3p interstitial deletion: novel case report and review

3p interstitial deletions have emerged in recent years as a new cause of neurodevelopmental delay and intellectual disability. Since the first report of this condition in 1979, 16 cases have been described in the literature, delineating it as a presumptive syndrome. Here, we add a novel case presenting severely delayed neurodevelopment and psychomotor development; facial dysmorphism (square facies, broad forehead, short palpebral fissures, epicanthic folds, broad nasal bridge, and low-set malformed ears); cerebral, cardiac, and genital malformations; hand and feet anomalies; sacral sinus; and hearing impairment. Genetic investigations revealed a del(3)(p12.3p14.1) of 12.5 Mb, including 31 ORFs, among which ROBO2, PDZRN3, MITF, and FOXP1 are known to act in neurodevelopment. The clinical features of our patient are compared with those previously reported in the literature, thus providing further support for the delineation of the 3p interstitial deletion syndrome.     

New advances in targeted gastric cancer treatment

Despite a decrease in incidence over past decades,gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours.     

Congenital diaphragmatic hernia: review of the literature in reflection of unresolved dilemmas

Background:  Congenital diaphragmatic hernia (CDH) is a rare but clinically and scientifically challenging condition. The introduction of ultrasound has enabled early prenatal detection and consequently, hope of early therapeutic intervention.
Aim:  We undertook the task to review the recent developments in understanding the pathology of CDH as well as the history and current management strategies to aid perinatologists in consultations with parents of CDH-affected foetuses.
Study design:  A Medline search was undertaken of all reports and reviews published between 1980 and 2008 using MeSH search terms 'diaphragmatic hernia', 'congenital' and 'newborn'.
Results:  The true incidence of CDH is still difficult to estimate because of the high incidence of hidden mortality of CDH. Complete case ascertainment also poses difficulties in assessment of the impact of new therapeutic modalities on overall survival. Recent improvements in prenatal detection are a milestone in affording time for re-assessments and parental counselling. The true benefit of antenatal therapy is circumscribed and should be offered only in selected cases of isolated severe CDH as defined by existing guidelines. Postnatal intensive respiratory supportive therapy and innovative surgical techniques within specialized tertiary centres has had a major impact on survival of babies with CDH.
Conclusion:  The high survival of 'selected cases' that are live births and benefit from optimal care will be difficult to improve by antenatal interventions. The multidisciplinary approach to basic research and randomized clinical trials will further define the best approach to the foetus and neonate with CDH.     

Stroke Mortality Rates and Trends in Romania, 1994-2017

Background and Aim: Romanian national level stroke mortality data is relatively scarce. The current study investigated stroke mortality rates and trends in Romania. Methods: All individual deaths registered in Romania during 1994-2017 were analyzed using an anonymized database, based on death certificates. Stroke crude mortality rates (CMR) and age-standardized mortality rates (ASMR) were calculated and expressed per 100,000 persons-year. Results: Between 1994 and 2017, 6,281,873 persons died in Romania, stroke being registered as the underlying cause of death in 959,319 cases. The overall stroke CMR was 188.2 (199.3 for women and 176.5 for men). The CMR for hemorrhagic stroke (HEMS) was 32.4 and for ischemic stroke (ISCS) 10.9. There was a significant decrease in stroke ASMR from 344.4 (95% confidence interval [CI] 343.4-345.4) in 1994 to 192.1 (95% CI 191.5-192.7) in 2017, with an annual percent change (APC) of 2.53% per year (95% CI 2.50-2.55, P < .001). Although compared with men, women had higher CMRs, when those rates were age-standardized men had higher ASMR as compared with women. The decline in HEMS ASMR had an APC of 4.65% per year (95% CI 4.59-4.70, P < .001). ISCS ASMR showed an initial increase in ASMR during 1994-2005, with APC 6.39% per year (95% CI 6.09-6.70, P < .001), followed by a significant decrease until 2017, with APC 2.83% per year (95% CI 2.59-3.07, P < .001). Conclusion: There was a significant reduction in stroke ASMR during 1994-2017. The decline was slow until 2002 and became steeper after that, with significant differences in gender analysis.     

