Comparing Patient-Reported Outcomes Among Anti-TNF-Experienced Patients with Crohn's Disease Initiating Vedolizumab Versus Ustekinumab.

BACKGROUND: Primary and secondary non-response to anti-tumor necrosis factor (TNF) therapy is common in patients with Crohn's disease (CD), yet limited research has compared the effectiveness of subsequent biological therapy. OBJECTIVE: We sought to compare the effectiveness of vedolizumab and ustekinumab in anti-TNF-experienced patients with CD, focusing on patient-prioritized patient-reported outcomes (PROs). METHODS: We conducted a prospective, internet-based cohort study nested within IBD Partners. We identified anti-TNF-experienced patients initiating with CD vedolizumab or ustekinumab and analyzed PROs reported approximately 6 months later (minimum 4 months, maximum 10 months). Co-primary outcomes were Patient-Reported Outcome Measurement Information System (PROMIS) domains of Fatigue and Pain Interference. Secondary outcomes included patient-reported short Crohn's disease activity index (sCDAI), treatment persistence, and corticosteroid use. Inverse probability of treatment weighting (IPTW) was used to control for a number of potential confounders and incorporated into linear and logistic regression models for continuous and categorical outcomes, respectively. RESULTS: Overall, 141 vedolizumab and 219 ustekinumab initiators were included in our analysis. After adjustment, we found no differences between treatment groups in our primary outcomes of Pain Interference or Fatigue or the secondary outcome of sCDAI. However, vedolizumab was associated with lower treatment persistence (OR 0.4, 95% CI 0.2-0.6) and higher corticosteroid use at follow-up assessment (OR 1.7, 95% CI 1.1-2.6). DISCUSSION: Among anti-TNF experienced patients with CD, Pain Interference or Fatigue was not significantly different 4-10 months after starting ustekinumab or vedolizumab. However, reduced steroid use and increased persistence suggest superiority of ustekinumab for non-PRO outcomes.

Changing hospitalization trends for systemic lupus erythematosus and rheumatoid arthritis in England.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic, multisystemic, immune-mediated disorder associated with a substantial hospitalization risk. As a comparatively rare disease, there is a sparsity of research examining the burden of hospital admission in the contemporary era. We aim to describe national trends in hospitalization rates in England between 1998 and 2015 for SLE, using rheumatoid arthritis (RA) and general population rates as comparison cohorts for benchmarking. METHODS: Hospital admission rates, emergency and day-case admission rates, length of stay and bed days used were calculated using finished consultant episodes from Hospital Episode Statistics data. Cochran-Armitage tests and linear regression quantified the significance and magnitude of change over time. RESULTS: SLE admissions increased from 8.97 to 9.04 per 100,000 (p < 0.001) between 1998 and 2015. By comparison, RA admissions rose from 71.0 to 171.6 per 100,000 (p < 0.001) and all-cause admissions rose from 24,500 to 34,500 per 100,000 (p < 0.001). Emergency admissions decreased both for SLE (2.6 to 1.2 per 100,000) and RA (12.8 to 4.4 per 100,000) despite all-cause emergency admissions increasing from 9400 to 10,300 per 100,000. SLE and RA day cases increased, whilst median length of stay decreased. Despite increasing admissions, total bed days for SLE and RA fell by 60% and 90%, respectively. CONCLUSIONS: Whilst all-cause emergency admissions rose in the general population, those for SLE fell. Length of stay and bed days reduced and day cases increased, probably reflecting changing therapeutic strategies. This potentially large reduction in resource utilization warrants consideration when assessing the impact of new therapies.

A non-randomised single centre cohort study, comparing standard and modified bowel preparations, in adults with cystic fibrosis requiring colonoscopy.

