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Aim The aim of this study was to determine the prevalence and predictors of dyslipidaemia in adults in Nigeria. Methods Using the WHO criteria, we determined dyslipidaemia using serum lipid levels of 3 211 adult Nigerians, aged at least 18 years, obtained between March 2017 and February 2018 from two communities (rural and urban) in a state from each of the six geopolitical zones of Nigeria. Results The overall prevalence of low high-density lipoprotein cholesterol (l-HDL), elevated low-density lipoprotein cholesterol (e-LDL), hypertriglyceridaemia (h-TG) and hypercholesterolaemia (h-CHL) were 72.5,13.6, 21.4 and 7.5%, respectively. The adjusted odds of h-CHL [odds ratio (95% confidence interval) 1.47 (1.10-1.95)], h-TG [1.89 (1.48-2.41)] and e-LDL [1.51 (1.03-2.15)] increased with obesity. Being a rural dweller increased the odds of h-TG [1.55 (1.29-1.85)], e-LDL [1.38 (1.10-1.73)] and l-HDL [1.34 (1.14-1.58)]. The odds of h-CHL [2.16 (1.59-2.95)], h-TG [1.21 (1.01-1.47)], e-LDL [1.42 (1.13-1.80)] and l-HDL [0.78 (0.65-0.93)] increased with hypertension. Diabetes mellitus doubled only the odds of h-TG [2.04(1.36-3.03)]. Conclusion The prevalence of dyslipidaemia, particularly low HDL-C, is high among adult Nigerians.

PURPOSE: African men are disproportionately affected by prostate cancer (PCa). Given the increasing prevalence of obesity in Africa, and its association with aggressive PCa in other populations, we examined the relationship of overall and central obesity with risks of total and aggressive PCa among African men. METHODS: Between 2016 and 2020, we recruited 2,200 PCa cases and 1,985 age-matched controls into a multicenter, hospital-based case-control study in Senegal, Ghana, Nigeria, and South Africa. Participants completed an epidemiologic questionnaire, and anthropometric factors were measured at clinic visit. Multivariable logistic regression was used to examine associations of overall and central obesity with PCa risk, measured by body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), respectively. RESULTS: Among controls 16.4% were obese (BMI≥30 kg/m(2)), 26% and 90% had WC>97 cm and WHR>0.9, respectively. Cases with aggressive PCa had lower BMI/obesity in comparison to both controls and cases with less aggressive disease, suggesting weight loss related to cancer. Overall obesity (odds ratio: OR=1.38, 95%CI 0.99–1.93), and central obesity (WC>97cm: OR=1.60, 95%CI 1.10-2.33; and WHtR >0.59: OR=1.68, 95%CI 1.24-2.29) were positively associated with D’Amico intermediate-risk PCa, but not with risks of total or high-risk PCa. Associations were more pronounced in West versus South Africa, but these differences were not statistically significant. DISCUSSION: The high prevalence of overall and central obesity in African men and their association with intermediate-risk PCa represent an emerging public health concern in Africa. Large cohort studies are needed to better clarify the role of obesity and PCa in various African populations.

Community respiratory viral infections (CRVIs) are associated with pulmonary function impairment, alloimmune lung syndromes and inferior survival in human leucocyte antigen (HLA)-matched allogeneic haematopoietic stem cell transplant (HCT) recipients. Although the incidence of viral infections in HLA-haploidentical HCT recipients who receive post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis is reportedly increased, there are insufficient data describing the incidence of CRVIs and the impact of donor source and PTCy on transplant outcomes. Analysing patients receiving their first HCT between 2012 and 2017 for acute myeloid leukaemia, acute lymphoblastic leukaemia and myelodysplastic syndromes, we describe comparative outcomes between matched sibling transplants receiving either calcineurin-based GVHD prophylaxis (SibCNI, N=1605) or PTCy (SibCy, N=403), and related haploidentical transplants receiving PTCy (HaploCy, N=757). The incidence of CRVIs was higher for patients receiving PTCy, regardless of donor type. Patients in the HaploCy cohort who developed a CRVI by day +180 had both a higher risk of treatment-related mortality [hazard ratio (HR) 2⋅14, 99% confidence interval (CI) 1⋅13-4⋅07; P=0⋅002] and inferior 2-year overall survival (HR 1⋅65, 99% CI 1⋅11-2⋅43; P=0⋅001) compared to SibCNI with no CRVI. This finding justifies further research into long-term antiviral immune recovery, as well as development of preventive and treatment strategies to improve long-term outcomes in such patients.

Prior studies suggest increased cytomegalovirus (CMV) infection after haploidentical donor transplantation with posttransplant cyclophosphamide (HaploCy). The role of allograft source and posttransplant cyclophosphamide (PTCy) in CMV infection is unclear. We analyzed the effect of graft source and PTCy on incidence of CMV infection, and effects of serostatus and CMV infection on transplant outcomes. We examined patients reported to the Center for International Blood and Marrow Transplantation Research between 2012 and 2017 who had received HaploCy (n = 757), matched related (Sib) with PTCy (SibCy, n = 403), or Sib with calcineurin inhibitor-based prophylaxis (SibCNI, n = 1605). Cumulative incidences of CMV infection by day 180 were 42%, 37%, and 23%, respectively (P < .001). CMV disease was statistically comparable. CMV infection risk was highest for CMV-seropositive recipients (R+), but significantly higher in PTCy recipients regardless of donor (HaploCy [n = 545]: hazard ratio [HR], 50.3; SibCy [n = 279]: HR, 47.7; SibCNI [n = 1065]: HR, 24.4; P < .001). D+/R− patients also had increased risk for CMV infection. Among R+ or those developing CMV infection, HaploCy had worse overall survival and nonrelapse mortality. Relapse was unaffected by CMV infection or serostatus. PTCy was associated with lower chronic graft-versus-host disease (GVHD) overall, but CMV infection in PTCy recipients was associated with higher chronic GVHD (P = .006). PTCy, regardless of donor, is associated with higher incidence of CMV infection, augmenting the risk of seropositivity. Additionally, CMV infection may negate the chronic GVHD protection of PTCy. This study supports aggressive prevention strategies in all receiving PTCy.

Background Evidence linking homocysteine (Hcy) with cardiovascular diseases (CVD) or its risk factors are limited in a sub-Saharan black population. Objective We set out to evaluate the association between Hcy and hypertension and other CVD risk factors in a population of adult Nigerians. Methods Data of 156 adults aged 18–70 years was accessed from the North Central study site of the REmoving the MAsk on Hypertension (REMAH) study. Homocysteine, blood glucose and lipid profile in whole blood/serum were measured using standard laboratory methods. Hypertension was diagnosed if average of 5 consecutive blood pressure (BP) measurements obtained using a mercury sphygmomanometer was equal to or higher than 140 systolic and/or 90 mmHg diastolic or the individual is on antihypertensive medication. Hyperhomocysteinemia (HHcy) was defined as Hcy > 10 µmol/L. Results Of the 156 participants, 72 (43.5%) were hypertensive, of whom 18 had HHcy. Subjects with HHcy were significantly (p Conclusion HHcy occurs among hypertensive Nigerians and it is independently associated with age, HDL-cholesterol, systolic and diastolic BP.

