Variable Clinical Presentation Research Articles

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.

Outcome Predictors of Acute-on-Chronic Liver Failure: A Narrative Review.

Complications of acute-on-chronic liver failure (ACLF) include increased short-term mortality. Extrahepatic organ failures result from chronic liver disease and acute hepatic injury. This combination characterizes end-stage liver disease. Its rapid progression makes it challenging for hepatologists and intensivists to treat. The varied definitions of this condition lead to varied clinical presentations. Hepatic or extrahepatic failures are more prevalent in chronic hepatitis B or cirrhosis patients who receive an additional injury. Numerous intensity parameters and prognosis ratings, including those for hepatitis B virus (HBV), have been developed and verified for various patients and causes of the disease. Liver regeneration, liver transplantation (LT), or antiviral therapy for HBV-related ACLF are the main treatment aims for various organ failures. LT is the best treatment for HBV-ACLF. In some HBV-related ACLF patients, nucleos(t)ide analogs and artificial liver assistance may enhance survival. Combining epidemiological and clinical studies, this review updates our understanding of HBV-ACLF's definition, diagnosis, epidemiology, etiology, therapy, and prognosis.

Congenital Myopathy-1B due to RYR 1 Gene Mutation in Three Libyan Families

Abstract Introduction We report a series of patients in three different Libyan families diagnosed with congenital myopathy to study the wide clinical variability between these families, and the genetic heterogeneity. Description of Cases We describe six patients, one patient presented with severe neonatal-onset RYR1-associated myopathy while the other five patients came mainly due to delay in motor development; genetic testing confirmed the diagnosis of CMY-1B disease due to RYR1 mutation in all patients. Clinical features of congenital widely varied between the families ranging from profound hypotonia during the neonatal period in one family to a motor delay and abnormal gait during childhood in other two families. Whereas the clinical picture is quite similar in the patients of same family, the patient who presented with severe neonatal presentation of RYR1-associated myopathy also had gastrostomy feeding, respiratory involvement, clubfeet, cleft palate, and undescended testes. The five patients who presented due to delay in motor development all were ambulatory without the need of support, except the youngest one aged 4 years still walking with support. The genetic study in the form of whole-exon sequencing as well as next-generation sequencing showed homozygosity of a gene mutation in five patients and a compound heterozygosity in one patient which presented with neonatal severe hypotonia. Conclusion CMY-1B disease is a rare autosomal dominant and recessive genetic disorder that has variable clinical presentations. The early diagnosis is very important for genetic counseling as well as avoiding malignant hyperthermia. We also report rare and unusual presentations that may further delay the diagnosis.

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.

Neoplasia endocrina múltiple

Multiple endocrine neoplasia (MEN) syndromes encompass a heterogeneous group of inherited disorders characterized by a genetic predisposition to developing tumors that mainly affect the endocrine glands. The four recognized syndromes (MEN1, MEN2A, MEN2B, and MEN4) are of autosomal dominant inheritance and are phenotypically distinguished by the development of synchronous or metachronous tumors with varied clinical presentations. Knowing the genetics and progression of each syndrome is useful for determining the tumor detection time frame. Treatments for each manifestation depend on the location, risk of malignancy or recurrence, excess hormones, and surgical morbidity; they require multidisciplinary management.

Clinical characteristics of SARS-CoV-2 Omicron BA.2 infection and its impact on pediatric emergency care in northern Taiwan

BackgroundThe SARS-CoV-2 Omicron BA.2 outbreak started in Taiwan in April 2022. The pandemic posed a challenge to pediatric emergency departments (PEDs) because of increased PED visits and diverse clinical presentations. MethodsWe analyzed the clinical characteristics and impact of the Omicron BA.2 pandemic in patients who visited our PED from April 2022 to July 2022. The data from the Alpha variant pandemic during the same period in 2021 were compared with these findings. ResultsOverall, 10,878 children were enrolled, and 7047 (64.8%) children were positive for SARS-CoV-2 infection. They had a mean ± SD age of 5.3 ± 4.1 years. The rates of patients with Pediatric Taiwan Triage and Acuity Scale (Ped-TTAS) level 1 (most urgent) (12.3%) and level 2 (27.6%) increased. More children were triaged as most urgent during the Omicron BA.2 pandemic than during the Alpha variant pandemic (p < 0.001). Patients with SARS-CoV-2 infection were likely to present with high fever, croup, dyspnea, febrile seizures, headache, dizziness, and myalgia (all p < 0.001). Four hundred and eleven (5.8%) patients were admitted; 25 (0.4%) patients needed intensive care, including 11 (44.0%) with encephalopathy or encephalitis. Three (0.04%) patients died due to fulminant encephalitis, encephalitis with septic shock, and respiratory failure. ConclusionsThe number of PED visits and the Ped-TTAS level of disease severity significantly increased during the SARS-CoV-2 Omicron BA.2 outbreak. The most common symptom was fever, and high fever was more common in patients with SARS-CoV-2 Omicron BA.2 infection. The rates of patients with croup and febrile seizures also increased.

