PIMGAVir and Vir-MinION: Two Viral Metagenomic Pipelines for Complete Baseline Analysis of 2nd and 3rd Generation Data

The taxonomic classification of viral sequences is frequently used for the rapid identification of pathogens, which is a key point for when a viral outbreak occurs. Both Oxford Nanopore Technologies (ONT) MinION and the Illumina (NGS) technology provide efficient methods to detect viral pathogens. Despite the availability of many strategies and software, matching them can be a very tedious and time-consuming task. As a result, we developed PIMGAVir and Vir-MinION, two metagenomics pipelines that automatically provide the user with a complete baseline analysis. The PIMGAVir and Vir-MinION pipelines work on 2nd and 3rd generation data, respectively, and provide the user with a taxonomic classification of the reads through three strategies: assembly-based, read-based, and clustering-based. The pipelines supply the scientist with comprehensive results in graphical and textual format for future analyses. Finally, the pipelines equip the user with a stand-alone platform with dedicated and various viral databases, which is a requirement for working in field conditions without internet connection.     

Practical guidelines for dose individualization of anticancer targeted drugs

For drugs such as anticancer agents every effort should be made to minimize inter-patient variability in drug exposure in order to maximize the benefit while maintaining an acceptable risk level of serious adverse effects. Anticancer drugs generally have a preferential route of elimination, either in urine or in bile and feces. In consequence, dose individualization to renal and liver function permits excessive toxicity to be avoided and expected therapeutic benefit to be achieved. However, less is known about the most appropriate starting doses of antineoplastic agents in these individuals. In this review, we discuss trials that have specifically assessed new targeted agents dosing strategies (mainly monoclonal antibodies and tyrosine kinase inhibitors) in the setting of overt biochemical renal and liver dysfunction and we proportionate recommendations and practical guidelines for dose individualization.     

Effect of chronic altitude hypoxia on the behavior of the respiratory center. Study on normal subjects living at the altitude of Mexico City (2,240 meters)

Respiratory center (RC) output has been shown to be increased in hypoxemic Chronic Obstructive patients at sea level. In order to asses the separate role of chronic hypoxia on the RC output we studied 30 normal subjects all of them native and residents of Mexico City (altitude: 2,240 m, PaO2: 65-70 torr.). The parameters studied were: occlussion pressure (P0.1), mean inspiratory flow (Vi), and the ratio inspiratory time to total duration of the respiratory cycle (Ti/Ttot). The inspiratory impedance of the respiratory system as well as the minute ventilation (VE) and lastly to ensure isocapnic conditions, the end-tidal CO2 (PECO2), were also measured. These parameters were determined: 1) While breathing room air (RA), 2) after 30 min of breathing an inspired oxygen fraction (FiO2) of 30% and again 3) after 30 min of breathing and FiO2 of 100%. Fifteen of the subjects were studied on supine and the other 15 in the seated position. In most of the subjects the baseline (RA) values of P0.1 were found to be higher than those reported for normals at sea level. In every case, independent of body position, the P0.1 decreased (less than 0.01) to normal sea level values after 30 min of breathing O2 30%. Likewise, Vi and mechanical impedance also decreased (p less than 0.01) and no changes in Ti/Ttot were noted at this FiO2. No further changes occurred after breathing 100%. The above results show that: 1) The RC output in normal people at altitude (i.e. without mechanical abnormalities but with chronic hypoxia) is increased as compared to sea level.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma Cholecystokinin Levels after Vertical Banded Gastroplasty: Effects of an Acidified Meal

Background: Although cholecystokinin (CCK) is involved in the short-term regulation of satiety, it has not been investigated in obese patients subjected to bariatric restrictive operations. Methods: 8 morbidly obese patients (BMI 49.1 ± 6.9), 7F and 1M, were investigated before and after vertical banded gastroplasty (VBG). 6 healthy lean volunteers served as the control group. CCK was determined (RIA) after an overnight fast and after the administration of an acidified (pH 3) liquid meal. Blood samples were taken 45 min before the meal, 5 min after it and then every 30 min for 3 hours. Results: There were no differences between groups in basal CCK levels. However, the peak of CCK after the meal was significantly higher (P <0.01) in obese patients after VBG (24.9 ± 18 pmol/l) than before VBG (9.8 ± 6.7 pmol/l) and when compared with the control group (8.0 ± 6.3 pmol/l).The time needed to reach the peak was longer in healthy volunteers (105 ± 24.9 min) than in obese patients before VBG (45 ± 40 min) and after VBG (7.5± 12 min) (P<0.01). Conclusions: VBG increases the peak of CCK secretion and shortens the time to reach it. These changes could contribute to the satiety effects of gastric restrictive operations.     

