A Retrospective Study of Short-term versus Long-term Use of High Flow Nasal Cannula after Extubation in the Intensive Care Unit.

BACKGROUND: The use of a high flow nasal cannula (HFNC) was examined for different clinical indications in the critically ill. OBJECTIVES: To describe a single center experience with HFNC in post-extubation critical care patients by using clinical indices. METHODS: In this single center study, the authors retrospectively evaluated the outcome of patients who were connected to the HFNC after their extubation in the intensive care unit (ICU). At 48 hours after the extubation, the patients were divided into three groups: the group weaned from HFNC, the ongoing HFNC group, and the already intubated group. RESULTS: Of the 80 patients who were included, 42 patients were without HFNC support at 48 hours after extubation, 22 and 16 patients were with ongoing HFNC support and already intubated by this time frame, respectively. The mean ROX index (the ratio of SpO2 divided by fraction of inspired oxygen to respiratory rate) at 6 hours of the weaned group was 12.3 versus 9.3 in the ongoing HFNC group, and 8.5 in the reintubated group (P = 0.02). The groups were significantly different by the ICU length of stay, tracheostomy rate, and mortality. CONCLUSIONS: Among patients treated with HFNC post-extubation of those who had a higher ROX index were less likely to undergo reintubation.

Mortality, cancer incidence, and survival in parents after bereavement.

PURPOSE: The study objective was to investigate whether child loss is related to mortality, cancer incidence, and cancer survival in parents. METHODS: We used a population-based birth cohort (1964-1976) in Jerusalem and ascertained mortality (average follow-up of 39.1 years) and any cancer (average follow-up of 35.6 years) among parents who lost a child (2838 mothers and 2532 fathers) and among nonbereaved parents (38,212 mothers and 36,433 fathers). We also assessed mortality among parents with cancer. Time-dependent Cox models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Overall mortality rates among bereaved parents were modestly increased when compared with nonbereaved parents (HR = 1.18, 95% CI: 1.05-1.32 in mothers; HR = 1.10, 95% CI: 1.01-1.20 in fathers). Hazard models indicated a significant relationship between bereavement and deaths from coronary heart disease in mothers (HR = 1.90, 95% CI: 1.23-2.95) and circulatory causes in both parents (HR = 1.69; 95% CI: 1.22-2.34 in mothers and HR = 1.25; 95% CI: 1.02-1.54 in fathers). Bereavement was not associated with parental risk of cancer disease and with survival from cancer. The association between bereavement and parental overall mortality was similar in the different parental sociodemographic characteristics. We observed a decrease in HRs for parental mortality associated with bereavement, with increasing time since the death of the child (HRs = 9-10, 0-3 years; HRs = 0.9-1.0, 9+ years; P(heterogeneity) ≤ 3 × 10(-32)). A similar decrease in HRs was observed for parental survival from cancer (HRs = 6.7-8.7, 0-3 years; HRs = 0.9-1.0, 9+ years). CONCLUSIONS: Our study suggests that child loss was associated with slightly increased risk of all-cause and circulatory mortality in parents but not with incidence of cancer and cancer survival. The considerable increased parental mortality during a short period after child loss support the involvement of pathways related to psychological stress.

A genome-wide association study of n-3 and n-6 plasma fatty acids in a Singaporean Chinese population.

Polyunsaturated fatty acids (PUFAs) have a major impact on human health. Recent genome-wide association studies (GWAS) have identified several genetic loci that are associated with plasma levels of n-3 and n-6 PUFAs in primarily subjects of European ancestry. However, the relevance of these findings has not been evaluated extensively in other ethnic groups. The primary aim of this study was to evaluate for genetic loci associated with n-3 and n-6 PUFAs and to validate the role of recently identified index loci using data from a Singaporean Chinese population. Using a GWAS approach, we evaluated associations with plasma concentrations of three n-3 PUFAs [alphalinolenic acid (ALA), eicosapentaenoic acid and docosahexaenoic acid], four n-6 PUFAs [linoleic acid (LA), gammalinolenic acid, dihomogammalinolenic acid (DGLA) and arachidonic acid], and estimates of delta-5 desaturase and delta-6 desaturase activities among the participants (N = 1361) of the Singaporean Chinese Health Study. Our results reveal robust genome-wide associations (p value <5 × 10(-8)) with ALA, all four n-6 PUFAs, and delta-6 desaturase activity at the FADS1/FADS2 locus. We further replicated the associations between common index variants at the NTAN1/PDXDC1 locus and n-6 PUFAs LA and DGLA, and between the JMJD1C locus and n-6 PUFA LA (p value between 0.0490 and 9.88 × 10(-4)). These associations were independent of dietary intake of PUFAs. In aggregate, we show that genetic loci that influence plasma concentrations of n-3 and n-6 PUFAs are shared across different ethnic groups.