Background Estimating the burden of hypertension in Nigeria hitherto relied on clinic blood pressure (BP) measurement alone. This excludes individuals with masked hypertension (MH), i.e., normotensive clinic but hypertensive out-of-clinic BP. Methods In a nationally representative sample of adult Nigerians, we obtained clinic BP using auscultatory method and out-of-clinic BP by self-measured home BP with semi-automated oscillometric device. Clinic BP was average of 5 consecutive measurements and home BP was average of 3 days duplicate morning and evening readings. MH was clinic BP Results Among 933 participants, the prevalence of sustained hypertension, MH, and white-coat hypertension was 28.3%, 7.9%, and 11.9%, respectively. Among subjects whose clinic BP were in the normotensive range (n = 558), the prevalence of MH was 13%; 12% among untreated and 27% among treated individuals. The mutually adjusted odds ratios of having MH among all participants with normotensive clinic BP were 1.33 (95% confidence interval, 1.10–1.60) for a 10-year higher age, 1.59 (1.09–2.40) for a 10 mm Hg increment in systolic clinic BP, and 1.16 (1.08–1.28) for a 10 mg/dl higher random blood glucose. The corresponding estimates in the untreated population were 1.24 (1.03–1.51), 1.56 (1.04–2.44), and 1.16 (1.08–1.29), respectively. Conclusions MH is common in Nigeria and increasing age, clinic systolic BP, and random blood glucose are the risk factors.

New guidelines for peanut allergy prevention in high-risk infants recommend introducing peanut during infancy but do not address breastfeeding or maternal peanut consumption. We assessed the independent and combined association of these factors with peanut sensitization in the general population CHILD birth cohort (N = 2759 mother–child dyads). Mothers reported peanut consumption during pregnancy, timing of first infant peanut consumption, and length of breastfeeding duration. Child peanut sensitization was determined by skin prick testing at 1, 3, and 5 years. Overall, 69% of mothers regularly consumed peanuts and 36% of infants were fed peanut in the first year (20% while breastfeeding and 16% after breastfeeding cessation). Infants who were introduced to peanut early (before 1 year) after breastfeeding cessation had a 66% reduced risk of sensitization at 5 years compared to those who were not (1.9% vs. 5.8% sensitization; aOR 0.34, 95% CI 0.14–0.68). This risk was further reduced if mothers introduced peanut early while breastfeeding and regularly consumed peanut themselves (0.3% sensitization; aOR 0.07, 0.01–0.25). In longitudinal analyses, these associations were driven by a higher odds of outgrowing early sensitization and a lower odds of late-onset sensitization. There was no apparent benefit (or harm) from maternal peanut consumption without breastfeeding. Taken together, these results suggest the combination of maternal peanut consumption and breastfeeding at the time of peanut introduction during infancy may help to decrease the risk of peanut sensitization. Mechanistic and clinical intervention studies are needed to confirm and understand this “triple exposure” hypothesis.

Background Facial deformities in syndromic craniosynostosis are not only functionally, psychosocially, and aesthetically impairing but also notoriously challenging to reconstruct. Whether facial suture synostosis plays a significant role in the pathogenesis of these deformities is inadequately studied in human patients. Methods The MEDLINE database was queried using a methodologically generated search term inventory. Article inclusion was adjudicated by 2 authors after independent review. Articles provided insight into facial suture involvement in either syndromic craniosynostosis patients or animal models of disease. Results Comprehensive review yielded 19 relevant articles meeting inclusion criteria. Mid-20th century craniofacial biologists characterized how patent facial sutures are essential for normal postnatal facial development. They also posited that premature ossification disrupts growth vectors, causing significant dysmorphologies. Recently, facial suture synostosis was found to cause midfacial deformities independent of cranial base pathology in mouse models of syndromic craniosynostosis. Few recent studies have begun exploring facial suture involvement in patients, and although they have paved the way for future research, they bear significant limitations. Conclusions The hypothesis that facial suture synostosis acts in conjunction with cranial base pathology to produce the prominent, multifocal facial deformities in syndromic craniosynostosis may fundamentally alter surgical management and warrants further investigation. Methodically evaluating the literature, this review synthesizes all basic science and human clinical research thus far on the role of facial sutures in syndromic craniosynostosis and elucidates important topics for future research. We ultimately identify the need for rigorous imaging studies that longitudinally evaluate facial osteology across patients with various craniosynostosis syndromes.

INTRODUCTION AND OBJECTIVE:Men of African descent have the highest burden of aggressive prostate cancer (PCa). However, the clinical features of PCa within sub-Saharan Africa (SSA) are understudied...

IMPORTANCE: Primary central nervous system lymphoma (PCNSL) requires induction and consolidation to achieve potential cure. High-dose therapy and autologous hematopoietic cell transplant (AHCT) is an accepted and effective consolidation strategy for PCNSL, but no consensus exists on the optimal conditioning regimens. OBJECTIVE: To assess the outcomes in patients with PCNSL undergoing AHCT with the 3 most commonly used conditioning regimens: thiotepa/busulfan/cyclophosphamide (TBC), thiotepa/carmustine (TT-BCNU), and carmustine/etoposide/cytarabine/melphalan (BEAM). DESIGN, SETTING, AND PARTICIPANTS: This observational cohort study used registry data from the Center for International Blood and Marrow Transplant Research registry. The Center is a working group of more than 380 transplantation centers worldwide that contributed detailed data on HCT to a statistical center at the Medical College of Wisconsin, Milwaukee. The participant data were from 603 adult patients with PCNSL who underwent AHCT as initial, or subsequent, consolidation between January 2010 and December 2018. Patients were excluded if they had a non-Hodgkin lymphoma subtype other than diffuse large B-cell lymphoma, systemic non-Hodgkin lymphoma, or HIV; received an uncommon conditioning regimen; or were not in partial remission or complete remission prior to AHCT. Statistical analysis was performed from July 5, 2020, to March 1, 2021. INTERVENTIONS: Patients received 1 of 3 conditioning regimens: TBC (n = 263), TT-BCNU (n = 275), and BEAM (n = 65). MAIN OUTCOMES AND MEASURES: The primary outcome was progression-free survival. Secondary outcomes included hematopoietic recovery, incidence of relapse, nonrelapse mortality, and overall survival. RESULTS: Of 603 patients, the mean age was 57 (range, 19-77) years and 318 (53%) were male. The 3-year adjusted progression-free survival rates were higher in the TBC cohort (75%) and TT-BCNU cohort (76%) compared with the BEAM cohort (58%) (P = .03) owing to a higher relapse risk in the BEAM cohort (hazard ratio [HR], 4.34; 95% CI, 2.45-7.70; P

Aim: To determine the relationship between maternal serum 25(OH) D concentrations and development of preeclampsia. Study Design: A cross sectional comparative study. Place and Duration of Study: Department of Obstetrics and Gynaecology, University of Abuja Teaching Hospital, Abuja, between March 2016 and February 2017. Methodology: We included 55 women with preeclampsia and 55 healthy women. Data obtained included sociodemographic characteristics, clothing style and duration of exposure to sun light. ELISA method was used for evaluation of serum vitamin D levels. Results: The prevalence of VD deficiency in the population was 15%, while 16.8% and 73% of the participants had insufficient and normal levels respectively. The prevalence of VD deficiency in women with preeclampsia was 20.4% while that in healthy pregnant women was 9.4% (P=.19). The mean serum 25-OH-D level of women with pre-eclampsia was significantly lower than that of healthy women (34.5±14.9 vs. 43.5±15.1, P = .003). Preeclamptic women with vitamin D insufficiency delivered at a higher gestational age than those with vitamin D deficiency (37.67(2.77) weeks vs. 33.55(2.38) weeks respectively, P = .007). In the adjusted analysis of cases with vitamin D defficiency, the odds of developing preeclampsia was not statistically significant [odds ratio (OR) = 3.27, CI = 0.99-10.83, P =.05]. However, the odds of developing preeclampsia in women with Vitamin D insufficiency was statistically significant (OR = 3.20, CI = 1.02–10.06, = 0.046). Conclusion: In conclusion, an association between vitamin D deficiency and preeclampsia was not demonstrated in this study. The results however suggest that maternal vitamin D insufficiency in late pregnancy is an independent risk factor for preeclampsia.

