Systematic review and meta-analysis of the etiology of heavy menstrual bleeding in 2,770 adolescent females.

BACKGROUND: Adolescent heavy menstrual bleeding(HMB), menorrhagia or abnormal uterine bleeding commonly occur in adolescent women. The differential diagnosis can be challenging. The pneumonic: PALM-COEIN (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not yet classified), is commonly used but it does not stratify as to the likelihood of a disorder. We have sought to develop a probability-based differential diagnosis for Adolescent HMB, menorrhagia or abnormal uterine bleeding. METHODS: A comprehensive literature search was conducted using PubMed, EMBASE, and SCOPUS databases. Case series describing adolescents from 10-19 years of age with HMB, menorrhagia or abnormal uterine bleeding was acceptable if: more than 10 patients were included; editorials, case reports, and secondary sources such as review articles, or book chapters were excluded. No language filter was used, but an English abstract was required. The etiology of HMB, menorrhagia or abnormal uterine bleeding, and the country of origin was extracted from articles that met inclusion criteria. Cumulative rate estimates were determined by Bayesian probability modeling. RESULTS: Seventeen full text articles were reviewed in detail; 2,770 patients were included. The most frequent causes of HMB were Ovarian Uterine Disorders (23.7%; 95% CredI 22-25.5%), Coagulation Disorders (19.4%; 95% CredI 17.8-21.1%), and Platelet Disorders (6.23%; 95% CredI 5.27-7.27%) with 45.9% (95% CredI 43.8-47.%9) of the cases of indeterminate origin. CONCLUSIONS: The leading causes of HMB in healthy adolescent females were varied. The sub-analysis identified distinct etiologies, suggesting that multiple factors must be considered in the evaluation of HMB. While PALM-COEIN (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not yet classified) provides us with a comprehensive picture of the possible causes of HMB in females, this systematic review assigns probabilities to the etiologies of HMB in adolescent females, providing physicians with a more focused and efficient pathway to diagnosis.

The Natural History of Severe Acute Respiratory Syndrome Coronavirus 2-Related Multisystem Inflammatory Syndrome in Children: A Systematic Review.

BACKGROUND: The clinical manifestations and natural history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related multisystem inflammatory syndrome in children (MIS-C) are poorly defined. Using a systematic review of individual cases and case series and collating elements of the clinical course, the objective of this study was to provide a detailed clinical description and natural history of MIS-C. METHODS: Case reports and series of MIS-C were recovered from repeated MEDLINE searches, a single EMBASE search, and table of contents reviews of major general medicine and pediatric journals performed between June 3 and July 23, 2020. Fever, evidence of inflammation, and evidence of organ dysfunction were required for inclusion. RESULTS: MEDLINE and EMBASE searches produced 129 articles, and 10 articles were identified from journal contents or article bibliographies; 16 reports describing 505 children with MIS-C comprise this review. Thirty-two children (14.7%) had negative results for SARS-CoV-2 by nucleic acid and/or antibody testing. The weighted median age was 9 years (6 months to 20 years). Clinical findings included fever (100%), gastrointestinal symptoms (88.0%), rash (59.2%), conjunctivitis (50.0%), cheilitis/ "strawberry tongue" (55.7%), or extremity edema/erythema (47.5%). Median serum C-reactive protein, ferritin, fibrinogen, and D-dimer concentrations were above the normal range. Intravenous gammaglobulin (78.1%) and methylprednisolone/prednisone (57.6%) were the most common therapeutic interventions; immunomodulation was used in 24.3% of cases. Myocardial dysfunction requiring ionotropic support (57.4%) plus extracorporeal membrane oxygenation (5.3%), respiratory distress requiring mechanical ventilation (26.1%), and acute kidney injury (11.9%) were the major complications; anticoagulation was used commonly (54.4%), but thrombotic events occurred rarely (3.5%). Seven (1.4%) children died. CONCLUSIONS: MIS-C following SARS-CoV-2 infection frequently presents with gastrointestinal complaints and/or rash; conjunctivitis, cheilitis, and/or extremity changes also occur frequently. Serious complications occur frequently and respond to aggressive supportive therapy.

Etiologies of hemoptysis in children: A systematic review of 171 patients.

