Significant pituitary siderosis is common in transfusion dependent sickle cell disease.

Chronically transfused sickle cell patients typically don't exhibit iron-mediated extrahepatic toxicity. However, we demonstrate that the pituitary gland is vulnerable to iron deposition, and it occurs regardless of other extrahepatic involvement. Severe pituitary siderosis is associated with early organ dysfunction.

Decreased erythrocyte aggregation in Glenn and Fontan: univentricular circulation as a rheologic disease model.

BACKGROUND: In the Fontan palliation for single ventricle heart disease (SVHD), pulmonary blood flow is non-pulsatile/passive, low velocity, and low shear, making viscous power loss a critical determinant of cardiac output. The rheologic properties of blood in SVHD patients are essential for understanding and modulating their limited cardiac output and they have not been systematically studied. We hypothesize that viscosity is decreased in single ventricle circulation. METHODS: We evaluated whole blood viscosity, red blood cell (RBC) aggregation, and RBC deformability to evaluate changes in healthy children and SVHD patients. We altered suspending media to understand cellular and plasma differences contributing to rheologic differences. RESULTS: Whole blood viscosity was similar between SVHD and healthy at their native hematocrits, while viscosity was lower at equivalent hematocrits for SVHD patients. RBC deformability is increased, and RBC aggregation is decreased in SVHD patients. Suspending SVHD RBCs in healthy plasma resulted in increased RBC aggregation and suspending healthy RBCs in SVHD plasma resulted in lower RBC aggregation. CONCLUSIONS: Hematocrit corrected blood viscosity is lower in SVHD vs. healthy due to decreased RBC aggregation and higher RBC deformability, a viscous adaptation of blood in patients whose cardiac output is dependent on minimizing viscous power loss. IMPACT: Patients with single ventricle circulation have decreased red blood cell aggregation and increased red blood cell deformability, both of which result in a decrease in blood viscosity across a large shear rate range. Since the unique Fontan circulation has very low-shear and low velocity flow in the pulmonary arteries, blood viscosity plays an increased role in vascular resistance, therefore this work is the first to describe a novel mechanism to target pulmonary vascular resistance as a modifiable risk factor. This is a novel, modifiable risk factor in this patient population.

Transfusional hemosiderosis in childhood cancer patients and survivors.

BACKGROUND: Children treated for cancer are at risk for adverse effects of iron due to transfusions administered during prolonged marrow suppression, which may increase exposure to toxic forms of iron, extrahepatic iron accumulation, and long-term organ damage. OBJECTIVE: This study aimed to characterize the severity and organ distribution of clinically significant, multisystem iron overload (IO) in an at-risk cohort of pediatric cancer patients. METHODS: This was a retrospective, cross-sectional study of childhood cancer patients who underwent a magnetic resonance imaging (MRI) due to clinical concern for IO. Data regarding cancer type and treatment, transfusion history, MRI and laboratory results, and treatment for IO were collected. Severity of IO was analyzed by non-parametric tests with respect to clinical characteristics. RESULTS: Of the 103 patients, 98% of whom had a Cancer Intensity Treatment Rating (ITR-3) of 3 or higher, 53% (54/102) had moderate or greater hepatic siderosis, 80% (77/96) had pancreatic siderosis, 4% (3/80) had cardiac siderosis, and 45% (13/29) had pituitary siderosis and/or volume loss. Pancreatic iron was associated with both cardiac (p = .0043) and pituitary iron (p = .0101). In the 73 off-therapy patients, ferritin levels were lower (p = .0008) with higher correlation with liver iron concentration (LIC) (p = .0016) than on-therapy patients. Fifty-eight subjects were treated for IO. CONCLUSION: In this heavily treated cohort of pediatric cancer patients, more than 80% had extrahepatic iron loading, which occurs with significant exposure to toxic forms of iron related to decreased marrow activity in setting of transfusions. Further studies should examine the effects of exposure to reactive iron on long-term outcomes and potential strategies for management.

Black Sexual Minority Men's Experiences in MPowerment Interventions: Implications for HIV Prevention.