Background Persisting atopic dermatitis (AD) is known to be associated with more serious allergic diseases at later ages; however, making an accurate diagnosis during infancy is challenging. We assessed the diagnostic performance of questionnaire-based AD measures with criteria-based in-person clinical assessments at age 1 year and evaluated the ability of these diagnostic methods to predict asthma, allergic rhinitis and food allergies at age 5 years. Methods Data relate to 3014 children participating in the Canadian Healthy Infant Longitudinal Development (CHILD) Study who were directly observed in a clinical assessment by an experienced healthcare professional using the UK Working Party criteria. The majority (2221; 73.7%) of these children also provided multiple other methods of AD ascertainment: a parent reporting a characteristic rash on a questionnaire, a parent reporting the diagnosis provided by an external physician and a combination of these two reports. Results Relative to the direct clinical assessment, the area under the Receiver Operating Characteristic curve for a parental report of a characteristic rash, reported physician diagnosis and a combination of both were, respectively, 0.60, 0.69 and 0.70. The strongest predictor of asthma at 5 years was AD determined by criteria-based in-person clinical assessment followed by the combination of parental and physician report. Conclusions These findings suggest that questionnaire data cannot accurately substitute for assessment by experienced healthcare professionals using validated criteria for diagnosis of atopic dermatitis. Combining the parental report with diagnosis by a family physician might sometimes be appropriate (eg to avoid costs of a clinical assessment).

Cell-line-derived xenografts (CDXs) or patient-derived xenografts (PDXs) in immune-deficient mice have revolutionized our understanding of normal and malignant human hematopoiesis. Transgenic approaches further improved in vivo hematological research, allowing the development of human-cytokine-producing mice, which show superior human cell engraftment. The most popular mouse strains used in research, the NOG (NOD.Cg-Prkdcscid Il2rγtm1Sug/Jic) and the NSG (NOD/SCID-IL2Rγ−/−, NOD.Cg-PrkdcscidIl2rγtm1Wjl/SzJ) mouse, and their human-cytokine-producing (interleukin-3, granulocyte-macrophage colony-stimulating factor, and stem cell factor) counterparts (huNOG and NSGS), rely partly on a mutation in the DNA repair protein PRKDC, causing a severe combined immune deficiency (SCID) phenotype and rendering the mice less tolerant to DNA-damaging therapeutics, thereby limiting their usefulness in the investigation of novel acute myeloid leukemia (AML) therapeutics. NRG (NOD/RAG1/2−/−IL2Rγ−/−) mice show equivalent immune ablation through a defective recombination activation gene (RAG), leaving DNA damage repair intact, and human-cytokine-producing NRGS (NRG-SGM3) mice were generated, improving myeloid engraftment. Our findings indicate that unconditioned NRG and NRGS mice can harbor established AML CDXs and can tolerate aggressive induction chemotherapy at higher doses than NSG mice without overt toxicity. However, unconditioned NRGS mice developed less clinically relevant disease, with CDXs forming solid tumors throughout the body, whereas unconditioned NRG mice were incapable of efficiently supporting PDX or human hematopoietic stem cell engraftment. These findings emphasize the contextually dependent utility of each of these powerful new strains in the study of normal and malignant human hematopoiesis. Therefore, the choice of mouse strain cannot be random, but must be based on the experimental outcomes and questions to be addressed.

Chronic graft-versus-host disease (cGvHD) is the most significant late complication of allogeneic hematopoietic cell transplantation (allo-HCT). cGvHD has protean manifestations and impacts long-term mortality, morbidity, disease control, and quality of life. Its worst manifestations may cause irreversible disfigurement, disability, and death. Early recognition and intervention is critical; however, proven treatment options remain limited.

Background Population wide salt reduction programmes are cost effective strategies for control of cardiovascular diseases (CVDs). Obtaining a nationwide salt consumption data in a multi-cultural setting as Nigeria's is key for proper implementation and monitoring of such strategy. Methods We measured sodium in 24-hour urine of free-living adult Nigerians selected from an urban and a rural site each from the 6 geopolitical zones of Nigeria to evaluate patterns of salt intake and its associations with blood pressures (BP). Results Across the 12 sites, sodium intake ranged from 97.9 in the rural South-South to 210 mmol/day in the urban site of the same zone. Overall, the median (IQR) daily sodium intake was 143.5 (97.8) mmol; with higher (p=0.0028) levels among the urban 149.7 (113.8) compared to the rural 133.1 (105.2) dwellers. Overall, 20% of the subjects consumed less than the recommended 2g (86mmol) of sodium daily. After adjustment for age, sex and BMI; sodium intake and BP (systolic and diastolic) were positively associated in 8 out of the 12 sites; significantly so in 2 (p Conclusion Salt intake among Nigerians is higher than the recommended. The impact of sodium intake on BP appears to be evident only among individuals with high salt intake. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Wellcome Trust

We studied 2,528 patients with upfront autologous haematopoietic cell transplantation (AHCT) for multiple myeloma (MM) from 2008-2017 to develop a prognostic model to predict outcomes. High-risk cytogenetics included t(4;14), t(14;16), t(14;20), del13q on karyotype, del17p, +1q or 1pdel. A Cox model identified factors prognostic of progression/relapse in a training subset (n = 1,246). A weighted score using these factors was assigned to a validation cohort (n = 774). Presence of high-risk cytogenetics [hazard ratio, (HR) 1·68 (1·3-2·17)] and pre-AHCT bone marrow plasma cells (BMPCs) ≥10% [1·68 (1·33-2·12)] were assigned 4 points each; albumin at diagnosis

ObjectiveMolecular testing can refine the diagnosis for the 20% of thyroid fine-needle aspiration biopsies that have indeterminate cytology. We assessed the diagnostic accuracy of molecular testing based on ultrasound risk classification.MethodsThis retrospective cohort study analyzed all thyroid nodules with indeterminate cytology at an academic US medical center (2012-2016). All indeterminate nodules underwent reflexive molecular testing with the Afirma Gene Expression Classifier (GEC). Radiologists performed blinded reviews to categorize each nodule according to the American Thyroid Association (ATA) ultrasound classification and the American College of Radiology Thyroid Imaging, Reporting and Data System. GEC results and diagnostic performance were compared across ultrasound risk categories.ResultsOf 297 nodules, histopathology confirmed malignancy in 65 (22%). Nodules by ATA classification were 8% high suspicion, 44% intermediate, and 48% low/very low suspicion. A suspicious GEC result was more likely in ATA high-suspicion nodules (81%) than in nodules of all other ATA categories (57%; P = .04). The positive predictive value (PPV) of GEC remained consistent across ultrasound categories (ATA high suspicion, 64% vs all other ATA categories, 48%; P = .39). The ATA high-suspicion category had higher specificity than a suspicious GEC result (93% vs 51%; P ConclusionThe PPV of molecular testing remained consistent across ultrasound risk categories. However, a suspicious GEC result was very likely in ATA high-suspicion nodules and did not improve specificity in this sonographic category.

BACKGROUND Upfront autologous hematopoietic stem cell transplantation (AHCT) remains an important therapy in the management of patients with multiple myeloma (MM), a disease of older adults. METHODS The authors investigated the outcomes of AHCT in patients with MM who were aged ≥70 years. The Center for International Blood and Marrow Transplant Research (CIBMTR) database registered 15,999 patients with MM in the United States within 12 months of diagnosis during 2013 through 2017; a total of 2092 patients were aged ≥70 years. Nonrecurrence mortality (NRM), disease recurrence and/or progression (relapse; REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models with age at transplantation as the main effect. Because of the large sample size, a P value

For recipients of allogeneic hematopoietic stem cell transplant (HSCT), mycophenolate mofetil (MMF) plus tacrolimus combination is mostly used in reduced-intensity (RIC), and nonmyeloablative conditioning (NMAC) whereas methotrexate and tacrolimus combination is preferred in myeloablative conditioning (MAC). We present single institution outcomes in patients undergoing allogeneic HSCT with both MAC and NMAC/RIC regimen using MMF and tacrolimus for graft-versus-host disease (GVHD) prophylaxis. Data from all adult patients who underwent allogeneic HSCT from 2007 to 2017 was collected from Data Back to Centers web-based application of Center for International Blood and Marrow Transplant Research (CIBMTR). A total of 150 patients were included with the mean age of 46.9 years. For the patients who received MAC (n=109), the cumulative incidence of grade II-IV acute GVHD at day 100 was 37%, grade II-IV acute GVHD at one year was 51%, and chronic GVHD at one year was 38%. For the patients who received NMAC/RIC (n=41), the cumulative incidence of grade II-IV acute GVHD at day 100 was 31%, grade II-IV acute GVHD at one year was 28%, and chronic GVHD at one year was 36%. This institutional analysis shows that the combination of MMF and tacrolimus yields acceptable outcomes for the prevention of acute and chronic GVHD.

Individuals with gender dysphoria often seek medical interventions, such as hormone treatment and surgery, to live as their identified gender. Cross-sex hormone therapy typically consists of various estrogen formulations which confer varying risks of venous thromboembolism (VTE). Currently, there is no standard practice by surgeons regarding the preoperative gender-affirming surgery (GAS) hormone regimen of male-to-female (MTF) patients to minimize thromboembolic postoperative complications. The aim of this review is to examine the current literature on VTE occurring in MTF transgender patients on cross-sex hormone therapy (CSHT) when undergoing various gender-affirming surgeries-facial feminization surgery (FFS), top surgery (TS), and bottom surgery (BS)-to understand how evidence-based recommendations regarding perioperative hormone regimens can be established to improve clinical outcomes. Within the past 25 years, 7 published studies have examined the incidence of VTE in MTF patients undergoing GAS procedures. Two of these articles examined MTF patients undergoing FFS, 1 article reported a patient who had undergone BS and FFS during the same hospitalization, and the remaining 4 articles investigated VTE risk in BS. Our review supports that plastic surgeons who perform GAS are divided on their preferred CSHT protocols, with some requiring patients to suspend their CSHT weeks before surgery and others allowing patients to continue CSHT through the day of surgery. Three of the 7 studies detailed a CSHT perioperative regimen which instructed patients to suspend CSHT sometime before surgery; 1 study tapered CSHT to lower levels before surgery; the remaining 3 studies did not specify a CSHT perioperative regimen. This review highlights the paucity of data failing to support that continuing CSHT through GAS elevates VTE risk. We conclude that in the absence of definitive VTE risk factors (e.g., smoking, clotting disorders, or malignancy), surgeons may engage MTF patients in joint decision-making process to determine the most optimal perioperative CSHT management plan on a case-by-case basis. Future studies are warranted to evaluate VTE risk based on patient age, type of surgery, operating time, prophylactic measures, follow-up time, and CSHT perioperative regimens.

Purpose Cancer of the prostate (CaP) is the leading cancer among men in sub-Saharan Africa (SSA). A substantial proportion of these men with CaP are diagnosed at late (usually incurable) stages, yet little is known about the etiology of CaP in SSA. Methods We established the Men of African Descent and Carcinoma of the Prostate Network, which includes seven SSA centers partnering with five US centers to study the genetics and epidemiology of CaP in SSA. We developed common data elements and instruments, regulatory infrastructure, and biosample collection, processing, and shipping protocols. We tested this infrastructure by collecting epidemiologic, medical record, and genomic data from a total of 311 patients with CaP and 218 matched controls recruited at the seven SSA centers. We extracted genomic DNA from whole blood, buffy coat, or buccal swabs from 265 participants and shipped it to the Center for Inherited Disease Research (Baltimore, MD) and the Centre for Proteomics and Genomics Research (Cape Town, South Africa), where genotypes were generated using the UK Biobank Axiom Array. Results We used common instruments for data collection and entered data into the shared database. Double-entered data from pilot participants showed a 95% to 98% concordance rate, suggesting that data can be collected, entered, and stored with a high degree of accuracy. Genotypes were obtained from 95% of tested DNA samples (100% from blood-derived DNA samples) with high concordance across laboratories. Conclusion We provide approaches that can produce high-quality epidemiologic and genomic data in multicenter studies of cancer in SSA.

Trypanosomiasis, leishmaniasis, and malaria are protozoan infections of public health importance with thousands of new cases recorded annually. Control of these infection(s) with existing chemotherapy is limited by drug toxicity, lengthy parenteral treatment, affordability, and/or the emergence of resistant strains. Medicinal plants on the other hand are used in the treatment of various infectious diseases although their chemical properties are not fully evaluated. In this study, we screened 112 crude extracts from 72 selected Ghanaian medicinal plants for anti-Trypanosoma, anti-Leishmania, and anti-Plasmodium activities in vitro and investigated their mechanisms of action. Twenty-three extracts from 20 plants showed significant antiprotozoan activity against at least 1 of 3 protozoan parasites screened with IC50 values less than 20 μg/ml. Eleven extracts showed high anti-Trypanosoma activity with Bidens pilosa whole plant and Morinda lucida leaf extracts recording the highest activities. Their IC50 (selectivity index [SI]) values were 5.51 μg/ml (35.00) and 5.96 μg/ml (13.09), respectively. Nine extracts had high anti-Leishmania activity with Annona senegalensis and Cassia alata leaf extracts as the most active. Their IC50 (SI) values were 10.8 μg/ml (1.50) and 10.1 μg/ml (0.37), respectively. Six extracts had high anti-Plasmodium activity with the leaf and stem-bark extracts of Terminalia ivorensis recording the highest activity. Their IC50 (SI) values were 7.26 μg/ml (129.36) and 17.45 μg/ml (17.17), respectively. Only M. lucida at 25 μg/ml induced significant apoptosis-like cell death in Trypanosoma parasites. Anti-Leishmania active extracts induced varying morphological changes in Leishmania parasites such as multiple nuclei and/or kinetoplast, incomplete flagella division, or nuclear fragmentation. Active extracts may be potential sources for developing new chemotherapy against these infections.

A significant percentage of patients with gastroesophageal reflux disease (GERD) will not respond to proton pump inhibitor (PPI) therapy. The causes of PPI-refractory GERD are numerous and diverse, and include adherence, persistent acid, functional disorders, nonacid reflux, and PPI bioavailability. The evaluation should start with a symptom assessment and may progress to imaging, endoscopy, and monitoring of esophageal pH, impedance, and bilirubin. There are a variety of pharmacologic and procedural interventions that should be selected based on the underlying mechanism of PPI failure. Pharmacologic treatments can include antacids, prokinetics, alginates, bile acid binders, reflux inhibitors, and antidepressants. Procedural options include laparoscopic fundoplication and LINX as well as endoscopic procedures, such as transoral incisionless fundoplication and Stretta. Several alternative and complementary treatments of possible benefit also exist.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocyte disorder most commonly characterized by multifocal osteosclerotic lesions of the long bones demonstrating sheets of foamy histiocyte infiltrates on biopsy with or without histiocytic infiltration of extraskeletal tissues. ECD can be difficult to diagnose since it is a very rare disease that can affect many organ systems. Diagnosis is based on the pathologic evaluation of involved tissue interpreted within the clinical context. Patients who have the BRAF V600E mutation are treated first line with vemurafenib. For those without the mutation with symptomatic ECD, conventional or PEGylated interferon alpha is recommended. For patients who are either intolerant or nonresponsive to interferon alpha, systemic chemotherapy with or without corticosteroids can be used. We present a rare case of Erdheim-Chester disease with concurrent Langerhans cell histiocytosis which occurs in only one fifth of the cases and often presents as a diagnostic and therapeutic challenge.

