Organ System Involvement Research Articles

P-103. Adenoviremia Clearance Following Treatment with Intravenous (IV) Brincidofovir (BCV) in Immunocompromised Patients is Associated with Positive Clinical Disease Response: Preliminary Outcomes from the ATHENA Phase IIa Study

Abstract Background Adenovirus (AdV) may cause fatal infections in immunocompromised patients. There are no drugs approved for treatment of serious AdV infections. BCV, a lipid conjugate of cidofovir, antiviral with enhanced ADV activity without renal or haematological toxicity. The value of viremia clearance in predicting clinical response has been a source of scientific debate. Athena is a multiple ascending dose study of the safety and efficacy of IV BCV in treatment of serious AdV infection. NCT04706923. Methods Eligible immunocompromised patients aged ≥ 2 months with adenoviremia were treated with IV BCV for 4 to 14 weeks (until viremia clearance). The dosing regimen was 0.2; 0.3; 0.4 mg/kg twice weekly (BIW) in Cohorts 1;2;3 respectively, or 0.4 mg/kg weekly (Cohort 4). For all cohorts the dose was capped at the 50kg equivalent. ADV-disease was defined by organ system involvement as localized (1 organ system) or disseminated ( >1 organ system or fever and elevated serum aminotransferases). All nine patients with baseline disease in Cohort 3 (0.4mg/kg BIW) achieved viremia clearance, 89% within 4 weeks. Clearance of adenoviremia was monitored by weekly quantitative PCR. Clinical response in terms of resolution or improvement of AdV disease as assessed by treating physicians is summarized here. Results Thirty-four patients were enrolled and treated. ADV-viremia response was dose-dependent. The majority 31/34 (91%) of patients had AdV disease at baseline (Table 1). Among the 20/31 patients who achieved viral clearance,19/20 (95%) showed a positive clinical response with resolution (75%) or improvement of the AdV disease(20%). Among the patients who failed to achieve viral clearance 2/11 (18%) showed resolution(9%) or improvement(9%) of the AdV disease. Conclusion IV BCV therapy cleared ADV viremia in a dose-dependent manner. ADV-viremia clearance was associated with positive clinical response rate. These results support the potential utility of IV BCV for the treatment of AdV infection and viremia clearance as a surrogate marker of clinical response. Disclosures Gabriela Maron, MD, MS, Astellas Inc: Grant/Research Support|NIH: Grant/Research Support|SymBio Pharma: Advisor/Consultant|SymBio Pharma: Grant/Research Support Michael J. Boeckh, MD PhD, Allovir: Advisor/Consultant|Allovir: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Symbio: Advisor/Consultant Genovefa Papanicolaou, MD, AlloVir: Advisor/Consultant|AlloVir: Data safety monitoring committee|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Investigator|Symbio: Advisor/Consultant Robert Wynn, MD, MRCP, FRCPath, AVRO BIO: Grant/Research Support|AVRO BIO: Milestone payments MPSII clinical trial|Orchard Therapeutics: Grant/Research Support|Orchard Therapeutics: Milestone payments MPSII clinical trial Thomas Lion, MD, PhD, SymBio Pharmaceuticals Limited: Advisor/Consultant|SymBio Pharmaceuticals Limited: Grant/Research Support Koji Fukushima, MD, PhD, SymBio Pharmaceuticals Limited: Employee|SymBio Pharmaceuticals Limited: Stocks/Bonds (Private Company) Rochelle Maher, MS, SymBio Pharma USA: Employee Nkechi Azie, MD MBA FIDSA, SymBio Pharma USA: Employee Michael Grimley, MD, SymBio Pharmaceuticals Limited: Advisor/Consultant

P-2004. Risk Factors for Death in Children with Multisystem Inflammatory Syndrome in Children — United States, 2020-2022

