Multigeneration maternal transmission in Italian families with neural tube defects

Periconceptional vitamin supplementation with folate prevents about three-quarters of expected cases of neural tube defects (NTDs) in clinical trials. However, vitamin action may be regulated at the level of the gene, and individual susceptibility to environmental agents, including dietary components, also may be under genetic control. We investigated the presence of familial factors in a retrospective case control study of neural tube defects in Genoa, Italy. Cases included all patients treated at a single pediatric neurosurgical service. Controls matched on age and sex came from the same hospital. We found strong evidence for the contribution of genetic factors in this study. There was an excess risk of 14 for the occurrence of NTDs in first-degree relatives compared to controls (P < .0005). There was no difference in sex ratio in any group of relatives, but maternal grandparents of children with a high spinal lesion had 14% fewer offspring than paternal grandparents (P < .005), possibly because of excess miscarriages. Our study is the first to show complex patterns of inheritance in spina bifida families affecting three generations in one clinical subgroup and preferentially on the mother's side. These results support a role for genomic imprinting and highlight the value of multidisciplinary epidemiologic and clinical studies that include multiple generations. New studies incorporating dietary and genetic approaches will help clarify and extend these findings. © 1996 Wiley-Liss, Inc.     

Statin use and pancreatic cancer risk in two prospective cohort studies

Background

Statins, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, are common lipid-lowering agents and may reduce the risk of several cancer types including pancreatic cancer. However, the association between statin use and pancreatic cancer risk has not been fully evaluated in prospective studies.

Methods

We studied the association between statin use and incident pancreatic cancer in 113,059 participants from the prospective Nurses’ Health Study and Health Professionals Follow-up Study. Statin use was self-reported via study questionnaires and updated biennially. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incidence of pancreatic cancer were estimated using multivariable Cox proportional hazards models with adjustment for potential confounders.

Results

In total, 583 participants developed incident pancreatic cancer during 1.4 million person-years of follow-up. No difference was identified in pancreatic cancer risk for regular versus non-regular statin users (multivariable-adjusted HR 0.98; 95% CI 0.82–1.16). There was no significant heterogeneity in the association of statin use with pancreatic cancer risk between the cohorts. Similarly, longer duration of regular statin use was not associated with decreased risk of pancreatic cancer (P_trend = 0.65). The results remained similar when we examined statin use status at baseline or accounting for 4-year latency period. We observed no statistically significant effect modification for the association of statin use with pancreatic cancer risk by body mass index, smoking status, or diabetes mellitus status (all P_interaction > 0.21).

Conclusions

Regular statin use was not associated with pancreatic cancer risk in two large prospective cohort studies in the U.S.

     

The predictive power of transcranial sonography in movement disorders: a longitudinal cohort study

Transcranial sonography (TCS) is a noninvasive, easily performed, and commonly available neuroimaging technique useful for the study of brain parenchyma in movement disorders. This tool has been increasingly used in the diagnosis of Parkinson’s disease and atypical parkinsonism. The aim of the study was to evaluate the applicability of this technique as supportive tool in the early diagnosis of movement disorders. We performed TCS on 315 individuals which were diagnosed as healthy controls or affected by idiopathic Parkinson’s disease, monogenetic subtypes of Parkinson’s disease, atypical parkinsonism, and Dementia with Lewy bodies. Five TCS diagnostic patterns were defined on the basis of substantia nigra’s and lenticular nuclei’s echogenicity. TCS evaluations were performed by two blinded neuro-sonographers. Clinical diagnosis on all individuals was performed at baseline and at 4-year follow-up. The concordance rate between TCS patterns and clinical diagnosis and the specificity of TCS pattern to discriminate each group of individuals were compared at baseline and at follow-up. The concordance rate between TCS patterns and clinical diagnosis of all individuals was 84% at baseline and increased at follow-up (91%) significantly (p?=?0.01). The specificity of TCS pattern in the comparison between patients diagnosed as affected by idiopathic Parkinson’s disease and atypical parkinsonism showed a significant increase at follow-up (p?=?0.03). Our study strongly confirms the role of TCS as a noninvasive and cost-effective tool in early diagnosis of movement disorders.     

