Update on Wild Poliovirus Type 1 Outbreak - Southeastern Africa, 2021-2022.

Since the Global Polio Eradication Initiative (GPEI) began in 1988, the number of wild poliovirus (WPV) cases has declined by >99.99%. Five of the six World Health Organization (WHO) regions have been certified free of indigenous WPV, and WPV serotypes 2 and 3 have been declared eradicated globally (1). WPV type 1 (WPV1) remains endemic only in Afghanistan and Pakistan (2,3). Before the outbreak described in this report, WPV1 had not been detected in southeastern Africa since the 1990s, and on August 25, 2020, the WHO African Region was certified free of indigenous WPV (4). On February 16, 2022, WPV1 infection was confirmed in one child living in Malawi, with onset of paralysis on November 19, 2021. Genomic sequence analysis of the isolated poliovirus indicated that it originated in Pakistan (5). Cases were subsequently identified in Mozambique. This report summarizes progress in the outbreak response since the initial report (5). During November 2021-December 2022, nine children and adolescents with paralytic polio caused by WPV1 were identified in southeastern Africa: one in Malawi and eight in Mozambique. Malawi, Mozambique, and three neighboring countries at high risk for WPV1 importation (Tanzania, Zambia, and Zimbabwe) responded by increasing surveillance and organizing up to six rounds of national and subnational polio supplementary immunization activities (SIAs).* Although no cases of paralytic WPV1 infection have been reported in Malawi since November 2021 or in Mozambique since August 2022, undetected transmission might be ongoing because of poliovirus surveillance gaps and testing delays. Efforts to further enhance poliovirus surveillance sensitivity, improve SIA quality, and strengthen routine immunization are needed to ensure that WPV1 transmission has been interrupted within 12 months of the first case, thereby preserving the WHO African Region's WPV-free status.

Are women in Uganda gaining adequate gestational weight? A prospective study in low income urban Kampala.

BACKGROUND: Pre-pregnancy weight and weight gained during pregnancy significantly influence maternal and infant health. Little information is available regarding optimal gestational weight gain (GWG) in relation to pre-pregnancy body mass index (BMI) in Uganda. The study aimed at determining gestational weight gain (GWG) in women pregnant for the first and second time. METHODS: The study was prospective cohort study which included 221 HIV negative women pregnant for the first or second time. It was conducted in the antenatal clinic of the directorate of gynecology and obstetrics, Mulago hospital and women were recruited at ≤18 weeks of gestation by dates. Follow up measurements were done at 26 and 36 weeks gestation. Measured maternal height and reported pre-pregnancy weight were used to calculate BMI. Depending on BMI category, GWG was categorized as inadequate, adequate and excessive based on the Uganda Ministry of Health guidelines. RESULTS: The participants' mean ± standard deviation (Sd) age was 20.9 ± 2.7 years and mean ± Sd BMI was 21.40 ± 2.73 kg/m2. None of the participants was obese and 68.8% (n = 132) were pregnant for the first time. The mean ± Sd GWG at time of delivery was 10.58 ± 2.44 kg. Inadequate GWG was recorded in 62.5% (n = 120/192) while only 3.1% (n = 6/192) of the participants gained excessive weight during pregnancy. CONCLUSION: About 62% of pregnant women in Kampala did not gain adequate weight during their first/second pregnancy. We recommend that studies be carried out to assess whether the Uganda Ministry of Health recommendations for weight gain during are appropriate for preventing adverse pregnancy outcomes across populations in Uganda.

Cervicovaginal Bacteriology and Antibiotic Sensitivity Patterns among Women with Premature Rupture of Membranes in Mulago Hospital, Kampala, Uganda: A Cross-Sectional Study.