The mortality of very low birth weight infants: the benefit and relative impact of changes in population and therapeutic variables

Objective: Very low birth weight (VLBW, ≤1500?g) infants’ mortality rates have decreased markedly. We aimed to quantify the relative contribution of changes in the distribution of population characteristics and changes in specific mortality rates on the decline in mortality rates of VLBW infants.

Study design: A population-based observational study of the Israel national VLBW infant database. The study population comprised singleton VLBW infants of 24–32 weeks’ gestation born during the epochs 1995–2000 (n?=?3728) and 2006–2010 (n?=?3246). The Kitagawa methodology was applied to determine the contribution of changes in demographic and perinatal characteristics and changes in specific mortality rates on the decline in mortality between the periods.

Results: During the study epochs, VLBW infant mortality rates decreased from 19.7 to 13.8%. Of the 5.9% decrease in mortality, 60.6% was attributed to the decrease in specific mortality rates and 39.4% to changes in the proportions of population characteristics and therapies, predominantly early initiation of prenatal care (8.1%), antenatal steroids (25.1%), and cesarean delivery (8.1%). For most of the demographic and perinatal categories considered the relative contribution of changes in their proportions was <3%, whereas >97% could be attributed to changes in the specific mortality rates for these characteristics.

Conclusions: The decrease in preterm VLBW infant mortality was attributable predominantly to changes in variable specific mortality rates whereas changes in the proportions of demographic, perinatal risk factors, and therapies had a limited impact on VLBW infant mortality. Future assessment of determinants of VLBW infant mortality data should be dissected by discriminatory models.     

Fine particulate matter and mortality: a comparison of the six cities and American Cancer Society cohorts with a medicare cohort

BACKGROUND: The American Cancer Society study and the Harvard Six Cities study are 2 landmark cohort studies for estimating the chronic effects of fine particulate air pollution (PM2.5) on mortality. Using Medicare data, we assessed the association of PM2.5 with mortality for the same locations included in these studies. METHODS: We estimated the chronic effects of PM2.5 on mortality for the period 2000-2002 using mortality data for cohorts of Medicare participants and average PM2.5 levels from monitors in the same counties included in the 2 studies. We estimated mortality risk associated with air pollution adjusting for individual-level (age and sex) and area-level covariates (education, income level, poverty, and employment). We controlled for potential confounding by cigarette smoking by including standardized mortality ratios for lung cancer and chronic obstructive pulmonary disease. RESULTS: Using the Medicare data, we estimated that a 10 microg/m increase in the yearly average PM2.5 concentration is associated with 10.9% (95% confidence interval = 9.0-12.8) and with 20.8% (14.8-27.1) increases in all-cause mortality for the American Cancer Society and Harvard Six Cities study counties, respectively. The estimates are somewhat higher than those reported by the original investigators. CONCLUSION: Although Medicare data lack information on some potential confounding factors, we estimated risks similar to those in the previously published reports, which incorporated more extensive information on individual-level confounders. We propose that the Medicare files can be used to construct on-going cohorts for tracking the risk of air pollution over time.     

Dental Sealant Composition-Retention Assessment in Young Permanent Molars

Tooth decay in children and adolescents remains a public health problem, despite prophylaxis and preventive measures being largely available. The aim of our study was to evaluate the clinical behavior of four dental sealants, related to first permanent molar topography and patient age (when sealant was applied for the first time). We assessed, by means of visual inspection and palpation with a dental probe, a group of 200 children, enrolled corresponding to school age-grade (mean age of 7 years at baseline) and randomly divided according to the material used as dental sealant (Admira seal©, Embrace Wet Bond©, Fotoseal©, GC Fuji Triaje©) in 4 groups (n = 50). Sealant clinical evaluation was made at 6-, 12-, 18-month intervals for dental material retention assessment. At 6 months, the sealant detached the most from 3.6 molars, and the material used was Fotoseal© (27.6%). At 12 months, Fotoseal© (48.3%) and GC Fuji Triaje© (41.4%) from 3.6 molars express detachment. At 18 months, 4.6. molars sealed with Admira Seal© (25.7%) and Embrace Wet Bond© (28.6%) lost the sealant. We noticed less detachment in maxillary molars and if sealant was applied around 7 years of age. In conclusion, sealant application on first permanent molars must be encouraged and practitioners can choose between various materials available.