Multisystem Involvement Research Articles

Permanent cutaneous vesicostomy: a pragmatic approach to safely manage lower urinary tract dysfunction in pediatric patients with chronic and life-limiting conditions and neuropathic bladders.

Lower urinary tract dysfunction (LUTD) in cerebral palsy (CP) and other neuromuscular diseases can present with chronic retention that leads to hydronephrosis, recurrent urinary tract infections (UTI), and stone formation. Whenever the conservative treatment of LUTD fails for any reason, it is considered to be complicated LUTD, in which a surgical approach is warranted. Cutaneous vesicostomy (CV) is a simple, well-tolerated, and potentially reversible procedure that protects the upper tracts. We describe our experience using CV for this complex population. Children with CP and other neuromuscular diseases admitted to pediatric long-term care units for palliative care between 2015 and 2019 were included in the study. They present multi-system involvement, polypharmacy, and Gross Motor Function Classification System levels of 4 or 5. We retrospectively studied this population's indications and results of CV. Of the 52 admitted patients, 18 presented LUTD with UTI (n:18; 100%), stones (n:5; 28%), progressive hydroureteronephrosis (n:3; 17%), or stones (n:2; 11%). Conservative initial management (catheterizations, prophylaxis antibiotics) was effective in half the cases. The remaining nine were defined as complicated LUTD and underwent CV. After a mean follow-up of 11.3 months, the follow-up showed improved hydronephrosis in all nine (100%) patients. Recurrent UTIs were no longer seen in eight of nine patients, although three patients required bladder irrigations; bladder stones did not recur after CV; the kidney stones needed further intervention. Revision of the CV was required in two (11%) cases at 12 and 24 months postoperatively due to stoma stenosis. CV is a relatively simple and effective procedure representing a pragmatic solution for managing complicated LUTD in complex long-term institutionalized pediatric palliative care patients with neuropathic bladders.

Adult Multissystem Inflamatory Síndrome (MIS-A): case report

Introduction: The COVID-19 pandemic has resulted in a global health crisis. SARS-CoV-2 infection and its broad spectrum of systemic involvement have demonstrated the existence of equally serious extrapulmonary complications in adult patients. In this context, Multisystem Inflammatory Syndrome (MIS), a serious complication that occurs after acute infection and has a hyperinflammatory nature with potential multisystem involvement, began to be reported as it developed in pediatric patients and in young and middle-aged adults. Experience report: Man, 36 years old, without previous comorbidities, with a history of COVID-19 infection, 4 months ago, with mild evolution and spontaneous resolution, seeks care for persistent fever for 20 days, generalized malaise, jaundice, choluria, chest pain and neck edema. Exams showed leukocytosis, with left shift, elevated PCR, negative blood culture. The tomography revealed an expansive lesion in the chest and cervical lymph node enlargement. The patient was admitted and underwent an exploratory cervicotomy for drainage and debridement, with prescription of intravenous antibiotics. Discussion: Multisystem Inflammatory Syndrome (MIS) associated with COVID-19 is a hyperinflammatory phenomenon that can cause organ dysfunction. Corticosteroids have been shown to be effective in treatment, but early diagnosis is crucial for a good prognosis. Conclusion: Adult Multisystem Inflammatory Syndrome (MIS-A) is a post-COVID-19 complication that can occur weeks after the initial infection. In this patient's case, multidisciplinary treatment, including surgery and various drug therapies, resulted in recovery. The case emphasizes the importance of raising awareness about MIS-A among health professionals and the need for research to improve diagnoses and treatments, as well as the importance of early interventions to manage the condition.

Association between COVID-19 severity with liver abnormalities: A retrospective study in a referral hospital in Indonesia.

