Genetic variation within the human papillomavirus type 16 genome is associated with oropharyngeal cancer prognosis.

PURPOSE: A significant barrier to adoption of de-escalated treatment protocols for human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is that few predictors of poor prognosis exist. We conducted the first large whole-genome sequencing (WGS) study to characterize the genetic variation of the HPV type 16 (HPV16) genome and to evaluate its association with HPV-OPC patient survival. PATIENTS AND METHODS: A total of 460 OPC tumor specimens from two large United States medical centers (1980-2017) underwent HPV16 whole-genome sequencing. Site-specific variable positions [single nucleotide polymorphisms (SNPs)] across the HPV16 genome were identified. Cox proportional hazards model estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival by HPV16 SNPs. Harrell C-index and time-dependent positive predictive value (PPV) curves and areas under the PPV curves were used to evaluate the predictive accuracy of HPV16 SNPs for overall survival. RESULTS: A total of 384 OPC tumor specimens (83.48%) passed quality control filters with sufficient depth and coverage of HPV16 genome sequencing to be analyzed. Some 284 HPV16 SNPs with a minor allele frequency ≥1% were identified. Eight HPV16 SNPs were significantly associated with worse survival after false discovery rate correction (individual prevalence: 1.0%-5.5%; combined prevalence: 15.10%); E1 gene position 1053 [HR for overall survival (HRos): 3.75, 95% CI 1.77-7.95; Pfdr = 0.0099]; L2 gene positions 4410 (HRos: 5.32, 95% CI 1.91-14.81; Pfdr = 0.0120), 4539 (HRos: 6.54, 95% CI 2.03-21.08; Pfdr = 0.0117); 5050 (HRos: 6.53, 95% CI 2.34-18.24; Pfdr = 0.0030), and 5254 (HRos: 7.76, 95% CI 2.41-24.98; Pfdr = 0.0030); and L1 gene positions 5962 (HRos: 4.40, 95% CI 1.88-10.31; Pfdr = 0.0110) and 6025 (HRos: 5.71, 95% CI 2.43-13.41; Pfdr = 0.0008) and position 7173 within the upstream regulatory region (HRos: 9.90, 95% CI 3.05-32.12; Pfdr = 0.0007). Median survival time for patients with ≥1 high-risk HPV16 SNPs was 3.96 years compared with 18.67 years for patients without a high-risk SNP; log-rank test P < 0.001. HPV16 SNPs significantly improved the predictive accuracy for overall survival above traditional factors (age, smoking, stage, treatment); increase in C-index was 0.069 (95% CI 0.019-0.119, P < 0.001); increase in area under the PPV curve for predicting 5-year survival was 0.068 (95% CI 0.015-0.111, P = 0.008). CONCLUSIONS: HPV16 genetic variation is associated with HPV-OPC prognosis and can improve prognostic accuracy.

Update on pulmonary Pneumocystis jirovecii infection in non-HIV patients.

Pneumocystis jirovecii is the only fungus of its kind to be pathogenic in humans. It is primarily responsible for pneumonia (PJP). The key to understanding immune defences has focused on T-cells, mainly because of the HIV infection epidemic. Patients presenting with PJP all have a CD4 count below 200/mm(3). The introduction of systematic primary prophylaxis and the use of new anti-retroviral drugs have significantly reduced the incidence of this disease in the HIV-infected population, mainly in developed countries. The increasingly frequent use of corticosteroids, chemotherapy, and other immunosuppressive drugs has led to an outbreak of PJP in patients not infected by HIV. These patients presenting with PJP have more rapid and severe symptoms, sometimes atypical, leading to delay the initiation of a specific anti-infective therapy, sometimes a cause of death. However, the contribution of new diagnostic tools and a better understanding of patients at risk should improve their survival.

Surgical care improvement project (SCIP): has its mission succeeded?