A Case Report on Dyschromatosis Universalis Hereditaria with Palmar Involvement

Dyschromatosis universalis hereditaria (DUH) is a rare genetic disorder characterized by hyper- and hypopigmented macules forming a reticulate pattern on the skin. This report presents an unusual case of a 14-year-old male patient with DUH involving the palms, a relatively uncommon manifestation of the condition. The patient presented with hyperpigmented lesions on the palms, which had developed over the previous eight years. Family history revealed similar pigmentary changes, suggesting a hereditary pattern. Clinical examination revealed no history of chemical or drug exposure, photosensitivity, or photophobia. Systemic evaluation was unremarkable, except for a low cortisol level of 1.12 mcg/dl (normal range: 6.2 to 19.4 mcg/dl) on the ACTH stimulation test. Skin biopsy from the left palm revealed diffuse hypermelanosis confined to the basal cell layer and occasionally extending to the lower third of the epidermis. Additionally, increased collagenization was observed in the deep dermis. Based on these findings, a diagnosis of DUH was established. The patient was initiated on long-term hydrocortisone therapy for cortisol hormone replacement. This case highlights the rare occurrence of palmar involvement in DUH and underscores the importance of thorough clinical evaluation and histopathological examination in establishing an accurate diagnosis. DUH is an uncommon genodermatosis, and reports of palmar involvement are scarce in the literature. This case contributes to the existing knowledge about the varied clinical presentations of DUH and emphasizes the need for increased awareness among clinicians

Parsonage-Turner Syndrome and SARS-CoV-2 Infection: A Literature Review With Case Presentation.

Neuralgic amyotrophy, also known as Parsonage-Turner syndrome (PTS), is characterized by severe pain and muscle wasting affecting the anterior body, including the head, shoulder, upper limb, and chest wall. Often triggered by an antecedent event, such as infection, PTS encompasses various conditions historically identified as separate entities. In 1948, Parsonage and Turner unified these conditions under the term neuralgic amyotrophy based on shared features of intense pain and muscular atrophy. Recent studies have highlighted PTS as a spectrum disorder with diverse manifestations, including pure sensory neuropathy, extensive neuropathy, spinal accessory nerve involvement, and diaphragmatic palsy. We reviewed 26 documented cases of PTS following SARS-CoV-2 infection, emphasizing the importance of considering PTS in individuals with a history of COVID-19 due to varied clinical presentations. Standardized diagnostic methods and comprehensive evaluations are crucial for accurate diagnosis and management. Future research should focus on consistent evaluation methods and employing a comprehensive differential diagnosis approach.

Visual Outcomes in Malignant Hypertensive Retinopathy Cases: A Clinical and Spectral Domain Optical Coherence Tomography Study.

Objective The objective is to correlate visual outcomes in malignant hypertensive retinopathy with changes in systemic causative factors and spectral domain optical coherence tomography (SD OCT) morphologic parameters. Materials and methods This is a prospective observational study including patients presenting within two weeks of acute rise of systolic blood pressure (SBP) ≥ 180 mm Hg or diastolic blood pressure (DBP) ≥ 120 mm Hg and with posterior segment involvement in both eyes. Baseline SBP, DBP, mean arterial pressure (MAP), best corrected visual acuity (BCVA), and SD OCT parameters such as central macular thickness (CMT), subfoveal choroidal thickness (SCT), and sub-retinal fluid (SRF) height were measured at presentation and followed monthly up to three months. These variables at baseline and three months were compared and correlated. Results Thirty-three patients (66 eyes) having malignant hypertension were included in the study. Diverse clinical presentations noted among patients were optic disc edema, hard exudates in the macula, peripapillary splinter hemorrhage, cotton wool spots, Elschnig spots, exudative retinal detachment, optic neuropathy, and severe exudative retinopathy. SD OCTshows hyperreflective dots and intraretinal fluid with or without SRF.At three months, the mean SBP, DBP, MAP, CMT, SRF, and SCT all decreased significantly from baseline (p<0.001). Changes in SBP, DBP, MAP, and SCT correlated significantly with changes in BCVA (p<0.001). Conclusion In malignant hypertensive retinopathy, macular edema with SRF is the major cause of mild-to-moderate decrease BCVA at presentation, but macular ischemia, exudative RD, and optic neuropathy can cause a significant decrease in vision. A decrease in SBP, DBP, MAP, and SCT correlatesignificantly with visual outcomes.

Assessment of the Clinical Utility of the FilmArrayTM Gastrointestinal Panel for Detecting Gastrointestinal Pathogens.

