Control of hyperphosphatemia in regular hemodialysis (HDx) patients by calcium acetate (CA) versus calcium carbonate (CC). A double blind crossover prospective study

This study included fourty chronic renal failure patients aged 37-83 years (mean 51.3±7) on thrice weekly HDx for 4-144 month (Kt/V >1.2). Acetate dialysate with calcium concentration of 3 mEq/L was used. All phosphate binders were discontinued for one month. Patients were divided in two groups. Group I (20 cases) received CA, while group II (20 cases) received CC in equimolar dose (10 mmol, of either t.i.d.) for one month. Crossover of treatment was done for another month while keeping patients on the same diet.Serum levels of total calcium (Ca), ionized Ca (iCa), phosphorus (P), alkaline phosphates (AP), urea (U), creatinine (Cr), ALT, AST, total proteins (TP) and albumin (Alb) were estimated before, and at the end of each month of CA and CC treatment. Serum Ca and iCa were significantly lower in group I after CA compared to values after CC (p<0.01). Similar results in Ca levels were observed in group II (P<0.05). In group II only serurn P was significantly lower after CA compared to its values after CC (P<0.05). There was no significant difference in AP, U, Cr, ALT, AST, TP and Alb before, and at the end of each month of CA and CC treatment (P>0.05 in all). We excluded 12.5% of cases due to CA intolerance while non of cases had similar intolerance to CC.Conclusion: 1) CA is not very superior to CC in control of hyperphosphataemia. 2) CA can be safely increased without the risk of hypercalcemia. 3) Active Vitamin D and high dialysate Ca can be used to suppress parathyroid activity more safely with CA than with CC. 4) Tolerability to CC is superior

Brown fat triglyceride content is associated with cardiovascular risk markers in adults from a tropical region

Brown adipose tissue (BAT) is regarded as an interesting potential target for the treatment of obesity, diabetes, and cardiovascular diseases, and the detailed characterization of its structural and functional phenotype could enable an advance in these fields. Most studies evaluating BAT structure and function were performed in temperate climate regions, and we are yet to know how these findings apply to the 40% of the world’s population living in tropical areas. Here, we used 18F-fluorodeoxyglucose positron emission tomography – magnetic resonance imaging to evaluate BAT in 45 lean, overweight, and obese volunteers living in a tropical area in Southeast Brazil. We aimed at investigating the associations between BAT activity, volume, metabolic activity, and BAT content of triglycerides with adiposity and cardiovascular risk markers in a sample of adults living in a tropical area and we showed that BAT glucose uptake is not correlated with leanness; instead, BAT triglyceride content is correlated with visceral adiposity and markers of cardiovascular risk. This study expands knowledge regarding the structure and function of BAT in people living in tropical areas. In addition, we provide evidence that BAT triglyceride content could be an interesting marker of cardiovascular risk

The Risk of Recurrence in Breast Cancer Patients Treated with Tamoxifen: Polymorphisms of CYP2D6 and ABCB1

CYP2D6 plays a major role in the metabolism of tamoxifen, and polymorphism of Pglycoprotein has been associated with resistance of many drug therapies. This study investigates the clinical impact of genetic variants of CYP2D6 and ABCB1 in breast cancer patients treated with tamoxifen. Blood samples from 95 breast cancer patients treated with tamoxifen were collected and genotyped for CYP2D6 and ABCB1 variants using allele-specific PCR method. Recurrence risks were calculated using Kaplan–Meier analysis and compared using the log-rank test. Patients carrying CYP2D6*10/*10 and heterozygous null allele (IM) showed higher risks of developing recurrence and metastasis (OR 13.14; 95% CI 1.57–109.94; P=0.004) than patients with CYP2D6*1/*1 and *1/*10 genotypes. Patients with homozygous CC genotypes of ABCB1 C3435T showed a shorter time to recurrence. Patients who were CYP2D6 IM and homozygous CC genotype of C3435T have statistically significant higher risks of recurrence (P=0.002). Similarly, median time to recurrence in these patients was only 12 months (95% CI=0.79–23.2) compared to those without this combination which was 48 months (95% CI=14.7–81.2). Patients with CYP2D6 IM and homozygous CC genotype of ABCB1 C3435T have shorter times to recurrence. The results confirmed the findings of previous studies and support FDA recommendation to perform pre-genotyping in patients before the choice of therapy is determined in breast cancer patients