Heart Transplant and Hepato-Renal Dysfunction: The Model of End-Stage Liver Disease Excluding International Normalized Ratio as a Predictor of Postoperative Outcomes

IntroductionPreoperative liver and renal dysfunction remain surgical risk factors for both postoperative morbidity and mortality. The Model of End-Stage Liver Disease Excluding INR (international normalized ratio), or MELD-XI, score calculation may help as a predictor in patients with advanced heart failure. We analyzed the impact of progressive elevated MELD-XI values among recipients of heart transplant at our institution.MethodsThe data of a total of 425 consecutive adult patients who underwent heart transplantation, between January 2000 and August 2018, have been reviewed and divided into 3 cohorts according to preoperative MELD-XI calculations (MELD-XI < 11; MELD-XI 11-18; and MELD-XI > 18). Early and late outcomes have been analyzed.ResultsPatients with a MELD-XI score > 18 had a more critical clinical condition preoperatively and had a higher risk of early mortality (hazard ratio [HR] 1.45 [1.11-1.67], P < .001). They showed high risk for postoperative dialysis (HR 2.8 [1.5-5.3], P < .001), rethoracothomy for bleeding (HR 2.1 [1.2-4.1], P = .001), prolonged time of mechanical ventilation, time of intensive care unit stay (HR 2.2 [1.3-3.8], P = .005), and graft failure requiring mechanical circulatory support (HR 1.9 [1.1-3.3], P = .003). After risk adjustment per MELD-XI cohort, ischemic dilated cardiomyopathy, redo operation, and cold ischemic time > 240 minutes resulted in being the strongest predictors of early mortality (P < .001). The 5-year and 10-year survival for MELD-XI > 18 cohort was 63% and 47% vs 72% and 59% in the control group (MELD-XI < 18) (log-rank, P < .001).ConclusionsPatients with an elevated preoperative MELD-XI profile presented more comorbidities and significantly lower survival. This suggests the MELD-XI score may provide further insight into appropriate recipient and eventual donor selection. Renal insufficiency and congestive hepatopathy should be properly optimized before heart transplantation.     

Validation of Fetal Medicine Foundation algorithm for prediction of pre-eclampsia in the first trimester in an unselected Brazilian population

Objective: The objective of this study is to evaluate the predictive performance of the Fetal Medicine Foundation (FMF) algorithm for prediction of preeclampsia (PE) between 11 and 14 weeks of gestation in an unselected Brazilian population.

Methods: We conducted a prospective cohort study with 617 singleton pregnancies of unselected risk. Biophysical markers (mean pulsatility index, mean arterial pressure) and biochemical markers (placental growth factor (PLGF) and PAPP-A) were inserted into the FMF software and converted into multiples of the median (MoM). The subjects were divided into five groups: early-onset PE, parturition <34 weeks’ gestation; preterm PE, parturition <37 weeks; PE, parturition at any gestational age; gestational hypertension (GH); and control group. Areas under the receiver operating characteristics curve (AUC) were calculated for the outcomes.

Results: Among 617 patients, seven developed early-onset PE, 18 developed preterm PE (seven early PE plus 11 delivered between 34 and 36?+?6 weeks gestation), 34 developed PE (18 preterm PE plus 16 delivered after 37-week gestation), 12 pregnant women developed GH, and 517 women comprised the control group. The best predictive performance using the FMF algorithm occurred in the early-onset PE group, with AUC?=?0.946 (95% CI 0.919–0.973) and the detection rate of 28.6% and 85.7% for 5% and 10% false-positive (FP), respectively.

Conclusions: The FMF algorithm to predict PE was effective in a Brazilian population, mainly in the early-onset form of the disease at 10% FP.