Multisystem Organ Involvement Research Articles

Advances in diabetes technology to improve the lives of people with cystic fibrosis.

People with cystic fibrosis (CF) are at risk for dysglycaemia caused by progressive beta cell dysfunction and destruction due to pancreatic exocrine disease and fibrosis. CF-related diabetes (CFRD) is a unique form of diabetes that has distinctive features from both type 1 and type 2 diabetes. Recent advances in diabetes technology may be of particular benefit in this population given the complex, multi-system organ involvement and challenging health issues that people with CFRD often face. This review summarises how diabetes technologies, such as continuous glucose monitors (CGMs) and insulin delivery devices: (1) have improved our understanding of CFRD, including how hyperglycaemia affects clinical outcomes in people with CF; (2) may be helpful in the screening and diagnosis of CFRD; and (3) offer promise for improving the management of CFRD and easing the burden that this diagnosis can add to an already medically complicated patient population.

Rectal thionamide administration in the setting of thyroid storm: a case report and review of the literature.

Thyroid storm is a clinical diagnosis characterized by life-threatening multisystemic organ involvement in the setting of uncontrolled hyperthyroidism. Current estimates suggest a mortality rate of up to 30%. Treatment often consists of the administration of thionamide medications, iodine solution(s), corticosteroids, and beta-blockers; in extreme circumstances, both plasmapheresis and thyroidectomy are subsequent therapeutic options. Thionamides are typically administered orally, with the intent of preventing further thyroid hormone synthesis; however, in the literature, there are instances whereby oral access cannot be obtained, and alternative routes of administration are required. We present a case of a patient who presented with a thyroid storm due to lack of adherence to methimazole. During admission, he was found to have significant abdominal pain and ultimately a duodenal perforation requiring strict nil-per-os (NPO) status, due to which he was unable to receive oral thionamides. Due to the lack of availability of intravenous formulations of thionamides in the United States, this patient was treated with an enema compound of propylthiouracil for a total of five per rectum (PR) doses. He would later develop hepatocellular injury, requiring discontinuation and eventual transition to oral methimazole. The literature pertaining to alternative-route thionamide administration is scant, and therefore this case report and literature review is written to provide an up-to-date review and further educate all levels of clinicians about this infrequent (but emergent) situation. Thyroid storm is a clinical diagnosis for which urgent recognition is required to prevent untoward mortality. Treatment for thyroid storm requires prompt administration of thionamides, iodine, corticosteroids, and beta-blockers. In extreme circumstances, treatment considerations include plasmapheresis and thyroidectomy. Infrequently, patients with a thyroid storm may not be able to tolerate oral medications, for which alternative routes of access are required. Currently, available alternatives include intravenous methimazole (in Europe and Japan), as well as both enema and suppository preparations of propylthiouracil and methimazole.

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.

An Analysis of the Readability of Online Sarcoidosis Resources.

Introduction Sarcoidosis is an inflammatory disease characterized by the formation of noncaseating granulomas in multiple organ systems. The presentation can vary widely; although some patients with sarcoidosis can be asymptomatic, sarcoidosis can also present in others with symptomatic multiorgan system involvement. Considering the potential severity of the disease, patients need to be well-informed about sarcoidosis to better manage their health. This study aims to assess the readability levels of online resources about sarcoidosis. Methods We conducted a retrospective cross-sectional study. The term "sarcoidosis" was searched online using both Google and Bing to find websites written in English. Each website was categorized by type: academic, commercial, government, nonprofit, and physician. The readability scores for each website were calculated using six different readability tests: the Flesch-Kincaid reading ease (FKRE), Flesch-Kincaid grade level (FKGL), Gunning fog score (GFS), Simple Measure of Gobbledygook (SMOG), automated readability index (ARI), and Coleman-Liau index (CLI). FKRE gives a score that corresponds to the difficulty of the text, while the remaining tests give a score that corresponds to a grade level in terms of reading ability. A one-sample t-test was used to compare all test scores with the national recommended standard of a sixth-grade reading level. Our null hypothesis was that the readability scores of the websites searched would not differ statistically significantly from the sixth-grade reading level and that there would be no significant differences across website categories. To evaluate the difference between the categories of websites, ANOVA testing was used. Results Thirty-four websites were analyzed. Each of the six readability tests for the websites had an average score, which corresponded to being significantly harder to read than the nationally recommended sixth-grade reading level (p<0.001). None of the mean readability scores showed a statistically significant difference across the five different website categories. Conclusions This is the first study, to our knowledge, to examine the readability of online English resources on sarcoidosis and calculate standardized readability scores for them. It implies that the online English material for sarcoidosis is above the health literacy recommended reading levels for patients. There is a need to simplify the material to be easier to read for patients.

