Immunotherapy: A new standard in the treatment of metastatic clear cell renal cell carcinoma

Renal cell cancer (RCC) represents 2%-3% of all adulthood cancers and is the most common malignant neoplasm of the kidney (90%). In the mid-nineties of the last century, the standard of treatment for patients with metastatic RCC was cytokines. Sunititib and pazopanib were registered in 2007 and 2009, respectively, and have since been the standard first-line treatment for metastatic clear cell RCC (mccRCC). Renal cell cancer is a highly immunogenic tumor with tumor infiltrating cells, including CD8+ T lymphocytes, dendritic cells, natural killer cells (NK) and macrophages. This observation led to the design of new clinical trials in which patients were treated with immunotherapy. With the growing evidence that proangiogenic factors can have immunomodulatory effects on the host’s immune system, the idea of combining angiogenic drugs with immunotherapy has emerged, and new clinical trials have been designed. In the last few years, several therapeutic options have been approved [immunotherapy and immunotherapy/tyrosine kinase inhibitors (TKI)] for the first-line treatment of mccRCC. Nivolumab/ipilimumab is approved for the treatment of patients with intermediate and poor prognoses. Several checkpoint inhibitors (pembrolizumab, nivolumab, avelumab) in combination with TKI (axitinib, lenvatinib, cabozantinib) are approved for the treatment of patients regardless of their International mRCC Database Consortium prognostic group and PD-L1 expression. There is no specific and ideal biomarker that could help in selecting the ideal patient for the appropriate first-line treatment.     

The uncalibrated prothrombinase-induced clotting time test. Equally convenient but more precise than the aPTT for monitoring of unfractionated heparin

The activated partial thromboplastin time test (aPTT) represents one of the most commonly used diagnostic tools in order to monitor patients undergoing heparin therapy. Expression of aPTT coagulation time in seconds represents common practice in order to evaluate the integrity of the coagulation cascade. The prolongation of the aPTT thus can indicate whether or not the heparin level is likely to be within therapeutic range. Unfortunately aPTT results are highly variable depending on patient properties, manufacturer, different reagents and instruments among others but most importantly aPTT's dose response curve to heparin often lacks linearity. Furthermore, aPTT assays are insensitive to drugs such as, for example, low molecular weight heparin (LMWH) and direct factor Xa (FXa) inhibitors among others. On the other hand, the protrombinase-induced clotting time assay (PiCT?) has been show to be a reliable functional assay sensitive to all heparinoids as well as direct thrombin inhibitors (DTIs). So far, the commercially available PiCT assay (Pefakit?PiCT?, DSM Nutritional Products Ltd. Branch Pentapharm, Basel, Switzerland) is designed to express results in terms of units with the help of specific calibrators, while aPTT results are most commonly expressed as coagulation time in seconds. In this report, we describe the results of a pilot study indicating that the Pefakit PiCT UC assay is superior to the aPTT for the efficient monitoring of patients undergoing UFH therapy; it is also suitable to determine and quantitate the effect of LMWH therapy. This indicates a distinct benefit when using this new approach over the use of aPPT for heparin monitoring.     

Investigating the time‐lapsed effects of rigid cervical collars on the dimensions of the internal jugular vein

Protocol advocates the use of rigid cervical collars (RCCs) in head trauma patients as they are at risk of concomitant cervical spine injury. Literature has shown RCCs to be a potential cause of venous outflow obstruction, changing internal jugular vein (IJV) cross‐sectional area (CSA), and raising intracranial pressure (ICP). This study aims to investigate the effects of applying a RCC, for a period of four hours, on the dimensions of the IJV, in healthy participants. Seventeen participants (nine male, eight female) took part in this study. Circumference and CSAs of the IJV were measured bilaterally by a single observer using a GE LOGIQ e ultrasound system. Measurements were taken pre‐RCC application, immediately after, every hour over four hours, and five minutes postcollar removal. The CSA of the IJV was 8.3 ±6.0 mm² pre‐RCC application. The CSA of the IJV doubled (18.92 ±10.55 mm²) after four hours and decreased back to 9.36 ±6.8 mm² five minutes postcollar removal. The circumference of the IJV was 17.29 ±6.03 mm pre‐RCC application, increasing to 20.34 ±5.59 mm by the end of the fourth hour and returning to 16.14 ±5.16 mm five minutes postcollar removal. Related‐samples Friedman's ANOVA test showed statistically significant differences for both left and right CSAs and circumferences of the IJV measured across the four hours (P‐value<0.05). Ultrasound assessment of CSA of the IJV may correlate with changes in ICP. Further studies may provide insight into the effects of collar design, and guide future trauma protocol to minimize intracranial pressure fluctuations. Clin. Anat. 32:196–200, 2019. © 2018 Wiley Periodicals, Inc.     

5‐Alpha reductase inhibitors in androgenetic alopecia: Shifting paradigms,current concepts,comparative efficacy,and safety

Androgenetic alopecia (AGA) is a multifactorial disease that carries a significant psychological burden with it. Dihydrotestosterone, the main pathogenic androgen in AGA, is produced by conversion of testosterone, which is catalyzed by the 5‐alpha reductase (5‐AR) isoenzyme family. Finasteride and dutasteride are inhibitors of these enzymes. Finasteride, which is a single receptor 5‐alpha reductase inhibitor (5‐ARI), acts by blocking dihydrotestosterone (DHT). Dutasteride, a dual receptor DHT blocker, has a higher potency than its predecessor, finasteride. This review corroborates the evidence of superiority of dutasteride over finasteride, and its comparable safety profile concerning fertility, teratogenicity, neurotoxicity, and hepatotoxicity.