Whole exome sequencing reveals intertumor heterogeneity and distinct genetic origins of sporadic synchronous colorectal cancer

Abstract

Sporadic synchronous colorectal cancer (CRC) refers to more than one primary tumor detected in a single patient at the time of the first diagnosis without predisposition of cancer development. Given the same genetic and microenvironment they raise, sporadic synchronous CRC is a unique model to study CRC tumorigenesis. We performed whole exome sequencing in 32 fresh frozen tumor lesions from 15 patients with sporadic synchronous CRC to compare their genetic alterations. This approach identified ubiquitously mutated genes in the range from 0.34% to 4.22% and from 0.8% to 7.0% in non-hypermutated tumors and hypermutated tumors, respectively, in a single patient. We show that both ubiquitously mutated genes and candidate cancer genes from different tumors in the same patient mutated at different sites. Consistently, obvious differences in somatic copy number variations (SCNV) were found in most patients with non-hypermutated tumor lesions, which had ubiquitous copy number amplification rates ranging from 0% to 8.8% and ubiquitous copy number deletion rates ranging from 0% to 8.2%. Hypermutated lesions were nearly diploid with 0% to 18.8% common copy number aberrations. Accordingly, clonal structures, altered signaling pathways, and druggable genes in a single patient with synchronous CRC varied significantly. Taken together, the disparate SCNVs and mutations in synchronous CRC supported the field effect theory of tumorigenesis. Moreover, the intertumor heterogeneity of synchronous CRCs implies that analysis of all tumor lesions from the same patient is necessary for appropriate clinical treatment decisions. This article is protected by copyright. All rights reserved.

http://ift.tt/2hfsQPM

Detection of Cryptosporidium and Cyclospora Oocysts from Environmental Water for Drinking and Recreational Activities in Sarawak, Malaysia

Cryptosporidiosis and cyclosporiasis are caused by waterborne coccidian protozoan parasites of the genera Cryptosporidium and Cyclospora, respectively. This study was conducted to detect Cryptosporidium and Cyclospora oocysts from environmental water abstracted by drinking water treatment plants and recreational activities in Sarawak, Malaysia. Water samples (12 each) were collected from Sungai Sarawak Kanan in Bau and Sungai Sarawak Kiri in Batu Kitang, respectively. In addition, 6 water samples each were collected from Ranchan Recreational Park and UNIMAS Lake at Universiti Malaysia Sarawak, Kota Samarahan, respectively. Water physicochemical parameters were also recorded. All samples were concentrated by the iron sulfate flocculation method followed by the sucrose floatation technique. Cryptosporidium and Cyclospora were detected by modified Ziehl-Neelsen technique. Correlation of the parasites distribution with water physicochemical parameters was analysed using bivariate Pearson correlation. Based on the 24 total samples of environmental water abstracted by drinking water treatment plants, all the samples (24/24; 100%) were positive with Cryptosporidium, and only 2 samples (2/24; 8.33%) were positive with Cyclospora. Based on the 12 total samples of water for recreational activities, 4 samples (4/12; 33%) were positive with Cryptosporidium, while 2 samples (2/12; 17%) were positive with Cyclospora. Cryptosporidium oocysts were negatively correlated with dissolved oxygen (DO).

http://ift.tt/2iy1MYw

Bioactive treatments in bone grafts for implant-based rehabilitation: Systematic review and meta-analysis

Abstract

Background

The use of bioactive proteins, such as rhBMP-2, may improve bone regeneration in oral and maxillofacial surgery.

Purpose

Analyze the effect of using bioactive proteins for bone regeneration in implant-based rehabilitation.

Materials and Methods

Seven databases were screened. Only clinical trials that evaluated the use of heterologous sources of bioactive proteins for bone formation prior to implant-based rehabilitation were included. Statistical analyses were carried out using a random-effects model by comparing the standardized mean difference between groups for bone formation, and risk ratio for implant survival (P ≤ .05).

Results

Seventeen studies were included in the qualitative analysis, and 16 in the meta-analysis. For sinus floor augmentation, bone grafts showed higher amounts of residual bone graft particles than bioactive treatments (P ≤ .05). While for alveolar ridge augmentation bioactive treatments showed a higher level of bone formation than control groups (P ≤ .05). At 3 years of follow-up, no statistically significant differences were observed for implant survival (P > .05).

Conclusions

Bioactive proteins may improve bone formation in alveolar ridge augmentation, and reduce residual bone grafts in sinus floor augmentation. Further studies are needed to evaluate the long-term effect of using bioactive treatments for implant-based rehabilitation.

http://ift.tt/2zjEu0q

Early participant-reported symptoms as predictors of adherence to anastrozole in the International Breast Cancer Intervention Studies II

Abstract

Background

Anastrozole reduces breast cancer risk in women at high risk, but implementing preventive therapy in clinical practice is difficult. Here, we evaluate adherence to anastrozole in the International Breast Cancer Intervention Study (IBIS) II prevention and Ductal Carcinoma in Situ (DCIS) trials, and its association with early symptoms.

Patients and methods

In the prevention trial, 3864 postmenopausal women were randomized to placebo vs. anastrozole. 2980 postmenopausal women with DCIS were randomized to tamoxifen vs. anastrozole. Adherence to trial medication was calculated using the Kaplan-Meier method and all P-values were two-sided.

Results

In the prevention trial, adherence was 65.8% (anastrozole (65.7%) vs. placebo (65.9%); HR = 0.97 (0.87-1.09), p=0.6). Adherence was lower for those reporting arthralgia in the placebo group (p=0.02) or gynecological symptoms in the anastrozole group (P=0.003), compared with those not reporting these symptoms at 6 months. In the DCIS study, adherence was 66.7% (anastrozole (67.5%) vs. tamoxifen (65.8%); HR = 1.06 (0.94-1.20), p=0.4). Hot flashes were associated with greater adherence in the anastrozole arm (p=0.02). In both studies, symptoms were mostly mild or moderately severe, and adherence decreased with increasing severity for most symptoms. Drop-outs were highest in the first 1.5 years of therapy in both trials.

Conclusions

In the IBIS-II prevention and DCIS trials, over two-thirds of women were adherent to therapy, with no differences by treatment groups. Participants who reported specific symptoms in the IBIS-II prevention trial had a small but significant effect on adherence, which strengthened as severity increased. Strategies to promote adherence should target the first year of preventive therapy.

http://ift.tt/2iyuad8

Impact of Neoadjuvant Chemoradiotherapy on Health Related Quality of Life In Long-Term Survivors of Esophageal or Junctional Cancer: Results from the Randomized Cross Trial

Abstract

Background

Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard of care for patients with esophageal or junctional cancer, but the long-term impact of nCRT on health-related quality of life (HRQOL) is unknown. The purpose of this study is to compare very long-term HRQOL in long-term survivors of esophageal cancer who received nCRT plus surgery or surgery alone.

Patients and methods

Patients were randomly assigned to receive nCRT (carboplatin/paclitaxel with 41.4Gy radiotherapy) plus surgery or surgery alone. HRQOL was measured using EORTC-QLQ-C30, EORTC-QLQ-OES24 and K-BILD questionnaires after a minimum follow-up of 6 years. To allow for examination over time, EORTC-QLQ-C30 and QLQ-OES24 questionnaire scores were compared to pre-treatment and 12-months-postoperative questionnaire scores. Physical functioning (QLQ-C30), eating problems (QLQ-OES24) and respiratory problems (K-BILD) were predefined primary endpoints. Predefined secondary endpoints were global quality of life and fatigue (both QLQ-C30).

Results

After a median follow-up of 105 months, 123/368 included patients (33%) were still alive (70 nCRT plus surgery, 53 surgery alone). No statistically significant or clinically relevant differential effects in HRQOL-endpoints were found between both groups. Compared to one-year postoperative levels, eating problems, physical functioning, global quality of life and fatigue remained at the same level in both groups. Compared to pre-treatment levels, eating problems had improved (Cohen's d -0.37, p = 0.011) during long-term follow-up, whereas physical functioning and fatigue were not restored to pre-treatment levels in both groups (Cohen's d -0.56 and 0.51, resp., both p < 0.001).

Conclusion(s)

Although physical functioning and fatigue remain reduced after long-term follow-up, no adverse impact of nCRT is apparent on long-term HRQOL compared to patients who were treated with surgery alone. In addition to the earlier reported improvement in survival and the absence of impact on short-term HRQOL, these results support the view that nCRT according to CROSS can be considered as a standard of care.

CLINICAL TRIALS NUMBER

Trial registration number: Netherlands Trial Register NTR487

http://ift.tt/2h6T1UT

Infant Group B Streptococcal Disease Incidence and Serotypes Worldwide: Systematic Review and Meta-analyses

Abstract

Background

Group B Streptococcus (GBS) remains a leading cause of neonatal sepsis in high-income contexts, despite declines due to intrapartum antibiotic prophylaxis (IAP). Recent evidence suggests higher incidence in Africa, where IAP is rare. We investigated the global incidence of infant invasive GBS disease and the associated serotypes, updating previous estimates.

Methods

We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data regarding invasive GBS disease in infants aged 0–89 days. We conducted random-effects meta-analyses of incidence, case fatality risk (CFR), and serotype prevalence.

Results

We identified 135 studies with data on incidence (n = 90), CFR (n = 64), or serotype (n = 45). The pooled incidence of invasive GBS disease in infants was 0.49 per 1000 live births (95% confidence interval [CI], .43–.56), and was highest in Africa (1.12) and lowest in Asia (0.30). Early-onset disease incidence was 0.41 (95% CI, .36–.47); late-onset disease incidence was 0.26 (95% CI, .21–.30). CFR was 8.4% (95% CI, 6.6%–10.2%). Serotype III (61.5%) dominated, with 97% of cases caused by serotypes Ia, Ib, II, III, and V.

Conclusions

The incidence of infant GBS disease remains high in some regions, particularly Africa. We likely underestimated incidence in some contexts, due to limitations in case ascertainment and specimen collection and processing. Burden in Asia requires further investigation.

http://ift.tt/2j3FD8v

Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children: Why, What, and How to Undertake Estimates?

Abstract

Improving maternal, newborn, and child health is central to Sustainable Development Goal targets for 2030, requiring acceleration especially to prevent 5.6 million deaths around the time of birth. Infections contribute to this burden, but etiological data are limited. Group B Streptococcus (GBS) is an important perinatal pathogen, although previously focus has been primarily on liveborn children, especially early-onset disease. In this first of an 11-article supplement, we discuss the following: (1) Why estimate the worldwide burden of GBS disease? (2) What outcomes of GBS in pregnancy should be included? (3) What data and epidemiological parameters are required? (4) What methods and models can be used to transparently estimate this burden of GBS? (5) What are the challenges with available data? and (6) How can estimates address data gaps to better inform GBS interventions including maternal immunization? We review all available GBS data worldwide, including maternal GBS colonization, risk of neonatal disease (with/without intrapartum antibiotic prophylaxis), maternal GBS disease, neonatal/infant GBS disease, and subsequent impairment, plus GBS-associated stillbirth, preterm birth, and neonatal encephalopathy. We summarize our methods for searches, meta-analyses, and modeling including a compartmental model. Our approach is consistent with the World Health Organization (WHO) Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER), published in The Lancet and the Public Library of Science (PLoS). We aim to address priority epidemiological gaps highlighted by WHO to inform potential maternal vaccination.

http://ift.tt/2AkLUR8

Maternal Disease With Group B Streptococcus and Serotype Distribution Worldwide: Systematic Review and Meta-analyses

Abstract

Background

Infections such as group B Streptococcus (GBS) are an important cause of maternal sepsis, yet limited data on epidemiology exist. This article, the third of 11, estimates the incidence of maternal GBS disease worldwide.

Methods

We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data on invasive GBS disease in women pregnant or within 42 days postpartum. We undertook meta-analyses to derive pooled estimates of the incidence of maternal GBS disease. We examined maternal and perinatal outcomes and GBS serotypes.

Results

Fifteen studies and 1 unpublished dataset were identified, all from United Nations–defined developed regions. From a single study with pregnancies as the denominator, the incidence of maternal GBS disease was 0.38 (95% confidence interval [CI], .28–.48) per 1000 pregnancies. From 3 studies reporting cases by the number of maternities (pregnancies resulting in live/still birth), the incidence was 0.23 (95% CI, .09–.37). Five studies reported serotypes, with Ia being the most common (31%). Most maternal GBS disease was detected at or after delivery.

Conclusions

Incidence data on maternal GBS disease in developing regions are lacking. In developed regions the incidence is low, as are the sequelae for the mother, but the risk to the fetus and newborn is substantial. The timing of GBS disease suggests that a maternal vaccine given in the late second or early third trimester of pregnancy would prevent most maternal cases.

http://ift.tt/2j41QDi

Neurodevelopmental Impairment in Children After Group B Streptococcal Disease Worldwide: Systematic Review and Meta-analyses

Group B Streptococcus (GBS) is a leading cause of invasive disease in infants, causing mortality and neurodevelopmental impairment (NDI) in survivors. This article estimates the percentage of survivors of infant GBS disease with NDI.

Background

Survivors of infant group B streptococcal (GBS) disease are at risk of neurodevelopmental impairment (NDI), a burden not previously systematically quantified. This is the 10th of 11 articles estimating the burden of GBS disease. Here we aimed to estimate NDI in survivors of infant GBS disease.

Methods

We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data on the risk of NDI after invasive GBS disease in infants <90 days of age. We did meta-analyses to derive pooled estimates of the percentage of infants with NDI following GBS meningitis.

Results

We identified 6127 studies, of which 18 met eligibility criteria, all from middle- or high-income contexts. All 18 studies followed up survivors of GBS meningitis; only 5 of these studies also followed up survivors of GBS sepsis and were too few to pool in a meta-analysis. Of meningitis survivors, 32% (95% CI, 25%–38%) had NDI at 18 months of follow-up, including 18% (95% CI, 13%–22%) with moderate to severe NDI.

Conclusions

GBS meningitis is an important risk factor for moderate to severe NDI, affecting around 1 in 5 survivors. However, data are limited, and we were unable to estimate NDI after GBS sepsis. Comparability of studies is difficult due to methodological differences including variability in timing of clinical reviews and assessment tools. Follow-up of clinical cases and standardization of methods are essential to fully quantify the total burden of NDI associated with GBS disease, and inform program priorities.

http://ift.tt/2AmFGjN

Stillbirth With Group B Streptococcus Disease Worldwide: Systematic Review and Meta-analyses

Abstract

Background

There are an estimated 2.6 million stillbirths each year, many of which are due to infections, especially in low- and middle-income contexts. This paper, the eighth in a series on the burden of group B streptococcal (GBS) disease, aims to estimate the percentage of stillbirths associated with GBS disease.

Methods

We conducted systematic literature reviews (PubMed/Medline, Embase, Literatura Latino-Americana e do Caribe em Ciências da Saúde, World Health Organization Library Information System, and Scopus) and sought unpublished data from investigator groups. Studies were included if they reported original data on stillbirths (predominantly ≥28 weeks' gestation or ≥1000 g, with GBS isolated from a sterile site) as a percentage of total stillbirths. We did meta-analyses to derive pooled estimates of the percentage of GBS-associated stillbirths, regionally and worldwide for recent datasets.

Results

We included 14 studies from any period, 5 with recent data (after 2000). There were no data from Asia. We estimated that 1% (95% confidence interval [CI], 0–2%) of all stillbirths in developed countries and 4% (95% CI, 2%–6%) in Africa were associated with GBS.

Conclusions

GBS is likely an important cause of stillbirth, especially in Africa. However, data are limited in terms of geographic spread, with no data from Asia, and cases worldwide are probably underestimated due to incomplete case ascertainment. More data, using standardized, systematic methods, are critical, particularly from low- and middle-income contexts where the highest burden of stillbirths occurs. These data are essential to inform interventions, such as maternal GBS vaccination.

http://ift.tt/2j459ui

Maternal Colonization With Group B Streptococcus and Serotype Distribution Worldwide: Systematic Review and Meta-analyses

Abstract

Background

Maternal rectovaginal colonization with group B Streptococcus (GBS) is the most common pathway for GBS disease in mother, fetus, and newborn. This article, the second in a series estimating the burden of GBS, aims to determine the prevalence and serotype distribution of GBS colonizing pregnant women worldwide.

Methods

We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus), organized Chinese language searches, and sought unpublished data from investigator groups. We applied broad inclusion criteria to maximize data inputs, particularly from low- and middle-income contexts, and then applied new meta-analyses to adjust for studies with less-sensitive sampling and laboratory techniques. We undertook meta-analyses to derive pooled estimates of maternal GBS colonization prevalence at national and regional levels.

