Outcomes 1 year after non-operative management of uncomplicated appendicitis in children : Children with AppendicitiS during the CoronAvirus panDEmic (CASCADE) study

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The impact of trisomy 21 on epidemiology, management, and outcomes of congenital duodenal obstruction: a population-based study.

PURPOSE: Congenital duodenal obstruction (CDO) is associated with trisomy 21 (T21), or Down's syndrome, in around a third of infants. The aim of this study was to explore the impact of T21 on the epidemiology, management, and outcomes of infants with CDO. METHODS: Data were prospectively collected from specialist neonatal surgical centres in the United Kingdom over a 12 month period from March 2016 using established population-based methodology for all babies with CDO. Infants with T21 were compared to those without any chromosomal anomaly. RESULTS: Of 102 infants with CDO that underwent operative repair, T21 was present in 33 [32% (95% CI 23-41%)] babies. Cardiac anomalies were more common in those with T21 compared to those without a chromosomal anomaly (91 vs 17%, p < 0.001), whereas associated gastrointestinal anomalies were less common in infants with T21 (3 vs 12%, p = 0.03). Surgical management was not influenced by T21. Time to achieve full enteral feed, need for repeat related surgery, and mortality were similar between groups. Infants with T21 had a longer median initial inpatient stay (23 vs 16.5 days, p = 0.02). CONCLUSIONS: Infants with T21 have a higher incidence of cardiac anomalies and a longer initial inpatient stay; however, it does not change CDO management or outcomes. This information is important for prenatal and postnatal counselling of parents of infants with CDO and T21

Genome-wide association study of borderline personality disorder reveals genetic overlap with the bipolar disorder, schizophrenia and major depression

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of Bipolar Disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was: (i) to detect genes and gene-sets involved in BOR; and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, Major Depression (MDD) and Schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests,and gene-set-analyses were performed in 998 BOR patients and 1,545 controls. LD score regression was used to detect genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Genebased analysis yielded two significant genes: DPYD (p=4.42x10-7) and PKP4 (p=8.67x10-7); and gene-set-analysis yielded a significant finding for exocytosis (GO:0006887, pFDR=0.019). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [p=2.99x10-3]), SCZ (rg=0.34 [p=4.37x10-5]), and MDD (rg=0.57 [p=1.04x10-3]). Our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies

Histone Deacetylase Inhibitor Romidepsin Induces HIV Expression in CD4 T Cells from Patients on Suppressive Antiretroviral Therapy at Concentrations Achieved by Clinical Dosing

Persistent latent reservoir of replication-competent proviruses in memory CD4 T cells is a major obstacle to curing HIV infection. Pharmacological activation of HIV expression in latently infected cells is being explored as one of the strategies to deplete the latent HIV reservoir. In this study, we characterized the ability of romidepsin (RMD), a histone deacetylase inhibitor approved for the treatment of T-cell lymphomas, to activate the expression of latent HIV. In an in vitro T-cell model of HIV latency, RMD was the most potent inducer of HIV (EC50 = 4.5 nM) compared with vorinostat (VOR; EC50 = 3,950 nM) and other histone deacetylase (HDAC) inhibitors in clinical development including panobinostat (PNB; EC50 = 10 nM). The HIV induction potencies of RMD, VOR, and PNB paralleled their inhibitory activities against multiple human HDAC isoenzymes. In both resting and memory CD4 T cells isolated from HIV-infected patients on suppressive combination antiretroviral therapy (cART), a 4-hour exposure to 40 nM RMD induced a mean 6-fold increase in intracellular HIV RNA levels, whereas a 24-hour treatment with 1 μM VOR resulted in 2- to 3-fold increases. RMD-induced intracellular HIV RNA expression persisted for 48 hours and correlated with sustained inhibition of cell-associated HDAC activity. By comparison, the induction of HIV RNA by VOR and PNB was transient and diminished after 24 hours. RMD also increased levels of extracellular HIV RNA and virions from both memory and resting CD4 T-cell cultures. The activation of HIV expression was observed at RMD concentrations below the drug plasma levels achieved by doses used in patients treated for T-cell lymphomas. In conclusion, RMD induces HIV expression ex vivo at concentrations that can be achieved clinically, indicating that the drug may reactivate latent HIV in patients on suppressive cART

The impact of trisomy 21 on epidemiology, management, and outcomes of congenital duodenal obstruction: a population-based study

Abstract: Purpose: Congenital duodenal obstruction (CDO) is associated with trisomy 21 (T21), or Down’s syndrome, in around a third of infants. The aim of this study was to explore the impact of T21 on the epidemiology, management, and outcomes of infants with CDO. Methods: Data were prospectively collected from specialist neonatal surgical centres in the United Kingdom over a 12 month period from March 2016 using established population-based methodology for all babies with CDO. Infants with T21 were compared to those without any chromosomal anomaly. Results: Of 102 infants with CDO that underwent operative repair, T21 was present in 33 [32% (95% CI 23–41%)] babies. Cardiac anomalies were more common in those with T21 compared to those without a chromosomal anomaly (91 vs 17%, p < 0.001), whereas associated gastrointestinal anomalies were less common in infants with T21 (3 vs 12%, p = 0.03). Surgical management was not influenced by T21. Time to achieve full enteral feed, need for repeat related surgery, and mortality were similar between groups. Infants with T21 had a longer median initial inpatient stay (23 vs 16.5 days, p = 0.02). Conclusions: Infants with T21 have a higher incidence of cardiac anomalies and a longer initial inpatient stay; however, it does not change CDO management or outcomes. This information is important for prenatal and postnatal counselling of parents of infants with CDO and T21

The impact of trisomy 21 on epidemiology, management, and outcomes of congenital duodenal obstruction: a population-based study

Abstract: Purpose: Congenital duodenal obstruction (CDO) is associated with trisomy 21 (T21), or Down’s syndrome, in around a third of infants. The aim of this study was to explore the impact of T21 on the epidemiology, management, and outcomes of infants with CDO. Methods: Data were prospectively collected from specialist neonatal surgical centres in the United Kingdom over a 12 month period from March 2016 using established population-based methodology for all babies with CDO. Infants with T21 were compared to those without any chromosomal anomaly. Results: Of 102 infants with CDO that underwent operative repair, T21 was present in 33 [32% (95% CI 23–41%)] babies. Cardiac anomalies were more common in those with T21 compared to those without a chromosomal anomaly (91 vs 17%, p < 0.001), whereas associated gastrointestinal anomalies were less common in infants with T21 (3 vs 12%, p = 0.03). Surgical management was not influenced by T21. Time to achieve full enteral feed, need for repeat related surgery, and mortality were similar between groups. Infants with T21 had a longer median initial inpatient stay (23 vs 16.5 days, p = 0.02). Conclusions: Infants with T21 have a higher incidence of cardiac anomalies and a longer initial inpatient stay; however, it does not change CDO management or outcomes. This information is important for prenatal and postnatal counselling of parents of infants with CDO and T21

Haematological consequences of acute uncomplicated falciparum malaria: a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data

Background: Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods: Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall ≥ 25% at day 3 and day 7. Results: A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0–19.7 g/dL) in Africa, 11.6 g/dL (range 5.0–20.0 g/dL) in Asia and 12.3 g/dL (range 6.9–17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to ≥ 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39–3.05], p < 0.001). Conclusions: In patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery