Migraine causes retinal and choroidal structural changes: evaluation with ocular coherence tomography

Few studies have evaluated whether the retina is involved in migraine through the evaluation of retinal nerve fiber layer (RNFL) examined with ocular coherence tomography (OCT) with conflicting results. Aim of this case–control study is to evaluate the retina and the choroid in migraine. Patients having migraine with aura (MwA) or without aura (MoA) and chronic migraine (CM) were evaluated. Age- and sex-matched normal subjects were selected as healthy controls (HC). Patients and HC were examined with OCT. RNFL, ganglion cell layer (GCL), foveal thickness (FT), choroidal thickness (CT) and total macular volume (TMV) were calculated for right eyes (RE) and left eyes (LE). Seventy-seven patients (62 women; 80.5%), 21 MoA, 12 MwA, 44 CM and 42 HC were enrolled in the study. Patients compared to HC had a significant reduction of RNFL (RE: 91.2 ± 9.2 vs 99.3 ± 7.5 μm; p < 0.001. LE: 93.3 ± 8.7 vs 100.2 ± 6.5 μm; p < 0.001). GCL (RE: 80.6 ± 6.4 vs 86.9 ± 2.1 μm; p < 0.0001. LE: 81.5 ± 5.7 vs 87.1 ± 2.6 μm; p < 0.0001) and CT (RE: 286.4 ± 31.4 vs 333.2 ± 3.1 μm; p < 0.0001. LE: 287.2 ± 31.6 vs 334.5 ± 4.1 μm; p < 0.0001) were thinner in patients compared to HC. Moreover, CM showed reduction of RNFL and of GCL compared to the other migraineurs. Finally, we found a significant inverse correlation between RNFL thickness and total number of headache attacks per months. Our data suggest the involvement of retina and choroid in migraineurs, especially in the CM group. Although migraine is an episodic and recurrent disease, its chronic nature might cause permanent structural abnormalities involving not only the brain, but also the retina.     

The novel synthetic microneurotrophin BNN27 protects mature oligodendrocytes against cuprizone‐induced death,through the NGF receptor TrkA

BNN27, a member of a chemical library of C17‐spiroepoxy derivatives of the neurosteroid DHEA, has been shown to regulate neuronal survival through its selective interaction with NGF receptors (TrkA and p75^NTR), but its role on glial populations has not been studied. Here, we present evidence that BNN27 provides trophic action (rescue from apoptosis), in a TrkA‐dependent manner, to mature oligodendrocytes when they are challenged with the cuprizone toxin in culture. BNN27 treatment also increases oligodendrocyte maturation and diminishes microglia activation in vitro. The effect of BNN27 in the cuprizone mouse model of demyelination in vivo has also been investigated. In this model, that does not directly involve the adaptive immune system, BNN27 can protect from demyelination without affecting the remyelinating process. BNN27 preserves mature oligodendrocyte during demyelination, while reducing microgliosis and astrogliosis. Our findings suggest that BNN27 may serve as a lead molecule to develop neurotrophin‐like blood–brain barrier (BBB)‐permeable protective agents of oligodendrocyte populations and myelin, with potential applications in the treatment of demyelinating disorders.     

Pooled Analysis of Clinical Outcome of Patients with Chemorefractory Metastatic Colorectal Cancer Treated within Phase I/II Clinical Studies Based on Individual Biomarkers of Susceptibility: A Single-Institution Experience

Background

Patients with metastatic colorectal cancer (mCRC) refractory to standard therapies have a poor prognosis. In this setting, recruitment into clinical trials is warranted, and studies driven by selection according to individual tumor molecular characteristics are expected to provide added value.

Objective

We retrospectively analyzed data from patients with mCRC refractory to or following failure of standard therapies who were enrolled into phase I/II clinical studies at the Niguarda Cancer Center based on the presence of a specific molecular profile expected to represent the target of susceptibility to the experimental drug(s).

Patients and Methods

From June 2011 to May 2016, 2044 patients with mCRC underwent molecular screening. Eighty patients (3.9%) were enrolled in ad hoc studies; the median age was 60 years (range 36–86) and the median number of previous treatment lines was five (range 2–8). Molecular characteristics exploited within these studies were MGMT promoter hypermethylation (48.7%), HER2 amplification (28.8%), BRAF ^V600E mutation (20%), and novel gene fusions involving ALK or NTRK (2.5%).

