Independent risk factors for renal damage in a series of primary vesicoureteral reflux: A multivariate analysis

Aim:   The aim of this study was to investigate risk factors associated with different extents of renal parenchyma involvement in a paediatric series of primary vesicoureteral reflux (VUR).
Methods:   A total of 549 patients with VUR were analyzed. The variable of interest was renal scar, assessed by technetium-99m dimercaptosuccinic acid scan, and classified into three subtypes: focal scar, multiple cortical scarring and diffuse scars with a contracted renal unit. The multinomial regression model was applied to identify independent variables associated with each subtype of renal damage.
Results:   After adjustment, four variables remained independently associated with a contracted renal unit: reflux grades III–V (odds ratio (OR) = 9.7; 95% confidence interval (CI) = 4.1–21.0), age at diagnosis (OR = 3; 95% CI = 1.6–5.1), unilateral reflux (OR = 2.1; 95% CI = 1.2–3.8), and male sex (OR = 2; 95% CI = 1.1–3.8). Two variables were associated with multiple scars: reflux grades III–V (OR = 13.8; 95% CI = 7.4–26.0) and age at diagnosis (OR = 1.9; 95% CI = 1.2–3.0). Two variables were associated with a focal scar: reflux grades III–V (OR = 7.9, 95% CI CI = 3.8–16.4) and male sex as a protective factor (OR = 0.5; 95% CI = 0.25–1.0).
Conclusion:   Our findings suggest that the development of a contracted renal unit is probably due to congenital malformation, more commonly observed in male infants with high-grade reflux.     

Prognosis of acute kidney injury requiring renal replacement therapy in solid organ transplanted patients

Solid organ transplanted patients represent a complex and multi-morbid population with potential acute illness. They are at high risk not only for chronic renal failure (CRF), but also for acute kidney injury (AKI) and little is known about the overall epidemiology or prognosis. We conducted a retrospective review of all solid organ transplant patients who required emergency renal replacement therapy (RRT) for AKI during a period of 7.5 years. We identified 53 episodes of AKI requiring RRT occurring in 51 transplanted patients, and 58.5% of them were freshly (<48 h) transplanted when admitted in ICU. The majority of episodes were a result of cardio-circulatory or septic events (84%), and a large proportion of the AKI episodes were a result of multifactorial causes (27%). Overall 90 days mortality was 49%, and no difference was detected between kidney and nonkidney transplants. On univariate analysis, the risk factors for death were smoking status [OR = 4.09 (CI 95%: 1.16–14.43); P  =   0.028] and sepsis [OR = 4.90 (CI95%: 1.39–17.31); P  =   0.014]. Transplanted patients with AKI are younger, more prone to be diabetic and to have previous chronic renal failure compared with the general ICU population, possibly in part because of their immunosuppressive therapy. Nevertheless, they have the same prognosis.     

Antithymocyte globulin use for treatment of biopsy confirmed acute rejection is associated with prolonged renal allograft survival

Antithymocyte globuline (ATG) and OKT3 have been used for treatment of severe biopsy confirmed acute renal allograft rejection (BCAR). We report results on graft and patient survival including 399 subjects diagnosed with BCAR treated with either ATG or OKT3. Multivariable analyses including Banff scores were performed following three different strategies to account for confounding variables. Fifty per cent of subjects in the OKT3 group had a functioning graft 6.3 years after diagnosis of BCAR, but 74% of ATG patients' grafts were still functioning at that time point (log rank P  = 0.006). Median actual graft survival was only 4.6 years in the OKT3 subjects, but 9.5 years for ATG-treated patients (log rank P  = 0.004). Multivariable analysis revealed that the risk for functional graft loss was significantly elevated in the OKT3 compared to ATG patients (HR = 1.79, 95% CI 1.06–3.02, P  = 0.029). The risk for actual graft loss, counting death as event, was also significantly elevated in the OKT3 patients (HR = 1.73, 95% CI 1.09–2.74, P  = 0.019). The hazard of death was not different between the groups (HR = 1.55, 95% CI 0.87–2.77, P  = 0.137). These data suggest that rejecting renal allografts treated with ATG exhibit longer graft survival than OKT3 treated transplant kidneys. Causal inference, however, cannot be drawn from this associational study.     