BACKGROUND: Adults with cystic fibrosis (CF) have been reported to be at five to ten-fold risk (25 to 30 fold risk after solid organ transplant) of colorectal cancer (CRC) than the general population. Limited publications to date have reported on practical aspects of achieving adequate colonic cleanse producing good visualisation. In this study, we compared two bowel preparation regimens, standard bowel preparation and a modified CF bowel preparation. METHODS: A non-randomised study of adults with CF attending a single centre, requiring colonoscopy investigation were selected. Between 2001 and 2015, 485 adults with CF attended the clinic; 70 adults with CF had an initial colonoscopy procedure. After five exclusions, standard bowel preparation was prescribed for 27 patients, and modified CF bowel preparation for 38 patients. Demographic and clinical data were collected for all consenting patients. RESULTS: There was a significant difference between modified CF bowel preparation group and standard bowel preparation group in bowel visualisation outcomes, with the modified CF bowel preparation group having a higher proportion of "excellent/good" GI visualisation cleanse (50.0% versus 25.9%) and lower rates of "poor" visualisation cleanse (10.5% versus 44.5%) than standard bowel preparation (p = 0.006). Rates of "fair" GI cleanse visualisation were similar between the two groups (39.4% versus 29.6%) (Additional file 1: Table S1). Detection rates of adenomatous polyps at initial colonoscopy was higher in modified CF bowel preparation cohort than with standard preparation group (50.0% versus 18.5%, p < 0.01). Positive adenomatous polyp detection rate in patient's age > 40 years of age was higher (62.5%) than those < 40 years of age (24.3%) (p = 0.003). Colonic adenocarcinoma diagnosis was similar in both groups. CONCLUSION: This study primarily highlights that standard colonoscopy bowel preparation is often inadequate in patients with CF, and that colonic lavage using modified CF bowel preparation is required to obtain good colonic visualisation. A higher rate of polyps in patients over 40 years of age (versus less than 40 years) was evident. These results support adults with CF considered for colonoscopy screening at 40 years of age, or prior to this if symptomatic; which is earlier than CRC screening in the non-CF Australian population.

Meta-analysis of biomarkers predicting risk of malignant progression in Barrett's oesophagus.

BACKGROUND: Barrett's oesophagus is a precursor to the development of oesophageal adenocarcinoma. This study sought to clarify the role of genetic, chromosomal and proliferation biomarkers that have been the subjects of multiple studies through meta-analysis. METHODS: MEDLINE, Embase, PubMed and the Cochrane Library were searched for clinical studies assessing the value of p53, p16, Ki-67 and DNA content abnormalities in Barrett's oesophagus. The main outcome measure was the risk of development of high-grade dysplasia (HGD) or oesophageal adenocarcinoma. RESULTS: Some 102 studies, with 12 353 samples, were identified. Mutation (diagnostic odds ratio (DOR) 10·91, sensitivity 47 per cent, specificity 92 per cent, positive likelihood ratio (PLR) 4·71, negative likelihood ratio (NLR) 0·65, area under the curve (AUC) 0·792) and loss (DOR 16·16, sensitivity 31 per cent, specificity 98 per cent, PLR 6·66, NLR 0·41, AUC 0·923) of p53 were found to be superior to the other p53 abnormalities (loss of heterozygosity (LOH) and overexpression). Ki-67 had high sensitivity in identifying high-risk patients (DOR 5·54, sensitivity 82 per cent, specificity 48 per cent, PLR 1·59, NLR 0·42, AUC 0·761). Aneuploidy (DOR 12·08, sensitivity 53 per cent, specificity 87 per cent, PLR 4·26, NLR 0·42, AUC 0·846), tetraploidy (DOR 5·87, sensitivity 46 per cent, specificity 85 per cent, PLR 3·47, NLR 0·65, AUC 0·793) and loss of Y chromosome (DOR 9·23, sensitivity 68 per cent, specificity 80 per cent, PLR 2·67, NLR 0·49, AUC 0·807) also predicted malignant development, but p16 aberrations (hypermethylation, LOH, mutation and loss) failed to demonstrate any advantage over the other biomarkers studied. CONCLUSION: Loss and mutation of p53, and raised level of Ki-67 predicted malignant progression in Barrett's oesophagus.

Vitamin D is associated with cardiopulmonary exercise capacity: results of two independent cohorts of healthy adults.

Vitamin D has an important role in calcium homeostasis and is known to have various health-promoting effects. Moreover, potential interactions between vitamin D and physical activity have been suggested. This study aims to investigate the relationship between 25-hydroxyvitamin D (25(OH)D) and exercise capacity quantified by cardiopulmonary exercise testing (CPET). For this, 1377 participants from the Study of Health in Pomerania (SHIP-1) and 750 participants from the independent SHIP-TREND cohort were investigated. Standardised incremental exercise tests on a cycle ergometer were performed to assess exercise capacity by VO2 at anaerobic threshold, peakVO2, O2 pulse and peak power output. Serum 25(OH)D levels were measured by an automated chemiluminescence immunoassay. In SHIP-1, 25(OH)D levels were positively associated with all considered parameters of cardiopulmonary exercise capacity. Subjects with high 25(OH)D levels (4th quartile) showed an up to 25% higher exercise capacity compared with subjects with low 25(OH)D levels (1st quartile). All associations were replicated in the independent SHIP-TREND cohort and were independent of age, sex, season and other interfering factors. In conclusion, significant positive associations between 25(OH)D and parameters of CPET were detected in two large cohorts of healthy adults.