Congenital diseases with multi-organ expression as an indication for liver transplantation in children during the first years of life: Integrative approach to improve the outcomes

Pediatric liver transplantation has evolved since the first transplant was performed by Dr. Starzl more than 50 years ago. Innovations in surgical techniques, immunosuppression, and infection control have significantly improved patient outcomes, graft survival, and quality of life. However, further progress depends not only on the discovery of new treatment option but should rely upon the identification of the factors in the perioperative care which contribute to successful outcomes and guide our decision-making process.Indications for pediatric liver transplantation can be divided into three major groups: cholestatic liver conditions, liver based metabolic disorders, and others represented by acute liver failure of different etiologies, tumors, inherited autoimmune diseases, and multiple infectious causes.Many of these conditions manifest themselves with multi organ pathologic expression, requiring earlier interventions to treat acute liver failure or chronic cholestasis leading to failure to thrive. Containment of patient pathology and maintenance of optimal neurologic and extra-hepatic visceral organ function is paramount during the pre - transplant period.Multidisciplinary management of comorbid conditions in complex pediatric liver transplant candidates during the perioperative period with the emphases on optimization and patient selection has never been summarized in the literature. Thant is why this review focuses on a comprehensive, multidisciplinary preoperative evaluation of pediatric patients in whom progressive liver disfunction manifests early in life and eventually requires liver transplantation. We will address multi-organ system involvement, preoperative optimization in anticipation of the complexity of intraoperative care, as well as short- and long-term postoperative management.

Longitudinal, natural history study reveals the disease burden of idiopathic multicentric Castleman disease.

Idiopathic multicentric Castleman disease (iMCD) is a rare hematologic disorder with heterogeneous presentations ranging from moderate constitutional symptoms to life-threatening multiorgan system involvement. There are vastly different clinical subtypes, with some patients demonstrating thrombocytopenia, anasarca, fever/elevated C-reactive protein, reticulin fibrosis/renal failure, and organomegaly (TAFRO) and others having milder/more moderate symptoms with potential for severe disease (not otherwise specified, NOS). Due to its rarity and heterogeneity, the natural history and long-term burden of iMCD are poorly understood. We investigated real-world medical data from ACCELERATE, a large natural history registry of patients with Castleman disease, to better characterize the long-term disease burden experienced by these patients. We found that iMCD-TAFRO patients face a significant hospitalization burden, requiring more time in the hospital than iMCDNOS patients during the year surrounding diagnosis (median [interquartile range]: 36 [18-61] days vs. 0 [0-4] days; P<0.001). In addition, we found life-sustaining interventions, such as mechanical ventilation (17%) and dialysis (27%), were required among iMCD patients, predominantly those with iMCD-TAFRO. iMCD-NOS patients, however, spent a significantly greater proportion of time following disease onset in a state of disease flare (median 52.3% vs. 18.9%; P=0.004). Lastly, we observed severe iMCD-related morbidities, such as acute renal failure, sepsis and pneumonia, among others, arising after iMCD diagnosis, impairing the patients' quality of life. These data demonstrate a substantial disease burden experienced by iMCD patients and emphasize the importance of ongoing research into iMCD to aid disease control.

