, adjusted for baseline age, sex and educational attainment. Results The linear regression analysis revealed a significant association between IgA nephropathy (IgAN) and the overall frequency of infections compared to the general population (β = 0.45; 95% CI: 0.37–0.54), women (β = 0.35; 95% CI: 0.19–0.50), men (β = 0.50; 95% CI: 0.40–0.60), and siblings (β = 0.37; 95% CI: 0.25–0.49) for women (β = 0.24; 95% CI: 0.06–0.41) and men (β = 0.43; 95% CI: 0.27–0.60). Similarly, a significant association was found for the frequency of prescribed antimicrobial agents compared to the general population (β = 0.66; 95% CI: 0.51–0.82), women (β = 0.92; 95% CI: 0.56–1.27), men (β = 0.55; 95% CI: 0.39–0.71), with similar estimates in the sibling analyses. The subtypes with the strongest association were urinary tract infections (β = 0.09; 95% CI: 0.07–0.11), ENT (ear, nose, and throat) infections (β = 0.08; 95% CI: 0.04–0.12), muscular infections (β = 0.08; 95% CI: 0.05–0.12), and infections in the GI (gastrointestinal) tract (β = 0.06; 95% CI: 0.04–0.09). Infections in the lower respiratory tract, skin and mycoses also had a significant positive association, however, no associations to infections in the central nervous system or infections caused by helminths and protozoans were identified. Cox regression showed an elevated risk of any infection with an adjusted hazard ratio (HR) of 2.05 (95% CI: 1.88–2.23), especially for sepsis (aHR = 3.13; 95% CI: 2.14–4.59), and time to the first prescription of antimicrobials with an aHR of 1.37 (95% CI: 1.30–1.45). Linear regression of prescribed antimicrobial treatments showed an overall β = 0.67; 95% CI: 0.51–0.82, and specifically for antibiotics (β = 0.64; 95% CI: 0.49–0.78). Conclusion Our study demonstrates an increased prevalence of infections and antibiotic prescriptions in IgAN patients compared to the general population and their siblings. Further studies on the potential impact of IgAN and its immunological aberrations on overall infection susceptibility is warranted.

A novel transmembrane CXCR4 variant that expands the WHIM genotype-phenotype paradigm

Warts, Hypogammglobulinemia, Infections, Myelokathexis (WHIM) syndrome is a rare immunodeficiency disease that results from impaired leukocyte trafficking (myelokathexis) predominately caused by gain-of-function variants in C-X-C chemokine receptor type 4 (CXCR4). Clinical manifestations of WHIM syndrome can differ in familial forms or in people harboring identical CXCR4 variants. All known pathogenic CXCR4 variants associated with WHIM syndrome (CXCR4WHIM) to date are localized in the intracellular C-terminus of CXCR4. We identified 4 unrelated patients with variable WHIM-like clinical presentations harboring a novel heterozygous CXCR4 variant (c.250G>C; p.D84H) localized at a highly conserved position in the transmembrane domain of the receptor outside the C-terminus. Functional characterization of the CXCR4D84Hvariant (CXCR4D84H) using patient-derived peripheral blood mononuclear cells and in vitro cellular assaysshow decreased CXCR4 internalization and increased chemotaxis in response to CXCL12, similar to known CXCR4WHIM, but also revealed unique features of CXCR4D84H signaling to cAMP, Ca2+ mobilization and AKT/ERK pathways. These findings are consistent with molecular dynamics simulations that show disruption of the Na+ binding pocket by D84H, resulting in collapse of the hydrophobic gate above and destabilization of the inactive state of CXCR4. Mavorixafor, a CXCR4 antagonist being evaluated in clinical trials for chronic neutropenia and WHIM syndrome, normalized CXCL12-mediated chemotaxis of CXCR4D84H patient lymphocytes ex vivo and improved WBC and subset counts in 1 patient with CXCR4D84H enrolled in the chronic neutropenia phase 1b clinical trial (NCT04154488). The present study expands the current understanding of CXCR4 function and genotype-phenotype correlations in WHIM syndrome and in people with WHIM-like phenotypes.

Origins of tissue and cell-type specificity in mitochondrial DNA (mtDNA) disease.

Mutations of mitochondrial (mt)DNA are a major cause of morbidity and mortality in humans, accounting for approximately two thirds of diagnosed mitochondrial disease. However, despite significant advances in technology since the discovery of the first disease-causing mtDNA mutations in 1988, the comprehensive diagnosis and treatment of mtDNA disease remains challenging. This is partly due to the highly variable clinical presentation linked to tissue-specific vulnerability that determines which organs are affected. Organ involvement can vary between different mtDNA mutations, and also between patients carrying the same disease-causing variant. The clinical features frequently overlap with other non-mitochondrial diseases, both rare and common, adding to the diagnostic challenge. Building on previous findings, recent technological advances have cast further light on the mechanisms which underpin the organ vulnerability in mtDNA diseases, but our understanding is far from complete. In this review we explore the origins, current knowledge, and future directions of research in this area.

The inability to belch: a neglected disease in the era of high-resolution esophageal manometry.