Evading cancer drugs by identity fraud Prostate cancer growth is fueled by male hormones called androgens. Drugs targeting the androgen receptor (AR) are initially efficacious, but most tumors eventually become resistant (see the Perspective by Kelly and Balk). Mu et al. found that prostate cancer cells escaped the effects of androgen deprivation therapy through a change in lineage identity. Functional loss of the tumor suppressors TP53 and RB1 promoted a shift from AR-dependent luminal epithelial cells to AR-independent basal-like cells. In related work, Ku et al. found that prostate cancer metastasis, lineage switching, and drug resistance were driven by the combined loss of the same tumor suppressors and were accompanied by increased expression of the epigenetic regulator Ezh2. Ezh2 inhibitors reversed the lineage switch and restored sensitivity to androgen deprivation therapy in experimental models. Science , this issue p. 84 , p. 78 ; see also p. 29

Context: Hairy cell Leukemia (HCL), a chronic B-cell neoplasm, accounts for 2% of all leukemias, mainly of males in their 50s. Diagnosis relies on morphology, flow cytometry, and immunohistochemistry. Purine analogues are first-line therapy since more than 20 years ago. Strategies such as combined chemoimmunotherapy, targeted therapy, and minimal residual disease (MRD) are taking over the landscape of HCL. Patient: A 47-year-old man presents with weakness, respiratory infections, pancytopenia, and a 19-cm spleen. Peripheral blood revealed mononuclear cells with hairlike projections, monocytopenia, and thrombocytopenia. Misdiagnosis of splenic lymphoma 2 years earlier had been managed with bendamustin and rituximab in a different center, having resulted in normalization of counts. At our assessment, his immunophenotype showed CD103/CD123/CD25/CD11c in 63% of cells, diagnostic of relapsed HCL. Interventions: Cladribine was initiated at 0.14 mg/kg/d, 2 h infusion for 5 days, and supportive measures. At 3 months, MRD was negative; 28 months later, he remains in remission. Results: Molecular identification of somatic BRAFV600 mutation is diagnostic, as well as an effective therapeutic target. MRD is thought to predict late relapse in HCL and select patients to benefit from additional or further treatment. Monoclonal antibodies anti-CD20 and anti-CD22 Moxetumomab have proven safe and efficacious in treating HCL. Conclusions: Hairy cell Leukemia is a rare hematologic malignancy that can be confused with other indolent lymphoid malignancies. Current treatment is effective, but clinical trials are needed to develop best practices to offer patients with HCL a normal life expectancy.

Context Infections cause substantial morbidity and mortality in acute leukemia patients. Neutropenic fever (NF) frequently complicates leukemia chemotherapy, but the mortality rate of NF and predictors of mortality are not fully defined for adult leukemia patients. We examined factors that influence mortality and type of infection in NF patients admitted to the hematologic malignancy service of a referral hospital. Design Retrospective chart review of NF patients admitted to University of Louisville from April 2016 to July 2018 who had AML, ALL, CML, CLL, or MDS, excluding active transplant patients. We used logistic regression and Cox proportional hazard analysis to evaluate mortality predictors and the Kaplan-Meier method for survival. Median follow-up was 16.6 months. Results Sixty-two patients had 101 episodes of NF. Median age was 56. Frequent primary diagnoses were AML (70%), ALL (24%), CML (2%), and CLL (2%). Infections and bacteremia occurred in 72% and 54% of episodes, respectively. Mean length of stay was 19 +/- 12 days. Refractory/relapsed (R/R) disease (RR 1.53, p=0.034) and ANC nadir of 0 (RR 2.64, p=0.001) correlated with bacteremia. Thirty-day mortality was 14% and increased for R/R disease (OR 3.13, CI=0.99–9.92), bacteremia (OR 3.58, CI=0.94-13.7), and ICU-level care (OR 15.24, CI=4.11-56.5) in univariate analysis. ICU-level care (OR 29.1, CI=5.42–156) and R/R disease (OR 7.30, CI=1.43–37.4) retained significance in multivariate logistic regression. Gram +/- status, resistance pattern, neutropenia severity, age, and neutropenia duration did not influence short-term mortality. Eighty-six episodes had a high-risk MASCC score ( 60 (HR 2.16, CI=1.22–3.84), R/R disease (HR 5.58, CI=2.74–11.4) and ICU-level care (HR 4.96, CI=2.14–11.5) predicted long-term mortality. High-risk MASCC approached significance for OS; median OS 7.8 months (high-risk) versus not reached (low-risk, p = 0.076). Conclusions Bacteremia occurred in the majority of NF episodes we recorded. Thirty-day NF mortality was 14%. Mortality increases for patients with age > 60, R/R disease, and ICU-level care. Identification of high-risk factors in NF may guide the study of interventions such as myeloid growth factor support in appropriate populations.

Although prostate cancer is the leading cause of cancer mortality for African men, the vast majority of known disease associations have been detected in European study cohorts. Furthermore, most genome-wide association studies have used genotyping arrays that are hindered by SNP ascertainment bias. To overcome these disparities in genomic medicine, the Men of African Descent and Carcinoma of the Prostate (MADCaP) Network has developed a genotyping array that is optimized for African populations. The MADCaP Array contains more than 1.5 million markers and an imputation backbone that successfully tags over 94% of common genetic variants in African populations. This array also has a high density of markers in genomic regions associated with cancer susceptibility, including 8q24. We assessed the effectiveness of the MADCaP Array by genotyping 399 prostate cancer cases and 403 controls from seven urban study sites in sub-Saharan Africa. Samples from Ghana and Nigeria clustered together, whereas samples from Senegal and South Africa yielded distinct ancestry clusters. Using the MADCaP array, we identified cancer-associated loci that have large allele frequency differences across African populations. Polygenic risk scores for prostate cancer were higher in Nigeria than in Senegal. In summary, individual and population-level differences in prostate cancer risk were revealed using a novel genotyping array. Significance: This study presents an Africa-specific genotyping array, which enables investigators to identify novel disease associations and to fine-map genetic loci that are associated with prostate and other cancers.

Purpose: Previous studies that evaluated the prevalence of hypertension in Nigeria were either clinic based, non-standardized or did not include out-of-clinic blood pressure (BP) measurement.Materi...

The benefits of pre-transplant induction chemotherapy in light chain (AL) amyloidosis, a low burden plasma cell (PC) neoplasm associated with multiorgan dysfunction, is debatable, although with the availability of bortezomib, this approach is being increasingly pursued. We analyzed the outcomes of AL amyloidosis patients undergoing autologous hematopoietic cell transplant between 2014 and 2018 that were reported to the Center for International Blood and Marrow Transplant Research database. Of 440 patients, 294 received bortezomib-based induction, and 146 received no induction. Patients receiving induction had greater PC burden compared to no induction (PC 10% or more, 39% versus 11%; P.01). At 2 years, the induction group compared to no induction had lower relapse/progression: 13% (9% to 18%) versus 23% (16% to 32%) (P = .02); better progression-free survival (PFS): 82% (77% to 87%) versus 69% (61% to 77%) (P.01); and similar overall survival (OS): 92% (88% to 95%) versus 89% (84% to 94%) (P = .22), findings that were confirmed on multivariate analysis. A subset analysis limited to patients with10% PC also showed superior relapse/progression (hazard ratio [HR], .43; 95% confidence interval [CI], .24 to .78; P.01) and PFS (HR, .43; 95% CI, .26 to .72; P.01) for induction compared to no induction. Thus, we conclude that pre-transplant bortezomib-based induction was associated with improved relapse/progression and PFS in AL amyloidosis. Longer survival follow-up is warranted, as OS was excellent in both cohorts at 2 years.