The German Thorotrast Cohort Study: a review and how to get access to the data.

It is well known that exposures like those from (226)Ra, (224)Ra and Thorotrast(®) injections increase the risk of neoplasia in bone marrow and liver. The thorium-based radioactive contrast agent Thorotrast(®) was introduced in 1929 and applied worldwide until the 1950s, especially in angiography and arteriography. Due to the extremely long half-life of several hundred years and the life-long retention of the thorium dioxide particles in the human body, patients suffer lifetime internal exposure. The health effects from the incorporated thorium were investigated in a few cohort studies with a German study being the largest among them. This retrospective cohort study was set up in 1968 with a follow-up until 2004. The study comprises 2326 Thorotrast patients and 1890 patients of a matched control group. For those being alive at the start of the study in 1968 follow-up was done by clinical examinations on a biannual basis. For the others, causes of death were collected in various ways. Additionally, clinical, radiological and biophysical studies of patients were conducted and large efforts were made to best estimate the radiation doses associated with incorporation of the Thorotrast. The aim of this paper is to describe the cohort, important results and some open questions. The data from the German Thorotrast Study are available to other interested researchers. Information can be found at http://storedb.org .

Acute and chronic rejection: compartmentalization and kinetics of counterbalancing signals in cardiac transplants.

Acute and chronic rejection impact distinct compartments of cardiac allografts. Intramyocardial mononuclear cell infiltrates define acute rejection, whereas chronic rejection affects large arteries. Hearts transplanted from male to female C57BL/6 mice undergo acute rejection with interstitial infiltrates at 2 weeks that resolve by 6 weeks when large arteries develop arteriopathy. These processes are dependent on T cells because no infiltrates developed in T cell-deficient mice and transfer of CD4 T cells restored T cell as well as macrophage infiltrates and ultimately neointima formation. Markers of inflammatory macrophages were up-regulated in the interstitium acutely and decreased as markers of wound healing macrophages increased chronically. Programmed cell death protein, a negative costimulator, and its ligand PDL1 were up-regulated in the interstitium during resolution of acute rejection. Blocking PDL1:PD1 interactions in the acute phase increased interstitial T cell infiltrates. Toll-like receptor (TLR) 4 and its endogenous ligand hyaluronan were increased in arteries with neointimal expansion. Injection of hyaluronan fragments increased intragraft production of chemokines. Our data indicate that negative costimulatory pathways are critical for the resolution of acute interstitial infiltrates. In the arterial compartment recognition of endogenous ligands including hyaluronan by the innate TLRs may support the progression of arteriopathy.

Cryptosporidium infection after renal transplantation in an endemic area.

BACKGROUND: Cryptosporidium is one of the common causes of infective diarrhea in post-transplant patients in endemic areas. However, data are limited on Cryptosporidium infection in recipients of solid organ transplantation. The aim of this study was to determine the incidence, disease manifestation, management, and outcome of Cryptosporidium infection in living-donor renal transplant recipients (RTR). METHODS: We performed a detailed retrospective review of the data on all RTR who had diarrheal illness requiring evaluation and hospitalization, and Cryptosporidium infection. RESULTS: During the study period, 119/1235 (8.98%) RTR developed diarrhea, and Cryptosporidium was found in 34/119 (28.5%). Nine of 680 (1.3%) patients were on a cyclosporine (CSA)-based regimen, and 25/643 (3.8%) patients were on a tacrolimus (Tac)-based regimen. The relative risk of developing Cryptosporidium infection was lower on the CSA-based regimen, compared with the Tac-based regimen (odds ratio [OR]: 0.35, 95% confidence interval [CI]: 0.17-0.72, P = 0.003). Twelve of the 34 patients had acute graft dysfunction, mainly caused by combined Tac toxicity and dehydration. Mean serum creatinine and trough Tac level were 2.04 ± 0.65 mg/dL and 8.24 ± 1.19 ng/dL, respectively. Nitazoxanide alone was used in 13 patients, and nitazoxanide in combination with fluoroquinolone in 21 patients, with duration of treatment ranging from 16 to 60 days. Tac was changed to CSA in 8/11 patients. The clearance of cysts and response to nitazoxanide alone were significantly lower, compared with combination therapy (61.53% vs. 95.23%, P = 0.01, 38.46 vs. 85.71%, P = 0.004, respectively). The OR for cyst clearance and response was also significantly lower with nitazoxanide alone, in comparison with combination therapy (OR: 0.65, 95% CI: 0.34-0.92, P = 0.01, OR: 0.45, 95% CI: 0.21-0.81, respectively). Four (16%) of 24 patients with response had relapse. CONCLUSION: Patients with Tac and mycophenolate mofetil combination therapy had a significantly high risk of Cryptosporidium infection. Cryptosporidial infection may require prolonged nitazoxanide therapy, either alone or in combination, with or without reduction in immunosuppression.