Background. A 2013 Cochrane review concluded that the choice of antibiotics for prophylaxis in PROM is not clear. In Uganda, a combination of oral erythromycin and amoxicillin is the 1st line for prophylaxis against ascending infection. Our aim was to establish the current cervicovaginal bacteriology and antibiotic sensitivity patterns. Methods. Liquor was collected aseptically from the endocervical canal and pool in the posterior fornix of the vagina using a pipette. Aerobic cultures were performed on blood, chocolate, and MacConkey agar and incubated at 35-37°C for 24-48 hrs. Enrichment media were utilized to culture for GBS and facultative anaerobes. Isolates were identified using colonial morphology, gram staining, and biochemical analysis. Sensitivity testing was performed via Kirby-Bauer disk diffusion and dilution method. Pearson's chi-squared (χ2) test and the paired t-test were applied, at a P value of 0.05. Results. Thirty percent of the cultures were positive and over 90% were aerobic microorganisms. Resistance to erythromycin, ampicillin, cotrimoxazole, and ceftriaxone was 44%, 95%, 96%, and 24%, respectively. Rupture of membranes (>12 hrs), late preterm, and term PROM were associated with more positive cultures. Conclusion. The spectrum of bacteria associated with PROM has not changed, but resistance to erythromycin and ampicillin has increased.

Effect of maternal Helicobacter Pylori infection on birth weight in an urban community in Uganda.

BACKGROUND: Helicobacter pylori, a widespread infection particularly in developing countries has been associated with many adverse effects during pregnancy including hyperemesis gravidarum, neural tube defects in newborns, intrauterine fetal growth restriction and miscarriage. We sought to document the effects of H. pylori infection on birth weight in a low-income setting in Kampala, Uganda. METHODS: This was a prospective cohort study conducted in Kampala between May 2012 and May 2013. The participants were H. pylori positive and H. pylori negative HIV negative primigravidae and secundigravidae. Recruitment was at ≤18 gestation weeks and follow up assessments were carried out at 26 and 36 gestation weeks and soon after delivery. H. pylori infection was determined using H. pylori stool antigen test. Maternal weight and height were measured, and body mass index (BMI) and gestational weight gain were calculated. Only term and live babies were considered. Low birth weight (LBW) was defined as a birth weight of <2500 gram. RESULTS: A total of 221 participants were enrolled with mean ± standard deviation (SD) age of 20.9 ± 2.7 years. The mean ± SD gestation age at delivery was 39.4 ± 1.0 weeks. Primigravidae were 61.5 % (n = 188) and 52.9 % (n = 117) of the participants were positive for H. pylori infection. Low pre-pregnancy BMI (<18.5 kg/m(2)) was recorded in 14.6 % (n = 28) while 38 % (n = 73) had a height <156 cm at recruitment. Of the infants born to the participants, 13.6 % (n = 26) had low birth weight (<2500 gram). Independent predictors for LBW were the mother being positive for H. pylori infection (odds ratio, OR, 3.6, 95 % CI 1.1 - 11.5; P = 0.031) maternal height at recruitment <156 cm (OR 3.4, 95 % CI 1.4-8.2; P = 0.008) and maternal weight gain rates <0.3 kg/week during the 2(nd) and 3(rd) trimesters (OR 3.8, 95 % CI 1.0-14.1; P = 0.044). CONCLUSION: H. pylori infection is associated with LBW among primigravidae and secundigravidae in Kampala, Uganda.

Effects of processing on the polyphenol and phenolic acid content and antioxidant capacity of semi-dried cherry tomatoes (Lycopersicon esculentum M.).

BACKGROUND: This study was performed to test the effects of pre-treating cherry tomatoes with a solution containing citric acid-NaCl-CaCl2 (10:10:24 g L(-1)), followed by one of three different drying regimes (40, 60, 80 °C) on the antioxidant capacity of their aqueous extracts and the extent of phenolic compound degradation. RESULTS: Chlorogenic acids, caffeic acid, ferulic acid, rutin and naringenin were all detected in the aqueous extracts. In fresh cherry tomatoes the predominant phenolic compound was rutin, followed by naringenin, which corresponded to 79% and 8% of the total phenolic compounds present, respectively. Pre-treatment was protective towards naringenin and had a modest protective effect on rutin and ferulic acid (0.1 > P > 0.05). Total phenolic content was similar in all samples, but there was a trend for the level of free polyphenols to be lower in treated tomatoes. The destruction of naringenin was confirmed by liquid chromatographic-mass spectrometric data. CONCLUSION: A significant effect of temperature on the antioxidant capacity was observed. After this treatment the industry might introduce some advances in the processing of tomatoes, preserving the main nutritive characteristics and saving the products as semi-dried.

Retrospective cohort analysis comparing the incidence of deep vein thromboses between peripherally-inserted and long-term skin tunneled venous catheters in hemato-oncology patients.

