Multiple Organ Involvement Research Articles

Antibiotic treatment for infection with Shiga toxin producing Escherichia coli infection inducing a hemolytic uremic syndrome

Background: Shiga toxin producing Escherichia coli (STEC) inducing hemolytic uremic syndrome (HUS) with multiple organ involvement is associated with significant morbidity and mortality. The treatment has mostly been focused on kidney, respiratory and cardiovascular supports and not against the bacteria that cause STEC-HUS. The use of bactericidal therapy has been shown to be antibiotic dependent and certain antibiotics inhibit the production and release of Shiga toxin, eradicate STEC without harmful effects, and improve outcome. Methods: A previously healthy 18-months-old girl with STEC causing severe colitis, kidney failure and multi-organ dysfunction was treated with antibiotics that were known to inhibit the release of Shiga toxin as a supplement to supportive care. Results: The antibiotic regime stopped the pathophysiological process with prompt clinical improvement in association with the disappearance of the Shiga toxins. Conclusions: The present case report fortifies and recommends appropriate antibiotic treatment during STEC-HUS, suggesting clinicians to consider the use of these in severe STEC-HUS as early as possible.

Immunity: Psoriasis comorbid with atherosclerosis.

Psoriasis is an immune-mediated, persistent inflammatory disease with a genetic predisposition, and the involvement of multiple organs in psoriasis remains indicative of systemic disease. Atherosclerosis (AS) is a common complication of patients with severe or prolonged psoriasis. The specific pathogenesis of psoriasis is still unclear. Current studies suggest that psoriasis is a polygenic genetic disease with the interaction of multiple factors such as heredity and environment. Keratinocytes are proliferated through immune-mediated inflammatory pathway, which leads to cell activation, infiltration of dermis cells and release of inflammatory factors. Activation of inflammatory cells and pro-inflammatory factors play an important role in the progression of psoriasis and atherosclerosis. Studies have found that there is a close relationship between psoriasis and atherosclerosis, and systemic inflammation may be the common feature of psoriasis and AS. This paper attempts to explore the possibility of the relationship between psoriasis and atherosclerotic comorbidities from the aspects of potential epidemiology and immune mechanism, in order to provide some reference for the subsequent scientific research.

591 SEQUENCE OF DIAGNOSTIC TESTING IN CARDIAC AMYLOIDOSIS: EARLY MONOCLONAL PROTEIN STUDY IS ASSOCIATED WITH BETTER OUTCOMES IN AL AMYLOIDOSIS

Abstract Background Isolated cardiac amyloidosis (CA) is a complex diagnostic scenario, highlighting the need for physician awareness in differential diagnosis. Among the different types of amyloidosis, nearly all cases of CA are caused by light chain (AL) and transthyretin amyloidosis (ATTR). Patients with suspect CA without monoclonal components (MC) in both serum and urine and normal free light chain (FLC) ratio can have a non-biopsy diagnosis of ATTR amyloidosis with bone scintigraphy (1). However, in all suspected CA with a MC (approximately 20% of patients with ATTR amyloidosis), amyloid typing is mandatory. Thus, the diagnostic pathway of CA diverges based on MC-studies. We aim to assess if different sequence of diagnostic tests can affect outcomes in patients with cardiac AL amyloidosis. Methods Pavia Amyloidosis prospectively maintained database was searched for patients with isolated cardiac AL amyloidosis referred to our Centre from January 2016 to December 2020. Patients with a known monoclonal gammopathy (MG) and with multiple organ involvement were excluded. We searched for the date of symptom onset and first suspect of CA (i.e. recognition of clinical, imaging or laboratory signs of CA). In addition, we recorded the date of the different diagnostic tests performed: i.e. echocardiogram; serum and urine immunofixation and FLC measurement (MC-study); bone scintigraphy and cardiac magnetic resonance (defined as advanced cardiac imaging). We calculated the interval between those time-points and the final diagnosis: (a) from symptom onset to diagnosis, (b) from first suspect to final diagnosis, (c) from first suspect to MC-study and (d) to advanced cardiac imaging tests. We then searched for possible intervals of time amongst those, that were able to predict death at 3 months, by means of a ROC analysis. Results A total of 94 patients were included in the analysis (25% of all patients with cardiac AL amyloidosis diagnosed in the study period). Six (6%) patients died <1 month from diagnosis, and 27 (29%) died <3 months. Median overall survival (OS) of the whole cohort was 8 months, and the median follow-up of living patients was 39 months (range 16-73). The median time from symptom onset to diagnosis was 9 months (range 1-44) and the median time from the first suspect to diagnosis was 2 months (range 0-9). An interval from the first suspect to MC-study ≥6 weeks was the only predictor of death at 3 months. None of the other tested periods were associated with a significant ability to predict survival. A delay in MC-study ≥6 weeks identified patients with more advanced cardiac stage (50% vs. 25% were stage IIIb, P=0.02) and was associated with a significantly worse outcome (median survival 13 months vs. 4 months, P=0.012). In the whole cohort, a total of 76 (81%) patients underwent at least one advanced imaging examination. Amongst those, 37 (49%) performed the imaging tests before MC-study with a higher percentage of patients who had a delay in MC-studies evaluation (69% vs. 27%; P<0.001). Conclusion In patients who present with isolated cardiac AL amyloidosis with previously unknown MG, a relatively short delay in identifying the amyloid MC results in a considerable reduction of survival. A delay in MC-study was associated with more advanced cardiac stage. MC studies should be the first step in the work-up of patients with suspected CA to guide biopsy vs. non-biopsy diagnostic approach.