Genetic variants of the cytochrome P450 and glutathione S-transferase associated with risk of bladder cancer in a south-eastern Chinese population

Objective:   To evaluate the association between genetic polymorphisms of CYP2E1 RsaI and GSTM1 and development of bladder cancer in a south-eastern Han Chinese population.
Methods:   We hypothesized that the CYP2E1 -1019T>A and GSTM1 polymorphisms were associated with risk of bladder cancer. In a hospital-based case-control study of 202 case patients with newly diagnosed bladder transitional cell carcinoma and 272 cancer-free controls frequency-matched by the age and sex, we genotyped these two polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism method.
Results:   We found that the GSTM1 null genotype was associated with an increased risk of bladder cancer (adjusted odds ratio [OR] = 1.73, 95% confidence interval [CI] = 1.17–2.56) compared with those with the non-null genotype, but the CYP2E1 -1019T>A polymorphisms did not show any association. In the stratification analysis of the GSTM1 polymorphism, we found that the increased risk was more pronounced among subgroups aged ≤60 years (OR = 2.02, 95% CI = 1.08–3.77), smokers (OR = 1.94, 95% CI = 1.11–3.38) and non-drinkers (OR = 3.86, 95% CI = 1.28–11.60).
Conclusion:   GSTM1 polymorphism (but not CYP2E1 RsaI polymorphism) appears to contribute to the etiology of bladder cancer in a south-eastern Chinese population.     

Genetic variants of the XRCC7 gene involved in DNA repair and risk of human bladder cancer

Objective:   To investigate the association between the polymorphisms of the KU70 and X-ray repair cross complementing group 7 ( XRCC7 ) genes and the risk of bladder cancer.
Methods:   This hospital-based case-control study included 213 patients with newly diagnosed bladder transitional cell carcinoma and 235 cancer-free controls frequency-matched by age and sex. Two polymorphisms, KU70 and XRCC7, using a method involving polymerase chain reaction-restriction fragment length polymorphism were genotyped.
Results:   The risk of bladder cancer decreased in a dose–response manner as the number of XRCC7 6721G alleles increased (adjusted odds ratio [OR] = 0.70, 95% confident interval [CI] = 0.47–1.03 for 6721GT and OR = 0.31, 95% CI = 0.10–0.99 for 6721GG; P _trend = 0.013). However, when we used 6721 (GT + GG) as the reference, we found a statistically significant increased risk of bladder cancer associated with the 6721TT genotype (OR = 1.53, 95% CI = 1.04–2.25). In the stratification analysis, this increased risk was more pronounced among subgroups of patients aged >65 years (OR = 2.27; 95% CI = 1.25–4.10) and ever smokers (OR = 2.06, 95% CI = 1.15–3.68). Furthermore, we observed a 3.24-fold increased risk (95% CI = 1.35–7.78) for smokers aged >65 years carrying 6721TT genotype compared with those carrying the 6721 (GG + GT) genotype. However, the KU70 −61C > G polymorphism was not associated with a significantly increased risk of bladder cancer.
Conclusions:   The XRCC7 but not the KU70 polymorphism appears to be involved in the etiology of human bladder cancer. Larger studies with more detailed data on environmental exposure are needed to verify these initial findings.     

Serum globulin levels in predicting the extent of hepatic fibrosis in patients with recurrent post-transplant hepatitis C infection

Abstract:  The progression of HCV-related disease is particularly aggressive in the post-transplantation setting. Recipients with recurrent HCV infection undergo repeated liver biopsies in order to estimate disease progression. A strong association was found between serum immunoglobulins levels and hepatic fibrosis in non-transplanted patients with chronic HCV infection. The aim of this study was to determine if serum globulin and immunoglobulins levels can predict the extent of fibrosis in patients with recurrent HCV infection. The records of 45 patients (mean age 51.6 ± 10.5 yr; 53.3% men) with biochemical, serologic, virologic, and histological evidence of recurrent HCV infection were reviewed. Recurrence developed after a median interval of 11.7 months (range: 3–106); in 14 patients (31.1%), the recurrent infection was severe. The mean duration of follow-up was 51.4 ± 35.4 months. A total of 96 liver biopsies were performed. The mean fibrosis score increased significantly with an increase in the number of biopsies (p < 0.0001, r = 0.44). On multivariate analysis, the only predictors of severe fibrosis were serum levels of globulin (OR: 5.97, 95% CI: 1.82–19.53; p = 0.0004) and IgG (OR: 1.003, 95% CI: 1.001–1.006; p = 0.018). On linear regression analysis, for each 0.5-g/dL increase in serum globulin level, there was a 0.22-point increase in fibrosis stage. In conclusion, serum levels of globulin and IgG can serve as a noninvasive marker of the extent of hepatic fibrosis in patients with post-transplant recurrent HCV infection, thus avoiding the need for repeated liver biopsies. These findings, if confirmed, have important implications for the prevention and treatment of fibrosis in this patient group.     

