Relationship between serum level of ionized calcium, magnesium, phosphate, vitamin d and parathyroid hormone with stages of CKD.

Chronic kidney disease is defined as either damage or a decreased Glomerular Filtration Rate of less than 60ml/min/1.73m for 3 or more months. There is destruction of renal mass with irreversible sclerosis and loss of nephron leading to a progressive decline in GFR.Secondary hyperparathyroidism hyperphosphataemia, hypocalcaemia and vitamin-D deficiency are common complications of CKD. Objective: To determine relationship between serum level of ionised calcium, magnesium, phosphate, vitamin-D and parathyroid hormone with stages of CKD. Method: This study was conducted at ABUTH Zaria. 125 consecutive adult patients in various stages of CKD who presented were enrolled and 125 apparently healthy matched for sex and age controls were also recruited. Results: 9% of patients were in stage-1, 16% in stage-2, 22% in stage-3, 12% in stage-4 and 41% in stage-5. Serum ionised calcium, vitamin-D and eCrCl showed a progressive decline as the stage of CKD advances, while serum phosphate, creatinine and iPTH showed a progressive increase as the stage of CKD advances. Changes in serum magnesium showed a slight change with advancing stages of CKD. The difference in mean serum levels of calcium, phosphorus, vitamin-D, parathyroid hormone, creatinine and eCrCl with different stages of CKD were statistically significant. eCrCl correlated negatively with phosphate and iPTH while serum creatinine correlated negatively with calcium and positively with phosphate and iPTH. Conclusion: Majority of CKD patients were in late stage. Correlation of analytes with stages was more in late stages and biochemical derangements occurred in late, rather than early stages of CKD

Abnormal T regulatory cells (tregs: FOXP3+, CTLA-4+), myeloid-derived suppressor cells (MDSCs: monocytic, granulocytic) and polarised T helper cell profiles (Th1, Th2, Th17) in women with large and locally advanced breast cancers undergoing neoadjuvant chemotherapy (NAC) and surgery: failure of abolition of abnormal treg profile with treatment and correlation of treg levels with pathological response to NAC

ABSTRACT: BACKGROUND: Host defences play a key role in tumour growth. Some of the benefits of chemotherapy may occur through modulation of these defences. The aim of this study was to define the status of regulatory cells in women with large and locally advanced breast cancers (LLABCs) undergoing neoadjuvant chemotherapy (NAC) and surgery. METHODS: Bloods were collected from patients (n = 56) before, during and following NAC, and surgery. Controls (n = 10) were healthy, age-matched females donors (HFDs). Blood mononuclear cells (BMCs) were isolated and T regulatory cells (Tregs) (n = 31) determined. Absolute numbers (AbNs) of Tregs and myeloid-derived suppressor cells (MDSCs) were ascertained from whole blood (n = 25). Reverse transcriptase polymerase chain reaction analysis determined Treg mRNA (n = 16). In vitro production of Th1, Th2 and Th17 cytokines (n = 30), was documented. Patients were classified as clinical responders by magnetic resonance mammography after two cycles of NAC and as pathological responders using established criteria, following surgery. RESULTS: Patients with LLABCs had significantly increased circulating Tregs (>= 6 fold AbN and percentage (%)) and MDSCs (>= 1.5 fold AbN (p = 0.025)). Percentage of FOXP3+ Tregs in blood predicted the response of the LLABCs to subsequent NAC (p = 0.04). Post NAC blood Tregs (%) were significantly reduced in patients where tumours showed a good pathological response to NAC (p = 0.05). Blood MDSCs (granulocytic, monocytic) were significantly reduced in all patients, irrespective of the pathological tumour response to chemotherapy. NAC followed by surgery failed to restore blood Tregs to normal levels. MDSCs, however, were reduced to or below normal levels by NAC alone. Invitro Th1 profile (IL-1beta, IL-2, INF-gamma, TNF-alpha) was significantly reduced (p <= 0.009), whilst Th2 (IL-4, IL-5) was significantly enhanced (P <= 0.004). Th1 and Th2 (IL-5) were unaffected by NAC and surgery. IL-17A was significantly increased (p <= 0.023) but unaffected by chemotherapy and surgery. CONCLUSION: Women with LLABCs have abnormal blood regulatory cell levels (Tregs and MDSCs) and cytokine profiles (Th1, Th2, Th17). NAC followed by surgery failed to abolish the abnormal Treg and Th profiles. There was a significant correlation between the circulatory levels of Tregs and the pathological response of the breast cancers to NAC

Enhanced infection prophylaxis reduces mortality in severely immunosuppressed HIV-infected adults and older children initiating antiretroviral therapy in Kenya, Malawi, Uganda and Zimbabwe: the REALITY trial

Meeting abstract FRAB0101LB from 21st International AIDS Conference 18–22 July 2016, Durban, South Africa. Introduction: Mortality from infections is high in the first 6 months of antiretroviral therapy (ART) among HIV‐infected adults and children with advanced disease in sub‐Saharan Africa. Whether an enhanced package of infection prophylaxis at ART initiation would reduce mortality is unknown. Methods: The REALITY 2×2×2 factorial open‐label trial (ISRCTN43622374) randomized ART‐naïve HIV‐infected adults and children >5 years with CD4 <100 cells/mm3. This randomization compared initiating ART with enhanced prophylaxis (continuous cotrimoxazole plus 12 weeks isoniazid/pyridoxine (anti‐tuberculosis) and fluconazole (anti‐cryptococcal/candida), 5 days azithromycin (anti‐bacterial/protozoal) and single‐dose albendazole (anti‐helminth)), versus standard‐of‐care cotrimoxazole. Isoniazid/pyridoxine/cotrimoxazole was formulated as a scored fixed‐dose combination. Two other randomizations investigated 12‐week adjunctive raltegravir or supplementary food. The primary endpoint was 24‐week mortality. Results: 1805 eligible adults (n = 1733; 96.0%) and children/adolescents (n = 72; 4.0%) (median 36 years; 53.2% male) were randomized to enhanced (n = 906) or standard prophylaxis (n = 899) and followed for 48 weeks (3.8% loss‐to‐follow‐up). Median baseline CD4 was 36 cells/mm3 (IQR: 16–62) but 47.3% were WHO Stage 1/2. 80 (8.9%) enhanced versus 108(12.2%) standard prophylaxis died before 24 weeks (adjusted hazard ratio (aHR) = 0.73 (95% CI: 0.54–0.97) p = 0.03; Figure 1) and 98(11.0%) versus 127(14.4%) respectively died before 48 weeks (aHR = 0.75 (0.58–0.98) p = 0.04), with no evidence of interaction with the two other randomizations (p > 0.8). Enhanced prophylaxis significantly reduced incidence of tuberculosis (p = 0.02), cryptococcal disease (p = 0.01), oral/oesophageal candidiasis (p = 0.02), deaths of unknown cause (p = 0.02) and (marginally) hospitalisations (p = 0.06) but not presumed severe bacterial infections (p = 0.38). Serious and grade 4 adverse events were marginally less common with enhanced prophylaxis (p = 0.06). CD4 increases and VL suppression were similar between groups (p > 0.2). Conclusions: Enhanced infection prophylaxis at ART initiation reduces early mortality by 25% among HIV‐infected adults and children with advanced disease. The pill burden did not adversely affect VL suppression. Policy makers should consider adopting and implementing this low‐cost broad infection prevention package which could save 3.3 lives for every 100 individuals treated