Results

One patient (1%) had RECIST (Response Evaluation Criteria In Solid Tumors) complete response (CR), 13 patients (16.5%) experienced a partial response (PR), and 28 (35%) stable disease (SD). Median progression-free survival (PFS) was 2.8 months (range 2.63–3.83), with 24% of patients displaying PFS >5 months. Median growth modulation index (GMI) was 0.85 (range 0–15.61) and 32.5% of patients had GMI >1.33. KRAS exon 2 mutations were found in 38.5% of patients, and among the 78 patients with known KRAS status, those with wild-type tumors had longer PFS than those with mutated tumors (3.80 [95% CI 2.80–5.03] vs. 2.13 months [95% CI 1.77–2.87], respectively, p = 0.001). Median overall survival (OS) was 7.83 months (range 7.17–9.33) for all patients, and patients with KRAS wild-type tumors had longer OS than those with mutated tumors (7.83 [95% CI 7.33–10.80] vs. 7.18 months [95% CI 5.63–9.33], respectively, p = 0.06).

Conclusions

This single-institution retrospective study indicates that in a heavily pretreated population approximately 4% of mCRC tumors display a potential actionable molecular context suitable for therapeutic intervention. Application of molecular selection is challenging but improves clinical outcome even in later lines of treatment.

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Does exist a correlation between endometriosis and thrombophilic disorders? A pilot study

Objective

At present, there is growing evidence of the existence of a genetic predisposition in both thrombophilic disorders and endometriosis. The aim of our study was to evaluate for the first time the prevalence of some thrombophilic disorders in patients with endometriosis.

Endoscopic management of esophageal stenosis in children: New and traditional treatments

Post-esophageal atresia anastomotic strictures and postcorrosive esophagitis are the most frequent types of cicatricial esophageal stricture. Congenital esophageal stenosis has been reported to be a rare but typical disease in children; other pediatric conditions are peptic, eosinophilic esophagitis and dystrophic recessive epidermolysis bullosa strictures. The conservative treatment of esophageal stenosis and strictures(ES) rather than surgery is a well-known strategy for children. Before planning esophageal dilation, the esophageal morphology should be assessed in detail for its length, aspect, number and level, and different conservative strategies should be chosen accordingly. Endoscopic dilators and techniques that involve different adjuvant treatment strategies have been reported and depend on the stricture’s etiology, the availability of different tools and the operator’s experience and preferences. Balloon and semirigid dilators are the most frequently used tools. No high-quality studies have reported on the differences in the efficacies and rates of complications associated with these two types of dilators. There is no consensus in the literature regarding the frequency of dilations or the diameter that should be achieved. The use of adjuvant treatments has been reported in cases of recalcitrant stenosis or strictures with evidence of dysphagic symptoms. Corticosteroids(either systemically or locally injected), the local application of mitomycin C, diathermy and laser ES sectioning have been reported. Some authors have suggested that stenting can reduce both the number of dilations and the treatment length. In many cases, this strategy is effective when either metallic or plastic stents are utilized. Treatment complications, such esophageal perforations, can be conservatively managed, considering surgery only in cases with severe pleural cavity involvement. In cases of stricture relapse,even if such relapses occur following the execution of well-conducted conservative strategies, surgical stricture resection and anastomosis or esophageal substitution are the only remaining options.     

Hepatocellular carcinoma and the risk of occupational exposure

Hepatocellular carcinoma(HCC)is the most common type of liver cancer.The main risk factors for HCC are alcoholism,hepatitis B virus,hepatitis C virus,nonalcoholic steatohepatitis,obesity,type 2 diabetes,cirrhosis,aflatoxin,hemochromatosis,Wilson’s disease and hemophilia.Occupational exposure to chemicals is another risk factor for HCC.Often the relationship between occupational risk and HCC is unclear and the reports are fragmented and inconsistent.This review aims to summarize the current knowledge regarding the association of infective and non-infective occupational risk exposure and HCC in order to encourage further research and draw attention to this global occupational public health problem.