The purpose of this study was to determine if adherence to the surgical care improvement project (SCIP) measures could further reduce rate of surgical site infection (SSI) and venous thromboembolism (VTE) in total joint arthroplasty (TJA) patients. We retrospectively identified all patients who underwent primary or revision TJA at our institution between July 2000 and June 2009. After implementation of SCIP measures, rate of superficial SSI increased (0.42% versus 0.60%, P=0.05) while rate of deep SSI decreased from 0.92% to 0.82% (P=0.46). The rate of DVT was 0.92% before and 0.83% after implementation of SCIP (P=0.51); however, rate of PE increased from 0.87% to 1.30% (P=0.002). Our findings indicated that SCIP has not been successful in reducing complications in TJA patients.

A moderate-intensity static magnetic field enhances repair of cartilage damage in rabbits.

BACKGROUND AND AIMS: Electromagnetic fields have been proposed to enhance healing of cartilage defects by stimulation of chondrocyte proliferation, proteoglycan synthesis as well as decreasing pain and improving motion in osteoarthritic patients. However, the effects of a moderate-intensity static magnetic field on cartilage repair have not been investigated. This study tries to determine the effects of a moderate-intensity permanent magnetic field of 40 mT on cartilage repair. METHODS: Defects of 3 mm in diameter and 6 mm in depth were made on the weight bearing surface of the right medial femoral condyle of 30 rabbits. The animals were divided randomly into three equal groups (magnet, sham and control). In the magnet group, cylindrical permanent magnets were implanted subcutaneously medial to the medial femoral condyle, while in the sham group the cylindrical ceramic were not magnetized, and nothing was implanted in controls. After 12 weeks of observation, Mankin's microscopic scoring was done on all specimens, and irregularity of surface characteristics, cell colonization, hypocellularity, cartilage matrix formation, and presence of empty lacunae were investigated. RESULTS: Each of these characteristics showed significant differences in magnet group relative to control and sham groups (p <0.05). Mankin's score was 1.6 ± 0.6 in magnet group, 7.2 ± 1.6 in sham group and 7.7 ± 1 in control group (p <0.001). CONCLUSIONS: [corrected] In this animal study, microscopic Mankin's scoring depicted histological improvement in cartilage of magnet group.

Arthroscopic anterior cruciate ligament reconstruction with modified "wireless" cross-screw transfix femoral fixation.

Among several graft fixation options in arthroscopic ACL reconstruction for hamstring tendons, transcondylar fixation has been suggested to offer mechanical advantages compared to other femoral fixation systems. Blind nature of the procedure may result in several complications including iliotibial band irritation syndrome, breakage of the bio absorbable cross-pin, stress fracture of the femoral cortex, and more commonly intraoperative wire loop twisting, resulting in fixation failure, wire breakage or graft laceration. We used "wireless" transfixation technique to avoid complications associated with wire loop.

A modification of tibial inlay fixation in posterior cruciate ligament reconstruction by interference screw: a biomedical study on calf tibial bone model.

This study presents a modification of tibial inlay technique in posterior cruciate ligament (PCL) reconstruction and evaluates the structural properties of tibial side fixation of the graft, comparing tibial inlay technique and a new modification, that is interference screw fixation of tibial side of the graft in suggested supine position which is more applicable, with less potential intraoperative neurovascular complications. Forty fresh calf knees that were prepared from 20 healthy 3 years old calves which were between 200 and 220 kg were the subject of this study. The tibias were separately used simulating tibial side PCL reconstruction with tibial tuberosity-patellar tendon-patellar bone graft. Tibial side of the graft was fixed using two cancellous screws in 20 tibiae and with interference screw in obliquely oriented canal in another 20 tibiae. Load-to-failure test was carried out on ten samples from each group. The remaining samples were used for cycling loading. Mann-Whitney U test was used to compare structural properties of each group. No significant differences were observed between two methods at load-to-failure test; but mean elongation at 1,000 cycles of new modification was significantly lower than tibial inlay technique.

[Potato leafroll virus: purification, serologic detection and quantitative analysis in plants]. / Le virus de l'enroulement de la pomme de terre: purification, détection sérologique et dosage dans la plante.

The Potato Leafroll Virus has been purified from Potato. An antiserum obtained allows the use of the Enzyme Linked-Immunosorbent Assay, a direct means to detect the PLRV in the plant and to assess its real concentration.