Factors influencing lymph node retrieval in colorectal cancer and its effect on survival

Introduction:  NICE has set standards for lymph node (LN) harvest in surgery for colorectal cancer (CRC). We report the effect of the operating surgeon and reporting pathologist on lymph node yield and the role of LN yield on survival.
Method:  Data on all patients with CRC treated in a single unit between 1999 and 2004 were collected in the ACPGBI database. Lymph node harvest was identified for each of three surgeons and three pathologists. Actuarial survival of all patients with Dukes' stage B with greater than or less than 8 reported LNs and Dukes' stage C were compared using log-rank test (Kaplan–Meier method).
Results:  A total of 380 cases had a curative resection with a unit median LN retrieval of 13.
There was no difference in survival between Dukes' stage B <8 LN (mean 42 months, 95% CI 29–55) and Dukes stage C (mean 45 months, 95% CI 29–51), log-rank P =  0.7618. Survival between Dukes stage B (8 LN and Dukes C was significantly different (mean 58 months, 95% CI 53–64 vs 45 months, 95% CI 29–51), log-rank P =  0.006.
 

     

Association of four DNA polymorphisms with acute rejection after kidney transplantation

Renal transplant outcomes exhibit large inter-individual variability, possibly on account of genetic variation in immune-response mediators and genes influencing the pharmacodynamics/pharmacokinetics of immunosuppressants. We examined 21 polymorphisms from 10 genes in 237 de novo renal transplant recipients participating in an open-label, multicenter study [Cyclosporine Avoidance Eliminates Serious Adverse Renal-toxicity (CAESAR)] investigating renal function and biopsy-proven acute rejection (BPAR) with different cyclosporine A regimens and mycophenolate mofetil. Genes were selected for their immune response and pharmacodynamic/pharmacokinetic relevance and were tested for association with BPAR. Four polymorphisms were significantly associated with BPAR. The ABCB1 2677T allele tripled the odds of developing BPAR (OR: 3.16, 95% CI [1.50–6.67]; P  =   0.003), as did the presence of at least one IMPDH2 3757C allele (OR: 3.39, 95% CI [1.42–8.09]; P  =   0.006). BPAR was almost fivefold more likely in patients homozygous for IL-10 -592A (OR: 4.71, 95% CI [1.52–14.55]; P  =   0.007) and twice as likely in patients with at least one A allele of TNF-α G-308A (OR: 2.18, 95% CI [1.08–4.41]; P  =   0.029). There were no statistically significant interactions between polymorphisms, or the different treatment regimens. Variation in genes of immune response and pharmacodynamic/pharmacokinetic relevance may be important in understanding acute rejection after renal transplant.     

A comparison of segmental vs subtotal/total colectomy for colonic Crohn's disease: a meta-analysis

Purpose:  To evaluate differences in short- and long-term outcomes of patients with colonic Crohn's disease (CD) undergoing either subtotal/total colectomy with ileorectal anastomosis (IRA) or segmental colectomy(SC).
Method:  Comparative studies from 1988 to 2002, of subtotal/total colectomy and IRA vs SC, were used. The study end points included surgical and overall recurrence, time to recurrence, postoperative morbidity and incidence of permanent stoma. Meta-analytical tools were used to evaluate the study outcomes.
Results:  Six studies, consisting of a total of 488 patients (223-IRA and 265-SC) were included. Meta-analysis suggested no significant difference between IRA and SC in recurrence of CD. Time to recurrence was longer in the IRA group by 4.4 years (95%CI, 3.1–5.8), P  < 0.001. There was no difference in postoperative complications (OR = 1.4, 95%CI, 0.16–12.74) or the need for a permanent stoma between the two groups (OR = 2.75, 95%CI, 0.78–9.71). Patients with two or more colonic segments involved were associated with lower re-operation rate in the IRA group, a difference which did not reach statistical significance ( P =  0.177).
Conclusions:  Both procedures were equally effective as treatment options for colonic CD, however, patients in the SC group exhibited recurrence earlier than those in the IRA group. The choice of operation is dependent on the extent of colonic disease, with a trend towards better outcomes with IRA for two or more colonic segments involved.     

