Association of Physical Function and Survival in Older-Adult Renal Transplant Recipients

There is an increase in older-adult renal transplant recipients in United States. The objective of this study was to assess the association between physical function (PF) and patient survival in renal transplant recipients who are aged 65 years or older. Using United Network for Organ Sharing (UNOS) data from 2007 to 2016, renal transplant recipients aged 65 years or older were included. Multivariable Cox regression was used to assess associations between survival and functional status adjusted for age, sex, race, donor quality, diabetes, and dialysis vintage. The study identified 26,721 patients. Patient survival was significantly higher in recipients who needed no assistance and lowest in patients in need of total assistance (P < .0001). In deceased donor (DD) transplants, the relative risk for mortality was 2.06 (1.74-2.43) for total assistance and 1.17 (1.08-1.28) for moderate assistance compared to no assistance (P < .0001). In living donor (LD) transplants, the relative risk of mortality was 1.38 (0.78-2.42) for patients needing total assistance and 1.37 (1.14-1.65) for patients needing moderate assistance compared to patients who did not need assistance (0.003). PF is an independent predictor of post-transplant mortality. Assessment of older potential renal transplant recipients should include assessment and standardization of functional status to counsel about post-transplant survival.     

Combined tumor plus nontumor interim FDG-PET parameters are prognostic for response to chemoradiation in squamous cell esophageal cancer

We have investigated the prognostic value of two novel interim ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) parameters in patients undergoing chemoradiation (CRT) for esophageal squamous cell carcinoma (ESCC): one tumor parameter (maximal standardized uptake ratio rSUR) and one normal tissue parameter (change of FDG uptake within irradiated nontumor-affected esophagus ∆SUV_NTO). PET data of 134 European and Chinese patients were analyzed. Parameter establishment was based on 36 patients undergoing preoperative CRT plus surgery, validation was performed in 98 patients receiving definitive CRT. Patients received PET imaging prior and during fourth week of CRT. Clinical parameters, baseline PET parameters, and interim PET parameters (rSUR and ∆SUV_NTO) were analyzed and compared to event-free survival (EFS), overall survival (OS), loco-regional control (LRC) and freedom from distant metastases (FFDM). Combining rSUR and ∆SUV_NTO revealed a strong prognostic impact on EFS, OS, LRC and FFDM in patients undergoing preoperative CRT. In the definitive CRT cohort, univariate analysis with respect to EFS revealed several staging plus both previously established interim PET parameters as significant prognostic factors. Multivariate analyses revealed only rSUR and ∆SUV_NTO as independent prognostic factors (p = 0.003, p = 0.008). Combination of these parameters with the cutoff established in preoperative CRT revealed excellent discrimination of patients with a long or short EFS (73% vs. 17% at 2 years, respectively) and significantly discriminated all other endpoints (OS, p < 0.001; LRC, p < 0.001; FFDM, p = 0.02), even in subgroups. Combined use of interim FDG-PET derived parameters ∆SUV_NTO and rSUR seems to have predictive potential, allowing to select responders for definitive CRT and omission of surgery.     

Mutational analysis of the CYP1B1 gene in Pakistani primary congenital glaucoma patients: Identification of four known and a novel causative variant at the 3′ splice acceptor site of intron 2

Primary congenital glaucoma (PCG) causes blindness in early age. It has an autosomal recessive pattern of inheritance, hence is more prevalent in populations with frequent consanguineous marriages that occur in the Pakistani population. Mutations in the CYP1B1 gene are commonly associated with PCG. The aim of the present study was to identify genetic mutations in the CYP1B1 gene in PCG cases belonging to 38 Pakistani families. DNA was extracted using blood samples collected from all enrolled patients, their available unaffected family members and controls. Direct sequencing of the CYP1B1 gene revealed a novel 3' splice acceptor site causative variant segregating in an autosomal recessive manner in a large consanguineous family with four PCG‐affected individuals. The novel variant was not detected in 93 ethnically matched controls. Furthermore, four already reported mutations, including p.G61E, p.R355X, p.R368H, and p.R390H were also detected in patients belonging to nine different families. All identified causative variants were evaluated by computational programs, that is, SIFT, PolyPhen‐2, and MutationTaster. Pathogenicity of the novel splice site variant identified in this study was analyzed by Human Splicing Finder and MaxEntScan. Ten out of 38 families with PCG had the disease due to CYP1B1 mutations, suggesting CYP1B1 was contributing to PCG in these Pakistani patients. Identification of this novel 3' splice acceptor site variant in intron 2 is the first report for the CYP1B1 gene contributing to genetic heterogeneity of disease.     

Predicting survival in anaplastic astrocytoma patients in a single-center cohort of 108 patients

Purpose

Stereotactic radiation therapy (SRT) and immune checkpoint inhibitors (ICI) may act synergistically to improve treatment outcomes but may also increase the risk of symptomatic radiation necrosis (RN). The objective of this study was to compare outcomes for patients undergoing SRT with and without concurrent ICI.