Gastrointestinal infections present a significant public health concern as they lead to diverse clinical presentations and healthcare challenges. The rapid and accurate identification of causative pathogens is imperative for effective patient management. This study aimed to assess the clinical utility of the FilmArrayTM Gastrointestinal (GI) Panel for detecting gastrointestinal pathogens. Between November 1, 2022, and December 31, 2023, we analysed gastrointestinal specimens collected from a cohort of patients aged 21 to 91 at Asia University Hospital. These specimens were analyzed using the FilmArrayTM GI Panel. The study included 76 patients for whom the FilmArrayTM GI assay was conducted, with 40 (52.6%) showing positive results. Among the positive specimens, 23 (57.5%) had a single pathogen, while the remaining 17 (42.5%) had multiple pathogens. The remaining 36 (47.4%) specimens showed no pathogens. The overall positivity rate of the specimens was 52.6%. The most frequently detected pathogens included Salmonella, Clostridium difficile (toxin A/B), and Enteropathogenic Escherichia coli (EPEC). This study underscores the clinical value of the FilmArrayTM GI assay as a rapid and reliable tool for diagnosing gastrointestinal infections. Its capacity to detect multiple pathogens simultaneously enhances diagnostic accuracy and gives information to use in clinical decision-making. We strongly recommend its integration into clinical practice to expedite the diagnosis and management of gastrointestinal infections, ultimately leading to improved patient care and healthcare efficiency.

Management and treatment of perioperative hypersensitivity.

Perioperative hypersensitivity reactions are rare but potentially catastrophic events. This review acts to summarize recent recommendations for both immediate and poststabilization management of suspected reactions, alongside practical advice for anaesthetists who may be faced with these events. Prompt treatment is essential but may be hampered by delay in recognition. This can occur because there are multiple differential diagnoses for the observed clinical signs as well as variations in clinical presentation. Resuscitation is dependent on the use of adrenaline and fluids. Adrenaline should be administered in small, titrated intravenous boluses. Low-dose infusions should be commenced early if the response to boluses is poor. Large volume fluid resuscitation may be required to maintain adequate circulating volume. Chest compressions are recommended when there is evidence of inadequate perfusion, rather than waiting until cardiac arrest is confirmed. Antihistamines and corticosteroids are no longer recommended in the immediate management phase. Once the patient has been stabilized, it is important to obtain serial tryptase concentrations to aid the subsequent clinic investigation. The decision to proceed or abandon surgery will be based on an individual risk-benefit analysis. All cases of suspected perioperative hypersensitivity, including fatal cases, must be referred for formal investigation. There have been recent updates to management guidelines in perioperative hypersensitivity. Treatment algorithms, treatment packs and referral packs can all help the anaesthetist manage these complex cases, aid the subsequent investigation and ensure patient safety in the future.

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.

GALACTOSEMIA: A CASE STUDY

Inborn errors of metabolism often manifest with varied clinical presentations in the neonatal period. Prevention of morbidity or mortality is frequently contingent on early diagnosis. Midwives have a role to play in recognizing symptoms that may be consistent with such a diagnosis. This paper describes the clinical findings in the case of a newborn in midwifery care who was diagnosed with galactosemia on day 10. This metabolic disorder is described and midwifery implications arising from this case are discussed.

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.

Application of Artificial Intelligence in Neuroendocrine Lung Cancer Diagnosis and Treatment: A Systematic Review.

Neuroendocrine tumors (NETs) represent a heterogeneous group of neoplasms with diverse clinical presentations and prognoses. Accurate and timely diagnosis of these tumors is crucial for appropriate management and improved patient outcomes.In recent years, exciting advancements in artificial intelligence (AI) technologies have been revolutionizing medical diagnostics, particularly in the realm of detecting and characterizing pulmonary NETs, offering promisingavenuesfor improved patient care. This article aims to provide a comprehensive overview of the role of AI in diagnosing lung NETs. We discuss the current challenges associated with conventional diagnostic approaches, including histopathological examination and imaging modalities.Despite advancements in these techniques, accurate diagnosis remains challenging due to the overlapping features with other pulmonary lesions and the subjective interpretation of imaging findings. AI-based approaches, including machine learning and deep learning algorithms, have demonstrated remarkable potential in addressing these challenges. By leveraging large datasets of radiological images, histopathological samples, and clinical data, AI models can extract complex patterns and features that may not be readily discernible to human observers. Moreover, AI algorithms can continuously learn and improve from new data, leading to enhanced diagnostic accuracy and efficiency over time. Specific AI applications in the diagnosis of lung NETs include computer-aided detection and classification of pulmonary nodules on CT scans, quantitative analysis of PET imaging for tumor characterization, and integration of multi-modal data for comprehensive diagnostic assessments. These AI-driven tools hold promise for facilitating early detection, risk stratification, and personalized treatment planning in patients with lung NETs.

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.