Autologous stem cell transplantation with low-dose cyclophosphamide to improve mucosal healing in adults with refractory Crohn's disease: the ASTIClite RCT

Some text in this abstract has been reproduced from Lindsay J, Din S, Hawkey C, Hind D, Irving P, Lobo A, et al. OFR-9 An RCT of autologous stem-cell transplantation in treatment refractory Crohn’s disease (low-intensity therapy evaluation): ASTIClite. Gut 2021;70(Suppl. 4):A4. Background Treatment-refractory Crohn’s disease is characterised by chronic symptoms, poor quality of life and high costs to the NHS, and through days of work lost by patients. A previous trial of autologous haematopoietic stem cell transplant (HSCT) failed its end point of medication-free clinical remission for 3 months with no evidence of disease activity, and reported high toxicity. Subsequent studies suggest that HSCT achieves complete mucosal healing in 50% of patients, and that toxicity likely relates to the cyclophosphamide dose. Objectives The primary objective was to assess the efficacy of HSCTlite (HSCT with low-dose cyclophosphamide) compared with standard care for inducing regression of intestinal ulceration in patients with refractory Crohn’s disease at week 48. Secondary objectives included the assessment of disease activity, quality of life and regimen safety. Mechanistic objectives included immune reconstitution after HSCTlite. Design Two-arm, parallel-group randomised controlled trial with a 2 : 1 (intervention : control) allocation ratio. Setting Nine NHS trusts (eight trusts were recruitment sites; one trust was a treatment-only site). Participants Adults with treatment-refractory Crohn’s disease, for whom surgery was inappropriate or who had declined surgery. Interventions The intervention treatment was HSCTlite using cyclophosphamide, and the control was any current available treatment for Crohn’s disease, apart from stem cell transplantation. Main outcomes The primary outcome was treatment success at week 48 [mucosal healing (Simple Endoscopic Score for Crohn’s Disease ulcer subscore of 0) without surgery or death], assessed by central readers blinded to allocation and timing of assessment. Key secondary outcomes were clinical remission, Simple Endoscopic Score for Crohn’s Disease scores at week 48, change in Crohn’s Disease Activity Index scores and safety. Results The trial was halted owing to Suspected unexpected serious adverse events that took place after randomising 23 patients (HSCTlite arm, n = 13; usual-care arm, n = 10). Ten out of the 13 patients randomised to the HSCTlite arm received the intervention and nine (one death) reached the 48-week follow-up. In the usual-care arm 9 out of the 10 patients randomised reached the 48-week follow-up (one ineligible). The primary outcome was available for 7 out of 10 HSCTlite patients (including the patient who died) and six out of nine usual-care patients. Absence of endoscopic ulceration without surgery or death was reported in three out of seven (43%) HSCTlite patients, compared with zero out of six (0%) usual-care patients. Centrally read Simple Endoscopic Score for Crohn’s Disease scores [mean (standard deviation)] were 10.8 (6.3) and 10.0 (6.1) at baseline, compared with 2.8 (2.9) and 18.7 (9.1) at week 48, in the HSCT and usual-care arms, respectively. Clinical remission (Crohn’s Disease Activity Index scores of < 150) occurred in 57% and 17% of patients in the HSCTlite and usual-care arms, respectively, at week 48. Serious adverse events were more frequent in the HSCTlite arm [38 in 13 (100%) patients] than in the usual-care arm [16 in 4 (40%) patients]. Nine suspected unexpected serious adverse reactions were reported in six HSCTlite patients, including three cases of delayed renal failure due to proven thrombotic microangiopathy. Two HSCTlite patients died. Conclusions Within the limitations of reduced patient recruitment and numbers of patients assessed, HSCTlite meaningfully reduced endoscopic disease activity, with three patients experiencing resolution of ulceration. Suspected unexpected serious adverse reactions, particularly relating to thrombotic microangiopathy, make this regimen unsuitable for future clinical use. Limitations The early trial closure prevented complete recruitment, and the impact of the coronavirus pandemic prevented completion of some study investigations. Small participant numbers meant analysis could only be descriptive. Future work Owing to undetermined aetiology of thrombotic microangiopathy, further trials of HSCTlite in this population are not considered appropriate. Priorities should be to determine optimal treatment strategies for patients with refractory Crohn’s disease, including those with a stoma or multiple previous resections