Ocular symptoms of Saul — Wilson syndrome in children

The genetic Saul — Wilson syndrome is so rare that the very few descriptions of its ocular manifestations available are of high clinical interest. Purpose. To offer a description of the ocular manifestations of the Saul — Wilson syndrome. Material and methods. Two children with a verified diagnosis of Saul — Wilson syndrome, observed from the age of 3 and 4 (the follow-up period was 6 months to 2.5 years), were subjected to a comprehensive ophthalmological examination. Results. The children, along with characteristic phenotypic manifestations (clubfoot, very short stature, short fingers and toes, hypermobile joints) were found to have a disordered visual system, associated with the particularities of the facial skeleton (exophthalmos or strabismus) and clinical and functional eye disorders: mild hypermetropia, hypermetropic astigmatism, partial complicated cataract. One child was diagnosed with changes in the structure and function of the retina, which indicates a dystrophic process. The diagnosis was genetically verified. Conclusion. Given the rarity of the disease, multiple organ involvement, an uncertain prognosis, an interdisciplinary approach to the management of such patients, constant dynamic monitoring and timely correction of detected disorders is necessary.

The impact of environmental and nutritional stresses on milk fat synthesis in dairy cows

Stress reduces milk and milk components synthesis and increases maintenance requirements of cows. The major stress-related alterations involve enhanced secretion of glucocorticoids and increased sympathetic nervous system activity, which results in biochemical and physiologic changes. In dairy cows exposed to social (ie housing conditions, overstocking, regrouping, feed delivery), physiological (ie initiation of lactation and parturition), or physical (ie heat or cold stress) stressors, responses involve alterations in energy balance and nutrient partitioning. The capacity of the animal to synthesize milk fat largely depends on the availability of substrates for lipid synthesis from the diet, ruminal fermentation or adipose tissue stores, all of which can be altered under stress conditions. Indeed, milk fat concentration is particularly responsive to diet and environment modifications, where a wide range of nutritional and non-nutritional factors influence milk fat output. Milk fat synthesis is an energy demanding process, and extremely sensitive to stress factors during lactation and the involvement of multiple organs. Recent studies examining social, physical, and physiological stressors have provided important insights into how differences in milk yield and milk components may be associated with biological responses to stress factors in dairy cows. This review focuses primarily on the role of stress sources and indicators to which the dairy cow is exposed in regulating milk fat synthesis. We will review the role of nutritional and non-nutritional factors on milk fat synthesis in dairy cows under stress conditions.