Results

The dataset regarding colonization included 390 articles, 85 countries, and a total of 299924 pregnant women. Our adjusted estimate for maternal GBS colonization worldwide was 18% (95% confidence interval [CI], 17%–19%), with regional variation (11%–35%), and lower prevalence in Southern Asia (12.5% [95% CI, 10%–15%]) and Eastern Asia (11% [95% CI, 10%–12%]). Bacterial serotypes I–V account for 98% of identified colonizing GBS isolates worldwide. Serotype III, associated with invasive disease, accounts for 25% (95% CI, 23%–28%), but is less frequent in some South American and Asian countries. Serotypes VI–IX are more common in Asia.

Conclusions

GBS colonizes pregnant women worldwide, but prevalence and serotype distribution vary, even after adjusting for laboratory methods. Lower GBS maternal colonization prevalence, with less serotype III, may help to explain lower GBS disease incidence in regions such as Asia. High prevalence worldwide, and more serotype data, are relevant to prevention efforts.

http://ift.tt/2Amuwvq

Preterm Birth Associated With Group B Streptococcus Maternal Colonization Worldwide: Systematic Review and Meta-analyses

Abstract

Background

Preterm birth complications are the leading cause of deaths among children <5 years of age. Studies have suggested that group B Streptococcus (GBS) maternal rectovaginal colonization during pregnancy may be a risk factor for preterm delivery. This article is the fifth of 11 in a series. We aimed to assess the association between GBS maternal colonization and preterm birth in order to inform estimates of the burden of GBS.

Methods

We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data from investigator groups on the association of preterm birth (<37 weeks' gestation) and maternal GBS colonization (GBS isolation from vaginal, cervical, and/or rectal swabs; with separate subanalysis on GBS bacteriuria). We did meta-analyses to derive pooled estimates of the risk and odds ratios (according to study design), with sensitivity analyses to investigate potential biases.

Results

We identified 45 studies for inclusion. We estimated the risk ratio (RR) for preterm birth with maternal GBS colonization to be 1.21 (95% confidence interval [CI], .99–1.48; P = .061) in cohort and cross-sectional studies, and the odds ratio to be 1.85 (95% CI, 1.24–2.77; P = .003) in case-control studies. Preterm birth was associated with GBS bacteriuria in cohort studies (RR, 1.98 [95% CI, 1.45–2.69]; P < .001).

Conclusions

From this review, there is evidence to suggest that preterm birth is associated with maternal GBS colonization, especially where there is evidence of ascending infection (bacteriuria). Several biases reduce the chance of detecting an effect. Equally, however, results, including evidence for the association, may be due to confounding, which is rarely addressed in studies. Assessment of any effect on preterm delivery should be included in future maternal GBS vaccine trials.

http://ift.tt/2j3WRT2

Neonatal Encephalopathy With Group B Streptococcal Disease Worldwide: Systematic Review, Investigator Group Datasets, and Meta-analysis

Abstract

Background

Neonatal encephalopathy (NE) is a leading cause of child mortality and longer-term impairment. Infection can sensitize the newborn brain to injury; however, the role of group B streptococcal (GBS) disease has not been reviewed. This paper is the ninth in an 11-article series estimating the burden of GBS disease; here we aim to assess the proportion of GBS in NE cases.

Methods

We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data from investigator groups reporting GBS-associated NE. Meta-analyses estimated the proportion of GBS disease in NE and mortality risk. UK population-level data estimated the incidence of GBS-associated NE.

Results

Four published and 25 unpublished datasets were identified from 13 countries (N = 10436). The proportion of NE associated with GBS was 0.58% (95% confidence interval [CI], 0.18%–.98%). Mortality was significantly increased in GBS-associated NE vs NE alone (risk ratio, 2.07 [95% CI, 1.47–2.91]). This equates to a UK incidence of GBS-associated NE of 0.019 per 1000 live births.