XPC gene polymorphisms and risk of idiopathic azoospermia or oligozoospermia in a Chinese population

A retrospective case–control study was carried out in the Han-Chinese population to determine the polymorphisms of xeroderma pigmentosum complementation group C ( XPC ) gene on the risk of idiopathic azoospermia or oligozoospermia. The Ala499Val (C>T) and Lys939Gln (A>C) polymorphism of XPC gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism in three groups of infertile men (172 patients of azoospermia, 25 patients of severe oligozoospermia, 55 patients of oligozoospermia) and 228 fertile men. Increased risk of idiopathic azoospermia, but not oligozoospermia was associated with the XPC variant genotypes of Ala499Val (C>T) [adjusted odds ratio (OR) = 1.67, 95% confidence interval (CI) = 1.04–2.68 for CT heterozygote and adjusted OR = 2.03, 95% CI = 1.10–3.75 for TT homozygote] compared with CC homozygous wide-type. The Lys939Gln (A>C) polymorphism was not related to spermatogenic failure. The combined risk alleles analysis and haplotype analysis showed that ORs increased as the number of the risk alleles increased and the 499T-939C haplotype had a significantly increased risk of idiopathic azoospermia (OR = 7.97; 95% CI = 3.51–18.07) compared with other haplotypes. The results suggest that XPC Ala499Val (C>T) polymorphism is correlated with high risk of idiopathic azoospermia in the Han-Chinese population.     

Ovarian metastases from colorectal cancer: a clinicopathological analysis of 103 patients

Objective  To improve management of ovarian metastasis through assessment of clinicopathological features and treatment outcomes associated with ovarian metastasis from colorectal cancer.
Method  We recruited 103 subjects who were diagnosed with ovarian metastasis and subjected to surgery between June 1989 and December 2005. Clinical and pathological variables were evaluated. Survival and its associated factors were analysed with a median follow-up of 31 months after ovarian surgery (range 1–129 months).
Results  The mean age at diagnosis was 46 years (range 14–72 years), synchronous ovarian metastasis occurred in 74 patients and metachronous in 29 patients. The primary tumour was more commonly associated with the colon rather than the rectum (84/1608, 5.2% vs 19/1534, 1.2%, P  <   0.001). Combined metastases occurred in 69 patients (67%). Complete resection was achieved in 34 (33%) patients without other metastases. The estimated 5-year disease free survival and overall survival rate were 40.1% and 26.6%, respectively. From univariate analysis, lymphovascular invasion (35.6% vs 12.8%, P  =   0.034), combined metastasis (50.9% vs 15.6%, P  =   0.0035) and bilaterale ovarian metastasis (36.4% vs 10.6%, P  =   0.015) were identified as significant poor prognosis factors, and from multivariate analysis combined metastasis and bilaterale ovarian metastasis were significant ( P  =   0.034 and P  =   0.015, respectively).
Conclusion  This study suggests a role for regular follow-up computed tomography scans within 6 months postoperatively and tumour marker assays for the early detection of ovarian metastasis in premenopausal women after primary surgery, especially in colonic patients with poor prognostic factors.     

A Prospective Longitudinal Study Evaluating the Usefulness of a T‐Cell‐Based Assay for Latent Tuberculosis Infection in Kidney Transplant Recipients