Maternal genetic variation accounts in part for the associations of maternal size during pregnancy with offspring cardiometabolic risk in adulthood.

BACKGROUND: Maternal pre-pregnancy body-mass index (ppBMI) and gestational weight gain (GWG) are associated with cardiometabolic risk (CMR) traits in the offspring. The extent to which maternal genetic variation accounts for these associations is unknown. METHODS/RESULTS: In 1249 mother-offspring pairs recruited from the Jerusalem Perinatal Study, we used archival data to characterize ppBMI and GWG and follow-up data from offspring to assess CMR, including body mass index (BMI), waist circumference, glucose, insulin, blood pressure, and lipid levels, at an average age of 32. Maternal genetic risk scores (GRS) were created using a subset of SNPs most predictive of ppBMI, GWG, and each CMR trait, selected among 1384 single-nucleotide polymorphisms (SNPs) characterizing variation in 170 candidate genes potentially related to fetal development and/or metabolic risk. We fit linear regression models to examine the associations of ppBMI and GWG with CMR traits with and without adjustment for GRS. Compared to unadjusted models, the coefficient for the association of a one-standard-deviation (SD) difference in GWG and offspring BMI decreased by 41% (95%CI -81%, -11%) from 0.847 to 0.503 and the coefficient for a 1SD difference in GWG and WC decreased by 63% (95%CI -318%, -11%) from 1.196 to 0.443. For other traits, there were no statistically significant changes in the coefficients for GWG with adjustment for GRS. None of the associations of ppBMI with CMR traits were significantly altered by adjustment for GRS. CONCLUSIONS: Maternal genetic variation may account in part for associations of GWG with offspring BMI and WC in young adults.

Delineation of C12orf65-related phenotypes: a genotype-phenotype relationship.

C12orf65 participates in the process of mitochondrial translation and has been shown to be associated with a spectrum of phenotypes, including early onset optic atrophy, progressive encephalomyopathy, peripheral neuropathy, and spastic paraparesis.We used whole-genome homozygosity mapping as well as exome sequencing and targeted gene sequencing to identify novel C12orf65 disease-causing mutations in seven affected individuals originating from two consanguineous families. In four family members affected with childhood-onset optic atrophy accompanied by slowly progressive peripheral neuropathy and spastic paraparesis, we identified a homozygous frame shift mutation c.413_417 delAACAA, which predicts a truncated protein lacking the C-terminal portion. In the second family, we studied three affected individuals who presented with early onset optic atrophy, peripheral neuropathy, and spastic gait in addition to moderate intellectual disability. Muscle biopsy in two of the patients revealed decreased activities of the mitochondrial respiratory chain complexes I and IV. In these patients, we identified a homozygous splice mutation, g.21043 T>A (c.282+2 T>A) which leads to skipping of exon 2. Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features. In addition, a clear genotype-phenotype correlation is anticipated in which deleterious mutations which disrupt the GGQ-containing domain in the first coding exon are expected to result in a more severe phenotype, whereas down-stream C-terminal mutations may result in a more favorable phenotype, typically lacking cognitive impairment.

Leukocyte blood count during early puerperium and its relation to puerperal infection†.