BACKGROUND: The introduction of central venous catheters has advanced medical care, particularly in hemato-oncology. However these can be associated with an increased thrombotic risk. Previous studies have compared the rate of thrombotic events between peripherally- inserted (PICCs) and long term skin tunneled catheters (LTSTCs) noting fewer complications associated with the latter, though this has rarely translated into clinical practice. The objectives of our study was to compare the cumulative incidence of thrombotic events between peripherally-inserted and long term skin tunneled venous catheters. PATIENTS/METHODS: We performed a retrospective, single center cohort analysis of patients with hematological malignancies who had either a PICC or LTSTC line inserted between January 2010 through January 2013. Cumulative incidences of thrombotic events were compared between the two groups, and post-thrombotic complications were also examined. RESULTS: 346 patients had a PICC inserted with cumulative incidence of symptomatic thrombosis of 5.8%, while 237 patients had a LTSTC inserted with a cumulative incidence of 1.7% (p = 0.003). Post-thrombotic complication rates, particularly infection, were higher in the PICC group compared to the LTSTC group (p = 0.597). CONCLUSIONS: Our study showed that the incidence of thrombotic events in hemato-oncology patients was significantly lower in those who had a LTSTC compared to PICC line. As the use of central venous lines increases in hemato-oncology patient care, a randomized trial comparing PICCs and LTSTCs is necessary to address which venous access is most appropriate in this cohort of patients, with minimal risk of morbidity and mortality.

CD, or not CD, that is the question: a digital interobserver agreement study in coeliac disease.

OBJECTIVE: Coeliac disease (CD) diagnosis generally depends on histological examination of duodenal biopsies. We present the first study analysing the concordance in examination of duodenal biopsies using digitised whole-slide images (WSIs). We further investigate whether the inclusion of immunoglobulin A tissue transglutaminase (IgA tTG) and haemoglobin (Hb) data improves the interobserver agreement of diagnosis. DESIGN: We undertook a large study of the concordance in histological examination of duodenal biopsies using digitised WSIs in an entirely virtual reporting setting. Our study was organised in two phases: in phase 1, 13 pathologists independently classified 100 duodenal biopsies (40 normal; 40 CD; 20 indeterminate enteropathy) in the absence of any clinical or laboratory data. In phase 2, the same pathologists examined the (re-anonymised) WSIs with the inclusion of IgA tTG and Hb data. RESULTS: We found the mean probability of two observers agreeing in the absence of additional data to be 0.73 (±0.08) with a corresponding Cohen's kappa of 0.59 (±0.11). We further showed that the inclusion of additional data increased the concordance to 0.80 (±0.06) with a Cohen's kappa coefficient of 0.67 (±0.09). CONCLUSION: We showed that the addition of serological data significantly improves the quality of CD diagnosis. However, the limited interobserver agreement in CD diagnosis using digitised WSIs, even after the inclusion of IgA tTG and Hb data, indicates the importance of interpreting duodenal biopsy in the appropriate clinical context. It further highlights the unmet need for an objective means of reproducible duodenal biopsy diagnosis, such as the automated analysis of WSIs using artificial intelligence.

High readmission rates are associated with a significant economic burden and poor outcome in patients with grade III/IV acute GvHD.

Graft-versus-host disease (GvHD) is a common complication following haematopoietic stem cell transplant but little is published about the impact of this condition on hospital readmission rates. We report a retrospective analysis of readmission rates and associated costs in 187 consecutive allogeneic transplant patients to assess the impact of GvHD. The overall readmission rate was higher in patients with GvHD (86% (101/118) vs. 59% (41/69), p < 0.001). The readmission rate was higher both in the first 100 d from transplant (p = 0.02) and in the first year following transplant (p < 0.001). 151/455 (33%) of all readmission episodes occurred within 100 d of transplant. The mean number of inpatient days was significantly higher in patients with grade III/IV acute GvHD (101 d) compared with those with grade I/II GvHD (70 d; p = 0.003). The mean cost of readmission was higher in patients with GvHD (£28 860) than in non-GvHD patients (£13 405; p = 0.002) and in patients with grade III/IV GvHD (£40 012) compared with those patients with grade I/II GvHD (£24 560; p = 0.038). Survival was higher in those with grade I/II GvHD (55%) compared to grade III/IV GvHD (14%; p < 0.001). This study shows the high economic burden and poor overall survival associated with grade III/IV GvHD.

A Phase 2, Double-blind, Randomized Controlled Trial of PROSTVAC in Prostate Cancer Patients on Active Surveillance.

BACKGROUND: There is an unmet clinical need for interventions to prevent disease progression in patients with localized prostate cancer on active surveillance (AS). OBJECTIVE: To determine the immunologic response to the PROSTVAC vaccine and the clinical indicators of disease progression in patients with localized prostate cancer on AS. DESIGN, SETTING, AND PARTICIPANTS: This was a phase 2, double-blind, randomized controlled trial in 154 men with low- or intermediate-risk prostate cancer on AS. INTERVENTION: Participants were randomized (2:1) to receive seven doses of subcutaneous PROSTVAC, a vaccinia/fowlpox viral vector-based immunotherapy containing a prostate-specific antigen (PSA) transgene and three T-cell co-stimulatory molecules, or an empty fowlpox vector (EV) over 140 d. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the change from baseline in CD4 and CD8 T-cell infiltration in biopsy tumor tissue. Key secondary outcomes were safety and changes in prostate biopsy tumor pathology, peripheral antigen-specific T cells, and serum PSA. Continuous variables were compared using nonparametric tests. Categorical variables were compared using Fisher's exact test. RESULTS AND LIMITATIONS: The PROSTVAC/EV vaccination was well tolerated. All except one participant completed the vaccination series. Changes in CD4 or CD8 density in biopsy tumor tissue did not differ between the PROSTVAC and EV arms. The proportions of patients with Gleason upgrading to grade group 3 after treatment was similar between the arms. There were no differences in postvaccination peripheral T-cell responses or the PSA change from baseline to 6-mo post-treatment follow-up between the groups. CONCLUSIONS: In this first-of-kind trial of immunotherapy in patients on AS for prostate cancer, PROSTVAC did not elicit more favorable prostate tissue or peripheral T-cell responses than the EV. There was no difference between the arms in clinicopathologic effects. Despite the null findings, this is the first study reporting the feasibility and acceptability of an immunotherapy intervention in the AS setting. PATIENT SUMMARY: We looked at responses after an experimental prostate cancer vaccine in patients with prostate cancer on active surveillance (AS). Participants who received the vaccine did not show more favorable outcomes than those receiving the control. Despite these findings, this is the first report showing the feasibility and acceptability of immunotherapy for prostate cancer in patients on AS.

Liver transplantation for acute intermittent porphyria is complicated by a high rate of hepatic artery thrombosis.

Acute intermittent porphyria (AIP) is an autosomal-dominant condition resulting from a partial deficiency of the ubiquitously expressed enzyme porphobilinogen deaminase. Although its clinical expression is highly variable, a minority of patients suffer recurrent life-threatening neurovisceral attacks despite optimal medical therapy. Because the liver is the major source of excess precursor production, liver transplantation (LT) represents a potentially effective treatment for severely affected patients. Using data from the U.K. Transplant Registry, we analyzed all transplants performed for AIP in the United Kingdom and Ireland. Between 2002 and 2010, 10 patients underwent LT for AIP. In all cases, the indication for transplantation was recurrent, biochemically proven, medically nonresponsive acute attacks of porphyria resulting in significantly impaired quality of life. Five patients had developed significant neurological morbidities such as paraplegia before transplantation. The median follow-up time was 23.4 months, and there were 2 deaths from multiorgan failure at 98 days and 26 months. Eight recipients were alive for 3.2 to 109 months after transplantation. Complete biochemical and symptomatic resolution was observed in all patients after transplantation. However, there was a high rate of hepatic artery thrombosis (HAT; 4/10), with 1 patient requiring regrafting. The effects of previous neuronal damage such as joint contractures were not improved by transplantation. Thus, impaired quality of life in the surviving patients was usually a result of preoperative complications. Refractory AIP is an excellent indication for LT, and long-term outcomes for carefully selected patients are good. There is, however, an increased incidence of HAT in these patients, and we recommend routine antiplatelet therapy after transplantation.

