Efficacy and Safety of Dapagliflozin by Baseline Glycemic Status: A Prespecified Analysis From the DAPA-CKD Trial

OBJECTIVEThe Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) study demonstrated risk reduction for kidney and cardiovascular outcomes with dapagliflozin versus placebo in participants with chronic kidney disease (CKD) with and without diabetes. We compared outcomes according to baseline glycemic status.RESEARCH DESIGN AND METHODSWe enrolled participants with CKD, estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73 m², and urinary albumin-to-creatinine ratio 200–5,000 mg/g. The primary composite end point was sustained eGFR decline ≥50%, end-stage kidney disease, or kidney or cardiovascular death.RESULTSOf 4,304 participants, 738 had normoglycemia, 660 had prediabetes, and 2,906 had type 2 diabetes. The effect of dapagliflozin on the primary outcome was consistent (P for interaction = 0.19) in normoglycemia (hazard ratio [HR] 0.62 [95% CI 0.39, 1.01]), prediabetes (HR 0.37 [0.21, 0.66]), and type 2 diabetes (HR 0.64 [0.52, 0.79]). We found no evidence for effect modification on any outcome. Adverse events were similar, with no major hypoglycemia or ketoacidosis in participants with normoglycemia or prediabetes.CONCLUSIONSDapagliflozin safely reduced kidney and cardiovascular events independent of baseline glycemic status.     

A genome-wide study of allelic imbalance in human testicular germ cell tumors using microsatellite markers

Testicular germ cell tumors (TGCT) arise by multistep carcinogenesis pathways involving selective losses and gains of chromosome material. To locate cancer genes underlying this selection, we performed a genome-wide study of allelic imbalance (AI) in 32 tumors, using 710 microsatellite markers. The highest prevalence of AI was found at 12p, in line with previous studies finding consistent gain of the region in TGCTs. High frequency of AI was also observed at chromosome arms 4p, 9q, 10p, 11q, 11p, 13q, 16q, 18p, and 22q. Within 39 candidate regions identified by mapping of smallest regions of overlap (SROs), the highest frequency of AI was at 12p11.21 approximately p11.22 (62%), 12p12.1 approximately p13.1 (53%), 12p13.1 approximately p13.2 (53%), 11q14.1 approximately q14.2 (53%), 11p13 approximately p14.3 (47%), 9q21.13 approximately q21.32 (47%), and 4p15.1 approximately p15.2 (44%). Two genes known to be involved in cancer reside in these regions, ETV6 at 12p13.2 (TEL oncogene) and WT1 at 11p13. We also found a significant association (P = 0.02) between AI at 10q21.1 approximately q22.2 and higher clinical stage. This study contributes to the ongoing search for genes involved in transformation of germ cells and provides a useful reference point to previous studies using cytogenetic techniques to map chromosome changes in TGCTs.     

CARM1 and BAF155: an example of how chromatin remodeling factors can be relocalized and contribute to cancer

In a recent article, Wang and colleagues reported the discovery of a mechanism by which CARM1 regulates the genomic localization of BAF155 (a SWI/SNF subunit involved in chromatin remodeling) through post-translational methylation at R1064 arginine residues. This modification leads to the relocalization of BAF155-containing SWI/SNF complexes to regions containing genes involved in the Myc oncogenic pathway. The results presented are evidence that these interactions constitute a mechanism by which the BAF155 chromatin remodeling factor contributes to cancer.     

Antidiabetic and haematological effect of aqueous extract of stem bark of Afzelia africana (Smith) on streptozotocin-induced diabetic Wistar rats

Objective

To investigate the antidiabetic properties of aqueous extract of stem bark of Afzelia africana (A. africana) and its beneficial effect on haematological parameters in streptozotocin induced diabetic rats.

Methods

A total of 30 rats including 24 diabetic and 6 normal rats were used for this study. Diabetes was induced in male Wistar rats by intraperitoneal injection of streptozotocin. After being confirmed diabetic, animals were orally treated with distilled water or extracts at 100 or 200 mg/kg body weight daily for 10 days. The haematological parameters including red blood and white blood cells and their functional indices were evaluated in diabetic treated groups compared with the controls.

Results

The extract significantly reduced the blood glucose levels while the best result was obtained at 200 mg/kg body weight. The feed and water intake in diabetic rats were significantly reduced while weight loss was minimized at both dosages. Similarly, the levels of red blood, white blood cells and their functional indices were significantly improved after extract administration at both doses.

Conclusions

It can be concluded that the aqueous extract of bark of A. africana possesses antihyperglycemic properties. In addition, the extract can prevent various complications of diabetes and improve some haematological parameters. Further experimental investigation is needed to exploit its relevant therapeutic effect to substantiate its ethnomedicinal usage.     