Fisetin reduces the senescent tubular epithelial cell burden and also inhibits proliferative fibroblasts in murine lupus nephritis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease characterized by the involvement of multiple organs. Lupus nephritis (LN) is a major risk factor for overall morbidity and mortality in SLE patients. Hence, designing effective drugs is pivotal for treating individuals with LN. Fisetin plays a senolytic role by specifically eliminating senescent cells, inhibiting cell proliferation, and exerting anti-inflammatory, anti-oxidant, and anti-tumorigenic effects. However, limited research has been conducted on the utility and therapeutic mechanisms of fisetin in chronic inflammation. Similarly, whether the effects of fisetin depend on cell type remains unclear. In this study, we found that LN-prone MRL/lpr mice demonstrated accumulation of Ki-67-positive myofibroblasts and p15INK4B-positive senescent tubular epithelial cells (TECs) that highly expressed transforming growth factor β (TGF-β). TGF-β stimulation induced senescence of NRK-52E renal TECs and proliferation of NRK-49F renal fibroblasts, suggesting that TGF-β promotes senescence and proliferation in a cell type-dependent manner, which is inhibited by fisetin treatment in vitro. Furthermore, fisetin treatment in vivo reduced the number of senescent TECs and myofibroblasts, which attenuated kidney fibrosis, reduced senescence-associated secretory phenotype (SASP) expression, and increased TEC proliferation. These data suggest that the effects of fisetin vary depending on the cell type and may have therapeutic effects in complex and diverse LN pathologies.

A multidisciplinary case report of multiple myeloma with renal and cardiac involvement: a look beyond amyloidosis

BackgroundMultiple myeloma (MM) is a malignant neoplasm associated with kidney involvement in nearly half of the patients. Cast nephropathy, monoclonal immunoglobulin deposition disease (MIDD), and light chain (AL) amyloidosis are the most common monoclonal immunoglobulin-mediated causes of renal injury.Cardiac involvement is also present in MM, characterized by restrictive cardiomyopathy generated by light chain deposit or amyloid. Thromboembolic complications such as deep vein thrombosis or pulmonary embolism are also described.Case presentationWe present an unusual multidisciplinary case of a woman with a newly diagnosed MM associated with severe proteinuria and high natriuretic peptide. A renal and fat pad biopsy with Congo red staining were performed but amyloid deposition was not discovered. While immunofluorescence on fresh frozen unfixed tissue was not contributory, the immunofluorescence on fixed tissue and electron microscopy revealed the correct diagnosis.During subsequent investigations, two intracardiac right-sided masses and massive pulmonary embolism were also detected.ConclusionsThis case highlights that multiple organ involvement in patients with MM may result from a combination of paraprotein-dependent and -independent factors. Moreover, renal diseases induced by monoclonal gammopathies are a group of complex and heterogeneous disorders. Their subtle presentation and their potential multiorgan involvement require the expertise of a multidisciplinary team able to provide the most appropriate diagnostic and therapeutic assessment.

High-fat diet aggravates experimental autoimmune pancreatitis through the activation of type I interferon signaling pathways

Autoimmune pancreatitis (AIP) is an autoimmune disorder of the pancreas characterized by enhanced IgG4 antibody responses and multiple organ involvement. AIP is a pancreatic manifestation of the systemic IgG4-related disease (IgG4-RD). Although AIP and IgG4-RD predominantly occur in middle-aged and elderly men, the roles of eating habits and lifestyle in the pathogenesis of these conditions are poorly understood. In this study, we examined whether a high-fat diet (HFD), preferred by middle-aged and elderly men, increases sensitivity to experimental AIP. We modeled AIP in MRL/MpJ mice by repeated injections of polyinosinic:polycytidylic acid. HFD exacerbated AIP development and promoted pancreatic accumulation of interferon (IFN)-α-producing plasmacytoid dendritic cells (pDCs). However, HFD did not increase the severity of autoimmune sialadenitis, another disorder associated with AIP and IgG4-RD. Neutralization of type I IFN signaling pathways prevented the development of severe AIP induced by HFD. In contrast, leaky gut was less likely to be associated with the HFD-induced exacerbation of AIP, as was evidenced by the lack of significant alterations in the jejunal or ileal expression of tight junction proteins. These data suggest that HFD exacerbates experimental AIP through the activation of pDCs producing IFN-α.

