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.     

Fetal cerebral ventriculomegaly: What do we tell the prospective parents?

Fetal cerebral ventriculomegaly is a relatively common finding, observed during approximately 1% of obstetric ultrasounds. In the second and third trimester, mild (≥10 mm) and severe ventriculomegaly (≥15 mm) are defined according to the measurement of distal lateral ventricles that is included in the routine sonographic examination of central nervous system. A detailed neurosonography and anatomy ultrasound should be performed to detect other associated anomalies in the central nervous system and in other systems, respectively. Fetal MRI might be useful when neurosonography is unavailable or suboptimal. The risk of chromosomal and non-chromosomal genetic disorders associated with ventriculomegaly is high, therefore invasive genetic testing, including microarray, is recommended. Screening for prenatal infections, in particular cytomegalovirus and toxoplasmosis, should also be carried out at diagnosis. The prognosis is determined by the severity of ventriculomegaly and/or by the presence of co-existing abnormalities. Fetal ventriculoamniotic shunting in progressive isolated severe ventriculomegaly is an experimental procedure. After delivery, ventricular-peritoneal shunting or ventriculostomy are the two available options to treat hydrocephalus in specific conditions with similar long-term outcomes. A multidisciplinary fetal neurology team, including perinatologists, geneticists, pediatric neurologists, neuroradiologists and neurosurgeons, can provide parents with the most thorough prenatal counseling. This review outlines the latest evidence on diagnosis and management of pregnancies complicated by fetal cerebral ventriculomegaly.     

Polyvictimization and Psychiatric Sequelae Associated with Female Genital Mutilation/Cutting (FGM/C)

Female Genital mutilation/cutting (FGM/C) is associated with enduring psychiatric complications. In this study, we investigate the rates of co-morbid abuses and polyvictimization experienced by survivors of FGM/C. This is a sub-analysis of a cohort study examining the patient population at the EMPOWER Center for Survivors of Sex Trafficking and Sexual Violence in New York City. A retrospective chart-review of electronic medical records was conducted for all consenting adult patients who had FGM/C and had an intake visit between January 16, 2014 and March 6, 2020. Of the 80 participants, ages ranged from 20 to 62 years with a mean of 37.4 (SD?=?9.1) years. In addition to FGM/C, participants were victims of physical abuse (43; 53.8%), emotional abuse (35; 43.8%), sexual abuse (35; 43.8%), forced marriage (20; 25%), child marriage (13; 16.3%), and sex trafficking (1; 1.4%). There was a high degree of polyvictimization, with 41 (51.2%) experiencing 3 or more of the aforementioned abuses. Having FGM/C on or after age 13 or having a higher total abuse score was also found to be strong predictors of depression and PTSD. The high rates of polyvictimization among survivors of FGM/C are associated with development of depression and PTSD. Despite co-morbid abuses, patients still attribute substantial psychiatric symptoms to their FGM/C. Health care providers should understand the high risk of polyvictimization when caring for this patient population.

     

Randomized clinical trial comparing monolithic and veneered zirconia three-unit posterior fixed partial dentures in a complete digital flow: three-year follow-up

Clinical Oral Investigations - To evaluate and to compare the clinical performance and survival rate of posterior monolithic and veneered zirconia fixed partial dentures (FPDs). Sixty 3-unit...     

New Hormonal Agents in Patients With Nonmetastatic Castration-Resistant Prostate Cancer: Meta-Analysis of Efficacy and Safety Outcomes

In the past few years several hormonal agents have been tested in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) leading to an impressive improvement in terms of metastases-free survival (MFS). We performed a meta-analysis aimed to: (1) estimate the pooled effect of new hormonal compounds in terms of MFS, overall survival (OS) in overall and specific subpopulations; and (2) estimate the effect of high-grade toxicities of these drugs. We identified 881 studies published between January 1, 2010 and February 16, 2018 on PubMed/Medline, Cochrane Library, and Scopus. Three randomized placebo controlled clinical trials were selected (PROSPER, SPARTAN, and ARAMIS). Because of the absence of individual data, all of the analyses performed were made on aggregated data provided in selected studies. We used the inverse variance technique for the meta-analysis of the hazard ratios collected for MFS and OS analysis. Fixed and randomized models were used. Relative risk and 95% confidence intervals and risk difference were estimated considering the number of Grade 3 adverse events in treatment and control arms. Administration of new hormonal compounds in nmCRPC patients led to a significant benefit in MFS in the overall population and in all subgroups analyzed. These agents might also improve OS but longer follow-up is needed to confirm this hypothesis. Indeed results of OS analysis should be carefully evaluated because none of the studies selected provided mature OS data. Administration of these agents resulted in a significant increased risk of treatment-related death, high cardiovascular toxicity, hypertension, fractures, and falls. Administration of new hormonal compounds prolongs the time of metastases occurrence and might prolong also survival in patients with nmCRPC. Treatment-related toxicity is an important issue because these agents increase the risk of death, cardiovascular toxicity, hypertension, fractures, and risk of falls.