An Interesting Case Series of Neuropsychiatric Lupus: A Combination of Inflammatory and Thrombotic Origin

Systemic Lupus Erythematosus (SLE) is a versatile autoimmune disorder with multisystem organ involvement, most commonly involving the skin, joints, vasculature, and associated immunological abnormalities. The hallmark of SLE is the presence of circulating non organ specific humoral autoantibodies synthesised by so-called T cell-dependent B cells, which are germline encoded. Patients with SLE can exhibit symptoms of Central Nervous System (CNS) involvement, termed CNS Lupus, which may also have associated psychiatric manifestations, where the entity gets the designation of Neuropsychiatric SLE (NPSLE). CNS Lupus is often a diagnosis of exclusion, as there are many other aetiological factors that could result in seizures and encephalitis picture. A detailed examination of patients presenting with isolated late-onset seizures is very helpful in uncovering Connective Tissue Disorder (CTD) as the cause of seizures. The manifestations of NPSLE (19 Neuropsychiatric syndromes) can be focal and diffuse, ranging from non specific symptoms such as headache and cognitive impairment to severe manifestations such as memory loss, seizures, stroke, and suicidal intentions. Neuropsychiatric symptoms often occur during the first year of SLE but can rarely also be the presenting symptom of the disease. Antiphospholipid antibodies (Anticardiolipin, Lupus anticoagulant, Anti β2 glycoprotein) and Anti Ribosomal P antibodies are among the frequently associated antibodies in NPSLE, which, in turn, increase the risk of both focal and diffuse neurological complications. A single episode of abortion or miscarriage is a vital clue for a detailed work-up of female patients for the possibility of an underlying occult potential of CNS Lupus in the absence of seizures. The present case series focuses on five female patients who presented with NP symptoms, and finally, the cause was attributed to the involvement of CNS in SLE after excluding other possible organic causes.

Efficacy and safety of intermediate-dose cytarabine in the treatment of children with refractory high risk Langerhans cell histiocytosis

Objective: To analyze the efficacy, safety, and long-term prognosis of intermediate-dose cytarabine (Ara-c) regimen in the treatment of children with refractory risk organ involvement Langerhans cell histiocytosis (LCH). Methods: Clinical data of 17 children with multisystem and risk organ involvement LCH who failed the first-line therapy and were treated with intermediate-dose Ara-c (250 mg/m2, twice daily) regimen in the Hematology Center, Beijing Children's Hospital from January 2013 to December 2016 were analyzed retrospectively. In addition to the basic treatment of vindesine and dexamethasone, the patients received two regimens: regimen A: the intermediate-dose Ara-c combined with cladribine and regimen B: the intermediate-dose Ara-c alone. The efficacy, safety and prognosis of the two regimens were analyzed. Results: Among all 17 patients, there were 11 males and 6 females, with the diagnosis age of 2.1 (1.6, 2.7) years. Ten children received regimen A, all of them achieved active disease-better (AD-B) after 8 courses of induction therapy. The disease activity scores (DAS) decreased from 5.5 (3.0, 9.0) to 1.0 (0, 2.3). Seven children received regimen B, and 6 of them achieved AD-B after 8 courses of induction therapy. The DAS decreased from 4.0 (2.0, 4.0) to 1.0 (0, 2.0). The follow-up time was 6.2 (4.9,7.2) and 5.2 (3.7,5.8) years in group A and B. The 5-year overall survival rate was 100.0% in both groups, and the 5-year event free survival rate was (88.9±10.5)% and (85.7±13.2)% in group A and B. Grade 3 or 4 myelosuppression was observed in 8 patients in group A and 2 patients in group B. Conclusions: The intermediate-dose Ara-c regimen (with or without cladribine) is effective and safe for patients with refractory high-risk LCH, with a good long-term prognosis.

EGS P06 Pattern of oesophago-gastric injuries and its outcome in major trauma and tertiary UGI centre