Nail involvement in patients with epidermolysis bullosa: Asystematic review.

Nail changes in patients with congenital epidermolysis bullosa (EB) are caused by abnormalities of the nail matrix and bed secondary to pathogenic alterations of the dermoepidermal junction. Even though ungual alterations are extremely frequent in these patients, there are scarce studies about their frequency and/or association with subtypes or clinical course of EB. To systematically review nail abnormalities in patients with EB reported in the literature. We searched all published articles in electronic databases until June 2020 reporting patients with EB with detailed descriptions of malformed/diseased nails using specific terms and inclusion/exclusion criteria. Clinical data were extracted by two independent authors. Descriptive statistics were used. We included 36 articles reporting 74 individual patients with a mean age of 28.23years: 29 (39.2%) had dominant dystrophic EB, 27 (36.4%) had junctional EB, 8 (10.8%) had EB simplex, 6 (8.1%) had Kindler syndrome and 4 (5.4%) had recessive dystrophic EB. The most common abnormalities were dystrophic nails (48.6%), anonychia (43.2%) and pachyonychia (40.5%). Anonychia was considered the most severe abnormality and was reported more frequently in patients with junctional (62.9%) and recessive dystrophic EB (50%). Multiple organ involvement was present in 52.7% of patients. Patients with severe junctional epidermolysis bullosa and recessive dominant epidermolysis bullosa presented anonychia since birth. In this summary of nail abnormalities in patients with EB, anonychia was more frequent in patients with severe EB subtypes and multiple organ involvement. Further prospective studies are required to understand the associations between nail abnormalities in specific EB subtypes and/or patient outcomes.

ODP648 MEN1 vs MEN4: when we cannot find a mutation

Abstract MEN1 is an autosomal dominant syndrome characterized by involvement of several endocrine and non-endocrine organs. The most common endocrine organs that are affected include pituitary, parathyroid, and/or pancreas. In 10-30% of patients, no germline mutations in the menin gene are identified, presenting a diagnostic challenge. This case raises the question of possible MEN4 syndrome, which shares a similar phenotype to MEN 1 with germline mutation in CDKN1B. Clinical case 59 y/o female with PMH HTN, obesity, hypothyroidism initially presented to our clinic in 2018 for evaluation of hypercalcemia. She prior was seen in 2005 for evaluation of prolactinoma by outside endocrinologist but was lost to follow up. Per history, she had a pituitary MRI in 1991 for work up of amenorrhea and found to have prolactinoma. She was placed on bromocriptine at that time; after repeat pituitary MRI and prolactin levels were found to be normal, bromocriptine was discontinued in 2019 but then restarted a few months later due to uptrending prolactin level. During the visit with us, work up for her hypercalcemia included calcium of 11. 0 mg/dL and PTH level of 93 pg/mL with normal albumin, vitamin D, and renal function. Patient had a negative sestamibi scan but was found to have a 10 mm×5 mm×12 mm enhancing nodule along the left thyroid gland and along left lateral margin of esophagus, suggesting parathyroid adenoma. She subsequently underwent successful left inferior parathyroidectomy in July 2019 with normalization of calcium and PTH levels. No other parathyroid was found to be enlarged. Given her pituitary and parathyroid adenoma, she was sent for genetic testing; she was evaluated for 7 gene variants and all were found negative including MEN1, CDKN1B, GNA11, AP2S1, CASR, CDC73, and RET. Of note, she has no family history of MEN1 or any endocrine tumors. However, further testing was still performed to evaluate for a pancreatic neuroendocrine tumor including CT abdomen, gastrin, C peptide, chromogranin-A, glucagon, VIP, and 5-HIAA. Her initial testing came back normal including normal CT abdomen in 2020. However, her most recently lab results in 2021 revealed an elevated gastrin level of 124 pg/mL and uptrending chromogranin A of 262 ng/mL (<=93), the diagnosis of gastrinoma was confirmed and PPIs were started. Discussion This case highlights the importance of continued surveillance in patients with multiple endocrine organ involvement or neoplasia despite negative genetic testing; it also supports the likelihood of unidentified mutations given the improbable chance this patient has 3 independent endocrine tumors. Possibilities including missed germline mutations on testing or phenocopies. This patient likely has an upstream mutation that was not identified and could represent either MEN1 vs MEN4 Presentation: No date and time listed