OBJECTIVE: To provide prevalence rates for the most common causes of hemoptysis in children. DATA SOURCES: A systematic review of articles from PubMed, the OVID Cochrane Reviews (1960-2015), and EMBASE (1991-2015) was undertaken. Additional articles were identified by reviewing the bibliographies of selected studies. Search terms included hemoptysis, children, and humans. STUDY SELECTION: Only case studies and cohorts that examined the causes of hemoptysis in children (birth to 21 years) were included; at least 10 patients were required of each study. DATA EXTRACTION: Inclusion criteria, patient number, age range, patient source, and categorical and specific etiologies of hemoptysis were recorded. DATA SYNTHESIS: From the 1,858 studies identified, seven were selected for inclusion. Eighty-nine percent of participants were found to have a specific etiology for hemoptysis. Of the categorical etiologies identified, infection (37.57%), "other causes" (31.79%), heart disease (6.36%), and neoplasia (4.05%) were the most common. Pneumonia, bronchitis, and pulmonary tuberculosis were the most common specific etiologies identified. LIMITATIONS: By its nature, this study was subject to selection bias and under representation of specific etiologies. CONCLUSIONS: Most pediatric patients presenting with hemoptysis have a specific etiology; pneumonia is the most common. A thorough history, physical exam, and focused laboratory evaluation is recommended for such patients. Pediatr Pulmonol. 2017;52:255-259. © 2016 Wiley Periodicals, Inc.

Etiologies of conjugated hyperbilirubinemia in infancy: a systematic review of 1692 subjects.

BACKGROUND: The etiologies of conjugated hyperbilirubinemia in infancy are diverse. OBJECTIVE: Determine the prevalence rates of the specific etiologies of conjugated hyperbilirubinemia in infancy. DATA SOURCES: EMBASE and Pubmed were searched electronically and the bibliographies of selected studies were search manually. The search was conducted independently by two authors. STUDY SELECTION: (1) prospective or retrospective case series or cohort study with 10 or more subjects; (2) consecutive infants who presented with conjugated hyperbilirubinemia; (3) subjects underwent appropriate diagnostic work-up for conjugated hyperbilirubinemia; (4) no specific diagnoses were excluded in the studied cohort. DATA EXTRACTION: Patient number, age range, country of origin, and categorical and specific etiologies. RESULTS: From 237 studies identified, 17 studies encompassing 1692 infants were selected. Idiopathic neonatal hepatitis (INH) occurred in 26.0% of cases; the most common specific etiologies were extrahepatic biliary atresia (EHBA) (25.89%), infection (11.47%), TPN- associated cholestasis (6.44%), metabolic disease (4.37%), alpha-1 anti-trypsin deficiency (4.14%), and perinatal hypoxia/ischemia (3.66%). CMV was the most common infection identified (31.51%) and galactosemia (36.49%) was the most common metabolic disease identified. LIMITATIONS: Major limitations are: (1) inconsistencies in the diagnostic evaluations among the different studies and (2) variations among the sample populations. CONCLUSIONS: INH is the most common diagnosis for conjugated hyperbilirubinemia in infancy while EHBA and infection are the most commonly identified etiologies. The present review is intended to be a guide to the differential diagnosis and evaluation of the infant presenting with conjugated hyperbilirubinemia.

Intravenous immunoglobulin in the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis: a meta-analysis with meta-regression of observational studies.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe disorders with significant morbidity and mortality. The therapeutic use of intravenous immunoglobulin (IVIG) is based on limited data. OBJECTIVES: This systematic review evaluates the existing literature to determine if IVIG impacts the standardized mortality rate (SMR) in patients with SJS or TEN. METHODS: The MEDLINE database was searched for the period 1966-2011 for pertinent studies. The bibliographies of selected references were also reviewed for additional studies. Inclusion criteria required the studies to refer to patients who received IVIG for SJS or TEN, the severity of which was determined using the SCORTEN system. Thirteen studies were used in the final analysis. Demographic data, IVIG dosing, SCORTEN score, and mortality rates were extracted. RESULTS: Of the 13 studies, eight included a control group. Meta-analysis revealed that differences in SMRs were not significant (-0.322, 95% confidence interval [CI] -0.766 to 0.122; P = 0.155). The overall SMR point estimate for all 13 studies was 0.814 (95% CI 0.617-1.076). Meta-regression demonstrated a strong inverse correlation between IVIG dosage and SMRs (slope: -0.59, 95% CI -0.14 to -1.03; P = 0.009). CONCLUSIONS: Intravenous IG at dosages of ≥2 g/kg appears to significantly decrease mortality in patients with SJS or TEN.

The etiologies of non-CF bronchiectasis in childhood: a systematic review of 989 subjects.