BACKGROUND: Black sexual minority men (BSMM) are disproportionately vulnerable to HIV acquisition; the MPowerment model is one community-based framework for preventing HIV in this population. It focuses on developing a supportive network of peers to promote health messaging, reduce stigma, and improve resilience. While these interventions have demonstrated general success, there are important challenges related to race, sexuality, and internalized stigma. Our study aimed to explore these experiences among BSMM in MPowerment models focused on HIV prevention. METHOD: We conducted 24 qualitative interviews of BSMM attending HIV prevention-related MPowerment events in the greater D.C. Metropolitan area. In-depth interviews were conducted via phone, and interviews were analyzed using thematic analysis. RESULTS: We identified four themes from the transcript analysis process: Black queer intersectional social support and community, HIV-related information and destigmatization, social status, and sexuality. Within each of these themes, we identified relationships with overall HIV prevention messaging, including barriers to PrEP use. Barriers related to social status were especially prevalent and described as unique to the D.C. metropolitan area. CONCLUSION: Overall, MPowerment event spaces provide a forum for BSMM to feel safe and supported while gaining important HIV-related knowledge and prevention access. Challenges related to social status and destigmatization of sexuality are important considerations in designing and implementing this model, especially related to PrEP promotion.

National Quality Indicators in Pediatric Sickle Cell Anemia.

OBJECTIVE: To assess nationally endorsed claims-based quality measures in pediatric sickle cell anemia (SCA). METHODS: Using data from the Sickle Cell Data Collection programs in California and Georgia from 2010 to 2019, we evaluated 2 quality measures in individuals with hemoglobin S/S or S/ß-zero thalassemia: (1) the proportion of patients aged 3 months to 5 years who were dispensed antibiotic prophylaxis for at least 300 days within each measurement year and (2) the proportion of patients aged 2 to 15 years who received at least 1 transcranial Doppler ultrasound (TCD) within each measurement year. We then evaluated differences by year and tested whether performance on quality measures differed according to demographic and clinical factors. RESULTS: Only 22.2% of those in California and 15.5% in Georgia met or exceeded the quality measure for antibiotic prophylaxis, with increased odds associated with rural residence in Georgia (odds ratio 1.61; 95% confidence interval 1.21-2.14) compared with urban residence and a trend toward increased odds associated with a pediatric hematologist prescriber (odds ratio 1.28; 95% confidence interval 0.97, 1.69) compared with a general pediatrician. Approximately one-half of the sample received an annual assessment of stroke risk using TCD (47.4% in California and 52.7% in Georgia), with increased odds each additional year in both states and among younger children. CONCLUSIONS: The rates of receipt of recommended antibiotic prophylaxis and annual TCD were low in this sample of children with SCA. These evidence-based quality measures can be tracked over time to help identify policies and practices that maximize survival in SCA.

Αlpha-thalassemia: A practical overview.

α-Thalassemia is an inherited blood disorder characterized by decreased synthesis of α-globin chains that results in an imbalance of α and ß globin and thus varying degrees of ineffective erythropoiesis, decreased red blood cell (RBC) survival, chronic hemolytic anemia, and subsequent comorbidities. Clinical presentation varies depending on the genotype, ranging from a silent or mild carrier state to severe, transfusion-dependent or lethal disease. Management of patients with α-thalassemia is primarily supportive, addressing either symptoms (eg, RBC transfusions for anemia), complications of the disease, or its transfusion-dependence (eg, chelation therapy for iron overload). Several novel therapies are also in development, including curative gene manipulation techniques and disease modifying agents that target ineffective erythropoiesis and chronic hemolytic anemia. This review of α-thalassemia and its various manifestations provides practical information for clinicians who practice beyond those regions where it is found with high frequency.

Systematic review and evidence gap assessment of the clinical, quality of life, and economic burden of alpha-thalassemia.

A recent evidence gaps assessment of the clinical, health-related quality of life, and economic burden associated with α-thalassemia is lacking. We conducted a systematic literature review (SLR) following the methodological and reporting requirements of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Cochrane Handbook for Systematic Reviews, using available literature over the past decade. This SLR identified a considerable evidence gap with regard to understanding the current burden of α-thalassemia as evident from paucity of studies published in the past 10 years. The limited data available still indicate that patients with α-thalassemia experience substantial morbidity and quality of life/economic burden that is generally comparable to patients with ß-thalassemia.

Implementing a male-specific ART counselling curriculum: a quality assessment with healthcare workers in Malawi.