Coronavirus disease 2019 (COVID-19) is characterized by an acute respiratory infection with multisystem involvement and the association of its severity to liver function abnormalities is not well characterized. The aim of this study was to assess the association between the severity of COVID-19 patients and liver function abnormalities. This retrospective study included adult patients with confirmed COVID-19, which were classified as non-severe or severe according to World Health Organization guidelines. Liver function test results were compared between the severity groups. A total of 339 patients were included of which 150 (44.25%) were severe cases. The male-to-female ratio was 0.9:1 and 3:2 in the non-severe and severe groups, respectively (p=0.031). Aspartate aminotransferase (AST), alanine transaminase (ALT), and total bilirubin levels and acute liver injury (ALI) incidence were significantly higher in the severe group compared to non-severe group (p<0.001, p<0.001, p=0.025, p=0.014, respectively). In contrast, albumin levels were significantly lower (p=0.001). Multivariate analysis showed that ALI was significantly associated with human immunodeficiency virus (HIV) infection (odds ratio (OR): 5.275; 95% confidence interval (CI): 1.165-23.890, p=0.031), hemoglobin level (OR: 1.214; 95%CI: 1.083-1.361, p=0.001), and hypoalbuminemia (OR: 2.627; 95%CI: 1.283-5.379, p=0.008). Pre-existing liver diseases were present in 6.5% of patients. No significant differences were observed between the groups based on COVID-19 severity and ALI presence. Liver function test abnormalities, including ALI, are more prevalent in patients with severe COVID-19 infection. HIV infection, high hemoglobin levels, and hypoalbuminemia may be potential risk factors for ALI.

Multisystem involvement and early onset of Danon’s disease in female children. Clinical cases

Multisystem involvement and early onset of Danon’s disease in female children. Clinical cases

Identification of patterns of microbiota influence on the pathogenetic mechanisms of systemic lupus erythematosus development

Systemic lupus erythematosus (SLE) is a complex, multifactorial autoimmune disease characterized by multisystem involvement. Although the pathogenesis of SLE is not fully understood, numerous studies have shown that the composition of the microbiota can influence the course of the disease. The microbiota plays a key role in the development of immune defense and is an integral part of immune homeostasis. Dysbiosis of the intestinal, oral and vaginal microbiota can have a significant impact on the development of inflammatory and autoimmune diseases. The review addresses recent studies on the microbiota, with a particular focus on changes in the composition of the gut microbiota and their impact on SLE. Data from several studies suggest that there is a link between SLE and certain patterns of dysbiosis.

Gastrointestinal involvement in neuromuscular disorders.

Although not often discussed, many of the neuromuscular disorders (NMDs) affect the gastrointestinal tract (GIT). Depending on the type of NMD, the prevalence of GIT involvement ranges from <5% (e.g. hereditary neuropathies, myofibrillar myopathies) to 100% (e.g. MNGIE, OPMD). Particularly in NMDs with multisystem affection, involvement of the GIT can dominate the clinical presentation or at least make up a significant part of the clinical picture. The most prominent representatives of NMDs with multisystem involvement are the mitochondrial disorders (MIDs) and the myotonic dystrophies. The best known syndromic MIDs with GIT involvement are MNGIE, MELAS, Leigh, and Pearson syndromes. Among neuropathies, GIT involvement is most commonly found in ALS and GBS. GIT involvement may also be a feature of myasthenia. The clinical manifestations of GIT involvement are diverse and can affect the entire GIT, from the teeth to the rectum, including the liver and pancreas. The most well-known clinical manifestations of GIT involvement are dysphagia, nausea, vomiting, reflux, hollow organ dysmotility, hepatopathy, diabetes, diarrhea, constipation, and fecal incontinence. Even if treatment can usually only be symptomatic, the therapeutic options are diverse, are often effective, and can significantly and beneficially influence the course of the underlying NMD.

Tuberculosis of the bone marrow with secondary hemophagocytic lympho-histiocytosis presenting as obstructive jaundice: A clinician's challenge for the ages

Tuberculosis. a disease of great public concern, is spread through inhalation of micro-droplets from an infected person. Despite lungs being the primary site, there may be multisystemic involvement, very rarely involving bone marrow, a dreaded manifestation of disseminated tuberculosis, associated with high mortality and morbidity. We report a case of tuberculosis of bone marrow with concomitant secondary hemophagocytic lympho-histiocytosis, bringing into light the importance of clinical suspicion and evaluation of bone marrow being a primary site of involvement in patients of disseminated tuberculosis.

Exploring the Pathophysiology of Long COVID: The Central Role of Low-Grade Inflammation and Multisystem Involvement.