Analysis and expansion of the eosinophilic esophagitis transcriptome by RNA sequencing.

Eosinophilic esophagitis (EoE) is an allergic inflammatory disorder of the esophagus that is compounded by genetic predisposition and hypersensitivity to environmental antigens. Using high-density oligonucleotide expression chips, a disease-specific esophageal transcript signature was identified and was shown to be largely reversible with therapy. In an effort to expand the molecular signature of EoE, we performed RNA sequencing on esophageal biopsies from healthy controls and patients with active EoE and identified a total of 1607 significantly dysregulated transcripts (1096 upregulated, 511 downregulated). When clustered by raw expression levels, an abundance of immune cell-specific transcripts are highly induced in EoE but expressed at low (or undetectable) levels in healthy controls. Moreover, 66% of the gene signature identified by RNA sequencing was previously unrecognized in the EoE transcript signature by microarray-based expression profiling and included several long non-coding RNAs (lncRNA), an emerging class of transcriptional regulators. The lncRNA BRAF-activated non-protein coding RNA (BANCR) was upregulated in EoE and induced in interleukin-13 (IL-13)-treated primary esophageal epithelial cells. Repression of BANCR significantly altered the expression of IL-13-induced proinflammatory genes. Together, these data comprise new potential biomarkers of EoE and demonstrate a novel role for lncRNAs in EoE and IL-13-associated responses.

The impact of the association between Val16Ala-SOD2 SNP and SOD2 immunohistochemistry expression in the prognosis of patients with esophageal cancer.

INTRODUCTION: Esophageal cancer is an extensive public health issue worldwide, warranting the search for biomarkers related to its risk and progression. Previous studies have indicated an association between Val16AlaSOD2 single nucleotide polymorphism in the gene encoding the enzyme superoxide dismutase 2 and esophageal cancer. However, further investigations are needed to clarify its role in disease risk and progression. OBJECTIVE: To investigate the role of Val16AlaSOD2-SNP in esophageal cancer progression and in the survival of patients METHODS: Tumor samples were utilized for Val16Ala-SNP genotyping, while SOD2 expression levels in tissue were assessed using immunohistochemistry. A SOD2 Val16Ala-SNP database was used to obtain information on the genotype of healthy individuals. Risk and overall survival analyzes were performed. RESULTS: The Val16Ala SNP was associated with an increased risk of esophageal cancer (RR 2.18, 95%CI 1.23-3.86), regardless of age and gender, but did not have a significant effect on patient survival. In contrast, weak SOD2 expression demonstrated a significantly associated with poor overall survival after treatment, independent of other clinicopathological variables (HR, 0.41; 95% CI, 0.22-0.79 P = 0.007). CONCLUSIONS: Val16Ala SNP was positively associated with esophageal cancer, and the expression of SOD2 was an independent prognostic marker.

Comparative evaluation of bone in mandibular implant retained overdentures using delayed and immediate loading protocol: an in-vivo study.