OBJECTIVE: To describe the white blood cell (WBC) and neutrophil counts in early puerperium and to investigate their contribution to the diagnosis of puerperal bacterial infection. METHODS: A retrospective cohort analysis through which clinical and laboratory data were collected from 67 695 term live births. Total leukocyte and neutrophil blood count percentiles were established for febrile parturients (FP) with puerperal fever (≥38 °C) and for non-FP (NFP), and stratified by mode of delivery. Rates of positive bacterial cultures were compared according to the total leukocyte and neutrophil blood counts. RESULTS: Mean WBC counts of parturients delivering vaginally and by cesarean section were 12.62 × 10(3) and 12.71 × 10(3)/µL for NFP, and 14.38 × 10(3) and 12.74 × 10(3)/µL for FP, respectively. The proportions of parturients with a WBC count of ≥15 × 10(3)/µL were 36.4% for FP and 21.8% for NFP (p < 0.001). Neutrophils comprised 80% or more of the leukocyte count in 57.6% of FP and in 30.6% of NFP (p < 0.001). However, no statistically significant differences in the rates of positive bacterial cultures were observed between those with high and low levels of leukocytes and neutrophils. CONCLUSIONS: Leukocytosis and non-extreme neutrophilia were not found to reliably associate with bacterial infection, and their value in determining antibiotic therapy is questioned.

The association of maternal intrapartum subfebrile temperature and adverse obstetric and neonatal outcomes.

BACKGROUND: Subfebrile intrapartum maternal temperature is very common, yet there is sparse evidence regarding its causes or its effects on perinatal outcomes. We examined whether mild temperature elevation during labour is a risk marker for adverse obstetric and neonatal outcomes. METHODS: A retrospective cohort analysis including 42 601 term, singleton live-births in two medical centres between 2003 and 2010 was performed. This study compared women who experienced a maximal intrapartum temperature of ≤37°C with women who experienced subfebrile intrapartum temperature (37.1-37.9°C). Adjusted risks for adverse obstetric and neonatal outcomes were calculated by using multivariable logistic regression models. RESULTS: Compared with maternal temperature ≤ 37°C, subfebrile temperature was associated with higher rates of primary caesarean deliveries {adjusted odds ratios [aOR] = 1.36 [95% confidence interval (CI) 1.25, 1.49])} and assisted vaginal deliveries (aOR = 1.20 [95% CI 1.11, 1.30]), as well as with greater risks of early neonatal sepsis (aOR = 2.66 [95% CI 1.88, 3.77]), neonatal intensive care unit admissions (aOR = 1.40 [95% CI 1.08, 1.83]), and neonatal asphyxia or seizures (aOR = 3.18 [95% CI 1.51, 6.70]). Mildly elevated maternal intrapartum temperature (37.1-37.5°C) was also associated with adverse outcomes. CONCLUSIONS: Maternal intrapartum subfebrile temperature may be an indicator of operative delivery and neonatal morbidity. Further research is needed to confirm these findings and to reveal underlying mechanisms.

Associations of maternal pre-pregnancy and gestational body size with offspring longitudinal change in BMI.

OBJECTIVES: Studies demonstrate associations between changes in obesity-related phenotypes and cardiovascular risk. Although maternal pre-pregnancy BMI (mppBMI) and gestational weight gain (GWG) may be associated with adult offspring adiposity, no study has examined associations with obesity changes. Associations of mppBMI and GWG with longitudinal change in offspring's BMI (ΔBMI) were examined, and whether associations are explained by offspring genetics was assessed. METHODS: A birth cohort of 1400 adults, with data at birth, age 17 and 32 years was used. After genotyping offspring, genetic scores, predictive of exposures and outcome were created, and linear regression models with and without scores were fit to examine the associations of mppBMI and GWG with ΔBMI. RESULTS: A one SD change in mppBMI and GWG was associated with a 0.83 and a 0.75 kg/m² increase in ΔBMI, respectively. The association between mppBMI and offspring ΔBMI was slightly attenuated (12%) with the addition of genetic scores. In the GWG model, a significant substantial 28.2% decrease in the coefficient was observed. CONCLUSIONS: This study points to an association between maternal excess weight in pregnancy and offspring BMI change from adolescence to adulthood. Genetic factors may account, in part, for GWG/ΔBMI association. These findings broaden observations that maternal obesity-related phenotypes have long-term consequences for offspring health.

Association between number of children and mortality of mothers: results of a 37-year follow-up study.