Abstract Background Although multisystem inflammatory syndrome in children (MIS-C) incidence has decreased, cases continue to occur and can have notable morbidity and mortality. This investigation evaluates clinical and demographic risk factors for death from MIS-C.Table 1.Demographic and clinical risk factors for death in children with Multisystem Inflammatory Syndrome in Children, United States, 2020-2022 Methods We evaluated children reported to CDC national MIS-C surveillance with illness onset February 2020–December 2022 and known illness outcome. We performed multivariable logistic regression to estimate odds of death compared with survival for patient characteristics and MIS-C organ involvement. Model covariates were selected a priori including age at MIS-C onset, date of MIS-C onset, race and ethnicity, and presence of any underlying medical condition. To compare risk of death across the pandemic we evaluated patients with date of MIS-C onset in five pandemic waves corresponding to peaks of MIS-C activity.Table 2.Organ system involvement risk factors for death in children with Multisystem Inflammatory Syndrome in Children, United States, 2020-2022 Results Of 8,767 MIS-C cases reported, there were 76 (9%) deaths (Table 1). Compared with children aged 5–11 years, children < 1 year and 16–20 years had increased odds of death (aOR 4.8 [1.7–13.6], p< 0.01, and 8.2 [4.6–14.8], p< 0.001, respectively). American Indian/alaska Native (AIAN) and Native Hawaiian/Pacific Islander (NHPI) children had increased odds of death compared with White non-Hispanic children (aOR 5.4 [1.4–20.9, p=0.01 and 5.9 [1.5–23.1, p=0.01, respectively). Children with MIS-C illness onset after wave 1 had decreased odds of death compared with those during wave 1. Presence of >1 underlying medical condition was associated with higher odds of death (aOR 2.3 [1.5–3.7, p< 0.001); diabetes, congenital heart disease, neurologic, immunosuppressive/autoimmune, and noncardiac congenital disorders were all independently associated with death. Cardiovascular, respiratory, neurologic, and renal MIS-C organ involvement increased odds of death while children with mucocutaneous involvement had decreased odds (Table 2). Conclusion Younger (< 1 year) and older (16-20 years) age, AIAN and NHPI race and ethnicity, MIS-C early in the pandemic, and underlying medical conditions are risk factors for death from MIS-C. Cardiovascular, respiratory, neurologic, and renal involvement increased risk of death. Identifying risk factors associated with death may help clinicians with management and prognosis. Disclosures Regina Simeone, PhD, Pfizer: Stocks/Bonds (Private Company)

The International Association for the Study of Lung Cancer Staging Project: The Database and Proposal for the Revision of the Staging of Pulmonary Neuroendocrine Carcinoma in the Forthcoming Ninth Edition of the TNM Classification for Lung Cancer.

Pulmonary high-grade neuroendocrine carcinoma (NEC) includes small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). The seventh and eighth editions of the TNM classification for lung cancer confirmed the applicability of this staging system for SCLC. With the proposal of N2 and M1c subcategories for the ninth edition classification, we assessed the applicability to NECs. The database included NEC cases diagnosed between January 2011 and December 2019. Eligible cases, with valid survival time and eighth edition TNM stage, were classified as pure SCLC, combined SCLC/non-small cell carcinoma and LCNEC. Survival was calculated by the Kaplan-Meier method, pairwise differences using log-rank test, and prognostic groups by a Cox regression analysis. There were 6181 pure/combined SCLC and 697 LCNEC cases available. For SCLC, survival outcome analyses included 4453 with clinical stage, and 583 with pathologic stage data. The corresponding numbers for LCNEC were 585 and 508. The SCLC data validated the ninth edition classification for lung cancer, including the proposed new subcategories, N2a, single-station ipsilateral mediastinal/subcarinal lymph node involvement, and N2b, involvement of multiple ipsilateral/subcarinal stations. The data also validated the subcategorization of M1c into M1c1 (multiple lesions in a single extrathoracic organ system) and M1c2 (involvement of multiple extrathoracic organ systems). The LCNEC data were insufficient for complete survival analysis, but the available data showed decreasing survival with increasing clinical and pathological stages. The ninth edition TNM classification applies to patients with NEC and is the appropriate standard for use in clinical practice.

