Clinical and Treatment History of Patients with Partial DiGeorge Syndrome and Autoimmune Cytopenia at Multiple Centers.

BACKGROUND: Patients with partial DiGeorge syndrome (pDGS) can present with immune dysregulation, the most common being autoimmune cytopenia (AIC). There is a lack of consensus on the approach to type, combination, and timing of therapies for AIC in pDGS. Recognition of immune dysregulation early in pDGS clinical course may help individualize treatment and prevent adverse outcomes from chronic immune dysregulation. OBJECTIVES: Objectives of this study were to characterize the natural history, immune phenotype, and biomarkers in pDGS with AIC. METHODS: Data on clinical presentation, disease severity, immunological phenotype, treatment selection, and response for patients with pDGS with AIC were collected via retrospective chart review. Flow cytometric analysis was done to assess T and B cell subsets, including biomarkers of immune dysregulation. RESULTS: Twenty-nine patients with the diagnosis of pDGS and AIC were identified from 5 international institutions. Nineteen (62%) patients developed Evan's syndrome (ES) during their clinical course and twenty (69%) had antibody deficiency syndrome. These patients demonstrated expansion in T follicular helper cells, CD19hiCD21lo B cells, and double negative cells and reduction in CD4 naïve T cells and regulatory T cells. First-line treatment for 17/29 (59%) included corticosteroids and/or high-dose immunoglobulin replacement therapy. Other overlapping therapies included eltrombopag, rituximab, and T cell immunomodulators. CONCLUSIONS: AIC in pDGS is often refractory to conventional AIC treatment paradigms. Biomarkers may have utility for correlation with disease state and potentially even response to therapy. Immunomodulating therapies could be initiated early based on early immune phenotyping and biomarkers before the disease develops or significantly worsens.

Insights into the Impact of Hesitancy on Cancer Care and COVID-19.

World Health Organization findings indicate that the COVID-19 pandemic adversely affected cancer diagnosis and management. The COVID-19 pandemic disrupted the optimal management of outpatient appointments, scheduled treatments, and hospitalizations for cancer patients because of hesitancy among patients and health-care providers. Travel restrictions and other factors likely affected medical, surgical, and radiation treatments during the COVID-19 pandemic. Cancer patients were more likely to be affected by severe illness and complications if they contracted COVID-19. A compromised immune system and comorbidities in cancer patients may have contributed to this increased risk. Hesitancy or reluctance to receive appropriate therapy or vaccination advice might have played a major role for cancer patients, resulting in health-care deficits. The purpose of this review is to evaluate the impact of COVID-19 on screening, entry into clinical trials, and hesitancy among patients and health-care professionals, limiting adjuvant and metastatic cancer treatment.

Primary immune thrombocytopenia: a 'diagnosis of exclusion'?

Current diagnosis of primary immune thrombocytopenia (ITP) is presumptive, centered on excluding other causes of thrombocytopenia. The diagnosis of ITP is challenging because of the wide range of potential inherited and acquired causes of thrombocytopenia. The treatment of ITP is empiric with steroids, high-dose immunoglobulin, immunosuppressants and thrombopoietin agonists with potential side effects. We searched Medline and Cochrane databases, reviewed the study data and analyzed the individual diagnostic tests for their evidence-based role in the diagnosis of ITP. We then analyzed the strength of the scientific evidence for each diagnostic test in the diagnosis of ITP and identified gaps in the diagnostic accuracy. The diagnostic challenges in ITP include: insufficient evidence for the individual test for diagnosis of ITP, no standardized protocol/guideline for diagnosis, hurdles in accessing the available resources and failure to correlate the clinical data while reviewing the blood smear. We did not identify a diagnostic test that clinicians can use to confirm the diagnosis of ITP. In the absence of a diagnostic test of proven value in ITP, the clinician is best served by a comprehensive history and physical examination, complete blood count and review of the peripheral blood smear in evaluating thrombocytopenia.

Primary Immunodeficiency in Children With Autoimmune Cytopenias: Retrospective 154-Patient Cohort.