Abstract Background Oesophago-gastric injuries in major trauma are relatively rare. These injuries are known to be associated with high morbidity and mortality. Major trauma involving oesophagus and stomach are linked with high velocity, high impact blunt or penetrating force. There is also a strong association between oesophago-gastric injuries and other systemic injuries including thoracic, major vessels, skull, brain and abdominal viscerae. In this study we aimed to evaluate the pattern of injury in oesophageal and gastric major trauma its association with widely used injury severity score (ISS), multi organ system involvement, survival and factors affecting mortality. Methods Patients presenting between January 2012 and December 2022 as major trauma as moderate / severe trauma (ISS &amp;gt; 9) with oesophageal and gastric injuries were included in this study. Retrospective analysis was carried out on prospectively maintained trauma data base in an urban major trauma centre with specialist tertiary upper GI cover. Mechanism of injury, ISS and mortality were calculated. Analysis was carried out on variables to identify factors contributing to overall index admission mortality. MedCalc ® was used to perform statistical analysis. Results A total of 8984 patients presented in urban major trauma centre with moderate to severe trauma (ISS &amp;gt;9). Among them 13 had gastric injuries and 3 had oesophageal injuries (total n=16). Mechanism of injury in gastric patients was blunt force in 8 (61.5%) and penetrating force was in 5 (38.5%) patients whereas all oesophageal injuries were linked with penetrating trauma. Median ISS in gastric injuries was 17 and in oesophageal injuries was 34. Overall mortality was 31.2%(n=5). Variables including high ISS, thoracic injury, diaphragmatic rupture, skull injuries &amp; blood transfusion were linked with mortality on multivariate logistic regression. Conclusions Our study finds an association of oesophago-gastric injuries with high impact penetrating and blunt trauma. Presence of oesophageal and gastric injuries are surrogate indicators of severity of trauma, it is not only associated with high ISS but also has relatively high mortality. Therefore, early involvement of specialist senior decision maker in time critical setting is recommended. Due to scarce volume of OG trauma, national UGI trauma collaborative can be helpful to share experience, learn lessons and promote research.

Multi-omics analysis of zebrafish response to tick saliva reveals biological processes associated with alpha-Gal syndrome

The alpha-Gal syndrome (AGS) is a tick-borne allergy. A multi-omics approach was used to determine the effect of tick saliva and mammalian meat consumption on zebrafish gut transcriptome and proteome. Bioinformatics analysis using R software was focused on significant biological and metabolic pathway changes associated with AGS. Ortholog mapping identified highly concordant human ortholog genes for the detection of disease-enriched pathways. Tick saliva treatment increased zebrafish mortality, incidence of hemorrhagic type allergic reactions and changes in behavior and feeding patterns. Transcriptomics analysis showed downregulation of biological and metabolic pathways correlated with anti-alpha-Gal IgE and allergic reactions to tick saliva affecting blood circulation, cardiac and vascular smooth muscle contraction, behavior and sensory perception. Disease enrichment analysis revealed downregulated orthologous genes associated with human disorders affecting nervous, musculoskeletal, and cardiovascular systems. Proteomics analysis revealed suppression of pathways associated with immune system production of reactive oxygen species and cardiac muscle contraction. Underrepresented proteins were mainly linked to nervous and metabolic human disorders. Multi-omics data revealed inhibition of pathways associated with adrenergic signaling in cardiomyocytes, and heart and muscle contraction. Results identify tick saliva-related biological pathways supporting multisystemic organ involvement and linking α-Gal sensitization with other illnesses for the identification of potential disease biomarkers.

A Multidisciplinary Approach as a Goal for the Management of Complications in Systemic Scleroderma: A Literature Review and Case Scenario

Systemic sclerosis (also known as scleroderma) is a chronic fibrosing autoimmune disease with both skin and multisystem organ involvement. Scleroderma has the highest mortality among all rheumatic diseases. The pathophysiology mechanism of systemic sclerosis is a progressive self-amplifying process, which involves widespread microvascular damage, followed by a dysregulation of innate and adaptive immunity and inflammation and diffuse fibrosis of the skin and visceral organs. Fibrosis of internal organs is a hint for systemic sclerosis, moreover associated with interstitial lung disease (SSc-ILD) is a complex process. In order to correlate scientific data from the literature with clinical experience, we present the case of a 56-year-old woman who was diagnosed with systemic sclerosis 16 years ago. The association of numerous comorbidities characterized by a considerable level of seriousness characterizes this case: the highly extensive systemic damage, the cardiovascular impact of the illness, and the existence of severe pulmonary arterial hypertension. The systemic and clinical manifestations, respiratory functional tests, radiological features, and specific therapy are discussed.