Purpose: Treatment of patients with relapsed or refractory lymphoid neoplasms represents a significant clinical challenge, largely due to the genetic heterogeneity of these malignancies. Our study goal was to design a rational treatment strategy that simultaneously targets multiple disease drivers to provide safe, efficacious, and durable responses in patients with relapsed or refractory non-Hodgkin lymphoma (NHL). Experimental procedures and data summary: Venetoclax is a selective BCL-2 inhibitor that induces apoptosis and is efficacious in chronic lymphocytic leukemia; however, single-agent efficacy in other lymphoid neoplasms is limited. Using pharmacologic and genetic studies, we identified the pro-survival BCL-2 protein family member MCL-1 as a venetoclax resistance factor in NHL cell lines. We found that the monomethyl auristatin E (MMAE) payload of the antibody-drug conjugate polatuzumab vedotin promotes MCL-1 degradation via the ubiquitin/proteasome system, thus providing a strong rationale for combination with venetoclax. Mechanistically, polatuzumab vedotin combined with venetoclax promoted apoptotic NHL cell death. In NHL animal models, venetoclax, polatuzumab vedotin, and the anti-CD20 antibody obinutuzumab, that activates targeted antibody- and complement-dependent cell cytotoxicity, produced durable tumor regressions. In a phase 1b clinical trial, 33 patients with relapsed or refractory follicular lymphoma were evaluable for response over 6 dose levels with 19 complete responses and 6 partial responses (overall response rate 76%). All patients (8 of 8) treated with the recommended phase 2 regimen (venetoclax 800mg + polatuzumab vedotin 1.8mg/kg + obinutuzumab 1000mg) achieved complete responses at end of induction. The median duration of follow-up for all dose levels was 17.7 months. This triplet combination was well-tolerated by most patients and had an expected and acceptable safety profile. Conclusions: Our studies implicate MCL-1 as a key venetoclax resistance factor in NHL that can be overcome by polatuzumab vedotin, which promotes MCL-1 degradation. Pre-clinical NHL animal models and early clinical data confirmed that the combination of venetoclax, polatuzumab vedotin, and obinutuzumab is safe and promotes durable responses. Because MMAE and other anti-tubulin agents are likely not the only therapeutics that antagonize MCL-1, our study provides scientific rationale to pursue the broader strategy of identifying other therapeutics that similarly neutralize MCL-1 function. Such agents could be used in combination with venetoclax in other malignancies where MCL-1 is a venetoclax resistance factor. Our mechanism-based treatment regimen that directly targets oncogenic drivers in NHL patients may serve as a framework for treating other malignancies with complex etiologies. Citation Format: Dhara N. Amin, Rajat Bannerji, Raghuveer Singh Mali, Jason Oeh, Eva Lin, Anuradha Zindal, MaryAnn Go, Shang-Fan Yu, Maxwell Krem, Chris Arthur, Uwe Hahn, Anna M. Johnston, Vinit G. Karur, Nadia Khan, Paula Marlton, Tycel Phillips, Giuseppe Gritti, John F. Seymour, Monica Tani, Sam Yuen Yuen, Scott Martin, Matthew T. Chang, Christopher M. Rose, Victoria C. Pham, Elizabeth A. Lasater, Andrew G. Polson, YiMeng Chang, Jamie Hirata, Lisa Musick, Deepak Sampath, Christopher R. Flowers, Ingrid E. Wertz. Targeting BCL-2 and MCL-1 overcomes treatment resistance in relapsed and refractory non-Hodgkin lymphoma: Pre-clinical rationale and results from an open-label phase 1b study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT133.

Gastroesophageal reflux disease (GERD) is the most common upper gastrointestinal disorder in the United States. Although proton pump inhibitors (PPIs) are the mainstay of therapy for GERD and its complications, they have several limitations, including incomplete symptom resolution. Potassium-competitive acid blockers (P-CABs) were developed to address the limitations of PPIs as well as the need for improved antisecretory effects. Tegoprazan, the newest P-CAB, was approved in 2018 in South Korea for the treatment of erosive esophagitis (EE) and nonerosive reflux disease (NERD). A highly selective inhibitor of the H+/K+-ATPase, tegoprazan is also safe and effective for nocturnal acid breakthrough (NAB) and motility. Further studies of tegoprazan are warranted to define its potential role in the treatment of acid-related disorders.

Introduction:Nigeria has the largest burden of Sickle Cell Disease (SCD) with estimated 100,000 new born affected annually. SCD is a Hemoglobin (Hb) disorder with the major form resulting from the substitution of a polar glutamate (Glu) by non-polar Valine (Val) in an invariant region of Hbβ chain-subunit. Species of Hb found in the sickle cell trait are HbA and HbS in a 60:40 proportion, in SCD only HbS, in the HbC disease only HbC, and in the SC disease it's HbS and HbC in a 50:50 equal proportion.Objective:This paper reviews herbal medicines usage in sub-Saharan Africa (sSA) to ameliorate the crisis associated with SCD. The model Hb tetramer suggests a higher membrane affinity of HbS and HbC, promoting dehydration of RBCs, with concomitant in vivo crystallization. Some drawbacks using these herbal drugs include; poor bioavailability and the lack of proper pharmacovigilance monitoring procedures arising from weak governance structure combined with under reporting of herbal usage to physicians were discussed. Probable epigenetic loci that could be targeted using phytomedicines for effective SCD management were also discussed.Methods:Using search engines, several databases including Google scholar, PubMed, Academic Resource Index were utilized as a source for relevant publications/ literature. The protein coordinates for the Hb tetramer were obtained from the Protein Data Bank (PDB).Conclusion:Manipulation of epigenetics to achieve better SCD management involves careful thinking. Herein, we discuss some epigenetic interactions that could be putatively tweaked with a view of enhancing soluble bioactive small molecular components with the potential to reactivate γ -globin genes, thereby boosting immune response in patient with SCD.

Background Melphalan 200 mg/m2 (MEL 200) is standard conditioning for autologous transplant (auto-HCT) in multiple myeloma (MM). Melphalan 140 or 100 mg/m2 (MEL 140/100) is given to patients with advanced age or renal dysfunction. Prior comparisons of MEL 200 versus MEL 140/100 raised concerns about reduced efficacy with MEL 140/100. However, those studies took place prior to the era of induction and post-auto-HCT maintenance with novel agents. We asked whether a diverse, unselected MM cohort treated with novel agents maintains the full benefit of auto-HCT from MEL 140/100. Methods We reviewed 55 consecutive auto-HCT episodes for MM and amyloidosis patients treated with proteasome inhibitors (PI) and/or immunomodulators (IMiD) followed by MEL 200 (n = 30), MEL 140 (n = 20), and MEL 100 (n = 5) from 2006 to 2018. Patients with age > 70 or reduced renal function, Karnofsky score, or cardiopulmonary function received MEL 140/100. We analyzed pre-auto-HCT prognostic factors. We examined post-transplant toxicities and disease control. Statistical analyses were performed with SPSS25. Results Female and non-Caucasian patients were well-represented. Pre-transplant therapy was similar. MEL 140/100 trended towards older age and worse Karnofsky score; MEL 140/100 had significantly worse HCT-CI, ISS stage, and renal function (GFR Conclusion MM patients with higher ISS and HCT-CI scores tolerated auto-HCT with MEL 140/ 100 conditioning, Post-transplant outcomes were indistinguishable. Conditioning with MEL 140/100 has equivalent safety and efficacy for patients who are not candidates for MEL 200.