Upper gastrointestinal endoscopy findings in Mbale Regional Referral Hospital,Eastern Uganda: a 10-year retrospective analysis

BackgroundEndoscopy is required for formal diagnosis of many upper gastrointestinal (UGI) conditions including oesophageal cancer (OC). There is a paucity of data on endoscopy findings in East Africa as access to testing is challenging for patients. We describe the findings of 10 years of UGI endoscopy in Mbale Regional Referral Hospital (MRRH).MethodRecords of patients that underwent UGI endoscopy in MRRH, November 2009 – March 2019 were retrospectively analysed. Indication, macroscopic findings, histology and patient demographics were retrieved. Sub-group analyses were performed on those with a histological diagnosis of oesophageal cancer.Results833 eligible patients received single UGI procedures during the study period. Mean age was 54.8 years, range 16-93 years and 56.9% of patients were male. The main indication was dysphagia (42%) and the most common findings OC (34%) and gastritis (28%). 151 patients had histologically proven OC with a median age of 60 years and a 2:1 male to female ratio. 145/151 (96%) of samples tested revealed squamous cell carcinoma (SCC).ConclusionThose undergoing endoscopy in MRRH are most commonly male patients presenting in their 5th decade with dysphagia. There is a high proportion of significant findings including gastritis, peptic ulcer disease, and oesophageal cancer.     

Recovery and economy; salary and allowances: a 10-year follow-up of income for persons diagnosed with first-time psychosis

Social Psychiatry and Psychiatric Epidemiology - Persons with severe mental health problems (SMHP) point out financial strain as one of their main problems. De-institutionalisation in welfare...     

High BMI is significantly associated with positive progesterone receptor status and clinico-pathological markers for non-aggressive disease in endometrial cancer

Background:

Endometrial cancer incidence is increasing in industrialised countries. High body mass index (BMI, kg m⁻²) is associated with higher risk for disease. We wanted to investigate if BMI is related to clinico-pathological characteristics, hormone receptor status in primary tumour, and disease outcome in endometrial cancer.

Patients and methods:

In total, 1129 women primarily treated for endometrial carcinoma at Haukeland University Hospital during 1981–2009 were studied. Body mass index was available for 949 patients and related to comprehensive clinical and histopathological data, hormone receptor status in tumour, treatment, and follow-up.

Results:

High BMI was significantly associated with low International Federation of Gynaecology and Obstetrics (FIGO) stage, endometrioid histology, low/intermediate grade, and high level of progesterone receptor (PR) mRNA by qPCR (n=150; P=0.02) and protein expression by immunohistochemistry (n=433; P=0.003). In contrast, oestrogen receptor (ERα) status was not associated with BMI. Overweight/obese women had significantly better disease-specific survival (DSS) than normal/underweight women in univariate analysis (P=0.035). In multivariate analysis of DSS adjusting for age, FIGO stage, histological subtype, and grade, BMI showed no independent prognostic impact.

Conclusion:

High BMI was significantly associated with markers of non-aggressive disease and positive PR status in a large population-based study of endometrial carcinoma. Women with high BMI had significantly better prognosis in univariate analysis of DSS, an effect that disappeared in multivariate analysis adjusting for established prognostic markers. The role of PR in endometrial carcinogenesis needs to be further studied.     

No association between a common single nucleotide polymorphism,rs4141463, in the MACROD2 gene and autism spectrum disorder

The Autism Genome Project (AGP) Consortium recently reported genome‐wide significant association between autism and an intronic single nucleotide polymorphism marker, rs4141463, within the MACROD2 gene. In the present study we attempted to replicate this finding using an independent case–control design of 1,170 cases with autism spectrum disorder (ASD) (874 of which fulfilled narrow criteria for Autism (A)) from five centers within Europe (UK, Germany, the Netherlands, Italy, and Iceland), and 35,307 controls. The combined sample size gave us a non‐centrality parameter (NCP) of 11.9, with 93% power to detect allelic association of rs4141463 at an alpha of 0.05 with odds ratio of 0.84 (the best odds ratio estimate of the AGP Consortium data), and for the narrow diagnosis of autism, an NCP of 8.9 and power of 85%. Our case–control data were analyzed for association, stratified by each center, and the summary statistics were combined using the meta‐analysis program, GWAMA. This resulted in an odds ratio (OR) of 1.03 (95% CI 0.944–1.133), with a P‐value of 0.5 for ASD and OR of 0.99 (95% CI 0.88–1.11) with P‐value = 0.85 for the Autism (A) sub‐group. Therefore, this study does not provide support for the reported association between rs4141463 and autism. © 2011 Wiley‐Liss, Inc.