UK experience of liver transplantation for erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is characterised by excess production of free protoporphyrin from the bone marrow, most commonly due to deficiency of the enzyme ferrochelatase. Excess protoporphyrin gives rise to the cutaneous photosensitivity characteristic of the disease, and in a minority of patients leads to end-stage liver disease necessitating liver transplantation (LT). There is limited information regarding the timing, impact and long-term outcome of LT in such patients, thus we aimed to identify the indications and outcomes of all transplants performed for EPP in the UK using data from the UK Transplant Registry. Between 1987 and 2009, five patients underwent LT for EPP liver disease. Median follow-up was 60 months, and there were two deaths at 44 and 95 months from causes unrelated to liver disease. The remaining recipients are alive at 22.4 years, 61 months and 55 months after transplant. A high rate of postoperative biliary stricturing requiring multiple biliary interventions was observed. Recurrent EPP-liver disease occurred in 4/5 (80%) of patients but graft failure has not been observed. Given the role of biliary obstruction in inducing EPP-mediated liver damage, we suggest that consideration should be given for construction of a Roux loop at the time of transplant. Thus we demonstrate that although EPP liver transplant recipients have a good long-term survival, comparable to patients undergoing LT for other indications, biliary complications and disease recurrence are almost universal, and bone marrow transplantation should be considered where possible.

The feasibility of plerixafor as a second-line stem cell mobilizing agent in children.

In patients heavily pretreated with myelosuppressive chemotherapy or irradiation, Granulocyte colony stimulating factor (G-CSF) may fail to mobilize stem cells from the bone marrow. Plerixafor is emerging as a reliable alternate option in such situations in adult patients. Robust data in support of the high efficacy and safety of plerixafor are available in adults. Very little evidence is available on the usefulness of this drug among children. We report our experience with plerixafor usage on 5 occasions in pediatric patients, with a success rate of 60%. No significant side effects were encountered in any patient.

Analysis, Modeling, and Visualization of Chromosome Conformation Capture Experiments.

Chromatin Conformation Capture techniques have unveiled several layers of chromosome organization such as the segregation in compartments, the folding in topologically associating domains (TADs), and site-specific looping interactions. The discovery of this genome hierarchical organization emerged from the computational analysis of chromatin capture data. With the increasing availability of such data, automatic pipelines for the robust comparison, grouping, and classification of multiple experiments are needed. Here we present a pipeline based on the TADbit framework that emphasizes reproducibility, automation, quality check, and statistical robustness. This comprehensive modular pipeline covers all the steps from the sequencing products to the visualization of reconstructed 3D models of the chromatin.

Dramatic and sustained increase in HIV-testing rates among antenatal attendees in Eastern Uganda after a policy change from voluntary counselling and testing to routine counselling and testing for HIV: a retrospective analysis of hospital records, 2002-2009.

BACKGROUND: The burden of mother-to-child transmission of HIV in Uganda is high. The aim of this paper is to describe the experience of the first 7 years of the prevention of mother- to- child transmission of HIV (PMTCT) programme in Mbale Regional Hospital, Eastern Uganda, with particular reference to the lessons learnt in changing from voluntary counselling and testing (VCT) to routine counselling and testing (RCT) for HIV testing in antenatal services. METHODS: The study was a retrospective analysis of the PMTCT records of Mbale Regional Referral Hospital, Uganda, from May 2002 to April 2009. The data on HIV testing of pregnant women and their male partners was extracted from the reports and registers using a standardized data extraction form, and data was analysed using descriptive statistics. Permission to conduct the study was obtained from School of Medicine, Makerere University College of Health Sciences; Uganda National Council of Science and Technology, and Mbale Hospital. RESULTS: A total of 54 429 new antenatal (ANC) attendees and 469 male-partners accessed antenatal services at Mbale Regional Referral Hospital. There was a sustained, significant increase in HIV testing among new ANC attendees from 22% during the VCT period to 88% during the RCT period (p = 0.002), while among male partners, HIV testing increased from 88% to 100% (p = 0.010) However, the overall number of male partners who tested for HIV remained very low despite the change from VCT to RCT approach in HIV testing. CONCLUSIONS: Routine offer of antenatal HIV testing dramatically increased HIV testing in pregnant women and their partners in Uganda. Our findings call for further strengthening of the policy for routine HIV testing in antenatal clinics. Our study also showed that male partner HIV testing in antenatal clinics is low and this area needs further work through research and innovative interventions in order to improve male partner involvement.