We evaluated whether ELISPOT assay can predict tuberculosis (TB) development in kidney‐transplantation (KT) recipients with a negative tuberculin skin test (TST). All adult patients admitted to a KT institute between June 2008 and December 2009 were enrolled; TB development after KT was observed between June 2008 and December 2010. Isoniazid (INH) was given to those patients with positive TST or clinical risk factors for latent TB infection (LTBI). ELISPOT assay was performed on all patients, and TB development after KT was observed by a researcher blinded to the results of ELISPOT. A total of 312 KT recipients including 242 (78%) living‐donor KT were enrolled. Of the 312 patients, 40 (13%) had positive TST or clinical risk factors for LTBI and received INH; none developed TB after KT. Of the remaining 272 patients, 4 (6%) of 71 with positive ELISPOT assay developed TB after KT, whereas none of the 201 patients with negative (n = 171) or indeterminate ELISPOTs (n = 30) developed TB after KT (rate difference between positive and negative/indeterminate ELISPOT, 3.3 per 100 person‐years [95% CI 1.4–5.1, p<0.001]). Positive ELISPOT results predict subsequent development of TB in KT recipients in whom LTBI cannot be detected by TST or who lack clinical risk factors for LTBI.     

What are the Risk Factors for Renal Failure following Open Elective Abdominal Aortic Aneurysm Repair?

ObjectivesRenal failure following abdominal aortic aneurysm (AAA) repair is a common and significant complication. The objective of this study was to identify risk factors for renal failure following open elective AAA repair.DesignA retrospective analysis of prospectively collected multi-centre data.MaterialsConsecutive data on patients undergoing open elective AAA repair were collected between January 2000 and December 2010. Patients with pre-operative serum creatinine >200 μmol/L were excluded.MethodsRenal failure was reported by clinicians and included all patients requiring post-operative renal-replacement therapy. Univariate and multivariate analyses were used to identify renal failure risk factors. A simplified clinical risk score was developed.ResultsPost-operative renal failure occurred in 140 (6.0%) of 2347 patients and was associated with age >75 (OR = 1.58, 95%CI 1.11–2.26), symptomatic AAA (OR = 1.77, 95%CI 1.24–2.52), supra/juxta renal AAA (OR = 2.17, 95%CI 1.32–3.57) pre-operative serum creatinine >150 (OR = 2.75, 95%CI 1.69–4.50), treated hypertension (OR = 1.87, 95%CI 1.28–2.74), and respiratory disease (OR = 2.08, 95%CI 1.45–2.97). Patients with post-operative renal failure had significantly higher 30-day mortality (35.0% vs. 4.3%, p < 0.001).ConclusionsRenal failure following open elective AAA repair was associated with an increased risk of mortality. Risk factors for post-operative renal failure were identified and a simple clinical risk score developed to facilitate focussed care strategies for high-risk patients.     

Dexmedetomidine and cardiac protection for non-cardiac surgery: a meta-analysis of randomised controlled trials

We conducted a systematic review of the effects of dexmedetomidine on cardiac outcomes following non-cardiac surgery. We included prospective, randomised peri-operative studies of dexmedetomidine that reported mortality, cardiac morbidity or adverse drug events. A PubMed Central and EMBASE search was conducted up to July 2007. The reference lists of identified papers were examined for further trials. Of 425 studies identified, 20 were included in the meta-analysis (840 patients). Dexmedetomidine was associated with a trend towards improved cardiac outcomes; all-cause mortality (OR 0.27, 95% CI 0.01–7.13, p = 0.44), non-fatal myocardial infarction (OR 0.26, 95% CI 0.04–1.60, p = 0.14), and myocardial ischaemia (OR 0.65, 95% CI 0.26–1.63, p = 0.36). Peri-operative hypotension (26%, OR 3.80, 95% CI 1.91–7.54, p = 0.0001) and bradycardia (17%, OR 5.45, 95% CI 2.98–9.95, p < 0.00001) were significantly increased. An anticholinergic did not reduce the incidence of bradycardia (p  =  0.43). A randomised placebo-controlled trial of dexmedetomidine is warranted.     