CLINICAL AND PROGNOSTIC CHARACTERISTICS OF ORGAN FAILURE PATTERNS IN ACUTE PANCREATITIS

Intoroduction. Acute pancreatitis remains one of the most challenging diseases in abdominal surgery, particularly due to the high incidence of organ failure, occurring in 15-20% of patients and associated with mortality rates up to 42% during the first week of hospitalization. Early identification of patients at high risk for organ failure development is of particular importance. It, in turn, is a key factor determining the severity of the course and prognosis of the disease, developing in 15-20% of patients with acute pancreatitis. At the same time, persistent organ failure is associated with mortality of up to 42% during the first week of hospitalization. There are several scales for assessing the severity of acute pancreatitis, including: Acute Physiologic Assessment and Chronic Health Evaluation II, Bedside Index of Severity in Acute Pancreatitis and the modified Marshall scale, but none of them demonstrates accuracy in predicting the development of organ failure, and the maximum sensitivity reaches only 75%. The objective of this study was to identify and characterize the main patterns of organ failure in acute pancreatitis based on comprehensive analysis of clinical indicators, laboratory parameters, and temporal disease characteristics. Subjects and methods. This retrospective study included 82 patients (2014-2019), stratified into groups with organ failure (n=41) and without it (n=41). The assessment protocol included clinical parameters, laboratory findings, and disease progression dynamics. Cluster analysis was used to determine organ failure patterns. Results. Three main patterns were identified: “early respiratory” (37.5% of cases), “late progressive” (57.5%), and “multisystem” (5.0%), each differing in onset timing, organ system involvement, and clinical outcomes. The "multisystem" pattern exhibited the most unfavorable profile, with the longest hospitalization duration (median 68.0 days) and highest mortality. The study identified key prognostic markers and developed a risk stratification system, enabling optimized monitoring and treatment strategies based on the organ failure pattern.

Epidemiological investigation of adult emergency infusion adverse drug reactions (EIADR) in Nanjing, China: a prospective cross-sectional study (EIADR II)

ABSTRACT Objective To analyze the clinical characteristics of adverse drug reactions (ADRs) in adults receiving emergency infusions at a tertiary hospital. Methods We conducted a prospective observational cohort study involving 585 adult patients who experienced adverse drug reactions (ADRs) between 20 November 2019, and 20 November 2023, during intravenous infusions in the emergency infusion room of a tertiary hospital. The analysis included patients’ gender, age, type of drugs involved, organ-system involvement, clinical manifestations of ADRs, severity grading of ADRs, and preventability of ADRs. Results The highest percentage of ADRs occurred in the 30–39 age group. Antimicrobials were the most common cause of ADRs, with skin manifestations being the predominant clinical feature. Approximately 23.93% of ADRs were deemed preventable. Conclusion Monitoring ADRs related to antimicrobials is crucial in adult emergency infusions. The 30–39 age group is particularly susceptible to ADRs. Preventive measures and a well-established Electronic Health Record (EHR) system can effectively reduce ADRs incidence.

Integrated management of concurrent traumatic penetrating brain injury and electrical injury: illustrative case.

Transorbital penetrating brain injury (PBI) accompanied by electrical injury is an extremely rare presentation. This type of traumatic injury has a unique set of diagnostic and therapeutic challenges due to the potential multiple organ system involvement and severe neurological complications. A 50-year-old male experienced a high-impact injury from a welding spike that penetrated the orbit just above the eyeball with a concurrent electrical injury; the electricity exited through the great toe. Initial assessments revealed extensive subarachnoid pneumocephalus and a linear hemorrhage extending from the left medial orbital wall through the ethmoid air cells to the right thalamic nucleus. Remarkably, the eye itself was not injured given the superior trajectory of the spike within the orbit. PBIs and electrical injuries usually cause serious sequelae, but the welding spike and electrical current managed to avoid major neuroanatomical structures and visceral organs, allowing the patient to recover with minimal deficits. https://thejns.org/doi/10.3171/CASE24418.

Mining and influencing factors analysis of sacituzumab govitecan adverse drug event based on FAERS database

ABSTRACT Objective Utilizing the FAERS database, this study aims to analyze the ADE signals of sacituzumab govitecan to provide references for clinical safety. Methods By searching the US FAERS database, we applied Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) methods to analyze ADE reports for sacituzumab govitecan from Q2 2020 to Q4 2023, covering 15 quarters. Results The total number of reports with sacituzumab govitecan as the first suspicion was 2854. A total of 139 signals involving 26 SOCs were obtained. The most reported were general disorders and administration site conditions (2,307 cases, 25.66%), followed by gastrointestinal disorders (1,125 cases, 12.52%), and investigations (810 cases, 9.01%). Frequent ADEs included sepsis and COVID-19 were not listed in the prescribing information. The signal strength analysis highlighted conditions like cholestasis and epilepsy not mentioned in the prescribing information. Furthermore, an analysis of influencing factors revealed differences in infections and infestations by gender and nationality (p < 0.05), and in gastrointestinal disorders and blood and lymphatic system disorders by gender, treatment duration, and nationality (p < 0.05). Conclusions Common ADEs generally correspond with the prescribing information. Clinicians should be vigilant regarding unlisted ADEs about sacituzumab govitecan, and close monitoring of laboratory indicators ensure patient medication safety.