Background: Primary immunodeficiency is common among patients with autoimmune cytopenia. Objective: The purpose of this study is to retrospectively identify key clinical features and biomarkers of primary immunodeficiency (PID) in pediatric patients with autoimmune cytopenias (AIC) so as to facilitate early diagnosis and targeted therapy. Methods: Electronic medical records at a pediatric tertiary care center were reviewed. We selected 154 patients with both AIC and PID (n=17), or AIC alone (n=137) for inclusion in two cohorts. Immunoglobulin levels, vaccine titers, lymphocyte subsets (T, B and NK cells), autoantibodies, clinical characteristics, and response to treatment were recorded. Results: Clinical features associated with AIC-PID included splenomegaly, short stature, and recurrent or chronic infections. PID patients were more likely to have autoimmune hemolytic anemia (AIHA) or Evans syndrome than AIC-only patients. The AIC-PID group was also distinguished by low T cells (CD3 and CD8), low immunoglobulins (IgG and IgA), and higher prevalence of autoantibodies to red blood cells, platelets or neutrophils. AIC diagnosis preceded PID diagnosis by 3 years on average, except among those with partial DiGeorge syndrome. AIC-PID patients were more likely to fail first-line treatment. Conclusions: AIC patients, especially those with Evans syndrome or AIHA, should be evaluated for PID. Lymphocyte subsets and immune globulins serve as a rapid screen for underlying PID. Early detection of patients with comorbid PID and AIC may improve treatment outcomes. Prospective studies are needed to confirm the diagnostic clues identified and to guide targeted therapy.

Chronic pain in patients with hemophilia: is it preventable?

: Current management of chronic pain in patients with hemophilia (PWH) focuses on pain relief with analgesics and symptom control. The clinical practice of managing chronic pain in PWH varies considerably across hemophilia treatment centers. Here, we aim to study the appropriate intervention of hemophilic arthropathy for prevention and treatment of chronic pain in PWH. Medline, Embase, Cochrane databases were searched for randomized controlled trials, and the European Hemophilia Therapy Standardization Board, The World Federation of Hemophilia, Nordic Hemophilia Guidelines, American Society of the International Pain Physicians and the Medical and Scientific Advisory Council guidelines were studied through November 2019 for chronic pain in PWH for a narrative review. We found no standardized approach for the prevention and management of chronic pain in PWH. Evidence suggests that prophylactic factor concentrate therapy, programmed exercise and educational intervention may help PWH manage their chronic pain.

Autoimmunity as a continuum in primary immunodeficiency.

PURPOSE OF REVIEW: Primary immunodeficiency disorders (PIDs) are no longer defined by infections alone. First clinical sign or sequelae of PID may include autoimmunity, such as cytopenias, arthritis or enteropathy. This review addresses the latest in multidisciplinary approaches for expanding clinical phenotypes of PIDs with autoimmunity, including new presentations of known entities and novel gene defects. We also discuss diagnostic tools for identifying the distinct changes in immune cells subsets and autoantibodies, mechanistic understanding of the process, and targeted treatment and indications for hematopoietic stem-cell transplantation (HSCT). RECENT FINDINGS: In the past years, increased awareness and use of genetic screening, confirmatory functional studies and immunological biomarkers opened the door for early recognition of PIDs among patients with autoimmunity. Large cohort studies detail the clinical spectrum and treatment outcome of PIDs with autoimmunity with specific immune genes (e.g., CTLA4, LRBA, PI3Kδ, NFKB1, RAG). The benefit of early recognition is initiation of targeted therapies with precise re-balancing of the dysregulated immune pathways (e.g., biologicals) or definitive therapy (e.g., HSCT). SUMMARY: Clinical presentation of patients with PID and autoimmunity is highly variable and requires in-depth diagnostics and precision medicine approaches.

Risk factors for hospital-associated venous thromboembolism in critically ill children following cardiothoracic surgery or therapeutic cardiac catheterisation.