Quadriceps Muscle Size, Quality, and Strength and Self-Reported Function in Individuals With Anterior Cruciate Ligament Reconstruction.

CONTEXT: Ultrasound imaging provides a cost-effective method of measuring quadriceps morphology, which may be related to self-reported function after anterior cruciate ligament reconstruction (ACLR). OBJECTIVE: To compare quadriceps morphology and strength between limbs in individuals with ACLR and matched control limbs and determine their associations with self-reported function. DESIGN: Cross-sectional study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Forty-two individuals with ACLR (females = 66%; age = 21.8 ± 2.6 years; time since ACLR = 50.5 ± 29.4 months) and 37 controls (females = 73%; age = 21.7 ± 1.2 years). MAIN OUTCOME MEASURE(S): Quadriceps peak torque (PT) and rate of torque development were assessed bilaterally. Ultrasonography was used to measure the cross-sectional area (CSA) and echo intensity (EI) of the rectus femoris, vastus lateralis (VL), and vastus medialis. Self-reported function was assessed via the International Knee Documentation Committee (IKDC) score and Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales. Paired-samples t tests were calculated to compare involved and uninvolved limbs. Independent t tests were conducted to compare groups (α = .05). Linear regression was performed to analyze associations between quadriceps function and self-reported function after accounting for time since ACLR, activity level, and sex, and models for EI added subcutaneous fat as a covariate. RESULTS: Isometric PT did not differ between limbs or groups. Involved limbs had a lower rate of torque development compared with the control (P = .01) but not the uninvolved limbs (P = .08). Vastus lateralis CSA was smaller in the involved than in the uninvolved (P < .01) but not the control limbs (P = .10). Larger VL CSA (ΔR2 = 0.103) and lower VL EI (ΔR2 = 0.076) were associated with a higher IKDC score (P < .05). Larger VL CSA was associated with greater KOOS Symptoms (ΔR2 = 0.09, P = .043) and Sport and Recreation (ΔR2 = 0.125, P = .014) scores. Lower VL EI was associated with higher KOOS Symptoms (ΔR2 = 0.104, P = .03) and Quality of Life (ΔR2 = 0.113, P = .01) scores. Quadriceps PT and rate of torque development were not associated with IKDC or KOOS subscale scores. CONCLUSIONS: Quadriceps morphology was associated with self-reported function in individuals with ACLR and may provide unique assessments of quadriceps function.

Favorable outcomes with alemtuzumab-conditioned unrelated donor stem cell transplantation in adults with high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in first complete remission.

BACKGROUND: Approximately 40% of adults with Philadelphia chromosome-negative acute lymphoblastic leukemia achieve long-term survival following unrelated donor hematopoietic stem cell transplantation in first complete remission but severe graft-versus-host disease remains a problem affecting survival. Although T-cell depletion abrogates graft-versus-host disease, the impact on disease-free survival in acute lymphoblastic leukemia is not known. DESIGN AND METHODS: We analyzed the outcome of 48 adults (median age 26 years) with high-risk, Philadelphia-chromosome-negative acute lymphoblastic leukemia undergoing T-cell depleted unrelated donor-hematopoietic stem cell transplantation (67% 10 of 10 loci matched) in first complete remission reported to the British Society of Blood and Marrow Transplantation Registry from 1993 to 2005. RESULTS: T-cell depletion was carried out by in vivo alemtuzumab administration. Additional, ex vivo T-cell depletion was performed in 21% of patients. Overall survival, disease-free survival and non-relapse mortality rates at 5 years were 61% (95% CI 46-75), 59% (95% CI 45-74) and 13% (95% CI 3-25), respectively. The incidences of grades II-IV and III-IV acute graft-versus-host disease were 27% (95% CI 16-44) and 10% (95% CI 4-25), respectively. The actuarial estimate of extensive chronic graft-versus-host disease at 5 years was 22% (95%CI 13-38). High-risk cytogenetics at diagnosis was associated with a lower 5-year overall survival (47% (95% CI 27-71) vs. 68% (95% CI 44-84), p=0.045). CONCLUSIONS: T-cell depleted hematopoietic stem cell transplantation from unrelated donors can result in good overall survival and low non-relapse mortality for adults with high-risk acute lymphoblastic leukemia in first complete remission and merits prospective evaluation.