Animal models of Long Covid: A hit-and-run disease.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) pandemic has caused more than 7 million deaths globally. Despite the presence of infection- and vaccine-induced immunity, SARS-CoV-2 infections remain a major global health concern because of the emergence of SARS-CoV-2 variants that can cause severe acute coronavirus disease 2019 (COVID-19) or enhance Long Covid disease phenotypes. About 5 to 10% of SARS-CoV-2-infected individuals develop Long Covid, which, similar to acute COVID 19, often affects the lung. However, Long Covid can also affect other peripheral organs, especially the brain. The causal relationships between acute disease phenotypes, long-term symptoms, and involvement of multiple organ systems remain elusive, and animal model systems mimicking both acute and post-acute phases are imperative. Here, we review the current state of Long Covid animal models, including current and possible future applications.

Belumosudil Is Efficacious for the Management of Heavily Pretreated and Prolonged Chronic Graft-Versus-Host Disease: A Retrospective Multi-Center Real-World Study By the Israel Association for Bone Marrow Transplantation and Cellular Therapy

Introduction : Chronic graft-versus-host disease (cGvHD) remains one of the most important complications of allogeneic stem cell transplantation (ASCT) and is a leading cause of morbidity, late non-relapse mortality, and impaired quality of life. Recent advances in understanding the cGVHD mechanisms have led to the development of the Rho-associated coiled-coil containing protein kinase 2 (ROCK-2) selective inhibitor, belumosudil. The pivotal ROCKstar trial demonstrated the efficacy and acceptable safety profile of belumosudil in cGVHD patients, which led to its FDA approval for the use after &amp;gt;2 prior lines of therapy (LOT). The current study aimed to investigate the efficacy and safety of belumosudil in patients with cGVHD in real-world settings across all transplant centers in Israel. Methods : Data on patients treated with belumosudil for cGVHD at 6 adult and 3 pediatric transplant centers via compassionate use programs were collected and analyzed. These data included patient demographics, underlying disease requiring ASCT, transplant details, cGVHD details, and outcomes of belumosudil treatment. Results : Forty-five patients were included in the final analysis: 42 were treated according to FDA indications, and 3 pediatric patients (ages 4, 4, and 6 years) were treated outside the FDA labeled indication. The median age was 46 (range, 4-75) years; 44.4% were females. GVHD prophylaxis included a calcineurin inhibitor and methotrexate in 66.7%, post-transplant cyclophosphamide in 13.3% and others in 20% of patients. Acute GVHD occurred in 48.9% of patients. The majority of patients (84.4%) had severe cGVHD with a median of 4 involved organ systems (range, 1-7) and received a median of 4 prior LOT (range, 2-6). Notably, 86.7% had prior ruxolitinib exposure, and 13.3% concurrently received belumosudil and ruxolitinib. Patients had been treated for cGVHD for a median of 2.3 (range, .08 - 19.1) years prior to belumosudil commencement. The median duration of belumosudil therapy was 7.8 (range: 1.2 - 28.8) months, with 73.3% of patients still on treatment. The median time to best response was 100 days (range: 32 - 328). Response rates were as follows: complete response (CR) 6.7%, partial response (PR) 48.9%, stable disease (SD) 40%, and progressive disease (PD) 4.4%, with an overall response rate (ORR) of 55.6%. Responses for skin cGVHD were: CR - 11.1%, PR - 50%, SD - 38.9%; for lung cGVHD: PR - 44.4%, SD - 48.1%, PD - 7.4%. The median reduction of the glucocorticoid dose was from 0.29 mg/kg/d of prednisone at the beginning of treatment to 0.02 mg/kg/d at the last follow-up or belumosudil cessation. The most common adverse events (AEs) were pulmonary infections (17.8%) and the primary reason for belumosudil discontinuation was cGHVD worsening. Only one patient stopped belumosudil due to AEs. While on treatment, 26.1% of patients had cGVHD progression. Six patients (13.3%) died, three from cGVHD worsening, two from pulmonary infections, and one from relapsed leukemia. At a median follow-up of 8 months (range 1.3-32), the GVHD relapse-free survival (RFS) was 72% (95% CI 59%-85%) and the estimated 12-month GVHD RFS was 66% (95% CI 46%-86%). Overall survival (OS) at 8 months was 92% (95% CI 81%-100%) and the estimated 12-month OS was 75% (95% CI 62%-88%). Conclusions : The findings of this real-world study, while comparable to those observed in the ROCKstar trial, are encouraging, considering the heavily pretreated patient population with prolonged and severe cGVHD. No new safety signals emerged. Future studies are warranted to optimize patient selection and timing for treatment initiation.