BACKGROUND: Paediatric hospital-associated venous thromboembolism is a leading quality and safety concern at children's hospitals. OBJECTIVE: The aim of this study was to determine risk factors for hospital-associated venous thromboembolism in critically ill children following cardiothoracic surgery or therapeutic cardiac catheterisation. METHODS: We conducted a retrospective, case-control study of children admitted to the cardiovascular intensive care unit at Johns Hopkins All Children's Hospital (St. Petersburg, Florida, United States of America) from 2006 to 2013. Hospital-associated venous thromboembolism cases were identified based on ICD-9 discharge codes and validated using radiological record review. We randomly selected two contemporaneous cardiovascular intensive care unit controls without hospital-associated venous thromboembolism for each hospital-associated venous thromboembolism case, and limited the study population to patients who had undergone cardiothoracic surgery or therapeutic cardiac catheterisation. Odds ratios and 95% confidence intervals for associations between putative risk factors and hospital-associated venous thromboembolism were determined using univariate and multivariate logistic regression. RESULTS: Among 2718 admissions to the cardiovascular intensive care unit during the study period, 65 met the criteria for hospital-associated venous thromboembolism (occurrence rate, 2%). Restriction to cases and controls having undergone the procedures of interest yielded a final study population of 57 hospital-associated venous thromboembolism cases and 76 controls. In a multiple logistic regression model, major infection (odds ratio=5.77, 95% confidence interval=1.06-31.4), age ⩽1 year (odds ratio=6.75, 95% confidence interval=1.13-160), and central venous catheterisation (odds ratio=7.36, 95% confidence interval=1.13-47.8) were found to be statistically significant independent risk factors for hospital-associated venous thromboembolism in these children. Patients with all three factors had a markedly increased post-test probability of having hospital-associated venous thromboembolism. CONCLUSION: Major infection, infancy, and central venous catheterisation are independent risk factors for hospital-associated venous thromboembolism in critically ill children following cardiothoracic surgery or cardiac catheter-based intervention, which, in combination, define a high-risk group for hospital-associated venous thromboembolism.

Development of a new risk score for hospital-associated venous thromboembolism in critically-ill children not undergoing cardiothoracic surgery.

BACKGROUND: Although risk of hospital-associated venous thromboembolism (HA-VTE) differs between critically and non-critically ill children, studies to date have not led to distinct, pragmatic risk scores. OBJECTIVE: To determine risk factors for HA-VTE in critically ill children not undergoing cardiothoracic surgery, in order to derive a novel HA-VTE risk score for this population. METHODS: We conducted a retrospective analysis from January 2006 through April 2013 at All Children's Hospital Johns Hopkins Medicine. HA-VTE cases were identified using ICD-9 discharge diagnosis codes, with subsequent validation via radiologic record review. Cases were restricted to Pediatric Intensive Care Unit (PICU) admissions. Patients who underwent cardiothoracic surgery were excluded; cardiac catheterization per se was not exclusionary. For each case, three non-HA-VTE PICU controls were randomly selected. Data were abstracted on putative risk factors, and associations between risk factors and HA-VTE were estimated using odds ratios (ORs) and 95% confidence intervals (95%CIs). RESULTS: There were 57 HA-VTE cases and 171 controls. HA-VTE occurrence was 3 per 1000 PICU admissions (0.3%). Central venous catheter (CVC) (OR:26.64; 95%CI:7.46-95.13), length of stay (LOS) ≥4days (OR:20.22; 95%CI:2.27-180.07), and significant infection (OR:3.41; 95%CI:1.13-10.29) were independent, statistically-significant risk factors for HA-VTE in a multivariate model. A risk score was derived in which HA-VTE risk exceeded 2% (threshold for anticoagulant thromboprophylaxis in hospitalized adults) with a score of 15, and was >1% but <2% (risk zone for mechanical thromboprophylaxis in hospitalized adults) with scores of 7-14. CONCLUSION: The presence of a CVC, LOS≥4days and infection are significant risk factors for HA-VTE in critically ill children not undergoing cardiothoracic surgery, forming the basis for a new risk score that warrants prospective validation.

Development of a new risk score for hospital-associated venous thromboembolism in noncritically ill children: findings from a large single-institutional case-control study.