The aim of the present study was to evaluate the changes in periimplant bone quality, crestal bone level and the implant stability (periotest) for mandibular implant retained overdentures with ball attachments using delayed and immediate loading protocols. Ten completely edentulous patients had two alpha bio dental implants placed in the anterior part of the mandible. The loading protocols for the patients was chosen randomly by drawing lots. Five patients were loaded under immediate loading protocols and other five following delayed. Crestal bone loss and bone quality were assessed around each implant. Periotest values were recorded for each implant at 3, 6 and 12 months after loading. Two implants were lost and were excluded from the study. However mean crestal bone loss around implants was 0.81 mm from the time of prosthetic loading to 12 months after prosthetic loading was seen and no significant result was found between the two groups for the crestal bone loss and the periotest values. Though the periotest value decreased (indicates increased stability) over the time period. The bone density changes were significant for both the groups at coronal level at all time intervals but at middle level significant only after 12 months of prosthetic loading, although individual variation was high. This study concluded that the changes in crestal bone level and periotest values were insignificant for the two groups. But the implant stability increased over the time and the crestal bone loss was evident with decreased rate over the period of time. There was wide individual variation for the bone density changes but overall increase in the density was seen.

Dengue virus infection in renal allograft recipients: a case series during 2010 outbreak.

Dengue virus infection is an emerging global threat caused by Arbovirus, a virus from Flaviridiae family, which is transmitted by mosquitoes, Aedes aegypti and Aedes albopictus. Renal transplant recipients who live in the endemic zones of dengue infection or who travel to an endemic zone could be at risk of this infection. Despite multiple epidemics and a high case fatality rate in the Southeast Asian region, only a few cases of dengue infection in renal transplant recipients have been reported. Here, we report a case series of 8 dengue viral infection in renal transplant recipients. Of the 8 patients, 3 developed dengue hemorrhagic shock syndrome and died.

Cytomegalovirus disease in renal transplant recipients: a single-center experience.

Cytomegalovirus (CMV) is the most common viral infection following kidney transplant, has been recognized as a major factor for graft loss and increased incidence of acute rejection. Different studies have reported a variable incidence of CMV disease with the use of Mycophenolate mofetil (MMF). We retrospectively analyzed our renal transplant recipients to review the results of CMV disease and to compare CMV disease in patient on Azathioprine and MMF for this purpose we retrospectively reviewed 521 live related kidney transplant recipients at our institute. 74 (14.2 %) live related allograft recipients developed CMV disease after a median interval of 7.18 ± 4.35 months from transplantation. The mean age was 36.15 ± 10.7 years. 63 of the patients were male. Malaise, fever and diarrhea were among most common symptoms. 20 (27.02 %) of the 74 recipients developed transaminitis, 13 (17.2 %) developed CMV gastritis, 5 (9.13 %) recipients developed pneumonia, and 3 (4.05 %) patient developed colitis. 59 (80 %) patients had leucopenia and 41 (56.5 %) developed thrombocytopenia. Mean serum creatinine level was 1.5 ± 0.4 (0.9-2.4) mg/dl before the disease, 1.9 ± 0.6 (1.3-3.6) mg/dl at the time of the diagnosis, and 1.7 ± 0.06 (0.8-4.2) mg/dl at the end of the treatment. CMV disease developed in 9 (36 %) of recipients who received basiliximab as induction therapy and 13 (30.24 %) of recipients who received ATG (p > 0.05). The incidence of CMV disease was similar in cyclosporine based regimen (13.2 %) and Tacrolimus based regimen 27 (16.16 %) (p = 0.137) and was also similar in Azathioprine 41 (9.5 %) and MMF group 33 (14.3 %) (p = 0.163). There was no significant difference in severity of CMV disease in both groups, except a higher incidence of leucopenia in Azathioprine group (86 vs. 74 %, p < 0.05) as compared to MMF group. 51 (68.91 %) patient developed graft dysfunction during CMV disease. In conclusion we report a low incidence (14.2 %) and milder form of cytomegalovirus disease at our center. Use of universal cytomegalovirus prophylaxis was associated with a low incidence and milder form of the disease. Incidence of CMV disease was similar between Azathioprine and MMF groups.

Outcome of mild SARS-CoV-2-infected renal transplant recipients managed by supervised home-based self-monitoring.