Predictors of surgical site infection in dirty urological surgery

Objectives:   Risk factors for surgical site infection (SSI) following urologic dirty operations have not been clearly identified. This study was conducted to describe incidence, potential risk factors and common causative pathogens of the SSI in such operations.
Methods:   Medical records of patients who had undergone simple nephrectomy or lumbotomy for suppurative renal infection at our institutions from 1999 to 2006 were retrospectively evaluated. The following data were retrieved: presence of SSI, demographic data, laboratory findings, comorbidities, microbiological data, type of renal suppuration, type of urological surgery and antibiotic regimen. Risk factors for SSI were evaluated using the multiple logistic regression model.
Results:   Sixty-five patients (mean age 55.6 ± 13.1 years) were eligible for data analysis. In 20 of them (30.8%) a SSI was identified. The most common isolated pathogens were gram-negative bacteria. At univariate logistic regression analysis risk factors significantly associated with SSI included: presence of emphysematous infection, hypoalbuminemia, number of predisposing conditions, emergency operations, isolation of Enterobacteriaceae, positive pus culture. The use of trimethoprim/sulfamethoxazole was associated with a decreased risk for SSI. Multiple logistic model identified only the emergency operations and isolated Enterobacteriaceae as independent predictors of SSI (odds ratio [OR] = 11.1) (95% confidence interval [CI] = 3.0–40.8) and OR = 3.9 (1.0–14.8), respectively.
Conclusions:   Patients with suppurative renal infections are submitted to life-saving emergency surgery. Urological surgeons should keep in mind that this carries a high risk for subsequent SSI. Effective preventive measures in these circumstance cannot be identified. Further research in this area is necessary to clarify this issue.     

A meta-analysis of the utility of C-reactive protein in predicting early, intermediate-term and long term mortality and major adverse cardiac events in vascular surgical patients

We conducted a meta-analysis of the utility of pre-operative C reactive protein (CRP) in predicting early (< 30 days), intermediate (30–180 days) and long term (> 180 days) mortality and major adverse cardiac events (MACE; cardiac mortality and nonfatal myocardial infarction (MI) combined) following vascular surgery. Of 291 studies identified, ten prospective patient cohorts were identified. A pre-operative CRP > 3 mg.l⁻¹ was not associated with 30-day all-cause mortality, cardiac mortality, nonfatal myocardial infarction or MACE. Intermediate-term all-cause mortality, cardiac death and MACE showed a trend to a worse outcome (odds ratio (OR) 9.07, 95% confidence interval (CI) 0.86–96.28, p = 0.07; OR 8.71, 95% CI 0.5–153.1, p = 0.14 and OR 2.81, 95% CI 0.78–5.18, p = 0.15 respectively). Long term all cause mortality (OR 2.40, 95% CI 1.15–5.02, p = 0.02), cardiac death (OR 5.66, 95% CI 1.71–18.73, p = 0.005) and MACE (OR 2.76, 95% CI 1.38–5.55, p = 0.004) were significantly increased.     

Long‐term outcomes and transmission rates in hepatitis C virus‐positive donor to hepatitis C virus‐negative kidney transplant recipients: Analysis of United States national data

The use of kidneys from hepatitis C virus (HCV)‐positive (D+) deceased donors for HCV‐negative recipients (R?) might increase the donor pool. We analyzed the national Organ Procurement and Transplant Network (OPTN) registry from 1994 to 2014 to compare the outcomes of HCV D+/R? (n = 421) to propensity‐matched HCV‐negative donor (D?)/R? kidney transplants, as well as with waitlisted patients who never received a transplant, in a 1:5 ratio (n = 2105, per matched group). Both 5‐year graft survival (44% vs 66%; P < .001) and patient survival (57% vs 79%; P < .001) were inferior for D+/R? group compared to D?/R?. Nevertheless, 5‐year patient survival from the time of wait listing was superior for D+/R? when compared to waitlisted controls (68% vs 43%; P < .001). Of the 126 D+/R? with available post‐transplant HCV testing, HCV seroconversion was confirmed in 62 (49%), likely donor‐derived. Five‐year outcomes were similar between D+/R? that seroconverted vs D+/R? that did not (n = 64). Our analysis shows inferior outcomes for D+/R? patients although detailed data on pretransplant risk factors was not available. Limited data suggest that HCV transmission occurred in half of HCV D+/R? patients, although this might not have been the primary factor contributing to the poor observed outcomes.     