Application of exome sequencing for prenatal diagnosis of fetal structural anomalies: clinical experience and lessons learned from a cohort of 1618 fetuses

BackgroundExome sequencing (ES) is becoming more widely available in prenatal diagnosis. However, data on its clinical utility and integration into clinical management remain limited in practice. Herein, we report our experience implementing prenatal ES (pES) in a large cohort of fetuses with anomalies detected by ultrasonography using a hospital-based in-house multidisciplinary team (MDT) facilitated by a three-step genotype-driven followed by phenotype-driven analysis framework.MethodsWe performed pES in 1618 fetal cases with positive ultrasound findings but negative for karyotyping and chromosome microarray analysis between January 2014 and October 2021, including both retrospective (n=565) and prospective (n=1053) cohorts. The diagnostic efficiency and its correlation to organ systems involved, phenotypic spectrum, and the clinical impacts of pES results on pregnancy outcomes were analyzed.ResultsA genotype-driven followed by phenotype-driven three-step approach was carried out in all trio pES. Step 1, a genotype-driven analysis resulted in a diagnostic rate of 11.6% (187/1618). Step 2, a phenotype-driven comprehensive analysis yielded additional diagnostic findings for another 28 cases (1.7%; 28/1618). In the final step 3, data reanalyses based on new phenotypes and/or clinical requests found molecular diagnosis in 14 additional cases (0.9%; 14/1618). Altogether, 229 fetal cases (14.2%) received a molecular diagnosis, with a higher positive rate in the retrospective than the prospective cohort (17.3% vs. 12.4%, p<0.01). The diagnostic rates were highest in fetuses with skeletal anomalies (30.4%) and multiple organ involvements (25.9%), and lowest in fetuses with chest anomalies (0%). In addition, incidental and secondary findings with childhood-onset disorders were detected in 11 (0.7%) cases. Furthermore, we described the prenatal phenotypes for the first time for 27 gene-associated conditions (20.0%, 27/135) upon a systematic analysis of the diagnosed cases and expanded the phenotype spectrum for 26 (19.3%) genes where limited fetal phenotypic information was available. In the prospective cohort, the combined prenatal ultrasound and pES results had significantly impacted the clinical decisions (61.5%, 648/1053).ConclusionsThe genotype-driven approach could identify about 81.7% positive cases (11.6% of the total cohort) with the initial limited fetal phenotype information considered. The following two steps of phenotype-driven analysis and data reanalyses helped us find the causative variants in an additional 2.6% of the entire cohort (18.3% of all positive findings). Our extensive phenotype analysis on a large number of molecularly confirmed prenatal cases had greatly enriched our current knowledge on fetal phenotype-genotype correlation, which may guide more focused prenatal ultrasound in the future. This is by far the largest pES cohort study that combines a robust trio sequence data analysis, systematic phenotype-genotype correlation, and well-established MDT in a single prenatal clinical setting. This work underlines the value of pES as an essential component in prenatal diagnosis in guiding medical management and parental decision making.

Cutaneous sarcoidosis: a marker of underlying systemic disease

&lt;p class="abstract"&gt;Sarcoidosis/Mortimer’s malady is a multisystem disease defined by presence of epithelioid cell granulomas without caseation in various organs.It involves mainly the lungs, eyes, skin, lymph node etc. We reported a 40 year old female who presented with multiple plaques over different regions of the body with past history of ulcerated lesion of scalp which healed with cicatricial alopecia. On thorough evaluation she was found to have involvement of multiple internal organs. Based on the clinical features and histopathological findings, a diagnosis of cutaneous sarcoidosis (plaque type) was made. Patient treated with systemic and topical corticosteroids resulting in marked improvement in her skin lesions were seen and pulmonary complaints also resolved.&lt;/p&gt;

Predictors of Survival in Elderly Patients with Metastatic Colon Cancer: A Population-Based Cohort Study.