BACKGROUND: While cystic fibrosis (CF) is the most common cause of bronchiectasis in childhood, non-CF bronchiectasis is associated with a wide variety of disorders. The objective of this study was to determine the relative prevalence and specific etiologies on non-CF bronchiectasis in childhood. METHODS: EMBASE, Medline, OVID Cochrane Reviews, Directory of Open Access Journals, Open Science Directory, EPSCO information services, and OAlster were searched electronically and the bibliographies of selected studies were searched manually. The search was conducted independently by 2 authors. STUDY SELECTION: (1) any clinical trial, observational study or cross-sectional case series of 10 or more patients with a description of the conditions associated with bronchiectasis; (2) subjects aged 21 years or younger; (3) cystic fibrosis was excluded and; (4) the diagnosis was confirmed by computed tomography of the chest. DATA EXTRACTION: Patient number, age range, inclusion criteria, diagnostic criteria, patient source, and categorical and specific etiology. RESULTS: From 491 studies identified, 12 studies encompassing 989 children with non-CF bronchiectasis were selected. Sixty-three percent of the subjects had an underlying disorder. Infectious (17%), primary immunodeficiency (16%), aspiration (10%), ciliary dyskinesia (9%), congenital malformation (3%), and secondary immunodeficiency (3%) were the most common disease categories; 999 etiologies were identified. Severe pneumonia of bacterial or viral etiology and B cell defects were the most common disorders identified. CONCLUSIONS: The majority of children with non-CF bronchiectasis have an underlying disorder. A focused history and laboratory investigated is recommended.

Use of serum procalcitonin in evaluation of febrile infants: a meta-analysis of 2317 patients.

BACKGROUND: Serum procalcitonin (PCT) concentrations have been studied as a diagnostic test for serious bacterial infections (SBIs) in children. However, the utility of a single measurement in the evaluation of SBIs in febrile infants younger than 91 days is not clear. OBJECTIVE: Use a systematic review and meta-analysis to determine: 1) the ability of serum PCT concentrations to identify febrile infants < 91 days of age at high and low risk for SBIs, and 2) to compare its utility with available clinical prediction rules. METHODS: The literature search identified studies of febrile infants segregated into risk groups using serum PCT concentrations. Some authors were contacted to provide subgroups < 91 days of age or to provide data with 0.3 ng/mL PCT cutoff values. Data were combined and validated using standard methodologies. RESULTS: Seven studies encompassing 2317 patients were identified; five of seven studies used a PCT discriminating concentration of 0.3 ng/mL. No heterogeneity or publication bias was identified. The overall relative risk (RR) was 3.97 (95% confidence interval [CI] 3.41-4.62) and was consistent by sensitivity analysis. The RR from a systematic review of clinical prediction rules was 30.6 (95% CI 7.0-68.13) and 8.75 (95% CI 2.29-15.2) for infants untreated and treated with antibiotics, respectively. CONCLUSIONS: Alone, measurement of serum PCT concentrations, though able to identify a group of young infants at risk for SBIs, is inferior to the available clinical prediction rules for identifying young, febrile infants at risk for SBIs. Serum concentrations ≤ 0.3 ng/mL may be helpful as an add-on test to current rules for identifying low-risk, febrile infants.

Tetrasomy 13q32.2qter due to an apparent inverted duplicated neocentric marker chromosome in an infant with hemangiomas, failure to thrive, laryngomalacia, and tethered cord.

BACKGROUND: Approximately 100 small supernumerary marker chromosomes (sSMCs) with a non-α-satellite neocentromere structure have been reported in the literature. Of the few derived from chromosome 13, five have consisted of inverted duplicated segment 13q32qter. CASE REPORT: We herein describe the sixth case, characterized by genome wide SNP array, conventional cytogenetics and FISH studies. The de novo occurrence of the marker, the poor prognosis and the presence of hemangiomas are consistent with previous cases. CONCLUSION: We hereby expand the clinical spectrum of this rare cytogenetic disorder and suggest a possible mechanism for the pathogenesis of associated congenital vascular malformations.

The Use of Albuterol in Young Infants Hospitalized with Acute RSV Bronchiolitis.

Objective. To evaluate the effects of albuterol use in young infants admitted with respiratory syncytial virus (RSV) bronchiolitis with regards to length of time on supplemental oxygen and length of stay (LOS). To consider the possibility that albuterol use may increase the need for supplemental oxygen and increase LOS. Design, Setting, and Participants. Full-term infants between the ages of 11 days and 90 days (N = 316) were included in this retrospective study. Infants included were hospitalized with a diagnosis of RSV bronchiolitis at a university-affiliated children's hospital. Results. In 4 of 5 severity groups, patients who received albuterol required more time on supplemental oxygen and had longer LOS. The differences only reached statistical significance in one of the severity groups in regards to LOS. Conclusions. The use of albuterol does not appear to be useful in the treatment of young infants with RSV bronchiolitis and may actually be harmful, in regards to increased supplemental oxygen need.