Conclusions

The consistent increased proportion of GBS disease in NE and significant increased risk of mortality provides evidence that GBS infection contributes to NE. Increased information regarding this and other organisms is important to inform interventions, especially in low- and middle-resource contexts.

http://ift.tt/2Amb3uR

Intrapartum Antibiotic Chemoprophylaxis Policies for the Prevention of Group B Streptococcal Disease Worldwide: Systematic Review

Abstract

Background

Intrapartum antibiotic chemoprophylaxis (IAP) prevents most early-onset group B streptococcal (GBS) disease. However, there is no description of how IAP is used around the world. This article is the sixth in a series estimating the burden of GBS disease. Here we aimed to review GBS screening policies and IAP implementation worldwide.

Methods

We identified data through (1) systematic literature reviews (PubMed/Medline, Embase, Literature in the Health Sciences in Latin America and the Caribbean [LILACS], World Health Organization library database [WHOLIS], and Scopus) and unpublished data from professional societies and (2) an online survey and searches of policies from medical societies and professionals. We included data on whether an IAP policy was in use, and if so whether it was based on microbiological or clinical risk factors and how these were applied, as well as the estimated coverage (percentage of women receiving IAP where indicated).

Results

We received policy information from 95 of 195 (49%) countries. Of these, 60 of 95 (63%) had an IAP policy; 35 of 60 (58%) used microbiological screening, 25 of 60 (42%) used clinical risk factors. Two of 15 (13%) low-income, 4 of 16 (25%) lower-middle–income, 14 of 20 (70%) upper-middle–income, and 40 of 44 (91%) high-income countries had any IAP policy. The remaining 35 of 95 (37%) had no national policy (25/33 from low-income and lower-middle–income countries). Coverage varied considerably; for microbiological screening, median coverage was 80% (range, 20%–95%); for clinical risk factor–based screening, coverage was 29% (range, 10%–50%). Although there were differences in the microbiological screening methods employed, the individual clinical risk factors used were similar.

Conclusions

There is considerable heterogeneity in IAP screening policies and coverage worldwide. Alternative global strategies, such as maternal vaccination, are needed to enhance the scope of global prevention of GBS disease.

http://ift.tt/2j3FBxp

Estimates of the Burden of Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children

Abstract

Background

We aimed to provide the first comprehensive estimates of the burden of group B Streptococcus (GBS), including invasive disease in pregnant and postpartum women, fetal infection/stillbirth, and infants. Intrapartum antibiotic prophylaxis is the current mainstay of prevention, reducing early-onset infant disease in high-income contexts. Maternal GBS vaccines are in development.

Methods

For 2015 live births, we used a compartmental model to estimate (1) exposure to maternal GBS colonization, (2) cases of infant invasive GBS disease, (3) deaths, and (4) disabilities. We applied incidence or prevalence data to estimate cases of maternal and fetal infection/stillbirth, and infants with invasive GBS disease presenting with neonatal encephalopathy. We applied risk ratios to estimate numbers of preterm births attributable to GBS. Uncertainty was also estimated.

Results

Worldwide in 2015, we estimated 205000 (uncertainty range [UR], 101000–327000) infants with early-onset disease and 114000 (UR, 44000–326000) with late-onset disease, of whom a minimum of 7000 (UR, 0–19000) presented with neonatal encephalopathy. There were 90000 (UR, 36000–169000) deaths in infants <3 months age, and, at least 10000 (UR, 3000–27000) children with disability each year. There were 33000 (UR, 13000–52000) cases of invasive GBS disease in pregnant or postpartum women, and 57000 (UR, 12000–104000) fetal infections/stillbirths. Up to 3.5 million preterm births may be attributable to GBS. Africa accounted for 54% of estimated cases and 65% of all fetal/infant deaths. A maternal vaccine with 80% efficacy and 90% coverage could prevent 107000 (UR, 20000–198000) stillbirths and infant deaths.

Conclusions

Our conservative estimates suggest that GBS is a leading contributor to adverse maternal and newborn outcomes, with at least 409000 (UR, 144000–573000) maternal/fetal/infant cases and 147000 (UR, 47000–273000) stillbirths and infant deaths annually. An effective GBS vaccine could reduce disease in the mother, the fetus, and the infant.

http://ift.tt/2AnvlUW

Risk of Early-Onset Neonatal Group B Streptococcal Disease With Maternal Colonization Worldwide: Systematic Review and Meta-analyses

Abstract

Background

Early-onset group B streptococcal disease (EOGBS) occurs in neonates (days 0–6) born to pregnant women who are rectovaginally colonized with group B Streptococcus (GBS), but the risk of EOGBS from vertical transmission has not been systematically reviewed. This article, the seventh in a series on the burden of GBS disease, aims to estimate this risk and how it varies with coverage of intrapartum antibiotic prophylaxis (IAP), used to reduce the incidence of EOGBS.