Long COVID (LC), also referred to as Post COVID-19 Condition, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and other terms, represents a complex multisystem disease persisting after the acute phase of COVID-19. Characterized by a myriad of symptoms across different organ systems, LC presents significant diagnostic and management challenges. Central to the disorder is the role of low-grade inflammation, a non-classical inflammatory response that contributes to the chronicity and diversity of symptoms observed. This review explores the pathophysiological underpinnings of LC, emphasizing the importance of low-grade inflammation as a core component. By delineating the pathogenetic relationships and clinical manifestations of LC, this article highlights the necessity for an integrated approach that employs both personalized medicine and standardized protocols aimed at mitigating long-term consequences. The insights gained not only enhance our understanding of LC but also inform the development of therapeutic strategies that could be applicable to other chronic conditions with similar pathophysiological features.

Delayed diagnosis of mild mucopolysaccharidosis type IVA

BackgroundMucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disease caused by biallelic variants in the N-acetylgalactosamine-6-sulfatase (GALNS) gene and is characterized by progressive and multi-system involvements, dominantly with skeletal deformities. A mild form of MPS IVA often presents with atypical symptoms and can go unrecognized for years.MethodsThe diagnosis of MPS IVA was confirmed via GALNS enzyme activity testing in leukocytes. Clinical features were collected. Molecular analysis was performed by next generation sequence and Sanger sequencing of the GALNS gene. The pathogenicity of the deep intron variant was verified by mRNA analyses.ResultsThirteen patients with mild MPS IVA from six families were included. All probands first visit pediatric orthopedists and it took 5.6 years to be diagnosed after the disease onset. The most common symptoms in our series were waddling gait (85%), short neck (69%) and flat feet (62%). Radiologic findings indicated skeletal abnormalities in all patients, especially modification of the vertebral bodies (100%) and acetabular and femoral head dysplasia (100%). Five novel GALNS variants, including c.121-2_121-1insTTTGCTGGCATATGCA, E2 deletion, c.569 A > G, c.898 + 2 T > A, and c.1139 + 2 T > C, were identified. The most common variant, a deep intron variant NM_000512.5: c.121–210 C > T (NM_001323544.2: c.129 C > T, p.G43G), was revealed to result in an 11 bp deletion (c.128_138delGCGATGCTGAG, p.Gly43Aspfs*5) on GALNS mRNA in the GALNS transcript of NM_001323544.2.ConclusionsThis study provides significant insights into the clinical features and molecular characteristics that contribute to the early diagnosis of mild MPS IVA. On the basis of our cohort, orthopedists need to be able to recognize signs and symptoms of mild MPS IVA as well as the molecular and biochemical diagnosis so that an early diagnosis and treatment can be instituted.

Prevalence and patterns of post-COVID-19 symptoms in recovered patients of Delhi, India: a population-based study.

Post-coronavirus disease 2019 (COVID-19) symptoms were widely reported. However, data on post-COVID-19 conditions following infection with the Omicron variant remained scarce. This prospective study was conducted to understand the prevalence, patterns, and duration of symptoms in patients who had recovered from COVID-19. A prospective study was conducted across 11 districts of Delhi, India, among individuals who had recovered from COVID-19. Study participants were enrolled, and then returned for post-recovery follow-up at 3 months and 6 months interval. The mean age of study participants was 42.07 years, with a standard deviation of 14.89 years. The majority of the participants (79.7%) reported experiencing post-COVID-19 symptoms. The most common symptoms included joint pain (36.0%), persistent dry cough (35.7%), anxiety (28.4%), and shortness of breath (27.1%). Other symptoms were persistent fatigue (21.6%), persistent headache (20.0%), forgetfulness (19.7%), and limb weakness (18.6%). The longest duration of symptom was observed to be anxiety (138.75±54.14 days), followed by fatigue (137.57±48.33 days), shortness of breath (131.89±60.21 days), and joint pain/swelling (131.59±58.76 days). At the first follow-up visit, 2.2% of participants presented with abnormal electrocardiogram readings, but no abnormalities were noticed during the second follow-up. Additionally, 4.06% of participants exhibited abnormal chest X-ray findings at the first followup, which decreased to 2.16% by the second visit. The most frequently reported post-COVID-19 symptoms were joint pain, dry cough, anxiety and shortness of breath. These clinical symptoms persisted for up to 6 months, with evidence of multi-system involvement. Consequently, findings highlighted the need for long-term follow-up during the post-COVID-19 period.