Understanding the pathogenesis of infertility in endometriosis - literature review

Introduction and objective Endometriosis is a complex systemic condition characterized by the growth of functional endometrial tissue outside the uterine cavity, affecting 10-15% of women of reproductive age. Up to 50% of these women face infertility challenges. Although there is a scientifically established connection between endometriosis and infertility, the underlying mechanisms remain not fully understood. Review methods The PubMed database was searched using phrases related to the topic of endometriosis-associated infertility. The search included original research articles, review papers, and guidelines, including the Polish guideline on managing women with endometriosis. Ultimately, 25 relevant sources presenting the latest knowledge were selected. Abbreviated description of the state of knowledge The pathogenesis of infertility associated with endometriosis is complex and involves multiple factors. The most frequently cited contributors in the scientific literature include pain and dyspareunia, mechanical factors, reduced ovarian reserve, oxidative stress, changes in embryo and oocyte quality, impaired ovulation, and compromised endometrial receptivity. Summary Endometriosis affects a growing number of women worldwide, with nearly half experiencing infertility. The complexity and involvement of multiple organ systems make it difficult to pinpoint a single cause, posing a challenge for clinicians. Addressing these diverse factors is essential for improving fertility management in women with endometriosis.

Managing Select Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitors.

The increased use of immune checkpoint inhibitors (ICIs) across cancer programs has created the need for standardized monitoring and management of immune-related adverse events (irAEs). Delayed recognition without appropriate treatment can have serious and life-threatening consequences. The management of irAEs presents a unique set of challenges that must be addressed at a multidisciplinary level. Although various national and international guidelines and working groups provide high-level recommendations for the management of irAEs, practical guidance is lacking. Furthermore, timely collaboration between specialists requires institutional protocols that enable the early recognition, assessment, and treatment of irAEs. Such protocols should be developed by institution specialists and include algorithms for all healthcare providers involved in the care of patients treated with ICIs. At William Osler Health System in Brampton, Ontario, practical step-by-step multidisciplinary treatment approaches with recommendations for the management of irAEs were developed in collaboration with experts across Canada. Here, we provide an in-depth description of the approaches, outlining baseline investigations prior to the initiation of ICIs, as well as the monitoring and management of irAEs based on symptoms, severity, and involved organ systems. We encourage other centres to adapt and modify our approaches according to their specific needs and requirements.

Systemic Sweet Syndrome Recurrence in Lung Allograft: Autopsy Findings from First Reported Case

Abstract Introduction/Objective Sweet syndrome is a non-vasculitic neutrophilic dermatosis characterized by acute, neutrophilic inflammation, most classically in the skin. Sweet syndrome can, however, manifest with systemic organ involvement including the lungs. Pulmonary involvement by Sweet syndrome is exceedingly rare, and its recurrence in a pulmonary allograft is understudied. Methods/Case Report A 43-year-old female with a history of Sweet syndrome with pulmonary involvement developed chronic bronchiolitis obliterans requiring bilateral lung transplantation. Seven years after transplantation, the patient began exhibiting shortness of breath requiring hospitalization. During the patient’s hospital stay, cytomegalovirus viremia and SARS-CoV-2 positivity were detected, and new oral lesions were concerning for a Sweet syndrome flare. Her respiratory status continued to decline requiring escalating ventilatory support. An autopsy limited to the chest and abdomen was performed after she expired. The pleural cavities had extensive adhesions, and both lungs were heavy. Microscopically, the lungs showed extensive, intralumenal acute inflammation of the bronchi and bronchioles with marked chronic inflammation of the submucosa, histologically similar to the patient’s explanted lung specimen. There was also focal endogenous lipoid pneumonia due to bronchiolar obstruction. In addition to the inflammatory findings, multiple infectious agents were identified in the patient’s respiratory tract including SARS-CoV-2, cytomegalovirus, Epstein-Barr virus, Candida glabrata, Klebsiella pneumoniae, and Stenotrophomonas maltophilia. No underlying malignancy was identified. (This patient’s earlier course was reported previously: PMC8411443) Results (if a Case Study enter NA) NA Conclusion Pulmonary involvement in Sweet syndrome can cause significant morbidity, and prior to this case, allograft recurrence of Sweet syndrome had not previously been reported. For transplant patients with a history of pulmonary Sweet syndrome, recurrence should be considered in cases of allograft dysfunction. This case also highlights the importance of thorough microbiological studies in autopsies of patients with systemic inflammatory diseases being treated with extensive immunosuppressive therapies.