INTRODUCTION: There is little HIV counselling that directly meets the needs of men in Eastern and Southern Africa, limiting men's knowledge about the benefits of HIV treatment and how to overcome barriers to engagement, contributing to poorer HIV-related outcomes than women. Male-specific approaches are needed to improve men's outcomes but may be difficult for healthcare workers (HCWs) to implement with fidelity and quality in low-resource settings. We developed a male-specific counselling curriculum which was implemented by male HCWs and then conducted a mixed-methods quality assessment. METHODS: We audio-recorded counselling sessions to assess the quality of implementation (n = 50) by male HCWs from two cadres (nurse, n = 10 and lay cadre, n = 10) and conducted focus group discussions (FGDs) with HCWs at 6 and 9 months after rollout to understand barriers and facilitators to implementation. Counselling sessions and FGDs were translated, transcribed and analysed using thematic analysis adapted from WHO Quality Counselling Guidelines. We assessed if sessions were respectful, informative, interactive, motivating and included tailored action plans for overcoming barriers to care. All data were collected September 2021-June 2022. RESULTS: All sessions used respectful, non-judgemental language. Sessions were highly interactive with most HCWs frequently asking open-ended questions (n = 46, 92%) and often incorporating motivational explanations of how antiretroviral therapy contributes to life goals (n = 42, 84%). Few sessions included individually tailored action plans for clients to overcome barriers to care (n = 9, 18%). New counselling themes were well covered; however, occasionally themes of self-compassion and safe sex were not covered during sessions (n = 16 and n = 11). HCWs believed that having male HCWs conduct counselling, ongoing professional development and keeping detailed counselling notes facilitated quality implementation. Perceived barriers included curriculum length and client hesitancy to participate in action plan development. Findings were similar across cadres. CONCLUSIONS: Implementing high-quality male-specific counselling using male nurses and/or lay cadre is feasible. Efforts to utilize lay cadres should be prioritized, particularly in low-resource settings. Programmes should provide comprehensive job aids to support HCWs. Ongoing training and professional development are needed to (1) improve HCWs' skills in tailored action plans, and (2) sensitize HCWs to the need for self-compassion within male clients to promote holistic sexual health.

A de novo germline RUNX1 variant preceding development of concurrent T-lymphoblastic leukemia and myelodysplastic syndrome.

Germline variants of the RUNX1 gene are associated with RUNX1 Familial Platelet Disorder with Associated Myeloid Malignancies (RUNX1-FPDMM), which is characterized by an increased risk of developing myelodysplastic syndrome (MDS) and/or acute myeloid leukemia. Patients with FPDMM have also been described to develop B- or T-cell acute lymphoblastic leukemia. We present a pediatric patient with RUNX1-FPDMM that evolved into concurrent MDS and T-cell acute lymphoblastic leukemia after a decade of monitoring with serial blood counts. We aim to highlight the treatment challenges and clinical decision-making that may be anticipated in this unique disorder, as well as the potentially curative role for allogenic hematopoietic stem cell transplant in the first complete remission.

Pregnancy outcomes following self-reported and objective-measured exposure to oral preexposure prophylaxis in South Africa.

OBJECTIVE: To compare pregnancy outcomes using self-reported and objective levels of intracellular tenofovir diphosphate (TFV-DP) in pregnant women using preexposure prophylaxis (PrEP). DESIGN: We enrolled pregnant women >15 years without HIV at first antenatal care visit in an observational cohort study to compare pregnancy outcomes by PrEP use. METHODS: Exposure defined as: any PrEP use [tenofovir disoproxil and emtricitabine (TDF/FTC]) prescription + reported taking PrEP], or objectively-measured TFV-DP in dried blood spots in PrEP-using pregnant women. The primary outcome was a composite of pregnancy loss, preterm birth (<37weeks), low birthweight (<2500 g), small for gestational age ([SGA] ≤ tenth percentile), or neonatal death. Multivariable logistic regression models evaluated individual and composite adverse outcomes by self-reported or objectively measured PrEP use adjusting for age, gestational age, gravidity and socio-economic status. RESULTS: Between August 19 and February 23, we followed 1195 pregnant women and ascertained 1145 pregnancy outcomes (96%); 72% ( n  = 826) reported taking PrEP while pregnant, 16% did not take PrEP ( n  = 178), 12% were unconfirmed ( n  = 141). Overall, 94.5% ( n  = 1082) had singleton live births with a median birthweight of 3.2 kg [interquartile range (IQR) = 2.9-3.5], with no difference in pregnancy loss between self-reported PrEP exposed vs. unexposed [4.0 vs. 5.6%; adjusted odds ratio (aOR) = 0.65, 95% confidence interval (CI) = 0.32-1.47]. Composite adverse outcomes did not differ by reported PrEP use (20% for both groups; aOR = 1.07, 95% CI = 0.71-1.63). Comparing objective PrEP use (any TFV-DP vs. no TFV-DP or not on PrEP), adverse outcomes did not differ (aOR = 0.64, 95% CI = 0.39-1.04), nor did other outcomes including preterm birth nor SGA. CONCLUSIONS: Pregnancy outcomes did not differ by PrEP exposure (self-reported or objective), suggesting real-world efficacy that TDF/FTC as PrEP is safe in pregnancy.