Relapse of primitive mediastinal lymphoma as a myeloid mass following beam autologous transplant and subsequent refractoriness to matched unrelated umbilical cord blood allograft.

Outlining the treatment for an unclassifiable lymphoid malignancy is often difficult. A highly undifferentiated lymphomatous mass that relapsed in spite of intense chemotherapy and autologous transplant is reported. At relapse, there was differentiation into myeloid lineage. Though remission was achieved with AML-type reinduction chemotherapy, the mass recurred post allogenic cord blood stem cell transplant.

Communicating Genome Architecture: Biovisualization of the Genome, from Data Analysis and Hypothesis Generation to Communication and Learning.

Genome discoveries at the core of biology are made by visual description and exploration of the cell, from microscopic sketches and biochemical mapping to computational analysis and spatial modeling. We outline the experimental and visualization techniques that have been developed recently which capture the three-dimensional interactions regulating how genes are expressed. We detail the challenges faced in integration of the data to portray the components and organization and their dynamic landscape. The goal is more than a single data-driven representation as interactive visualization for de novo research is paramount to decipher insights on genome organization in space.

A Type 1 Diabetes Genetic Risk Score Can Identify Patients With GAD65 Autoantibody-Positive Type 2 Diabetes Who Rapidly Progress to Insulin Therapy.

OBJECTIVE: Progression to insulin therapy in clinically diagnosed type 2 diabetes is highly variable. GAD65 autoantibodies (GADA) are associated with faster progression, but their predictive value is limited. We aimed to determine if a type 1 diabetes genetic risk score (T1D GRS) could predict rapid progression to insulin treatment over and above GADA testing. RESEARCH DESIGN AND METHODS: We examined the relationship between T1D GRS, GADA (negative or positive), and rapid insulin requirement (within 5 years) using Kaplan-Meier survival analysis and Cox regression in 8,608 participants with clinical type 2 diabetes (onset >35 years and treated without insulin for ≥6 months). T1D GRS was both analyzed continuously (as standardized scores) and categorized based on previously reported centiles of a population with type 1 diabetes (<5th [low], 5th-50th [medium], and >50th [high]). RESULTS: In GADA-positive participants (3.3%), those with higher T1D GRS progressed to insulin more quickly: probability of insulin requirement at 5 years (95% CI): 47.9% (35.0%, 62.78%) (high T1D GRS) vs. 27.6% (20.5%, 36.5%) (medium T1D GRS) vs. 17.6% (11.2%, 27.2%) (low T1D GRS); P = 0.001. In contrast, T1D GRS did not predict rapid insulin requirement in GADA-negative participants (P = 0.4). In Cox regression analysis with adjustment for age of diagnosis, BMI, and cohort, T1D GRS was independently associated with time to insulin only in the presence of GADA: hazard ratio per SD increase was 1.48 (1.15, 1.90); P = 0.002. CONCLUSIONS: A T1D GRS alters the clinical implications of a positive GADA test in patients with clinical type 2 diabetes and is independent of and additive to clinical features.

Familial T-cell non-Hodgkin lymphoma caused by biallelic MSH2 mutations.

Familial non-Hodgkin lymphoma (NHL) is rare and in most cases, no underlying cause is identifiable. We report homozygous truncating mutations in the mismatch repair gene MSH2 (226C-->T; Q76X) in three siblings who each developed T-cell NHL in early childhood. All three children had hyperpigmented and hypopigmented skin lesions. Constitutional biallelic MSH2 mutations have previously been reported in five individuals, all of whom developed malignancy in childhood. Familial lymphoma has not been reported in this context or in association with biallelic mutations in the other mismatch repair genes MLH1, MSH6 or PMS2. In addition, hypopigmented skin lesions have not previously been reported in biallelic MSH2 carriers. Our findings therefore expand the spectrum of phenotypes associated with biallelic MSH2 mutations and identify a new cause of familial lymphoma. Moreover, the diagnosis has important management implications as it allows the avoidance of chemotherapeutic agents likely to be ineffective and mutagenic in the proband, and the provision of cascade genetic testing and tumour screening for relatives.