Systemic Lupus Erythematosus, An Unusual Presentation: A Case Report In Azal Hospital, Sana’a, Yemen

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by various clinical presentations and potential involvement of multiple organ systems; it exhibits a significant female predominance, with a peak incidence of middle-aged individuals. In this article, we report a case of a 19 years old female patient who presented with fever, headache, fatigue and neck stiffness. Initial investigations revealed a normal white blood cell count (WBC) with neutrophilia, leading to a diagnosis of bacterial meningitis. The patient responded to antibiotic and analgesic treatment. However, subsequent development of arthritis and skin lesions raised suspicion of systemic lupus erythematosus, which was confirmed by positive anti-dsDNA and antinuclear antibody (ANA) tests.

A case of VEXAS (vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic) syndrome presenting as progressive multisystem involvement with parenchymal infiltrates following infection with Epstein Barr virus

AbstractVEXAS (vacuoles, E1 enzyme, X‐linked, autoinflammatory, and somatic) syndrome is a rare multisystem disease affecting predominantly males over 50 and manifesting as widespread progressive inflammatory sequelae and haematological dysfunction. We describe a patient who presented with systemic symptoms of fevers, night sweats and weight loss, and developed progressive inflammatory sequelae including cutaneous lesions, haematological dysfunction, lymphadenopathy, migratory inflammatory arthropathies, with new pulmonary infiltrates, following infection with Epstein Barr Virus. Laboratory investigations, bronchoscopy, bone marrow biopsy and imaging were consistent with an inflammatory aetiology. The constellation of organ system involvement, laboratory, biopsy, and imaging results were suspicious for VEXAS syndrome, and this diagnosis was confirmed by identification of a somatic mutation in the UBA1 gene following extensive exclusion of infectious and autoimmune causes. Interestingly the onset of the VEXAS syndrome coincided with serological confirmation of Epstein Barr Virus raising the importance of further exploration into the underlying aetiology of VEXAS syndrome.

Cannabinoids Used for Medical Purposes in Children and Adolescents

Cannabinoids are increasingly used for medical purposes in children. Evidence of the safety of cannabinoids in this context is sparse, creating a need for reliable information to close this knowledge gap. To study the adverse event profile of cannabinoids used for medical purposes in children and adolescents. For this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched for randomized clinical trials published from database inception to March 1, 2024, for subject terms and keywords focused on cannabis and children and adolescents. Search results were restricted to human studies in French or English. Two reviewers independently performed the title, abstract, and full-text review, data extraction, and quality assessment. Included studies enrolled at least 1 individual 18 years or younger, had a natural or pharmaceutical cannabinoid used as an intervention to manage any medical condition, and had an active comparator or placebo. Two reviewers performed data extraction and quality assessment independently. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline and PRISMA-S guideline were used. Data were pooled using a random-effects model. The primary outcome was the incidence of withdrawals, withdrawals due to adverse events, overall adverse events, and serious adverse events in the cannabinoid and control arms. Secondary outcomes were the incidence of specific serious adverse events and adverse events based on organ system involvement. Of 39 175 citations, 23 RCTs with 3612 participants were included (635 [17.6%] female and 2071 [57.3%] male; data not available from 2 trials); 11 trials (47.8%) included children and adolescents only, and the other 12 trials (52.2%) included children, adolescents, and adults. Interventions included purified cannabidiol (11 [47.8%]), nabilone (4 [17.4%]), tetrahydrocannabinol (3 [13.0%]), cannabis herbal extract (3 [13.0%]), and dexanabinol (2 [8.7%]). The most common indications were epilepsy (9 [39.1%]) and chemotherapy-induced nausea and vomiting (7 [30.4%]). Compared with the control, cannabinoids were associated with an overall increased risk of adverse events (risk ratio [RR], 1.09; 95% CI, 1.02-1.16; I2 = 54%; 12 trials), withdrawals due to adverse events (RR, 3.07; 95% CI, 1.73-5.43; I2 = 0%; 14 trials), and serious adverse events (RR, 1.81; 95% CI, 1.21-2.71; I2 = 59%; 11 trials). Cannabinoid-associated adverse events with higher RRs were diarrhea (RR, 1.82; 95% CI, 1.30-2.54; I2 = 35%; 10 trials), increased serum levels of aspartate aminotransferase (RR, 5.69; 95% CI, 1.74-18.64; I2 = 0%; 5 trials) and alanine aminotransferase (RR, 5.67; 95% CI, 2.23-14.39; I2 = 0%; 6 trials), and somnolence (RR, 2.28; 95% CI, 1.83-2.85; I2 = 8%; 14 trials). In this systematic review and meta-analysis, cannabinoids used for medical purposes in children and adolescents in RCTs were associated with an increased risk of adverse events. The findings suggest that long-term safety studies, including those exploring cannabinoid-related drug interactions and tools that improve adverse event reporting, are needed.