Higher tacrolimus trough levels on days 2–5 post-renal transplant are associated with reduced rates of acute rejection

Abstract:  We analyzed the association between whole-blood trough tacrolimus (TAC) levels in the first days post-kidney transplant and acute cellular rejection (ACR) rates. Four hundred and sixty-four consecutive, deceased-donor kidney transplant recipients were included. All were treated with a combination of TAC, mycophenolate mofetil and prednisolone. Patients were analyzed in four groups based on quartiles of the mean TAC on days 2 and 5 post-transplant: Group 1: median TAC 11 ng/mL (n = 122, range 2–13.5 ng/mL), Group 2: median 17 ng/mL (n = 123, range 14–20 ng/mL), Group 3: median 24 ng/mL (n = 108, range 20.5–27 ng/mL) and Group 4: median 33.5 ng/mL (n = 116, range 27.5–77.5 ng/mL). A graded reduction in the rates of ACR was observed for each incremental days 2–5 TAC. The one-yr ACR rate was 24.03% (95% CI 17.26–32.88), 22.20% (95% CI 15.78–30.70), 13.41% (95% CI 8.15–21.63) and 8.69% (95% CI 4.77–15.55) for Groups 1–4, respectively (p = 0.003). This study suggests that higher early TACs are associated with reduced rates of ACR at one yr.     

Risk factors for multidrug‐resistant tuberculosis in northwest Ethiopia: A case–control study

Ethiopia is one of 30‐high burden multidrug‐resistant tuberculosis (MDR‐TB) countries globally. The aim of this study was to describe the characteristics of patients with MDR‐TB and to investigate risk factors for MDR‐TB relative to having drug‐susceptible tuberculosis (TB), in northwest Ethiopia. A hospital‐based, unmatched case–control study was conducted. Cases were all MDR‐TB patients (i.e., resistant to at least rifampicin and isoniazid) who were confirmed by culture and drug‐susceptibility testing whilst enrolled on treatment at Gondar University Hospital. Controls were all drug‐susceptible tuberculosis (DS‐TB) patients who were confirmed by Gene Xpert MTB/RIF at Gondar University Hospital. Univariable and multivariable logistic regression models were used for comparisons, and odds ratios with 95% confidence intervals (CI) were computed to measure the strength of association between the dependent and independent variables. A total of 452 patients (242 MDR‐TB and 210 DS‐TB) were included in this study. The mean age of the study participants was 33 years (SD ± 14 years). Approximately one‐fifth (78, 17%) of all study participants were human immunodeficiency virus (HIV) positive; 21% (51) of cases and 13% (27) of controls. Risk factors associated with MDR‐TB were a history of previous TB treatment (Adjusted Odds Ratio (AOR): 83.8; 95% CI: 40.7, 172.5), low educational status (AOR: 5.32; 95% CI: 1.43, 19.81); and ages less than 20 years (AOR: 9.01; 95% CI: 2.30, 35.25) and 21–30 years (AOR: 2.61; 95% CI: 1.02, 6.64). HIV infection was also significantly associated with MDR‐TB among new TB patients (AOR: 5.55; 95% CI: 1.17, 26.20). This study shows that clinical and demographic features can be used to indicate higher risks of drug resistance in this setting.     

Excessive immunosuppression as a potential cause of poor survival in simultaneous liver/kidney transplantation for hepatitis C

Appropriate recipient selection of simultaneous liver/kidney transplantation (SLKT) remains controversial. In particular, data on liver graft survival in hepatitis C virus‐infected (HCV+) SLKT recipients are lacking. We conducted a single‐center, retrospective study of HCV+ SLKT recipients (N = 25) in comparison with HCV? SLKT (N = 26) and HCV+ liver transplantation alone (LTA, N = 296). Despite backgrounds of HCV+ and HCV? SLKT being similar, HCV+ SLKT demonstrated significantly impaired 5‐year liver graft survival of 35% (HCV? SLKT, 79%, P = 0.004). Compared with HCV+ LTA, induction immunosuppression was more frequently used in HCV+ SLKT. Five‐year liver graft survival rate for HCV+ SLKT was significantly lower than that for LTA (35% vs. 74%, respectively, P < 0.001). Adjusted hazard ratio of liver graft loss in HCV+ SLKT was 4.9 (95% confidence interval 2.0–12.1, P = 0.001). HCV+ SLKT recipients were more likely to succumb to recurrent HCV and sepsis compared with LTA (32% vs. 8.8%, P < 0.001 and 24% vs. 8.8%, P = 0.030, respectively). Ten HCV+ SLKT recipients underwent anti‐HCV therapy for recurrent HCV; only 1 achieved sustained virological response. HCV+ SLKT is associated with significantly decreased long‐term prognosis compared with HCV? SLKT and HCV+ LTA.