Multi-system involvement—including purpura fulminans—as an adverse effects of immune checkpoint inhibitor therapy for clear cell renal cell carcinoma

Multi-system involvement—including purpura fulminans—as an adverse effects of immune checkpoint inhibitor therapy for clear cell renal cell carcinoma

Causes of death and patterns of metastatic disease at the end of life for patients with advanced melanoma in the immunotherapy era.

e21522 Background: Despite the drastic improvement in survival of patients with metastatic melanoma from immune checkpoint inhibitors (ICIs), almost half of patients still die from their disease. Factors surrounding death including mechanisms of death, sites of disease, and settings of death remain poorly described. A better understanding of these factors is paramount to optimize management for these patients. Methods: A retrospective observational cohort study was performed for patients age &gt; 18 who died after treatment for advanced melanoma with anti-PD1 therapy or ipilimumab + nivolumab (Ipi/Nivo) at Yale Cancer Center (YCC) between 1/2009 and 6/2023. Primary outcome was cause of death. Statistical analyses were performed with Stata SE, version 15.0 (StataCorp, College Station, TX). This study was approved by the Yale Institutional Review Board (Protocol #2000034631). Results: Overall, 287 patients with melanoma who received ICIs were documented to be deceased; 183 met inclusion criteria. Median time from metastatic diagnosis to death was 16.1 mos (range 0.3 to 135.1 mos). Median age at death was 70 (range 22-101), 62.8% were male, and 90.2% were white. Most patients (52.5%) received Ipi/Nivo first line, and 79.8% of patients received both anti-PD1 and anti-CTLA4 treatment at some point. The median number of metastatic sites at death was 4 (range 0-13). The majority (90.1%) of patients with measurable disease had multi-system involvement of melanoma. Eleven patients had no evidence of disease at death and died due to non-melanoma causes. The most common sites of metastatic disease at death were distant lymph nodes (62.8%), lung (57.9%), liver (50.8%), brain (38.8%), and bone (37.7%). In total, 80.3% (147/183) experienced hospitalization within 3 months prior to death or hospice enrollment. Most died in the hospital (31.7%) or while enrolled in hospice (31.2% inpatient vs. 29.4% home). Overall, 10.9% of patients had survival &gt; 5 years after metastatic diagnosis; 76.2% of long-term survivors died due to melanoma. Of 174 patients with evaluable causes of death, 87.9% of deaths were due to melanoma (Table 1). Patients with pleural metastases were more likely to die of respiratory failure (p = 0.036, OR 2.41 95% CI 1.06-5.50). Conclusions: The majority of deaths were a consequence of metastatic melanoma, with the most common causes including FTT, respiratory failure, and infection. [Table: see text]

Clinical profile, otologic, and auditory outcomes in patients with Down syndrome

Introduction and objectivesEven though the incidence has decreased in recent years, Down syndrome (DS) remains the most common chromosomal disorder today. Despite being a condition with multisystemic involvement, it often tends to affect the head and neck area, making it a frequent reason for consultation with pediatric otolaryngologists or otologists. The purpose of this work is to be one of the first in Spain to characterize and describe the pathology and therapeutic approach typically provided to these patients, analyzing the evolution from a clinical and auditory perspective. Material and methodsWe aim to analyze a sample of 16 pediatric patients recruited over the past 24 years, diagnosed with Down syndrome, and experiencing a wide range of diseases affecting the ear and its auditory function. Results62.50% of the patients were women, whose main reason for seeking specialist care was acute and serous otitis media, accounting for 31.25%. These patients have an indication for treatment for various entities within the otological sphere that usually do not differ from those of a healthy child. However, the evolution and response to treatments can take on a torpid character due to the anatomical characteristics of the ears of these patients. ConclusionsAlthough the frequency of children with DS in the pediatric otolaryngologist's clinic is decreasing, these patients have a predisposition to ear diseases with auditory repercussions, with variable evolution depending on the disease and the child's intrinsic characteristics.