A rare case of high risk multisystem Langerhans Cell Histiocytosis in infant

Objective: Langerhans cell histiocytosis (LCH) stands as the most common histiocytic disorder. It is categorized into single-system single site, single-system multi-site, and multisystem types, with or without involvement of risk organs. Clinical presentation exhibits considerable variability, contingent upon the affected organ systems. Given its rarity, diverse locations, and varying severity, there are currently no established treatment guidelines for LCH. Case Presentation: We documented the case of a 5-month-old male diagnosed with Langerhans cell histiocytosis (LCH), presenting with high-risk multisystem organ involvement and concurrent unifocal bone involvement. Bone marrow aspiration revealed infiltration by multinucleated giant cells within the marrow. Skin biopsy demonstrated Langerhans cell proliferation with epidermotrophism and the characteristic reniform nucleus resembling a coffee bean. The patient was treated following the histiocytosis protocol, which included daily oral prednisone and 6-mercaptopurine, in addition to weekly intravenous vinblastine and methotrexate administered every two weeks. Unfortunately, the patient displayed limited response during the initial phase of treatment and, tragically, passed away during the eighth week of therapy. Conclusion: Langerhans cell histiocytosis (LCH) is a rare disease characterized by variable disease presentations and is associated with significant morbidity and mortality. Timely recognition of clinical manifestations and risk factors, coupled with appropriate treatment, is crucial to reduce mortality and long-term complications associated with the condition.

A rare case of high risk multisystem Langerhans Cell Histiocytosis in infant

Objective: Langerhans cell histiocytosis (LCH) stands as the most common histiocytic disorder. It is categorized into single-system single site, single-system multi-site, and multisystem types, with or without involvement of risk organs. Clinical presentation exhibits considerable variability, contingent upon the affected organ systems. Given its rarity, diverse locations, and varying severity, there are currently no established treatment guidelines for LCH. Case Presentation: We documented the case of a 5-month-old male diagnosed with Langerhans cell histiocytosis (LCH), presenting with high-risk multisystem organ involvement and concurrent unifocal bone involvement. Bone marrow aspiration revealed infiltration by multinucleated giant cells within the marrow. Skin biopsy demonstrated Langerhans cell proliferation with epidermotrophism and the characteristic reniform nucleus resembling a coffee bean. The patient was treated following the histiocytosis protocol, which included daily oral prednisone and 6-mercaptopurine, in addition to weekly intravenous vinblastine and methotrexate administered every two weeks. Unfortunately, the patient displayed limited response during the initial phase of treatment and, tragically, passed away during the eighth week of therapy. Conclusion: Langerhans cell histiocytosis (LCH) is a rare disease characterized by variable disease presentations and is associated with significant morbidity and mortality. Timely recognition of clinical manifestations and risk factors, coupled with appropriate treatment, is crucial to reduce mortality and long-term complications associated with the condition.

The Long Road of Long COVID: Specific Considerations for the Allergist/Immunologist

Long COVID (coronavirus disease 2019) syndrome, also known as post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a new disorder that can develop after an acute infection with the SARS-CoV-2 virus. The condition is characterized by multiorgan system involvement with a wide range of symptoms that can vary in severity from mild to debilitating. Some of the common symptoms associated with long COVID syndrome include cardiovascular issues such as heart palpitations and chest pain; thrombotic events (eg, blood clotting disorders); metabolic problems (eg, type 2 diabetes); dysautonomia; paroxysmal orthostatic tachycardia syndrome; myalgic encephalomyelitis/chronic fatigue syndrome; reactivation of the Epstein-Barr virus; the presence of autoantibodies; chronic spontaneous urticaria (hives); and connective tissue diseases. Whereas long COVID syndrome can affect individuals from various backgrounds, certain populations may be at higher risk such as individuals of Hispanic and Latino heritage, as well as those with low socioeconomic status, although approximately one-third of affected patients have no known risk factors or preexisting conditions. Many survivors of COVID-19 struggle with multiple symptoms, increased disability, reduced function, and poor quality of life. Whereas vaccination has been the most significant intervention able to decrease the severity of acute SARS-Cov2 infection and curtail deaths, limited data are available related to its modulating effect on long COVID necessitating the need for further investigation. Furthermore, several inflammatory pathways have been proposed for the pathogenesis of long COVID that are the targets for ongoing clinical studies evaluating novel pharmacological agents. The purpose of the present report is to review the many factors associated with long COVID with a focus on those aspects that have relevance to the allergist-immunologist.