Early diagnosis of lupus: A possibilty. A multicentric study from SLE Special Interest Group (SIG) of Indian Rheumatology Association (IRA).

Systemic Lupus Erythematosus (SLE) warrants an early diagnosis and prompt management. Delay in diagnosis can result in repeated flares, permanent damage, and even death. There is a large variability in the time taken to diagnose SLE across the world. We undertook this study to determine the time taken for diagnosis of SLE in India and to identify the factors associated. Patients with SLE diagnosed within the previous 1year as per Systemic Lupus Erythematosus International Collaborating Clinics criteria (SLICC) 2012 criteria were included in a cross-sectional multicentre questionnaire-based survey. Demographic profile, self-reported socioeconomic status as per Kuppuswamy classification of socioeconomic status (version 2022) (SES), and several healthcare related parameters including referral pattern were recorded. Median time taken for diagnosis was used to demarcate early or late diagnosis and associated factors were explored. We included 488 patients with SLE from 10 rheumatology centres. The median time to diagnosis was 6months Interquartile Range (IQR 3,14.7) and within 3months in about one third [150(30.7%)]. Very early diagnosis (<1month) was established in 78(16.0%) patients. The mean SLE Disease Activity Index (SLEDAI) at diagnosis was 10.28+7.24. In univariate analysis, an older age, lower SES, non-southern state of residence and larger family size were significantly associated with late diagnosis. In the multivariate analysis, higher SES (AOR 0.95, 95% CI: 0.92-0.98), multiple organ system involvement at initial presentation (AOR1.75 95%CI: 1.08-2.84) and place of residence in south Indian states (AOR1.92 95%CI: 1.24-2.97) had lesser odds of being associated with late diagnosis. Distance from the closest medical centre/professional did not influence the time to diagnosis. Majority of patients had first consulted a medical graduate (42.5%) or postgraduate doctor (48.2%), and referral to rheumatologist was largely done by postgraduate (65%) doctors. More than half of our patients (61%) self-finance their treatment. Median time to diagnosis of SLE was 6months, 1/3rd being diagnosed within 3months and 78(16.0%) with 1month of symptom onset. Delay in diagnosis was noted in those belonging to lower socioeconomic strata and those with single organ disease. Distance to the health care facility did not influence time to diagnosis.

Vaping-associated illness: a reassessment

BackgroundIn 2019, there was widespread presentation of respiratory distress as well as other organ system involvement in patients with a history of vaping. There continue to be reports of vaping-associated illness (VAI). This has come to be known as e-cigarette and vaping product associated lung injury (EVALI). The mechanism of injury remains unclear.ObjectivesThis study reexamines the clinical characteristics of patients affected by vaping and suggests that lung injury may not be the primary organ dysfunction but be part of a larger systemic illness.MethodsThis is a retrospective chart review of all patients presenting to one hospital identified as having vaping-associated illnessResultsFourteen patients were identified ranging in age from 15 to 33 years. Patients had a broad range of clinical severity. Respiratory symptoms occurred in 64%, gastrointestinal symptoms in 57%, fever in 78%, neurological symptoms in 15% and other constitutional symptoms in 50%. 35% presented with no respiratory symptoms.ConclusionWhile the lungs are certainly involved in vaping-associated illness, recognizing the extent of involvement of other organ systems may provide insight into the pathophysiology of the disease. Providers should be aware that vaping-associated illness presents with a multitude of symptoms outside of lung injury, such as abdominal pain, headache or even fever.