Oncological strategies in the elderly population are debated. The objective of this study was to determine the predictive factors of survival in patients aged 80 years and older with metastatic colon cancer. Data from four digestive tumour registry databases were used in this analysis. This population-based retrospective study included 1115 patients aged 80 years and older with stage IV colon adenocarcinoma diagnosed between 2007 and 2016. Cox regression was used to assess the impact of different prognostic factors. Age was significantly correlated with the surgical treatment (p < 0.001) but not with overall survival. Patients with a low comorbidity burden had better survival than patients with higher comorbidities scores (9.4 (0−123) versus 7.9 (0−115) months) (p = 0.03). Surgery was more common for proximal colon cancer (p < 0.001), but the location of the primary lesion was not correlated with improved survival (p = 0.07). Patients with lung metastases had a better prognosis than those with liver metastases (HR 0.56 95% CI 0.40, 0.77 p < 0.001); multiple organ involvement had the worst survival (HR 1.32 95% CI 1.15, 1.51 p < 0.001). Chemotherapy was associated with improved survival for both operated (HR 0.45 95% CI 0.35, 0.58 p < 0.001) and non-operated patients (HR 0.41 95% CI 0.34, 0.50 p < 0.001). The majority of patients receiving adjuvant treatment had a low comorbidity burden. In our study, the location of metastases but not the primary tumor location had an impact on overall survival. Low comorbidity burden, curative surgery, and chemotherapy had a significant advantage for elderly patients with metastatic colon cancer.

Baseline Eosinophil Count as a Potential Clinical Biomarker for Clinical Complexity in EGPA: A Real-Life Experience.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-vessel necrotizing vasculitis with multiple organ involvement. Despite improvements in clinical management, biomarkers for organ involvement and disease prognosis are still an unmet need. EGPA patients referred to our immunology clinic were retrospectively reviewed. Demographic/clinical features, eosinophils, ANCA status, eosinophil cationic protein (ECP) and total serum IgE were evaluated at the baseline. Eosinophils, total serum IgE, ECP and ANCA were studied as possible biomarkers for lung and extrapulmonary disease. In total, 167 EGPA patients were recruited for our study. A positive association between eosinophils and peripheral nervous system (PNS) involvement was demonstrated (p &lt;0.001; chi-squared test). Receiver operating characteristic (ROC) curves using the eosinophil count or percentage as predictors of PNS involvement yielded AUC values of 0.75 and 0.67, respectively. ANCA positivity was associated with PNS involvement, while no correlations with clinical parameters were found for ECP and total serum IgE. Patients without extrapulmonary involvement had lower eosinophils (eosinophils: 2844.7 ± 1698 vs. 6373 ± 5468, p &lt; 0.001; eosinophil percentage: 24.6 ± 10% vs. 36.2 ± 15.8, p &lt; 0.001) and were less likely to be ANCA+ (p &lt; 0.001, chi-squared test). Eosinophils in EGPA are an important biomarker and are associated with extrapulmonary involvement. These findings could strengthen the role of anti-eosinophilic drugs in improving extrapulmonary disease.

A Case Report on Antiphospholipid Syndrome

Antiphospholipid syndrome is a systemic autoimmune disease characterized by the presence of antiphospholipid antibodies in association with thrombosis and/or obstetric complications. APS is also be presented with multiple organ involvement. We recently encountered a case of primary phospholipid syndrome in a young adult with newly diagnosed pulmonary embolism, immune thrombocytopenia and deep vein thrombosis of left leg. The diagnosis of APS was initially suspected with his prolonged APTT and elevated D-Dimmer values and later confirmed by triple positive antiphospholipid antibody profile and multiple organ involvement Keywords: Antiphospholipid syndrome, Thrombosis, Autoimmune disease.