The impact of surveillance and rapid reduction in immunosuppression to control BK virus‐related graft injury in kidney transplantation

We prospectively screened 609 consecutive kidney (538) and kidney‐pancreas (71) transplant recipients for BK viremia over a 4‐year interval using polymerase chain reaction viral load detection and protocol kidney biopsies. We found that BK viremia is common at our center: total cases 26.7%, cases during first year 21.3% (mean 4 months), and recipients with ≥10 000 copies/ml 12.3%. We found few predictive clinical or demographic risk factors for any BK viremia or viral loads ≥10,000 copies/ml, other than prior treatment of biopsy confirmed acute rejection and/or higher immunosuppressive blood levels of tacrolimus (P = 0.001) or mycophenolate mofetil (P = 0.007). Viral loads at diagnosis (<10 000 copies/ml) demonstrated little impact on graft function or survival. However, rising copy numbers demand early reductions in immunosuppressive drug doses of at least 30–50%. Viral loads >185 000 copies/ml at diagnosis were predictive of BK virus‐associated nephropathy (BKVAN; OR: 113.25, 95% CI: 17.22–744.6, P < 0.001). Surveillance for BK viremia and rapid reduction of immunosuppression limited the incidence of BKVAN to 1.3%. The addition of leflunomide or ciprofloxacin to immunosuppressive dose reduction did not result in greater rates of viral clearance. These data support the role of early surveillance for BK viremia to limit the impact on transplant outcome, although the most effective schedule for screening awaits further investigation.     

Predictive factors of excess body weight loss 1?year after laparoscopic bariatric surgery

Background

Bariatric surgery (BS) is widely accepted for the treatment of patients with morbid obesity (MO). We aimed to determine presurgical predictors of and surgical technique-related differences in excess weight loss (EWL) 1?year after BS.

Methods

This retrospective study included 407 subjects (F/M 3:1, median age?=?44?years) who underwent laparoscopic Roux-en-Y gastric bypass (RYGB, n?=?307) or sleeve gastrectomy (SG, n?=?100) at our University Hospital and were evaluated 1?year after surgery.

Results

Baseline median (min–max) body mass index (BMI) was 47?kg/m² (range?=?36–71). BMI was higher in the SG than in the RYGB group (53 vs. 46?kg/m², p?p?p?=?0.2), was lower in diabetic than in nondiabetic subjects (71?±?17% vs. 79?±?17%, p?p?p?=?0.4) after taking into account baseline BMI. Multiple regression and logistic analysis showed that younger individuals with lower BMI but higher WC, and lower HbA1c and TG, had higher EWL and a higher rate of successful (EWL?≥?60%) weight loss.

Conclusions

Our data indicate that some of the characteristics that would have subjects referred early for BS were associated with higher weight loss. Therefore, the timing of laparoscopic BS might be an important factor for MO individuals in which medical weight loss intervention has failed.     

Giant earlobe epidermoid cyst

Epidermoid cysts represent the most common cutaneous cysts. They are usually small and benign; however, sometimes they can grow to giant epidermoid cists, and occasionally malignancies develop. Giant epidermoid cysts at the earlobe have never been described but in other locations. We describe a case of a giant epidermoid cyst at the earlobe, a location where such a large cyst has never been reported before. The mass was completely resected and the wound of the pedunculated base was sutured with four stitches of nylon 5/0. Histopathology confirmed the presumptive diagnosis of an epidermoid cyst. Six months after the resection, the patient did not have any relapse of the epidermoid cyst. The earlobe is a potential location for giant epidermoid cysts. Although the clinical diagnosis could be enough, due to the possibility of malignancy and to ensure appropriate diagnosis, we consider that all cysts should be sent to the anatomic pathology laboratory for histological evaluation.     

Prognostic influence of the third Gleason grade in prostatectomy specimens

BackgroundGleason grading of prostatic specimens remains as one of the most powerful factors predicting prognosis in patients with prostate cancer. This grading system was created by Donald Gleason about 49 years ago and it takes into account the 2 most prevalent grades in the tumor sample, but it does not consider the presence of a third high grade pattern when it represents less than 5% of the whole radical prostatectomy specimen.ObjectiveThe objective of the present study is to determine whether the existence of a third pattern of growth in the radical prostatectomy samples correlates with a shorter recurrence free survival.Material and methodsWe have reviewed 85 consecutive specimens of radical prostatectomy from patients with clinical localized disease. Those who received previous hormonal or radiation therapy were excluded. We have determined the Gleason grade and also the presence of a third higher grade pattern, surgical margins status, capsular, vascular, and lymphatic invasion. We have analyzed whether the existence of this high grade third pattern areas influences prognosis. Recurrence was defined with PSA levels (biochemical recurrence).ResultsWe have shown that the presence of a Gleason's grade 5 pattern of growth worsens prognosis in patients with tumors grade 7 (both 3 + 4 and 4 + 3), with a shorter time to recurrence. The latter group of patients behaves more like patients with Gleason 8 tumors. This worse prognosis should be taken into account for patient surveillance and future adjuvant therapies. We feel this information is relevant and should be reported in the pathology reports.