Chlamydia trachomatis infection and associated risk factors in a low-income marginalized urban population in coastal Peru / Infección por Chlamydia trachomatis y factores de riesgo asociados en una población marginal urbana de bajos ingresos de la costa peruana

OBJECTIVES: To estimate Chlamydia trachomatis (CT) infection prevalence and associated risk factors among a low-income marginalized urban population in Peru. METHODS: Between April 2003 and April 2005, men and women at high-risk for sexually transmitted infections (STIs) were recruited from low-income urban areas in three coastal cities in Peru (Chiclayo, Lima, and Trujillo). Consenting participants were studied using a sero-epidemiologic survey. Urine and vaginal swabs collected from men and women were evaluated using polymerase chain reaction (PCR) (COBAS® AMPLICOR (CT/NG) Test, Roche Molecular Diagnostics, Branchburg, NJ, USA) for CT. RESULTS: Among the 2 440 participants recruited for the study (2 145 men and 295 women), overall prevalence of CT infection was 6.6 percent (95 percent CI, 5.6-7.6 percent): 5.5 percent (95 percent CI, 4.5-6.5 percent) in men and 14.9 percent (95 percent CI, 11.7-27.1 percent) in women. Chlamydial infection was inversely associated with age and positively associated with HIV infection and dysuria in men. Among women, chlamydial infection was inversely associated with age and positively associated with number of sex partners. CONCLUSIONS: CT infection was common among high-risk men and women in urban coastal Peru. Because chlamydial infection is associated with complications related to female reproduction, including infertility and ectopic pregnancy, interventions to prevent and treat infection and studies to determine the feasibility of population-based screening for CT should be conducted among the high-risk female population.

OBJETIVOS: Estimar la prevalencia de la infección por Chlamydia trachomatis y los factores de riesgo asociados en una población marginal urbana de bajos ingresos de Perú. MÉTODOS: Entre abril de 2003 y abril de 2005 se captaron hombres y mujeres con alto riesgo de contraer infecciones de transmisión sexual, en áreas urbanas de bajos ingresos de tres ciudades costeras de Perú (Chiclayo, Lima y Trujillo). Los participantes que aceptaron colaborar respondieron una encuesta seroepidemiológica y se analizaron muestras de orina de los hombres y exudados vaginales de las mujeres mediante la reacción en cadena de la polimerasa con el sistema para C. trachomatis COBAS® AMPLICOR (Roche Molecular Diagnostics, NJ, EE.UU.) RESULTADOS: En el estudio participaron 2 440 personas (2 145 hombres y 295 mujeres). La prevalencia general de infección por C. trachomatis fue de 6,6 por ciento (intervalo de confianza de 95 por ciento [IC95 por ciento]: 5,6 a 7,6 por ciento): 5,5 por ciento (IC95 por ciento: 4,5 a 6,5 por ciento) en hombres y 14,9 por ciento (IC95 por ciento: 11,7 a 27,1 por ciento) en mujeres. La infección por clamidia se asoció inversamente con la edad y directamente con la infección por VIH y la disuria en los hombres. En las mujeres, esta infección se asoció inversamente con la edad y directamente con el número de parejas sexuales. CONCLUSIONES: La infección por C. trachomatis fue frecuente en los hombres y mujeres con alto riesgo en las zonas urbanas costeras de Perú. Como esta infección está asociada con complicaciones que afectan la salud reproductiva de las mujeres, como infertilidad y embarazos ectópicos, se deben realizar intervenciones para prevenir y tratar la infección por C. trachomatis y se deben emprender estudios para determinar la factibilidad del tamizaje general de esta infección en la población femenina de alto riesgo.

Influencia del contexto sociocultural en la percepción del riesgo y la negociación de protección en hombres homosexuales pobres de la costa peruana / Influence of socio-cultural context on risk perception and negotiation of protection among poor homosexual males on the Peruvian coast

Este trabajo utiliza un enfoque del riesgo concebido, no como una acción individual, sino tomando su dimensión social. Busca analizar las diferentes formas en que el contexto sociocultural, relacionado a la homofobia internalizada y a las normas de género hegemónicas, permite la construcción de barreras en la percepción del riesgo. Estas barreras impiden la negociación de protección entre hombres homosexuales que han asumido una identidad de género femenina y habitan en barrios pobres de Lima y Trujillo, Peru. El análisis de la percepción del riesgo desde el plano sociocultural, nos va a permitir explicar las razones por las cuales la capacidad de negociación en esta población se ve restringida, no obstante, posee, más que otras, un mayor conocimiento del VIH/SIDA y sus consecuencias.