Clinical characteristics and outcomes of acute respiratory distress syndrome caused by severe Chlamydia psittaci pneumonia

Objective: To investigate the clinical characteristics and outcomes of acute respiratory distress syndrome (ARDS) caused by Chlamydia psittaci pneumonia. Methods: From June 2016 to January 2021, 10 cases were diagnosed as severe Chlamydia psittaci pneumonia induced ARDS in Intensive Care Unit of Respiratory and Critical Care Medicine Department (RICU) of Beijing Chao-Yang Hospital Affiliated to Capital Medical University. We collected the clinical data including clinical features, laboratory tests, imaging and outcomes of the patients. Results: The pathogenic diagnosis was confirmed by metagenomic Next-generation Sequencing (mNGS) in these 10 patients, with a median age of 59 (46, 67) years. In addition to high fever, cough and dyspnea, the patients also had multiple organ involvement. Six patients had elevated peripheral leukocyte count, 10 cases had increased type B natriuretic peptide, 7 cases had increased aspartate aminotransferase/alanine aminotransferase, 9 cases had hyponatremia and 3 cases had elevated creatinine. The imaging findings were bilateral consolidation with air bronchogram and infiltrates, and pleural effusion were found in 5 cases. All cases were combined with respiratory failure. Six patients received invasive mechanical ventilation. Nine patients received moxifloxacin and one patient was administrated with Azithromycin. All the patients were improved and discharged after the treatment, and the mean duration of RICU stay was 13.5 (11, 16.7) days. One month follow-up of nine patients showed significant improvement in lung lesions. Conclusions: Severe Chlamydia psittiaci pneumonia may be complicated with respiratory failure and/or multiple organ involvement. For severe pneumonia with an exposure history of sick birds, the possibility of Chlamydia psittaci infection should be considered. mNGS may help etiological diagnosis. All patients in this study had a good prognosis after targeted treatment.

FP.31 ANXA11 related adult-onset muscular dystrophy in Greek families

Pathogenic mutations in the low complexity domain of many RNA binding proteins have been reported in both neurogenic and myopathic disorders. Frequent involvement of multiple organs in patients often leads to associated diseases classified as multisystem proteinopathies (MSP) because of the shared aggregate pathology in the affected tissues. These mutations and associated molecular pathomechanisms are part of the dysfunctional cellular clearance of protein aggregates and stress responses. Interestingly, the same causative variant has often been observed in patients with ALS and large families with primary myopathies with or without ALS. Recently, we identified the c.118G>T; p.D40Y variant in <i>ANXA11</i> (NM_0145869.1) segregating with an autosomal dominant myopathy phenotype in five large Greek families from the relatively isolated island of Aegean Sea. However, this variant has been reported in French ALS patients and Brazilian MSP families with ALS patients. In our cohort, none of the patients have an ALS phenotype or family history of ALS. The age of onset in our patients was in the 3^rd-5^th decade of life. Muscle MRI shows myopathic fatty degeneration-replacement of adductors, semitendinosus, semimembranosus, and gastrocnemius muscles. However, none of our patients report any axial involvement with head drop described in the Brazilian MSP families with the same mutation. We present strong genetic evidence that <i>ANXA11</i> p.D40Y causes the observed phenotype in the Greek families. Further studies will unravel the additional molecular factors that can explain the involvement of different target organs causing either ALS or the primary myopathy phenotype.

Patient Characteristics and Outcome of Multi-organ Involvement in Dengue with Reference to SOFA Score

Background: Mortality in severe Dengue infection is attributed to development of MODS. Clinical profile, outcome and utility of SOFA score in Dengue MODS is not well studied in Indian context. Hence, this study was conducted to describe the “patient`s” characteristics and outcome in Dengue MODS with reference to SOFA score.&#x0D; Methods: We conducted an observational cross –sectional study in medicine department, Sassoon General Hospital Pune between January 2016 to January 2020. Adult dengue patients with multiorgan dysfunction based on SOFA score were included. Demographic, clinical and laboratory data were collected and analyzed. SOFA score was calculated at admission and monitor throughout admission course.&#x0D; Results: Total 69 patients were included. Male were 53.6% and mean age was 38.7±18.7 years. Most common symptoms were fever (98.6%), body ache &amp; joint pain (69.6%), generalized weakness (62.3%), breathlessness (59.4%), headache (58%), anorexia (58%), abdominal pain &amp; vomiting (55.1%) and bleeding manifestations (47.8%). Total 28% patients had two, 33% had three, 24.6% had four and 14.4% had ≥ 5 organs involvement. Maximum number of patients had hematological involvement (95.7%) followed by respiratory system involvement (63.8%). Mean duration of hospital stay was 9.8 days. Mortality was 43.5%. There was significant correlation of number of organs involved, pulse rate, respiratory rate, serum albumin, nervous system, respiratory system, SOFA score at admission and delta SOFA score with outcome.&#x0D; Conclusion: Dengue MODS has high mortality. Tachypnoea, tachycardia, hypoalbuminemia, respiratory failure and nervous system involvement are predictors of poor outcome. SOFA score at admission and its monitoring can serve as a useful marker to predict prognosis in dengue with multiple organ involvement.