A Misdiagnosis of MIS-C: Acute Pneumococcal Meningitis Due to Serotype 19F in A Child with Acute SARS-CoV-2 Infection with a Severe Disease Course.

According to the 2020 CDC criteria, multisystem inflammatory syndrome in children (MIS-C) due to Coronavirus disease-19 (COVID-19) is diagnosed when all of the following criteria are met: fever for+≥+24 hours, laboratory evidence of inflammation, multisystem (+≥+2) organ involvement, evidence of SARS-CoV-2 infection or exposure, and no alternative plausible diagnoses (CDC, 2020). Alternative diagnosis need to be excluded before coming upon an MIS-C diagnosis since there are plenty of infectious diseases that may mimic MIS-C (Dworsky et al., Pediatr Infect Dis J 2021; 40; e159-e161; Yalçinkaya et al., Pediatr Infect Dis J 2021; 40; e524-e525; Kaneta et al., Pediatr Infect Dis J 2023; 42; 590-593; Stanzelova et al., Pediatr Infect Dis J 2023; 42; e201-e203; Kolsi et al., Arch Pediatr 2023; 30; 521-523). Herein, we present a 6-year-old girl who was preliminarily diagnosed with MIS-C and received intravenous immunoglobulin (IVIG) treatment before referral to our center. She was diagnosed with acute pneumococcal meningitis due to serotype 19 F and ultimately suffered from sensorineural hearing loss (SNHL) as a sequela. We present this case to remind physicians that MIS-C should not be diagnosed unless other infectious causes are excluded.

Experiences of Children and Young People with a Disability in Out-of-Home Care in Australia: A Scoping Review

Children with disabilities in out-of-home care (OOHC) are an overrepresented group in Australia, yet little is known about their circumstances, needs, and experiences within OOHC. Utilising a systematic scoping review methodology, we explored the state of knowledge about the experiences of children and young people with a disability in out-of-home care in Australia. Findings in this review speak to the unmet needs and challanges that children with disabilities face in child welfare systems and how systemic failures can lead to institutional pipelines of further maltreatment, adversity, and marginalisation. The review discusses the key themes in the literature, including (i) compounding trauma and placement failures, (ii) concerns of safety, stability, and neglect, (iii) limited control and choice, and (iv) disability and multisystem involvement.

Generation of a human iPSC line CIPi004-A from a patient with neurofibromatosis type 1 and epilepsy harboring a heterozygous mutation in NF1 gene

The NF1 gene is related to neurofibromatosis type 1 (NF1), which is an autosomal dominant disorder associated with multisystem involvement and epilepsy susceptibility. A human induced pluripotent stem cell (iPSC) line was derived from a pediatric patient with NF1 and epilepsy, harboring a heterozygous NF1 gene mutation. The iPSC line exhibits high levels of pluripotency markers, maintains the NF1 gene mutation, and demonstrates the capacity to undergo differentiation potential in vitro into three germ layers. The iPSC line will serve as a valuable resource for investigating the underlying mechanisms and conducting drug screening related to NF1 and NF1-associated epilepsy.

A rare Case Report of Hurler syndrome with multisystem involvement including glucose intolerance

Background: Mucopolysaccharidosis type I (Hurler syndrome) is a rare autosomal recessive inborn deficiency in the metabolism of glycosaminoglycans (GAGs) heparan sulfate and dermatan sulfate, resulting from deficiency of Alpha-L-iduronidase enzyme. An interesting case of a 19 year old male with a combination of skeletal, neurological, ophthalmologic, and radiological findings with MPS I-(Hurler syndrome) has been presented here in this case report.

Incontinentia Pigmenti In a Female Infant: A Case Report

Incontinentia pigmenti (IP) is an X-linked disorder characterized by a variety of findings that affect different systems, including cutaneous, ophthalmologic, neurologic, and dental. The cutaneous findings occur in 4 consecutive stages, generally referred to as vesicular, verrucous, hyperpigmented, and atrophic. The first stage is often observed in infancy, and this may be the first indication of IP in an infant. Early diagnosis is critical so that interventions can be implemented as soon as possible to monitor for complications and mitigate the effects of IP given the potential for multisystem involvement. Here, we describe a case of IP that was diagnosed in a female infant with no prior family history of IP. Prompt diagnosis and family counseling is critical, as early interventions can help optimize patients’ quality of life and genetic testing may help families make informed future family planning decisions.

