Encorafenib in combination with binimetinib for unresectable or metastatic melanoma with BRAF mutations

Introduction: Combination treatment with a BRAF inhibitor and MEK inhibitor is the standard of care for patients with advanced BRAF^V600 mutation-positive melanoma. With the currently available combinations of dabrafenib plus trametinib and vemurafenib plus cobimetinib, median progression-free survival (PFS) of over 12 months has been achieved. However, treatment resistance and disease recurrence remain a clinical challenge.

Areas covered: Encorafenib in combination with bimetinib offers a new approach that may offer benefits over existing BRAF/MEK inhibitor combinations.

Expert opinion: While other BRAF/MEK inhibitor combinations have achieved a median overall survival (OS) of 22 months, patients with advanced BRAF mutation-positive melanoma treated with encorafenib plus binimetinib achieved a median OS of 33.6 months in the phase III COLUMBUS trial. PFS also appears to be improved with encorafenib plus binimetinib. This improved efficacy may be related to the distinct pharmacokinetics of encorafenib, with prolonged binding to the target molecule providing greater BRAF inhibition and increased potency compared with other drugs in the same class. Increased specificity of encorafenib may also result in better tolerability with less off-target effects, including reduced occurrence of pyrexia and photosensitivity. Encorafenib plus binimetinib seems likely to emerge as a valuable therapeutic alternative to established BRAF/MEK inhibitor combinations.     

Obstetric brachial plexus palsy: a population-based retrospective case-control study and medicolegal considerations

Aims: The aim of this study was to examine 24 cases of obstetric brachial plexus palsy (OBPP) in 41,002 deliveries occurred at San Camillo–Forlanini Hospital in Rome, during the period 2000–2012.

Materials and methods: A population-based retrospective case-control study was designed and the database of the hospital was searched; for each case, maternal and fetal records were examined and some risk factors were evaluated.

Results: A statistically significant association between the 24 cases OBPP and the following risk factors: primiparity (p?p?p?p?p?Conclusions: The absence of OBPP cases in cesarean deliveries highlighted in this study supports the option of proposing an elective cesarean in the presence of known risk factors after a full disclosure with the mother of risks and benefits in order to obtain a valid consent. Furthermore, when cases of OBPP occur, communication between the physician and the parents of newborns is crucial and it may represent a valid risk-management tool to reduce malpractice lawsuits.     

Is proliferative colonic disease presentation changing?

AIM: To compare the site, age and gender of cases of colorectal cancer (CRC) and polyps in a single referral center in Rome, Italy, during two periods.METHODS: CRC data were collected from surgery/pathology registers, and polyp data from colonoscopy reports. Patients who met the criteria for familial adenomatous polyposis, hereditary non-polyposis colorectal cancer syndrome or inflammatory bowel disease were excluded from the study. Overlap of patients between the two groups (cancers and polyps) was carefully avoided. The χ² statistical test and a regression analysis were performed.RESULTS: Data from a total of 768 patients (352 and 416 patients, respectively, in periods A and B) who underwent surgery for cancer were collected. During the same time periods, a total of 1693 polyps were analyzed from 978 patients with complete colonoscopies (428 polyps from 273 patients during period A and 1265 polyps from 705 patients during period B). A proximal shift in cancer occurred during the latter years for both sexes, but particularly in males. Proximal cancer increased > 3-fold in period B compared to period A in males [odds ratio (OR) 3.31, 95%CI: 2.00-5.47; P < 0.0001). A similar proximal shift was observed for polyps, particularly in males (OR 1.87, 95%CI: 1.23-2.87; P < 0.0038), but also in females (OR 1.62, 95%CI: 0.96-2.73; P < 0.07).CONCLUSION: The prevalence of proximal proliferative colonic lesions seems to have increased over the last decade, particularly in males.     

Adding Blood to Agitated Saline Significantly Improves Detection of Right-to-Left Shunt by Contrast-Transcranial Color-Coded Duplex Sonography