Polymorphisms in NFkB, PXR, LXR and risk of colorectal cancer in a prospective study of Danes

<p>Abstract</p> <p>Background</p> <p>Transcription factors and nuclear receptors constitute a link between exposure to heterocyclic amines and polycyclic aromatic hydrocarbons from meat and tobacco smoke and colorectal cancer (CRC) risk. The aim of this study was to investigate if polymorphisms in nuclear factor kappa-B, pregnane X receptor, and liver X receptor were associated with risk of CRC, and to investigate possible interactions with lifestyle factors such as smoking, meat consumption, and NSAID use.</p> <p>Methods</p> <p>The polymorphisms nuclear factor kappa-B (<it>NFkB, NFKB1) </it>-94 insertion/deletion ATTG (rs28362491), pregnane X receptor (<it>PXR, NR1I2) </it>A-24381C (rs1523127), C8055T (rs2276707), A7635G (rs6785049), liver X receptor (<it>LXR-β, NR1H3) </it>C-rs1405655T, T-rs2695121C were assessed together with lifestyle factors in a nested case-cohort study of 378 CRC cases and 756 random participants from the Danish prospective Diet, Cancer and Health study of 57,053 persons.</p> <p>Results</p> <p>Carriers of <it>NFkB </it>-94deletion were at 1.45-fold higher risk of CRC than homozygous carriers of the insertion allele (incidence rate ratio (IRR) = 1.45, 95% confidence interval (95% CI): 1.10-1.92). There was interaction between this polymorphism and intake of red and processed meat in relation to CRC risk. Carriers of <it>NFkB </it>-94deletion were at 3% increased risk pr 25 gram meat per day (95% CI: 0.98-1.09) whereas homozygous carriers of the insertion were not at increased risk (p for interaction = 0.03). <it>PXR </it>and <it>LXR </it>polymorphisms were not associated with CRC risk. There was no interaction between use of nonsteroid antiinflammatory drugs (NSAID) or smoking status and <it>NFkB</it>, <it>PXR </it>or <it>LXR </it>polymorphisms.</p> <p>Conclusions</p> <p>A polymorphism in <it>NFkB </it>was associated with CRC risk and there was interaction between this polymorphism and meat intake in relation to CRC risk. This study suggests a role for NFkB in CRC aetiology.</p

Relationship of depression, disability, and family caregiver attitudes to the quality of life of Kuwaiti persons with multiple sclerosis: a controlled study

<p>Abstract</p> <p>Background</p> <p>Assessment of subjective quality of life (QOL) of persons with multiple sclerosis (MS) could facilitate the detection of psychosocial aspects of disease that may otherwise go unrecognized. The objectives of the study were to (i) compare the QOL ratings of relapsing remitting (RRMS) and progressive (PMS) types of MS with those of a general population group and the impression of their family caregivers; and (ii) assess the association of demographic, clinical, treatment, depression, and caregiver variables with patients' QOL.</p> <p>Methods</p> <p>Consecutive clinic attendees at the national neurology hospital were assessed with the 26 -item WHOQOL Instrument, Beck's Depression Inventory and Expanded Disability Scale. Caregivers rated their impression of patients' QOL and attitudes to patients' illness.</p> <p>Results</p> <p>The 170 patients (60 m, 109 f) consisted of 145(85.3%) with RRMS and 25 with PMS, aged 32.4(SD 8.8), age at onset 27.1(7.7), EDSS score 2.9 (1.8), and 76% were employed. The patients were predominantly dissatisfied with their life circumstances. The RRMS group had higher QOL domain scores (P < 0.001), and lower depression(P > 0.05) and disability (P < 0.0001) scores than the PMS group. Patients had significantly lower QOL scores than the control group (P < 0.001). Caregiver impression was significantly correlated with patients' ratings. Depression was the commonest significant covariate of QOL domains. When we controlled for depression and disability scores, differences between the two MS groups became significant for only one (out of 6) QOL domains. Patients who were younger, better educated, employed, felt less sick and with lesser side effects, had higher QOL. The predictors of patients' overall QOL were disability score, caregiver impression of patients' QOL, and caregiver fear of having MS.</p> <p>Conclusion</p> <p>Our data indicate that MS patients in stable condition and with social support can hope to have better QOL, if clinicians pay attention to depression, disability, the impact of side effects of treatment and family caregiver anxieties about the illness. The findings call for a regular program of psychosocial intervention in the clinical setting, to address these issues and provide caregiver education and supports, in order to enhance the quality of care.</p