OBJECTIVE: To determine risk factors for pediatric hospital-associated venous thromboembolism (HA-VTE) in noncritically ill children to derive a novel HA-VTE risk model for this population. STUDY DESIGN: Patients with HA-VTE were identified retrospectively via the electronic health record at All Children's Hospital Johns Hopkins Medicine from April 10, 2013 through January 1, 2006. Seven contemporaneous, noncritically ill control children were randomly selected for each case of HA-VTE. The association between putative risk factors and HA-VTE was estimated with ORs and 95% CIs, which were calculated using the Wald method. A P-value threshold ≤.2 was used in univariate analysis for inclusion into a multivariate (adjusted) model. RESULTS: Fifty cases of HA-VTE occurred in noncritically ill children. The presence of a central venous catheter (OR 27.67, 95% CI, 8.40-91.22), infection (OR 10.40, 95% CI, 3.46-31.25), and length of stay ≥4 days (OR 5.26, 95% CI, 1.74-15.88) were found to be statistically significant risk factors for HA-VTE. An 8-point risk score was derived in which scores of 8 points, 7 points, and ≤6 points corresponded to venous thromboembolism risks of 12.5%, 1.1%, and 0.1%, respectively. CONCLUSION: The presence of a central venous catheter, infection, and length of stay ≥4 days are significant risk factors for HA-VTE in noncritically ill children, forming the basis for a new risk score that could inform venous thromboembolism prophylaxis decision-making. These findings warrant prospective validation.

Risk factors for hospital-sssociated venous thromboembolism in the neonatal intensive care unit.

OBJECTIVE: To determine hospital-associated venous thromboembolism (HA-VTE) risk factors in critically ill neonates. METHODS: We conducted a case-control study in the neonatal intensive care unit (NICU) of All Children's Hospital Johns Hopkins Medicine (St. Petersburg, FL), from January 1, 2006 - April 10, 2013. We identified HA-VTE cases using electronic health record. Four NICU controls were randomly selected for each HA-VTE case. Associations between putative risk factors and HA-VTE were estimated using odds ratios (ORs) and ninety-five percent confidence intervals (95%CIs) from univariate and multivariate regression analyses. RESULTS: Twenty-three HA-VTE cases and 92 controls were included. The annual HA-VTE incidence was approximately 1.4 HA-VTE cases per 1,000 NICU admissions. In univariate analyses, mechanical ventilation (OR=7.27, 95%CI=2.02-26.17, P=0.002), central venous catheter (CVC; OR=52.95, 95%CI=6.80-412.71, P<0.001), infection (OR=7.24, 95%CI=2.66-19.72, P<0.001), major surgery (OR=5.60, 95%CI=1.82-17.22, P=0.003) and length of stay ≥15days (OR=6.67, 95%CI=1.85-23.99, P=0.004) were associated with HA-VTE. Only CVC (OR=29.04, 95%CI=3.18-265.26, P=0.003) remained an independent risk factor in the multivariate analysis. Based on this result, the estimated risk of HA-VTE in NICU patients with a CVC was 0.9%. CONCLUSION: This study identifies CVC as an independent risk factor for HA-VTE in critically ill neonates. However, the level of risk associated with CVC is below the conventional threshold for primary anticoagulation thromboprophylaxis. Larger studies are needed to substantiate these findings and identify novel putative risk factors to further distinguish NICU patients at highest HA-VTE risk.

Monitoría intensiva neurodiagnóstica para pacientes con epilepsia complicada: experiencia con los primeiros cincuenta pacientes en el Hospital Municipal de San Juan / Intensive neurodiagnostic monitoring for patients with complicated epilepsy: our experience with the first 50 patients in the San Juan City Hospital

Estudio descriptivo para reportar los hallazgos más importante durante la admisión de los primeros cincuenta pacientes a la Unidad de Monitoría Intensiva de epilepsia. Por ejemplo: Razón de referido, historial, distribución por edad y sexo, factores precipitantes y hallazgos de estudios diagnósticos. Se evidencia la utilidad de monitoría intensiva en el diagnóstico y manejo de pacientes con epilepsia complicada, en la diferenciación de episodios que sugieren ser epilepsia y en el diagnóstico de otras condiciones neurológicas como lo son desórdenes de movimiento, tics y otros. Con la utilización de esta técnica, el 68% de los pacientes fueron diagnosticados correctamente, lo cual permitió la recomendación del régimen terapéutico óptimo