Lymphocytes are unique among cells in that they undergo programmed DNA breaks and translocations, but that special property predisposes them to chromosomal instability (CIN), a cardinal feature of neoplastic lymphoid cells that manifests as whole chromosome- or translocation-based aneuploidy. In several lymphoid malignancies translocations may be the defining or diagnostic markers of the diseases. CIN is a cornerstone of the mutational architecture supporting lymphoid neoplasia, though it is perhaps one of the least understood components of malignant transformation in terms of its molecular mechanisms. CIN is associated with prognosis and response to treatment, making it a key area for impacting treatment outcomes and predicting prognoses. Here we will review the types and mechanisms of CIN found in Hodgkin lymphoma, non-Hodgkin lymphoma, multiple myeloma and the lymphoid leukaemias, with emphasis placed on pathogenic mutations affecting DNA recombination, replication and repair; telomere function; and mitotic regulation of spindle attachment, centrosome function, and chromosomal segregation. We will discuss the means by which chromosome-level genetic aberrations may give rise to multiple pathogenic mutations required for carcinogenesis and conclude with a discussion of the clinical applications of CIN and aneuploidy to diagnosis, prognosis and therapy.

The proteasome inhibitor bortezomib has been widely used to treat patients with multiple myeloma (MM). However, some patients show primary or secondary resistance. In recent work published in The Journal of Pathology, Beyar-Katz et al demonstrate that bortezomib treatment stimulates a host inflammatory response, which in turn promotes MM cell migration, viability, and proliferation. These effects appear to be mediated by pro-inflammatory M1-like stromal macrophages partly via secretion of cytokine IL-16. These unexpected findings imply that the binary M1/M2 definition of macrophages may not accurately describe the complexity and heterogeneity of macrophages associated with MM tumour growth and progression, and further suggest that bortezomib treatment stimulates host-driven tumour-promoting activity in addition to its cytotoxic activity, thus leading to potential bortezomib resistance in MM patients. Understanding the underlying mechanisms may identify novel targets to overcome or prevent bortezomib resistance. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Background The atopic march describes the progression from atopic dermatitis during infancy to asthma and allergic rhinitis in later childhood. In a Canadian birth cohort we investigated whether concomitant allergic sensitization enhances subsequent development of these allergic diseases at age 3 years. Methods Children completed skin prick testing at age 1 year. Children were considered sensitized if they produced a wheal 2 mm or larger than that elicited by the negative control to any of 10 inhalant or food allergens. Children were also assessed for atopic dermatitis by using the diagnostic criteria of the UK Working Party. At age 3 years, children were assessed for asthma, allergic rhinitis, food allergy, and atopic dermatitis. Data from 2311 children were available. Results Atopic dermatitis without allergic sensitization was not associated with an increased risk of asthma at age 3 years after adjusting for common confounders (relative risk [RR], 0.46; 95% CI, 0.11-1.93). Conversely, atopic dermatitis with allergic sensitization increased the risk of asthma more than 7-fold (RR, 7.04; 95% CI, 4.13-11.99). Atopic dermatitis and allergic sensitization had significant interactions on both the additive (relative excess risk due to interaction, 5.06; 95% CI, 1.33-11.04) and multiplicative (ratio of RRs, 5.80; 95% CI, 1.20-27.83) scales in association with asthma risk. There was also a positive additive interaction between atopic dermatitis and allergic sensitization in their effects on food allergy risk (relative excess risk due to interaction, 15.11; 95% CI, 4.19-35.36). Conclusions Atopic dermatitis without concomitant allergic sensitization was not associated with an increased risk of asthma. In combination, atopic dermatitis and allergic sensitization had strong interactive effects on both asthma and food allergy risk at age 3 years.

BACKGROUND The association of electrocardiographic left ventricular hypertrophy (ECG-LVH) with blood pressure (BP) in Blacks living in sub-Saharan Africa remains poorly documented. METHODS In 225 Black Nigerians and 729 White Flemish, we analyzed QRS voltages and voltage-duration products and 12 criteria diagnostic of ECG-LVH in relation to office BP (mean of 5 consecutive readings) and home BP (duplicate morning and evening readings averaged over 1 week). RESULTS In multivariable analyses, QRS voltage and voltage-duration indexes were generally higher in Blacks than Whites. By using any of 12 criteria, ECG-LVH was more prevalent among Black than White men (54.4% vs. 36.0%) with no ethnic difference among women (17.1%). Precordial voltages and voltage-duration products increased with office and home systolic BP (SBP), and increases were up to 3-fold steeper in Blacks. In Blacks vs. Whites, increases in the Sokolow-Lyon voltage associated with a 10-mm Hg higher SBP were 0.18 mV (95% confidence interval [CI], 0.09-0.26) vs. 0.06 mV (0.02-0.09) and 0.17 mV (0.07-0.28) vs. 0.11 mV (CI, 0.07-0.15) for office and home BP, respectively, with a significant ethnic gradient (P < 0.05). The risk of ECG-LVH increased more with office and home BP in Blacks than Whites. CONCLUSIONS Associations of ECG voltages and voltage-duration products and risk of ECG-LVH with BP are steeper in Black Nigerians compared with a White reference population. In resource-poor settings of sub-Saharan Africa, the ECG in combination with office and home BP is an essential instrument in risk stratification across the entire BP range. The authors gratefully acknowledge the expert clerical assistance of Mrs. Vera De Leebeeck and Mrs. Renilde Wolfs (Studies Coordinating Centre, Leuven, Belgium). The European Union (HEALTH-FP7-278249-EUMASCARA, HEALTH-F7-305507 HOMAGE and the European Research Council (Advanced Researcher Grant 2011-294713-EPLORE and Proof-of-Concept Grant 713601-uPROPHET) and the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium (G.0881.13, G.088013, and 11Z0916N) currently support the Studies Coordinating Centre in Leuven.

treated with aqueous extract of C. sanguinolenta for two weeks whilst groups 1 (no drug) and 4 (Art) served as negative and positive controls, respectively and were given water. The rats were inoculated with P. berghei after the two weeks pretreatment period and were either not treated (no drug) or treated with artesunate (Art) or C. sanguinolenta (Cryp and Cryp/Art) 2 days post-inoculation. Parasitemia and chemosuppression were then determined in 4 and 6-day suppressive tests. The parasitemia in group 3 rats (Cryp/Art) was significantly (p < 0.05) higher (270%) than in group 4 (Art) on day 8. Consequently, the chemosuppression of artesunate only group was significantly (p < 0.05) higher (133%) than that of the concurrently administered Cryp/Art group. The findings show that concurrent usage of C. sanguinolenta and artesunate reduces the effectiveness of artesunate as an antimalarial. Therefore, patients should be advised on the implication of the practice of taking C. sanguinolenta and artesunate concurrently.

5085 Background: Historically, the use of testosterone replacement therapy (TRT) has not been recommended in men with a history of prostate cancer (PC). However, low testosterone levels are significantly associated with metabolic complications, decreased sexual function, and (more recently) high-grade PC. In 2009, in hopes of improving sexual function outcomes in men following radical prostatectomy (RP), we began treating low-risk patients with TRT. The current study examines the impact of TRT on biochemical recurrence (BCR). Methods: Between December 2009 and June 2018, a cohort of 850 patients underwent RP by a single surgeon. 152 (18%) men were postoperatively placed on TRT for recovery of sexual function. All data was prospectively collected and retrospectively analyzed. TRT patients were proportionately matched to 419 control patients by pathologic Gleason Grade Group (GGG) and stage. Univariate and multivariate comparisons were used to compare rates and time to BCR (two consecutive PSAs ≥ 0.2 ng/dl); Cox regression modeling was used to generate a survival function at the mean of covariates. Results: There were no statistically significant differences in preoperative PSA, age, prostate weight, pathologic GGG and stage between the control versus TRT groups. Median follow-up time was 3 years in both groups. 7/152 (4.6%) and 39/419 (9.3%) patients experienced BCR in the TRT versus control groups, respectively (unadjusted, p=0.068). In adjusted time to-analysis, TRT was an independent predictor of recurrence-free survival, after controlling for GGG, p-stage, preoperative FT and PSA. A patient on TRT was approximately 53% less likely to experience a BCR (OR: 0.534, 95%CI: 0.288-0.993). Conclusions: After accounting for pathologic GGG, stage, and other significant covariates, the use of TRT independently reduced recurrence post-RP. These results suggest the need for a multi-center randomized control trial.