OBJECTIVES: We aimed to compare the outcomes of COVID-19 Renal Transplant Recipients (RTRs) managed on an ambulatory basis to that of inpatient management. DESIGN, SETTING, MATERIALS, AND METHODS: We performed a retrospective study in Lucknow, India, comparing the ambulatory management with the historical cohort managed in the hospital.R RTRs with mild COVID-19 were managed by supervised home-based self-monitoring (HBSM), a strategy to manage this high-risk group on an outpatient basis during the second wave of the pandemic. The primary outcome was the clinical deterioration to a higher severity category among RTRs with mild COVID-19 managed by HBSM compared to hospitalized patients within two weeks of disease onset. RESULTS: Of the 149 RTRs with mild COVID-19, 94 (63%) and 55 (37%) were managed by HBSM and in the hospital, respectively. The proportion of RTRs who clinically deteriorated to a higher severity category (moderate or severe category) was similar among both groups (28.7% versus 27.2%, P=0.849). Among RTRs with clinical deterioration, COVID-19-related death was reported in two patients of the HBSM group and in none of the patients of the hospitalized group. Graft dysfunction was higher in the hospitalized group (7.4% versus 27.2%, P=0.002). Median time to complete clinical recovery (7 days in both groups), secondary bacterial infections (25% versus 33.3%, P=0.41), and the mean decline in EQ-5D score from baseline at six weeks (-6.6 versus-4.3, P=0.105) were found to be similar in both groups.

Early versus Late acute graft pyelonephritis: A retrospective analysis of graft and patient outcomes.

BACKGROUND: Acute graft pyelonephritis (AGPN) is thought to affect graft and patient survival among renal transplant recipients. The objective was to compare outcomes among early AGPN (< 6 months from transplant) versus late AGPN (> 6 months from transplant). METHODS: This retrospective study analyzed 150 patients with AGPN dividing them into early and late AGPN from 2008 to 2016. Predictors of graft loss and mortality were compared using logistic regression analysis. Graft survival and patient survival were analyzed using Kaplan-Meyer survival plots. RESULTS: 55.3% (n = 83) had early AGPN and 44.7% (n = 67) had late AGPN. In early AGPN group, 13.3% had CMV disease on follow up compared to 3% in late AGPN group (p < 0.05). 26.5% had history of prolonged Foley's catheterization (> 5 days), 38.6% had prolonged DJ stent in-situ (> 2 weeks) following transplant surgery in the early AGPN compared to 7.5% and 19.4% respectively in the late AGPN group (p < 0.05). Recurrent GPN was more common in the late AGPN group - (35.8% versus 18.1%). Presence of renal abscess was predictive of graft loss in Univariate analysis (HR-6.12, p < 0.004). There was decreased death censored graft survival in the early AGPN group (p-0.035) with no significant difference in patient survival among the two groups. CONCLUSION: Occurrence of early AGPN had a significant impact on long term graft survival in renal transplant recipients with no significant effect on patient survival. This study underlines the paramount importance of the prevention of UTIs in renal transplant recipients.

Psycho-social health and quality of life among kidney donors following transplantation.

INTRODUCTION: Living kidney donation is a complex psychological experience for donors. The present study examined the psychosocial impact of kidney donation on donors. METHODS: The retrospective study included 506 donors who donated a kidney between 2010 and 2018 at a transplant centre in India. These donors responded via a donor insight questionnaire about their hospital anxiety, and their possible level of depression. The information included socio-demographic form with multiple information. The health survey was used periodically evaluate the psychosocial impact among donors following donation, including the transplant outcomes. RESULTS: The majority of donors were females (79.4%). There was a significant improvement in the quality of life among donors (SF-36) following the donation of a kidney, especially among those donors who maintained good graft functions themselves as well as those who were informed about good kidney function in transplanted recipients. These donors showed a lesser degree of depressive and anxiety scores (HAD score 3.5 and BDI II 4.8) than donors who had problems themselves and/or whose donated kidneys did not function well. Most living donors (89.1%) felt that the act of donation had a positive impact on their lives and those donors would encourage others to donate a kidney. Overall, the graft outcomes impacted the donor's state of mind. CONCLUSION: The study showed a very positive impact of the acknowledgment of the donor by the recipient, especially those donors whose kidney transplants were well functioning. The state of depression, anxiety, and psycho-social outcomes correlated with the graft outcomes. Donors showed positive insight towards donation, with inner conscience still conclusively willing to donate and encourage others.

Cardiovascular disease in live related renal transplantation.