Efficacy and Safety of Artemether in the Treatment of Chronic Fascioliasis in Egypt: Exploratory Phase-2 Trials

Fasciola hepatica and F. gigantica are two liver flukes that parasitize herbivorous large size mammals (e.g., sheep and cattle), as well as humans. A single drug is available to treat infections with Fasciola flukes, namely, triclabendazole. Recently, laboratory studies and clinical trials in sheep and humans suffering from acute fascioliasis have shown that artesunate and artemether (drugs that are widely used against malaria) also show activity against fascioliasis. Hence, we were motivated to assess the efficacy and safety of oral artemether in patients with chronic Fasciola infections. The study was carried out in Egypt and artemether administered according to two different malaria treatment regimens. Cure rates observed with 6×80 mg and 3×200 mg artemether were 35% and 6%, respectively. In addition, high efficacy was observed when triclabendazole, the current drug of choice against human fascioliasis, was administered to patients remaining Fasciola positive following artemether treatment. Concluding, monotherapy with artemether does not represent an alternative to triclabendazole against fascioliasis, but its role in combination chemotherapy regimen remains to be investigated

Comparative analysis of inflamed and non-inflamed colon biopsies reveals strong proteomic inflammation profile in patients with ulcerative colitis

<p>Abstract</p> <p>Background</p> <p>Accurate diagnostic and monitoring tools for ulcerative colitis (UC) are missing. Our aim was to describe the proteomic profile of UC and search for markers associated with disease exacerbation. Therefore, we aimed to characterize specific proteins associated with inflamed colon mucosa from patients with acute UC using mass spectrometry-based proteomic analysis.</p> <p>Methods</p> <p>Biopsies were sampled from rectum, sigmoid colon and left colonic flexure from twenty patients with active proctosigmoiditis and from four healthy controls for proteomics and histology. Proteomic profiles of whole colonic biopsies were characterized using 2D-gel electrophoresis, and peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was applied for identification of differently expressed protein spots.</p> <p>Results</p> <p>A total of 597 spots were annotated by image analysis and 222 of these had a statistically different protein level between inflamed and non-inflamed tissue in the patient group. Principal component analysis clearly grouped non-inflamed samples separately from the inflamed samples indicating that the proteomic signature of colon mucosa with acute UC is strong. Totally, 43 individual protein spots were identified, including proteins involved in energy metabolism (triosephosphate isomerase, glycerol-3-phosphate-dehydrogenase, alpha enolase and L-lactate dehydrogenase B-chain) and in oxidative stress (superoxide dismutase, thioredoxins and selenium binding protein).</p> <p>Conclusions</p> <p>A distinct proteomic profile of inflamed tissue in UC patients was found. Specific proteins involved in energy metabolism and oxidative stress were identified as potential candidate markers for UC.</p

An international survey on the pragmatic management of epistaxis

Epistaxis is one of the most common ear, nose and throat emergencies. The management of epistaxis has evolved significantly in recent years, including the use of nasal cautery and packs. However, a correct treatment requires the knowledge of nasal anatomy, potential risks, and complications of treatment. Epistaxis is often a simple and readily treatable condition, even though a significant bleed may have potentially severe consequences. At present, there are very few guidelines concerning this topic. The current Survey explored the pragmatic approach in managing epistaxis. A questionnaire, including 7 practical questions has been used. The current International Survey on epistaxis management reported a relevant prevalence (21.7%), mainly during childhood and senescence, an important hospitalization rate (11.8%), the common use of anterior packing and electrocoagulation, and the popular prescription of a vitamin supplement and intranasal creams