Hydatid Disease in Children from Diagnosis to Treatment: A 10-year Single Center Experience

Hydatid disease caused by Echinococcus granulosus is a parasitic zoonosis and is endemic in Turkey. Clinical manifestations vary and are related to the anatomical location. In this report, we shared the diagnosis, treatment and follow-up of hydatid disease in children with a 10-year experience. A total of fifty-seven children diagnosed with hydatid disease were analyzed retrospectively from hospital records. Diagnosis was based on clinical, serological and radiological findings. Treatment response was evaluated with clinical, radiological and serological findings. The male/female ratio of 57 cases was 2.4:1 and the mean age was 113.6±45.9 months. The most common presenting complaint was abdominal pain (42.1%). While 22 (38.6%) of the cases had eosinophilia; indirect hemagglutination test positivity was detected in 27 cases (47.4%). Multiple organ involvement was present in 18 cases (31.6%). In patients with multiple organ involvement, the possibility of cysts being located in the abdomen was higher (p=0.005). Of the 50 cases (87.7%), 45 (78.9%) were operated with open surgery and 5 (8.8%) with percutaneous aspiration-injection-reaspiration method for treatment. There were 52 (91.2%) patients who were given albendazole in conservative treatment and the mean duration of treatment was 15.5±17.2 months. There were 10 cases (17.5%) who developed cyst rupture and the symptom duration was shorter than the cases without cyst rupture (p=0.017). Cyst rupture was more common in cases with dyspnea and fluid discharge from the mouth called rock water (p=0.001, p=0.005, respectively). Recurrence was observed in five cases (8.8%) during follow-up. In areas where the disease is endemic, despite prevention and control programs consisting of personal habits and health education, active transmission of hydatid disease is seen in children and continues to be an important public health problem. Hydatid disease should definitely be considered in the presence of suspicious radiological and clinical findings in endemic areas. Controlled clinical studies are required for diagnosis and treatment procedures.

Rhabdomyosarcoma with unknown primary tumor site: A report from European pediatric Soft tissue sarcoma Study Group (EpSSG).

Rhabdomyosarcoma (RMS) is an aggressive malignancy, and 20% of children present with metastases at diagnosis. Patients presenting with disseminated disease very occasionally have no clear evidence of a primary tumor mass. As these patients have rarely been investigated, we report on a series of patients with RMS and unknown primary tumor site registered in the Metastatic (MTS) RMS 2008 protocol (October 2008 to December 2016) coordinated by the European pediatric Soft tissue sarcoma Study Group. Patients were administered nine cycles of induction chemotherapy, and 48weeks of maintenance chemotherapy. Surgery and/or radiotherapy were planned after the first assessment of tumor response, and implemented after six cycles of chemotherapy. If feasible, radiotherapy to all sites of metastasis was recommended. We identified 10 patients with RMS and unknown primary site, most of them adolescents (median age 15.8years, range: 4.6-20.4). Nine had fusion-positive alveolar RMS. Multiple organ involvement was identified in seven patients, two only had bone marrow disease, and one only had leptomeningeal dissemination. All patients were given chemotherapy, four were irradiated, and none had surgery. Three patients underwent allogeneic bone marrow transplantation. At the time of this analysis, only two patients are alive in complete remission: one had received radiotherapy; and one had a bone marrow transplant. RMS with unknown primary tumor occurs mainly in adolescents and is typically fusion-positive alveolar. Radiotherapy may be important, but survival is poor and patients should be offered enrollment in investigational trials.