Methods and materials

Patients treated for BMs with single or multi-fraction SRT were retrospectively reviewed. Concurrent ICI with SRT (SRT-ICI) was defined as administration within 3 months of SRT. Local control (LC), radiation necrosis (RN) risk and distant brain failure (DBF) were estimated by the Kaplan-Meier method and compared between groups using the log-rank test. Wilcoxon rank sum and Chi-square tests were used to compare covariates. Multivariate cox regression analysis (MVA) was performed.

Results

One hundred seventy-nine patients treated with SRT for 385 brain lesions were included; 36 patients with 99 lesions received SRT-ICI. Median follow up was 10.3 months (SRT alone) and 7.7 months (SRT- ICI) (p = 0.08). Lesions treated with SRT-ICI were more commonly squamous histology (17% vs 8%) melanoma (20% vs 2%) or renal cell carcinoma (8% vs 6%), (p < 0.001). Non-small cell lung cancer (NSCLC) compromised 60% of patients receiving ICI (n = 59). Lesions treated with SRT-ICI had significantly improved 1-year local control compared to SRT alone (98 and 89.5%, respectively (p = 0.0078). On subset analysis of NSCLC patients alone, ICI was also associated with improved 1 year local control (100% vs. 90.1%) (p = 0.018). On MVA, only tumor size ≤2 cm was significantly associated with LC (HR 0.38, p = 0.02), whereas the HR for concurrent ICI with SRS was 0.26 (p = 0.08). One year DBF (41% vs. 53%; p = 0.21), OS (58% vs. 56%; p = 0.79) and RN incidence (7% vs. 4%; p = 0.25) were similar for SRT alone versus SRT-ICI, for the population as a whole and those patients with NSCLC.

Conclusion

These results suggest SRT-ICI may improve local control of brain metastases and is not associated with an increased risk of symptomatic radiation necrosis in a cohort of predominantly NSCLC patients. Larger, prospective studies are necessary to validate these findings and better elucidate the impact of SRT-ICI on other disease outcomes.

     

Pharmacokinetics of 2'',3''-dideoxyinosine (BMY-40900), a new anti-human immunodeficiency virus agent, after administration of single intravenous doses to beagle dogs.

The pharmacokinetics of 2',3'-dideoxyinosine (ddI) were investigated in four adult male beagle dogs that received 15-min infusions of 20-, 50-, and 100-mg/kg doses in a randomized crossover study design. Plasma and urine samples were collected for 10 and 24 h, respectively, and assayed for ddI by high-performance liquid chromatographic methods. The mean maximum concentrations of drug in plasma at the end of 15-min infusions for the 20-, 50-, and 100-mg/kg doses were 33.3, 90.0, and 202 micrograms/ml, respectively. Area under the concentration-time curve data deviated significantly from linearity. The mean total clearance for the low dose (250 ml/min) was significantly greater than that for the high dose (190 ml/min). Renal clearance, which averaged between 98 and 116 ml/min, was dose independent. Renal clearance implied that nonrenal clearance decreased at the high dose (92 ml/min) when compared with that of the low dose (134 ml/min). The average urinary recovery of ddI for the high dose (51.2% of dose) was significantly greater than that for the low dose (45.8%). The volume of distribution at steady state averaged between 7.6 and 10.5 liters and decreased with increasing dose; however, it was not statistically significant. The mean half-life and mean residence time were invariant with respect to dose and averaged between 0.94 and 1.07 h and 0.61 and 0.71 h, respectively. In this dose range, ddI pharmacokinetics are dose dependent.     

Utilization of maternal and child health services in rural areas of Jammu and Kashmir.

Researchers analyzed data on 100 14-45 year old mothers who had a child whose age was 0-3 years old and lived in Gurihaker village in Zachaldara block in Kupwara district of Jammu and Kashmir in India to determine use of maternal and child health care (MCH) services, their perception of needing these services, and the relationship between MCH utilization and social, economic, and demographic factors. 68 had 1-3 children. Only 57 registered with a health facility, mainly primary health centers (26), during their last pregnancy. Most (30) registered during the 4th-6th month of pregnancy. 56.14% of registered mothers visited the facility 4 times. The major reason for visiting the facility was problems (87.72%). 60 mothers were not vaccinated against tetanus. Only 15% of the 40 who did receive the tetanus toxoid received 2 doses. Just 54 took iron/folic acid tablets. Only 13 went to a facility for postpartum follow up; 8 went to a private practitioner. 84% gave birth to their child a home. A traditional birth attendant (dai) were present for all home births. The leading reasons for delivering at home were tradition (79.76%), no obstetric problems (75%), family demanded a home delivery (61.9%), convenience (48.8%), and high hospital costs (48.85%). Reasons for having a dai present included tradition (77.38%), family preferences (65.47%), privacy (60.71%), and less expensive (47.61%). Only 18 children did not receive any vaccinations. 29 used family planning methods especially female sterilization (10) and copper T IUD (7). 61 believed they need prenatal services. 78 perceived the need for intranatal care. 70 and 80 expressed the need for child care/immunization and family planning, respectively. Women of the high socioeconomic group, 15-29 years old, and with 3 children were more likely to adequately use prenatal care. These results highlighted the need to develop a strong health education program using the mass media, recruiting more female health guides than male, and training dais in MCH services.