Age- and Elicitor-Dependent Characterization of Hymenoptera Venom-Induced Anaphylaxis in Children and Adolescents

BackgroundHymenoptera venom is one of the most frequent causes of anaphylaxis. Studies from adults indicate the clinical profiles and risk factors of Hymenoptera venom induced anaphylaxis (VIA). Much less is known about pediatric VIA. ObjectiveTo better understand elicitor and age related factors determining pediatric VIA by analyzing data from the anaphylaxis registry. MethodsWe selected pediatric VIA, pediatric food induced anaphylaxis (FIA) and adult VIA cohorts from the anaphylaxis registry and performed a comparative data analysis regarding elicitors, symptoms and management. Results725 pediatric VIA, 3,149 pediatric FIA and 5,534 adult VIA were identified. In pediatric VIA, boys were more frequently affected, atopy was not increased and the onset of the reaction after exposure was fast (≤ 30 min; 91%) when compared to pediatric FIA. Symptoms in pediatric VIA were age dependent, and although respiratory symptoms occurred besides skin symptoms most frequent in both, pediatric VIA and FIA, cardiovascular symptoms were more frequently reported in pediatric VIA than pediatric FIA.The analysis of pediatric versus adult VIA reveled clear differences of the frequency of involved organ systems (skin: 93/78%, respiratory: 77/64%, and cardiovascular: 61/85%). Among both, the pediatric and adult VIA, the rates of adrenaline application by a professional were low (29/31%) but the hospitalization rates were higher in children than in adults (61%/42%). Venom immunotherapy (VIT) was initiated frequently regardless of age (78% each). ConclusionPediatric VIA is more frequent in boys, symptoms are age dependent and often hospitalization is required. Adrenaline should be applied according the current guidelines. VIT is an important treatment option in pediatric VIA and should be considered in severely affected children.

An efficient and successful outcome after haematopoietic stem cell transplantation in a patient with an LPS-responsive beige-like anchor gene mutation.

Lipopolysaccharide (LPS)-responsive beige ankyrin (LRBA) gene mutations were first reported as the cause of immunodeficiency syndromes and autoimmunity in 2012. The majority of LRBA patients have multiple organ system involvement and a complex clinical phenotype. Herein we present a comprehensive account on the disease progression and transplantation procedure in a patient with LRBA deficiency who exhibited progressive autoimmune disease symptoms along with recurrent pulmonary infections since the age of 6 years old. Despite receiving abatacept therapy and immunoglobulin replacement treatments to manage the symptoms, but the symptoms still progressed. Therefore, nine years after disease onset, patients were treated with allogeneic haematopoietic stem cell transplantation (allo-HSCT). The patient experienced acute and chronic graft-versus-host disease (GVHD) and recurrent infections after transplantation. During one and a half years of follow-up, we found that allogeneic haematopoietic stem cell transplantation can relieve the symptoms of autoimmune disease in patients with LRBA deficiency, and marked clinical improvement and recovery of immune function were observed following stem cell transplantation.

Case report of a child with nephronophthisis from South Africa

BackgroundNephronophthisis (NPHP) is an autosomal recessive disorder with a subset of patients presenting with extrarenal manifestations such as retinal degeneration, cerebella ataxia, liver fibrosis, skeletal abnormalities, cardiac malformations, and lung bronchiectasis. However, the involvement of other organ systems has also been documented. Extrarenal manifestations occur in approximately 10–20% of patients. In developed countries, it has been reported as one of the most common causes of monogenic chronic kidney failure (CKF) during the first three decades of life, with more than 25 genes associated with this condition. The current treatment options for managing NPHP include supportive care, management of complications, and kidney replacement therapy when necessary.The index patient is a 10-year-old Caucasian female who presented with recurrent attacks of abdominal pain. Her elder sister, TN, who was 17 years old, was diagnosed with CKF and noted to have persistently elevated liver enzymes (gamma-glutamyl transferase, alanine, and aspartate transaminases). Following genetic testing, her elder sister was shown to have Nephronophthisis Type 3, and a liver biopsy showed early fibrotic changes. Subsequent genetic testing confirmed the index patient as having NPHP Type 3. A kidney biopsy showed focal sclerosed glomeruli with patchy areas of tubular atrophy and related tubulointerstitial changes in keeping with NPHP. We present the first confirmatory case of NPHP from South Africa based on histopathology and genetic testing in a 10-year-old Caucasian female who presented with recurrent attacks of abdominal pain, whose elder sister also presented with CKF and early liver fibrosis, confirmed on biopsy and genetic testing.ConclusionIn low-middle-income countries, genetic testing should be undertaken whenever possible to confirm the diagnosis of NPHP, especially in those with a suggestive biopsy or if there is CKF of unknown aetiology with or without extra-renal manifestations.