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.     

Biomarker-Driven Therapy in Metastatic Gastric and Esophageal Cancer: Real-Life Clinical Experience

Background

Precision treatment of cancer uses biomarker-driven therapy to individualize and optimize patient care.

Objective

To evaluate real-life clinical experience with biomarker-driven therapy in metastatic gastric and esophageal cancer in Israel.

Patients and Methods

This multicenter retrospective cohort study included patients with metastatic gastric or esophageal cancer who were treated in the participating institutions and underwent biomarker-driven therapy. Treatment was considered to have a benefit if the ratio between the longest progression-free survival (PFS) post biomarker-driven therapy and the last PFS before the biomarker-driven therapy was ≥1.3. The null hypothesis was that ≤15% of patients gain such benefit.

Results

The analysis included 46 patients (61% men; median age, 58 years; 57% with poorly-differentiated tumors). At least one actionable (i.e., predictive of response to a specific therapy) biomarker was identified for each patient. Immunohistochemistry was performed on all samples and identified 1–8 (median: 3) biomarkers per patient (most commonly: low TS, high TOPO1, high TOP2A). Twenty-eight patients received therapy after the biomarker analysis (1–4 lines). In the 1st line after biomarker analysis, five patients (18%) achieved a partial response and five (18%) stable disease; the median (range) PFS was 129 (12–1155) days. Twenty-four patients were evaluable for PFS ratio analysis; in seven (29.2%), the ratio was ≥1.3. In a one-sided exact binomial test vs. the null hypothesis, p?=?0.019; therefore, the null hypothesis was rejected.

Conclusions

Our findings demonstrated that implementing biomarker-driven analysis is feasible and could provide clinical benefit for a considerable proportion (~30%) of patients with metastatic gastric or esophageal cancer.

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Preliminary results of immune modulating antibody MDV9300 (pidilizumab) treatment in children with diffuse intrinsic pontine glioma

Journal of Neuro-Oncology - Diffuse intrinsic pontine glioma (DIPG) is an incurable disease with a median overall survival of 10 months. Immune modulating antibodies have recently emerged...     

The relationship between short-term antibiotic treatments and fatigue in healthy individuals

Summary Antibiotic treatment tends sometimes to result in sensations of fatigue and decreased physical performance. The effects of antibiotics were therefore studied in 50 healthy, male trainees, aged 18–25 years, assigned in a random, double-blind fashion to one of the following treatments: tetracycline, ampicillin, trimethoprim/sulphamethoxazole, placebo I and placebo II. Duration of treatment was five times the half-life of each agent and the placebo was matched accordingly. Muscle enzyme activity (serum glutamine oxaloacetate transaminase, lactate dehydrogenase, creatine phosphokinase), maximal aerobic capacity ( O_2max), muscle strength (MS), and rating of subjective sensation of fatigue were assessed prior to and upon conclusion of treatment. Compared to pretreatment values, plasma enzymes activity was elevated in all five groups (P<0.005). No differences in O_2max or in MS were found among the subjects treated with either one of the antibiotics or those given a placebo. A significant difference in O_2max was found between the groups treated for 1 day (antibiotic and placebo) and the groups treated for 3 days (antibiotic and placebo) (P<0.0001). The rating of subjective sensation was not affected by any of the agents. We concluded that in healthy individuals, a short-term antibiotic treatment had no deleterious effect on aerobic capacity or on muscle strength and was not associated with subjective side effects. The time interval between the two maximal tests could, however, have affected the aerobic capacity. Physiological disturbances associated with a sensation of fatigue following a longer period of antibiotics cannot be excluded.     

Cardiac Disease‐Induced Post‐traumatic Stress Symptoms (CDI‐PTSS) Among Patients' Partners

It is well established that a patient's partner can be deeply affected by the traumatizing nature of the patient's illness. Yet, no study to date has focused on post‐traumatic stress symptoms (PTSS) among partners of patients coping with an acute coronary syndrome (ACS). The current study's main aims were to address this gap and to evaluate cardiac disease‐induced (CDI) PTSS prevalence in partners of patients who experienced ACS. Patients who experienced ACS and their partners were interviewed by telephone 2 to 6 months after patients' hospitalization. All patients and partners were screened for CDI‐PTSS. Demographic and medical variables as well as partners' level of exposure to the cardiac event were assessed. Prevalence of CDI‐PTSS was higher among partners than among patients. Partners' number of CDI‐PTSS was not significantly associated with patients' number of CDI‐PTSS or with any of the other explanatory factors measured, except for education level. The preliminary results that arose from the current study point to the vast number of individuals who must act as caregivers for their ill partners while having to cope with their own PTSS. Much effort should be channelled into integrating partners into cardiac recovery programmes. Copyright © 2016 John Wiley & Sons, Ltd.     

Clinical utility and treatment outcome of comprehensive genomic profiling in high grade glioma patients

Genomic research of high grade glioma (HGG) has revealed complex biology with potential for therapeutic impact. However, the utilization of this information and impact upon patient outcome has yet to be assessed. We performed capture-based next generation sequencing (NGS) genomic analysis assay of 236/315 cancer-associated genes, with average depth of over 1000 fold, to guide treatment in HGG patients. We reviewed clinical utility and response rates in correlation to NGS results. Forty-three patients were profiled: 34 glioblastomas, 8 anaplastic astrocytomas, and one patient with anaplastic oligodendroglioma. Twenty-five patients were profiled with the 315 gene panel. The median number of identified genomic alterations (GAs) per patient was 4.5 (range 1–23). In 41 patients (95?%) at least one therapeutically-actionable GA was detected, most commonly in EGFR [17 (40?%)]. Genotype-directed treatments were prescribed in 13 patients, representing a 30?% treatment decision impact. Treatment with targeted agents included everolimus as a single agent and in combination with erlotinib; erlotinib; afatinib; palbociclib; trametinib and BGJ398. Treatments targeted various genomic findings including EGFR alterations, mTOR activation, cell cycle targets and FGFR1 mutations. None of the patients showed response to respective biologic treatments. In this group of patients with HGG, NGS revealed a high frequency of GAs that lead to targeted treatment in 30?% of the patients. The lack of response suggests that further study of mechanisms of resistance in HGG is warranted before routine use of biologically-targeted agents based on NGS results.     

Increasing chronic subdural hematoma after endoscopic III ventriculostomy

Object: Endoscopic III ventriculostomy (ETV) is an effective and a rather safe treatment for noncommunicating hydrocephalus secondary to aqueductal stenosis and other obstructive pathologies. Though not devoid of risk, ETV is increasingly replacing shunt operations, and it prevents related complications, including overdrainage. Methods: We report a rare case of a large chronic subdural hematoma (ChSDH) after ETV in a patient with aqueductal stenosis. Three weeks after he was shunted elsewhere, he presented to us with clinical symptoms of intracranial hypotension and overdrainage. ETV was performed and the shunt removed uneventfully. On routine postoperative MRI a few weeks later, a large ChSDH was noted, the patient being totally asymptomatic. Since the ChSDH grew significantly, causing a mass effect on the follow-up MRI, it was finally drained. Large and increasing ChSDHs have previously been reported secondary to overdrainage after shunt placement, but not after ETV. Conclusions: We conclude that though rare, a ChSDH may evolve even after ETV, if there is a substantial decrease in previously elevated intracranial pressure. Received: 28 December 1999