PURPOSE: To examine the association between parity and long-term, all-cause mortality and mortality owing to specific causes in women. METHODS: This prospective population-based study included 40,454 mothers who gave birth in Western Jerusalem, Israel, to 125,842 children and were followed for an average of 37 years after the birth of their first child. Cox proportional hazards models were used to evaluate long-term total and specific-cause mortality of women by their parity. RESULTS: We found a U-shaped relationship between the number of offspring and risk of all-cause mortality in mothers. After adjustment for sociodemographic characteristics and maternal health and obstetric conditions, higher mortality rates were observed for mothers of 1 child (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.04-1.4), mothers of 5 to 9 children (HR, 1.21; 95% CI, 1.09-1.33), and mothers of 10 or more children (HR, 1.49; 95% CI, 1.12-1.99) compared with mothers of 2 to 4 children. Mortality risk from specific causes including coronary disease, circulatory disease, and cancer were increased for multiparous women. CONCLUSIONS: In this long-term follow-up study, there was an association between number of children and mortality risk for mothers. These findings suggest that maternal pregnancies and postnatal characteristics as reflected by number of children may have consequences for long-term maternal health.

Associations of maternal prepregnancy body mass index and gestational weight gain with adult offspring cardiometabolic risk factors: the Jerusalem Perinatal Family Follow-up Study.

BACKGROUND: Accumulating evidence demonstrates that both maternal prepregnancy body mass index (mppBMI) and gestational weight gain (GWG) are associated with adult offspring adiposity. However, whether these maternal attributes are related to other cardiometabolic risk factors in adulthood has not been comprehensively studied. METHODS AND RESULTS: We used a birth cohort of 1400 young adults born in Jerusalem who had extensive archival data and clinical information at 32 years of age to prospectively examine the associations of mppBMI and GWG with adiposity and related cardiometabolic outcomes. Greater mppBMI, independently of GWG and confounders, was significantly associated with higher offspring BMI, waist circumference, systolic and diastolic blood pressures, insulin, and triglycerides and with lower high-density lipoprotein cholesterol. For example, the effect sizes were translated to nearly 5 kg/m(2) higher mean BMI, 8.4 cm higher waist circumference, 0.13 mmol/L (11.4 mg/dL) higher triglycerides, and 0.10 mmol/L (3.8 mg/dL) lower high-density lipoprotein cholesterol among offspring of mothers within the upper mppBMI quartile (mppBMI >26.4 kg/m(2)) compared with the lower quartile (mppBMI <21.0 kg/m(2)). GWG, independently of mppBMI, was positively associated with offspring adiposity; differences of 1.6 kg/m(2) in BMI and 2.4 cm in waist were observed when offspring of mothers in the upper (GWG >14 kg) and lower (GWG <9 kg) quartiles of GWG were compared. Further adjustment for offspring adiposity attenuated the observed associations to the null. CONCLUSIONS: Maternal size both before and during pregnancy is associated with cardiometabolic risk factors in young adult offspring. The associations appear to be driven mainly by offspring adiposity. Future studies that explore mechanisms underlying the intergenerational cycle of obesity are warranted to identify potentially novel targets for cardiometabolic risk-reduction interventions.

Evidence for clinical and genetic heterogeneity in hereditary benign telangiectasia.

BACKGROUND: Telangiectases are abnormal dilatations of end vessels in the subpapillary plexus of the papillary dermis. Hereditary benign telangiectasia (HBT) (OMIM 187260) is a genetic skin disorder, characterized by multiple cutaneous telangiectases appearing in the first years of life in various locations. Several familial cases of HBT have been described displaying autosomal dominant inheritance. In some of the described pedigrees, telangiectases are limited to sun-exposed areas, whereas in others lesions are randomly distributed over the body. The disorder has been previously mapped to a 7Mb interval on chromosome 5q14 (CMC1 locus) in an Italian pedigree with randomly distributed telangiectases. OBJECTIVES: A large pedigree of HBT with photodistributed lesions is described. We sought to determine whether photodistributed HBT is linked to the CMC1 locus. METHODS: In all, 35 family members were examined. DNA was extracted from blood and saliva samples. Linkage analysis to CMC1 locus on chromosome 5q14 was screened by using 3 polymorphic markers. RESULTS: In all, 23 family members were found to have variable numbers of cutaneous radiating macular telangiectases, measuring 1 to 3 cm and distributed over the face, back of the hands, and forearms. HBT in this family is inherited in an autosomal dominant pattern with incomplete penetrance. Linkage to the CMC1 locus was excluded. LIMITATION: Only one family, although very large, was studied in this project. CONCLUSIONS: Clinical and genetic heterogeneity is evident in HBT. Photodistributed HBT is not related pathogenically to capillary malformations or to randomly distributed hereditary telangiectases and should be recognized as a separate entity.