Anti-neutrophil cytoplasmic antibody associated vasculitis following rituximab: Outcomes of 50 patients in a tertiary single centre

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an uncommon condition with heterogeneous multisystem organ involvement and significant morbidity and mortality. This study aimed to characterize the clinical features and laboratory characteristics, including B cell depletion, the ability to reduce corticosteroid dosage, and outcomes, of patients with AAV following rituximab treatment. Methods: Retrospective clinical and laboratory data were collected from patients with AAV who visited our lupus unit, including 50 treated with rituximab. Numeric response variables (median and range) were collected, including age, follow-up duration, disease duration, and Birmingham Vasculitis Activity Score (version 3). Statistical analyses were conducted using the SPSS 25.0 software. Statistical significance was considered a p-value &lt;.05. Results: Of the 50 patients, 40 (80%) had granulomatosis with polyangiitis, 30 (75%) achieved remission, and 10 (25%) had active disease. Fifteen patients (30%) had positive ANCA levels at their last ANCA level assessment follow-up. Thirty-seven patients (74%) had B cell depletion, and 30 (81.1%) were in remission. Their median immunoglobulin levels were 7.6 (2.7–21.2) g/L for IgG, 0.5 (0.07–1.71) g/L for IgM, and 1.83 (0.14–4.87) g/L for IgA. Forty-two patients (84%) were able to lower their steroid dose to &lt;7.5 mg, with 36 (85.7%) in remission and six (14.3%) having active disease ( p = .003). Conclusion: Our data suggests that most patients experience clinical remission after rituximab maintenance treatment. Half the patients were in remission, with normal creatinine levels and inflammatory markers. In addition, our patients could reduce steroid use.

LncRNAs in Kawasaki disease and Henoch-Schönlein purpura: mechanisms and clinical applications.

Kawasaki disease (KD) and Henoch-Schönlein purpura (HSP) are the two most predominant types of childhood vasculitis. In childhood vasculitis, factors such as lack of sensitive diagnostic indicators and adverse effects of drug therapy may cause multiorgan system involvement and complications and even death. Many studies suggest that long noncoding RNAs (lncRNAs) are involved in the mechanism of vasculitis development in children and can be used to diagnose or predict prognosis by lncRNAs. In existing drug therapies, lncRNAs are also involved in drug-mediated treatment mechanisms and are expected to improve drug toxicity. The aim of this review is to summarize the link between lncRNAs and the pathogenesis of KD and HSP. In addition, we review the potential applications of lncRNAs in multiple dimensions, such as diagnosis, treatment, and prognosis prediction. This review highlights that targeting lncRNAs may be a novel therapeutic strategy to improve and treat KD and HSP.

Cladribine and cytarabine in children refractory high risk multisystem Langerhans cell histiocytosis

There is no uniform regimen for refractory Langerhans cell histiocytosis (LCH). We retrospectively described patients with refractory multisystem and risk organ involvement LCH treated with the low-dose (Ara-c, 100 mg/m2/d × 5day; 2-CDA, 5 mg/m2/d × 5day) chemotherapy (LDC) and the intermediate-dose (Ara-c, 500 mg/m2/d × 5day; 2-CDA, 9 mg/m2/d × 5day) chemotherapy (IDC). 26 patients and 10 patients receiving the LDC and IDC regimen from January 2013 to December 2016 were included in the study. The overall response rate exhibited no significant difference between the LDC and IDC groups after four courses (76.9% vs 90%, P = 0.375) and eight courses (80.8% vs 100%, P = 0.135) of treatment. No statistical differences in the overall survival rate were observed between the two groups, but 5-year event-free survival rate of patients in the IDC group was higher than that in the LDC group at the median follow-up of 6.16 and 5.07 years (88.9% vs 52.9%, P = 0.033). The patients in the IDC group had more severe myelosuppression than those in the LDC group (grade 3/4 myelosuppression, 80% vs 19.2%, P = 0.001). The intermediate-dose regimen of 2CDA and Ara-c had a higher event-free survival rate and a similar overall survival rate compared with the low-dose regimen.