Contrast-transcranial Doppler and contrast-transcranial color-coded duplex sonography (c-TCCD) have been reported to have high sensitivity in detecting patent foramen ovale as compared with transesophageal echocardiography. An international consensus meeting (Jauss and Zanette 2000) recommended that the contrast agent for right-to left-shunt (RLS) detection using contrast-transcranial Doppler be prepared by mixing 9 mL of isotonic saline solution and 1 mL of air. The aim of our study was to determine whether adding blood to the contrast agent results in improved detection of RLS. We enrolled all consecutive patients admitted to our neurosonology laboratory for RLS diagnosis. For each patient, we performed c-TCCD both at rest and during the Valsalva maneuver using two different contrast agents: ANSs (1 mL of air mixed with 9 mL of normal saline) and ANSHBs (1 mL of air mixed with 8 mL of normal saline and 1 mL of the patient's blood). To classify RLS, we used a four-level visual categorization: (i) no occurrence of micro-embolic signals; (ii) grade I, 1–10 signals; (iii) grade II, >10 signals but no curtain; grade III, curtain pattern. We included 80 patients, 33 men and 47 women. RLS was detected in 18.8% at rest and in 35% during the Valsalva maneuver using ANSs, and in 31.3% and in 46.3% using ANSHBs, respectively (p < 0.0001). There was a statistically significant increase in the number of micro-embolic signals with the use of ANSHBs. The use of blood mixed with saline solution and air as a c-TCCD contrast agent produced an increase in positive tests and a higher grade of RLS compared with normal saline and air alone, either with or without the Valsalva maneuver.     

Development and characterization of sixteen microsatellite loci for Geosmithia morbida, the causal agent of thousand canker disease in black walnut (Juglans nigra)

Sixteen polymorphic microsatellite loci were identified from the fungal pathogen Geosmithia morbida. Loci were characterized for 13 different isolates collected in 2010 from symptomatic black walnut trees in Tennessee. A total of 77 loci were tested and 16 of those were optimized, screened and selected for diversity studies of G. morbida. Number of alleles per locus ranged from 3 to 8. These microsatellite loci will be useful for rapid disease diagnostic, population genetic analyses on a global scale as well as further epidemiological studies of G. morbida.     

Is facial pattern a predisposing factor for otitis media with effusion in children?

Abnormalities in craniofacial morphology are associated with Eustachian tube dysfunction and otitis media with effusion (OME).Aim: to evaluate the relationship between facial pattern and craniofacial growth direction, and OME in children with enlarged tonsils and adenoids (ETA).Methods: Clinical prospective survey in 79 children (41 male and 38 female), ranging from 4 to 10 years of age, with tonsil and adenoid enlargement (Brodsky's grades III and IV). Forty children presented with OME (study group) and 39 did not (control group). Cephalometric analysis was used to determine the facial pattern.Results: There was no correlation observed between facial pattern and OME (c 2 = 0.25 p = 0.88). Facial Axis was larger in the OME group (F(1.75) = 3.68 p = 0.05) and the Lower Anterior Facial height was smaller (F(1. 75) = 3.99 p = 0.05) in children with otitis media with effusion.Conclusions: There was no correlation between OME and facial pattern in children with ETA although a more horizontal facial growth direction, and a smaller lower anterior facial height was observed consistently among subjects in this group. This suggests that abnormal positioning of the eustachian tube influences the development of OME in children with ETA.     

Annoyed with Haemorrhoids? Risks of the Emborrhoid Technique

Digestive Diseases and Sciences - Haemorrhoids, a common ailment afflicting mostly Western patients, can produce bothersome symptoms, in particular pain, pruritus, and bleeding. There is a wide...     

Liver frailty and all-cause mortality in the older participants of the Salus in Apulia Study

The liver contribution to the biological network underlying physical frailty in aging is underestimated. How best to measure this contribution magnitude and impact on health risk trajectories in frail individuals is not yet entirely clear. We analyzed the association of a novel liver frailty phenotype with the risk of death in older participants of the Salus in Apulia Study cohort. Clinical and physical examination, routine biomarkers, medical history, and anthropometry were analyzed in 1929 older adults (65?+). Physical frailty was classified by Cardiovascular Health Study criteria, and liver fibrosis risk by fibrosis-4 (FIB-4). The liver frailty phenotype was defined as physical frailty plus high-risk liver fibrosis (score?>?2.67). Physical frailty, high-risk liver fibrosis, and liver frailty subjects were compared to subjects without these conditions (non-frail). Proportional Cox regression tested the adjusted association between liver frailty and all-cause mortality for each category. The liver frailty prevalence was relatively low (3.8%), but higher in men (58.1%). Compared to non-frail older subjects, liver frailty subjects were significantly older (effect size (ES)???1.11, 95% confidence interval (CI)???1.35 to???0.87), with a lower education (ES 0.48, 95%CI 0.24 to 0.71) and higher multimorbidity (ES 15.81, 95%CI 4.20 to 27.41). Cox multivariate analyses showed a two-fold increased risk of overall mortality (hazard ratio 2.09, 95%CI 1.16–3.74) even after the adjustment for age, sex, education, and alcohol consumption. The liver frailty phenotype runs twice the risk of overall mortality compared with the non-frail population. This clinical tool, validated in a Southern Italian population, is based on simple sets of measures that can conveniently be assessed also in the primary care setting.