Retrograde upper esophageal sphincter dysfunction (R-UESD) is characterized by the inability to belch. Evidence of using high-resolution manometry (HRM) in diagnosing R-UESD has emerged in recent years. We describe the clinical picture and HRM patterns of two patients with R-UESD. Case 1: A 23-year-old female presented with a two-year complaint of inability to belch. We performed HRM with a belch provocation test for which the patient drank 500 ml of carbonated water. The study revealed increased esophageal pressure, an absence of UES relaxation and secondary peristalsis once the patient mentioned the need to belch. Case 2: A 21-year-old male presented to our medical office with a history of an incapacity to belch during the last three years. We performed HRM with a belch provocation test. During the study, he reported an incapacity to belch and his symptoms coincided with increased esophageal pressure, an absence of UES relaxation, and secondary peristalsis. Retrograde upper esophageal sphincter dysfunction is a rare condition characterized by a lack of UES relaxation during esophageal distension. The incapacity to belch is the hallmark of the disease. We encourage the use of HRM, looking for an increase in esophageal pressure to the level of gastric pressure, failure of UES relaxation with consequently no venting of air across the UES, and secondary peristalsis. In conclusion, diverse R-UESD clinical presentations represent a diagnostic challenge for physicians. This case series highlights the need to actively search for typical HRM findings when encountering patients referring an incapacity to belch.

It is Not a Curse! It is Neurofibromatosis 1 (NF1): A Case Report from Rural Kenya

Neurofibromatosis 1 (NF1) is an autosomal dominant genetic disorder caused by mutations in the NF1 gene, with near complete penetrance and variable clinical presentation. Patients classically have café-au-lait macules, neurofibromas, skin freckles, and Lisch nodules, among other multisystemic features. Long-term management in a multidisciplinary team focuses on surveillance and treating complications. NF1 is a rare disease in Kenya, often leading to myths and misconceptions about its nature, especially among rural communities. We present a classical case from rural Kenya whose diagnosis was delayed by a belief that it was the result of a curse. We aim to highlight the importance of making this diagnosis and its linkage to a long-term care plan within a primary health care setting.

A rare case of aortitis presenting as chest pain: a case report and literature review

Introduction and Importance: Chest pain is a frequent reason patients seek medical attention. The broad spectrum of potential etiologies makes determining the underlying cause of chest pain complex. Among cardiovascular etiologies, aortitis is a rare but life-threatening possibility that should be considered in the differential diagnosis. Case Presentation: A 53-year-old female with a history of smoking presented with progressively worsening chest and epigastric pain over several weeks. She had seen multiple physicians previously for the same symptoms with unremarkable workups. Physical exam was notable for severe tenderness upon palpation of her lower abdomen. Electrocardiogram and troponins were unremarkable. Computed tomography of the abdomen revealed aneurysmal dilatation of the abdominal aorta, soft tissue thickening, and surrounding inflammatory stranding, consistent with aortitis. Infectious and autoimmune workups were unremarkable. Intravenous steroids were initiated, and her symptoms improved significantly. Her aortitis was attributed to inflammation secondary to chronic smoking. Clinical Discussion: Aortitis is a rare condition with varied clinical presentations. Etiologies of aortitis include infection and non-infectious inflammation. Diagnosis of aortitis requires a thorough clinical assessment and prompt imaging of the aorta, with CT being the preferred imaging modality. Conclusion: Evaluation for cardiovascular chest pain must extend beyond an electrocardiogram and troponin level. Imaging should be considered in patients with atypical symptoms. Aortitis is a rare but important diagnosis requiring immediate treatment.

Inflammatory myofibroblastic tumor of urinary bladder in young male: A case report and literature review

The objective of this study is to present a rare case of inflammatory myofibroblastic tumor (IMT) of the urinary bladder in young male, detailing its clinical presentation, diagnostic approach, treatment strategy, and outcome. Additionally, the objective includes conducting a literature review to provide insights into the characteristics, management, and prognosis of this uncommon tumor entity.A 20-year-old male presenting with dysuria and dribbling of urine underwent diagnostic workup including imaging studies, cystoscopy. On cystoscopy there was a presence of 5x4 cm sized pedunculated mass in the urinary bladder. Partial cystectomy is done and specimen is examined for histopathology. Histopathological examination and Immunohistochemistry study of the tumor specimen was performed to confirm the diagnosis of inflammatory myofibroblastic tumor. A thorough literature review was conducted to gather relevant studies on IMT of the urinary bladder, focusing on clinical presentations, diagnostic modalities, treatment approaches, and outcomes. Diagnostic evaluation revealed a mass lesion in the urinary bladder, and histopathological examination following partial cystectomy confirmed the diagnosis of inflammatory myofibroblastic tumor. The patient underwent surgical excision of the tumor followed by adjuvant therapy. Regular follow-up examinations showed no evidence of tumor recurrence. The literature review identified a limited number of reported cases of IMT of the urinary bladder in young male, emphasizing its rarity and diverse clinical presentations. Various diagnostic modalities and treatment options, including surgery, chemotherapy, and targeted therapy, were discussed in the reviewed literature. Inflammatory myofibroblastic tumor of the urinary bladder is a rare neoplasm at younger age that can present with nonspecific symptoms, making its diagnosis challenging. However, timely recognition and appropriate management, including surgical resection and adjuvant therapy, can lead to favorable outcomes with low recurrence rates. This case report highlights the importance of considering IMT in the differential diagnosis of bladder masses in young patient and underscores the need for further research to better understand the pathogenesis and optimal treatment strategies for this rare tumor entity.