Introduction:High-risk hematologic malignancies are associated with significant treatment-related morbidity, particularly due to infectious events. Neutropenic fever/Febrile neutropenia (NF) is one of the most common infectious complications of chemotherapy; however, mortality rates associated with NF and the factors predictive of mortality are not well-established in the adult leukemia literature. We sought to examine factors that influence mortality and length of stay in patients admitted with NF to the inpatient hematologic malignancy service of a tertiary care center.Materials and Methods:We performed a retrospective chart review of patients admitted to our hematologic malignancy service between April 2016 and July 2018 who carried a diagnosis of NF, based upon absolute neutrophil count < 500/microL and temperature =>38.3C. We included patients who developed fever during planned admission for treatment or who were admitted for complications. Patients had primary diagnoses of AML, ALL, CML, CLL, and MDS. Patients undergoing autologous or allogenic stem cell transplant were excluded. Our analysis included demographics, primary diagnosis, primary disease status (remission, relapse, refractory), line of therapy prior to admission, duration of neutropenia, and nutritional status. We included infection-specific factors such as the presence of bacteremia, identification of an infection source, gram stain of bacteria isolated, resistance patterns, and need for ICU care. We used linear regression analysis to evaluate potential predictors of length of stay and mortality. Statistical analyses were performed with SAS.Results:We identified 100 episodes of NF that occurred in 63 patients. Median age was 58. Malignancies with the highest representation among NF episodes were AML (69%), ALL (24%), CML (3%), and CLL (2%). Infection sources were identified in 62% of episodes, with bacteremia identified in 54% of cases, accounting for 87% of sources. Mean length of stay was 18.7 (+/- 2.3 days). 14 deaths occurred, with 13 (93%) being AML patients and 11 (79%) having bacteremia. Factors associated with mortality were recurrent or relapsed disease status (RR 3.05, p = 0.034), bacteremia (RR 3.1, p = 0.047), and need for ICU-level care as defined by intubation or pressor requirements (RR 8.2, p Disclosures No relevant conflicts of interest to declare.

Background: In the Canadian Healthy Infant Longitudinal Development (CHILD) cohort, early introductions of egg, cow9s milk products and peanut were associated with reduced sensitization to these foods at 1 year. We investigated whether these effects differed by specific parental atopy and child sex. Methods: We analyzed feeding patterns in 2284 children in relation to food sensitization at 1 year, stratified by paternal and maternal atopy independently and child sex. Results: In male infants with atopic fathers/non-atopic mothers (n=215), using introduction after 12 months as reference, introduction of cow9s milk products by 6 months reduced sensitization to egg (OR 0.13, 95% CI 0.02,0.91) and peanut (OR 0.08, 95%CI 0.01,0.63); introduction of peanut between 7-12 months reduced sensitization to egg (OR 0.31, 95%CI 0.08,0.94); and introduction of milk between 7-12 months reduced peanut sensitization (OR 0.05, 95%CI 0.01,0.44). Sensitization to any of these 3 foods was reduced by 87% by milk products and 67% by peanut introduction before 12 months. In contrast, among males with atopic mothers/non-atopic fathers (n=110), egg introduction by 6 months reduced the risk of sensitization to any of these 3 foods but no other associations were significant. Female infants with only atopic fathers (n=125) had less milk sensitization if introduced to cow9s milk by 6 months (OR 0.04, 95%CI 0.0,0.69) or between 7-12 months (OR 0.03, 95%CI 0.0,0.77), but among females with only atopic mothers (n=127), no effect of timing of food introduction was evident. Conclusions: Early introduction of allergenic foods was more protective against food sensitization in male infants with atopic fathers.

Classical Hodgkin lymphoma (cHL) is a cancer in which malignant "Reed-Sternberg" cells comprise just a fraction of the bulk of the tumor and are characteristically binucleated. We recently identified a novel gene, KLHDC8B, which appears responsible for some familial cases of cHL. KLHDC8B encodes a midbody kelch protein expressed during cytokinesis. Deficiency of KLHDC8B leads to binucleated cells, implicating its involvement in Reed-Sternberg cell formation. Interestingly, other cancer genes, such as BRG41 and BRCA2, also encode proteins locating to the midbody during cytokinesis, even though their participation in other pathways has received greater attention. Midbody components may be an over-looked source of tumor suppressor genes.

Classical Hodgkin lymphoma (cHL) is a malignancy of B-cell origin in which the neoplastic cells, known as “Reed-Sternberg” (RS) cells, are characteristically binucleated. Here we describe a family where multiple individuals developing cHL have inherited a reciprocal translocation between chromosomes 2 and 3. The translocation disrupts KLHDC8B , an uncharacterized gene from a region (3p21.31) previously implicated in lymphoma and related malignancies, resulting in its loss of expression. We tested KLHDC8B as a candidate gene for cHL and found that a 5′-UTR polymorphism responsible for decreasing its translational expression is associated with cHL in probands from other families with cHL and segregates with disease in those pedigrees. In one of three informative sporadic cases of cHL, we detected loss of heterozygosity (LOH) for KLHDC8B in RS cells, but not reactive T lymphocytes, purified from a malignant lymph node. KLHDC8B encodes a protein predicted to contain seven kelch repeat domains. KLHDC8B is expressed during mitosis, where it localizes to the midbody structure connecting cells about to separate during cytokinesis, and it is degraded after cell division. Depletion of KLHDC8B through RNA interference leads to an increase in binucleated cells, implicating its reduced expression in the formation of cHL's signature RS cell.

Non-Hodgkin's lymphoma (NHL) accounts for 4% of new cancer cases and 3% of cancer deaths in both men and women [1]. The majority of patients present with painless peripheral lymphadenopathy, though...

Trypanosoma brucei parasites are kinetoplastid protozoa that devastate the health and economic well-being of millions of people in Africa through the disease human African trypanosomiasis (HAT). New chemotherapy has been eagerly awaited due to severe side effects and the drug resistance issues plaguing current drugs. Recently, there has been an emphasis on the use of medicinal plants worldwide. Morinda lucida Benth. is a popular medicinal plant widely distributed in Africa, and several research groups have reported on the antiprotozoal activities of this plant. In this study, we identified three novel tetracyclic iridoids, molucidin, ML-2-3, and ML-F52, from the CHCl 3 fraction of M. lucida leaves, which possess activity against the GUTat 3.1 strain of T. brucei brucei . The 50% inhibitory concentrations (IC 50 ) of molucidin, ML-2-3, and ML-F52 were 1.27 μM, 3.75 μM, and 0.43 μM, respectively. ML-2-3 and ML-F52 suppressed the expression of paraflagellum rod protein subunit 2, PFR-2, and caused cell cycle alteration, which preceded apoptosis induction in the bloodstream form of Trypanosoma parasites. Novel tetracyclic iridoids may be promising lead compounds for the development of new chemotherapies for African trypanosomal infections in humans and animals.