Cornelia de Lange Spectrum

Cornelia de Lange syndrome (CdLS) is a rare congenital developmental disorder with multisystemic involvement. The clinical presentation is highly variable, but the classic phenotype, characterized by distinctive craniofacial features, pre- and postnatal growth retardation, extremity reduction defects, hirsutism and intellectual disability can be distinguished from the nonclassic phenotype, which is generally milder and more difficult to diagnose. In addition, the clinical features overlap with those of other neurodevelopmental disorders, so the use of consensus clinical criteria and artificial intelligence tools may be helpful in confirming the diagnosis.Pathogenic variants in NIPBL, which encodes a protein related to the cohesin complex, have been identified in more than 60% of patients, and pathogenic variants in other genes related to this complex in another 15%: SMC1A, SMC3, RAD21, and HDAC8. Technical advances in large-scale sequencing have allowed the description of additional genes (BRD4, ANKRD11, MAU2), but the lack of molecular diagnosis in 15% of individuals and the substantial clinical heterogeneity of the syndrome suggest that other genes and mechanisms may be involved.Although there is no curative treatment, there are symptomatic/palliative treatments that paediatricians should be aware of. The main medical complication in classic SCdL is gastro-esophageal reflux (GER), which should be treated early.

E050 Angiotensin converting enzyme for the diagnosis of childhood sarcoidosis

Abstract Background/Aims Childhood sarcoidosis is a rare multisystem inflammatory granulomatous disease. The prevalence of sarcoidosis in children is unknown due to its rarity. A review of sarcoidosis in Denmark found an incidence in children &amp;lt; 15 years of 0.22-0.27 per 100 000/year. Diagnosis can be challenging given the varied presentations due to multisystem involvement. There is no one laboratory test that is diagnostic for sarcoidosis. Angiotensin converting enzyme (ACE) has been shown to be elevated in 50% of late-onset childhood sarcoidosis. Reference levels are laboratory and age dependent, and healthy children can have levels that are 40-50% higher than in adults. Our aim was to gain a better understanding of the use of ACE in clinical practice and to review its role in diagnosis and management of sarcoidosis. Methods We collated the list of all patients under 18 years who had ACE levels done at our hospital between 1/12/2021 and 30/11/2022 via clinical pathology. Electronic patient records were reviewed for all patients to gather information on demographics, and clinical symptoms. Results We had a total of 98 ACE blood tests done for 58 patients. Clinical notes and results were available for 34 of these patients with a total of 48 ACE results. Age range of patients was 3-17 years with a mean age of 12 years. 19 (56%) patients were female, 15 (44%) were male. 50% were of white ethnicity, 12% of black ethnicity, 3% Indian ethnicity, 3% Pakistani ethnicity, 3% Chinese ethnicity and 29% ethnicity not recorded. 45 were requested by in hospital specialties, 2 from other hospitals and 1 from a GP. Of those requested in hospital 73% had been requested by ophthalmology, rheumatology or dermatology, with the remainder requested by a range of other paediatric specialties. Results ranged from 11-195 U/L, with a median of 76 U/L. Hospital reference range is 13-64 U/L and 18 patients had results &amp;gt;64 U/L. Reference ranges for paediatric patients in literature is 29-112 U/L. 6 patients had a result&amp;gt;112U/L. One patient had a diagnosis of sarcoidosis. Following the initial results a further 4 years of results were analysed from 02/01/2018-30/11/2022. 10 further patients had ACE results &amp;gt;112U/L. Of these, none had sarcoidosis. Conclusion These results support that the diagnosis of sarcoidosis is rare. ACE results need to be interpreted being mindful that normal childhood ACE levels may be higher than the reference ranges given by hospitals, which may be based on adult ranges. There is need for more research in this area to ascertain diagnostic ACE levels and role of ACE in disease monitoring. I plan to lead a trainee multicentre retrospective project looking at the diagnosis of paediatric sarcoidosis, and within this review the role of ACE levels. Disclosure M.C. Mackay: None. S. Deepak: None. K. Warrier: None. S. Rangaraj: None.