FGF21 and GDF15 are elevated in Barth Syndrome and are correlated to important clinical measures

Barth Syndrome (BTHS) is a rare X-linked disorder that is caused by defects TAFAZZIN, which leads to an abnormal cardiolipin (CL) profile of the inner mitochondrial membrane and clinical features including cardiomyopathy, neutropenia and skeletal myopathy. The ratio of monolysocardiolipin (MLCL, the remodeling intermediate of cardiolipin) to remodeled CL is always abnormal in Barth Syndrome and 3-methylglutaconic acid is often elevated affected patients, however neither of these biomarkers has been shown to temporally correlate to clinical status. In this study, we measured plasma FGF21 and GDF15 levels in 16 individuals with Barth Syndrome and evaluated whether these biomarkers were correlated to the MLCL/CL ratio in patient bloodspots and clinical laboratory parameters indicative of organ involvement in Barth Syndrome including: neutrophil and monocyte counts, liver function, and cardiac function (NT-proBNP). We found that FGF21 and GDF15 were elevated in all 16 patients and that FGF21 was significantly correlated to AST, ALT GGT, percentage of neutrophils comprising total white blood cells, percent monocytes comprising total white blood cells, and NT-proBNP levels. GDF-15 was significantly positively associated with NT-proBNP. We conclude that clinical measurements of FGF21 and GDF-15 may be relevant in the monitoring multi-organ system involvement in Barth Syndrome.

Treatment Failure in Patient with Severe Mpox and Untreated HIV, Maryland, USA.

A 33-year-old man in Baltimore, Maryland, USA, with untreated HIV infection had a 74-day course of mpox with multiorgan system involvement and unique clinical findings. In this clinical experience combining 3 novel therapeutic regimens, this patient died from severe mpox in the context of untreated HIV and advanced immunodeficiency.

Neurological and endocrinological involvement in neonatal lupus erythematosus: a retrospective study at a tertiary hospital in Eastern China.

Neonatal lupus erythematosus (NLE) is a rare autoimmune disease that causes transient impairment of multi-organ functions and is mainly caused by maternally transmitted antibodies. This study aims to investigate the clinical features of infants with NLE, focusing on the presence of neurological and endocrinological involvement. The clinical data of infants diagnosed with NLE at the Children's Hospital of Soochow University from 2011 to 2022 were collected and retrospectively analyzed. In all, 39 patients with NLE were included, and the most common symptom was rash, followed by hematological, hepatic, cardiac, gastrointestinal, neurological, and endocrine symptoms. Among the 10 patients with neurological impairment, intracranial hemorrhage was the most common, followed by convulsions, hydrocephalus, extracerebral space enlargement, and aseptic meningitis. All patients with neurological impairment were positive for anti-SSA/Ro antibodies. Five of these patients were double positive for anti-SSA/Ro and anti-SSB/La antibodies. All 10 patients had multi-organ system involvement, with hematological involvement being the most common, and three patients had varying degrees of developmental delay at the post-discharge follow-up. Nine patients with endocrine impairment were positive for anti-SSA/Ro antibodies, with pancreatic impairment being the most common. There were four cases of hyperinsulinemia and hypoglycemia, one case of diabetes mellitus with ketoacidosis, two cases of hypothyroidism, one case of hypoadrenocorticism, and one case of lysinuric protein intolerance, all of which were normalized before discharge. All patients with endocrine impairment showed hematological involvement, and some showed feeding intolerance as their first symptom. One patient had abnormal liver function at post-discharge follow-up, and two patients had a rash caused by a severe allergy to milk protein. At our hospital, no significant gender differences were observed in the occurrence of NLE, and a predominance of skin, blood, liver, and heart involvement was observed. Patients with multiple central nervous system injuries and organ involvement are more likely to have growth retardation. Endocrine disorders are transient in NLE patients, and some showed feeding intolerance as the first manifestation. Key Points •A retrospective investigation of the clinical characteristics and prognosis of 39 NLE patients was performed, focusing on the clinical features of patients with neurological and endocrine system involvement to improve clinicians' understanding of this disease.