Cardiovascular disease has become the leading cause of morbidity and mortality in renal transplant recipients, although its pathogenesis and treatment are poorly understood. Modifiable cardiovascular risk factors and graft dysfunction both play an important role in development of post transplant cardiovascular events. Prevalence of cardiovascular disease was studied in stable kidney transplant patients on cyclosporine based triple immunosuppression in relation to the various risk factors and post transplant cardiovascular events. Analysis of 562 post transplant patients with stable graft function for 6 months, the patients were evaluated for cardiovascular events in post transplant period. Pre and post transplant risk factors were analyzed using the COX proportional hazard model. 174 patients had undergone pre transplant coronary angiography, 15 of these patients underwent coronary revascularization (angioplasty in 12, CABG in 3). The prevalence of CAD was 7.2% in transplant recipients. Of 42 patients with CAD 31 (73.8%) had cardiovascular event in post transplant period. Age > or = 40 yrs, male sex, graft dysfunction, diabetes as primary renal disease, pre transplant cardiovascular event, chronic rejection showed significant correlation in univariate analysis and there was significant between age > or = 40 years (OR = 2.16 with 95% CI, 0.977-4.78) S creatinine > or = 1.4 mg % (OR = 2.40 with 95% CI, 1.20 - 4.82), diabetes as primary disease (OR with 95% CI 3.67, 3.2-14.82), PTDM (OR 3.67, 95% CI 1.45-9.40), pre-transplant cardiovascular disease (OR 4.14, 95% CI .38-13.15) with post transplant cardiovascular event on multivariate analysis. There was poor patient and graft survival among those who suffered post transplant cardiovascular event. The incidence of cardiovascular disease continues to be high after renal transplantation and modifiable risk factors should be identified to prevent occurrence of events in post transplant period.

Spectrum of hypertension in post transplant.

AIM: Elucidate the incidence and causes of post transplant hypertension in our transplant population. METHODS: All patients transplanted between June 1989 Dec 2002 who had a functioning graft of 6 months post transplant were studied. Hypertension was defined as Systolic BP > or = 140 mmHg/Diastolic BP > or = 90 mmHg/usage of antihypertensive medication. Donor and recepient characteristics were recorded and compared. 86.2% (485) were hypertensive in post renal transplant period. RESULTS: Age > or = 40 years, male sex, graft dysfunction, use of calcineurin inhibitors, high doses of steroids, chronic rejection were statistically significant correlate of post RTHT in univariate analysis. On multivariate analysis, age > or = 40 yrs (RR 2.06, 95% CI, 1.20-3.54), use of cyclosporine (RR 2.70, 95% CI, 1.54-4.75), usage of high doses of steroids (RR 2.56, 95% CI, 1.31-4.98) only were associated with post transplant hypertension. The patient and graft survival was inferior in patients with post transplant hypertension. The systolic BP at 12 months, diastolic BP at 6 months and 12 months post transplant, had significant detrimental effect on renal allografts survival. CONCLUSION: Diagnosis, identification of risk factors and aggressive treatment of post transplant HT and of the various modifiable risk factors is important for improving renal allograft and patient survival.

X chromosome aneuploidy and micronuclei in fertile mares.

Abnormalities of chromosomes are an important and well documented cause of disorders of sexual development, fertility problems and congenital anomalies in mammals. Detection of low-level 63,X/64,XX mosaicism during routine cytogenetic evaluation is a challenge because its clinical significance is not yet fully clear. This study describes the prevalence and levels of 63,X mosaicism for a cohort of fertile mares and compares the results with eight problem mares for which no clinical cause of sub-fertility was found. The study design allowed for the analysis of micronuclei which are biomarkers of genomic instability and can disturb cell divisions, drive cancer development or cause congenital diseases. Although 27% of the fertile mares were identified to be 63,X mosaics, the results showed that the rates of abnormal cells were very low (1-3%). Levels of abnormal cells in problem mares with 63,X mosaicism were similar or higher. The average rate of micronuclei in the blood of the fertile mares was ∼1%, well below the baseline (5%) which was proposed for peripheral blood of normal healthy humans. We found weak to modest, but not significant, correlations between the age of fertile mares and 63,X cells (Kendall's tau b = 0.2905; p > 0.05) as well as the rate of micronuclei (Kendall's tau b = 0.1896; p > 0.05). Likewise, the correlation between presence of a 63,X cell line and micronuclei rate was not significant (Kendall's tau b = 0.3201; p > 0.05). The presence of 63,X cells in rates greater than 3% may indeed indicate a higher risk for sub-fertility and eventually for associated health problems in such mares. Detection and elimination of mares with high level of X aneuploidies from breeding may have a positive effect on the fertility within the general horse population. This data may support the evaluation of problem mares with mosaic karyotypes involving the X chromosome.