Methods

We conducted systematic reviews (Pubmed/Medline, Embase, Latin American and Caribbean Health Sciences Literature (LILACS), World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data from investigator groups on maternal GBS colonization and neonatal outcomes. We included articles with ≥200 GBS colonized pregnant women that reported IAP coverage. We did meta-analyses to determine pooled estimates of risk of EOGBS, and examined the association in risk of EOGBS with IAP coverage.

Results

We identified 30 articles including 20328 GBS-colonized pregnant women for inclusion. The risk of EOGBS in settings without an IAP policy was 1.1% (95% confidence interval [CI], .6%–1.5%). As IAP increased, the risk of EOGBS decreased, with a linear association. Based on linear regression, the risk of EOGBS in settings with 80% IAP coverage was predicted to be 0.3% (95% CI, 0–.9).

Conclusions

The risk of EOGBS among GBS-colonized pregnant women, from this first systematic review, is consistent with previous estimates from single studies (1%–2%). Increasing IAP coverage was linearly associated with decreased risk of EOGBS disease.

http://ift.tt/2j63RP7

Cover

http://ift.tt/2AnuW4S

Rare Cancers and Social Media: Analysis of Twitter Metrics in the First 2 Years of a Rare-Disease Community for Myeloproliferative Neoplasms on Social Media—#MPNSM

Abstract

Purpose of review

The use of social media has now become a standard 13 means of communication for many individuals worldwide. 14 The use of one specific form of social media, Twitter, has 15 increased among healthcare providers, both as a means of 16 information gathering and as a conduit for original content 17 creation. Recently, major efforts by users have been put for- 18 ward to help streamline the unprecedented amount of infor- 19 mation that can be found on Twitter. These efforts have led to 20 the creation of diseasespecific hashtag (#) medical communi- 21 ties and have greatly enhanced the ability to understand and 22 better categorize the available data on Twitter. Specifically, for 23 those involved in rare cancer fields, adhering to organically 24 designed and consistently used hashtags has led to the rapid, 25 reliable dissemination of information and the ability to effi- 26 ciently discuss and debate topics of interest in the field. For the 27 field of myeloproliferative neoplasms (MPNs), the creation of #MPNSM (myeloproliferative neoplasms on social media) in 28 2015 has facilitated interactions among healthcare stake- 29 holders from all over the world in the MPN field.

Recent findings

In order to 30 better understand the trends and topics of interest to Twitter 31 users of this novel medical community, we conducted the 32 present analysis which focuses on Twitter analytics from the 33 first two years of #MPNSM.

Summary

In this analysis, we observed a 34 sustained increase in the number of Twitter users, number of 35 tweets, number of impressions, and number of retweets over 36 time, demonstrating the feasibility of creating and maintaining 37 a disease-specific hashtag for a rare cancer over time.

http://ift.tt/2zks1tp

Generational shift in melanoma incidence and mortality in Queensland, Australia, 1995-2014

Abstract

Public campaigns encouraging sun protection for skin cancer prevention began in Queensland, Australia, in the early 1980s. We examined recent trends to assess whether earlier evidence of stabilizing melanoma incidence in young people has persisted. Anonymised incidence and mortality data for in situ and invasive melanoma for the 20 years 1995-2014 were obtained from the Queensland Cancer Registry. Time trends were analysed using joinpoint regression. Birth cohort patterns were assessed using age-period-cohort models. Melanoma incidence in Queensland remains the highest recorded in the world (age-standardised incidence of invasive melanoma (2010-2014) = 72/100,000/annum). Over the 20-year period, incidence of in situ melanoma increased in all age groups. Incidence of both thin (≤1mm) and thick (>1mm) invasive melanoma was either stable or decreased in people under 60, while it increased in those aged 60 and above, particularly in men. Age-period-cohort analysis revealed decreasing age-specific incidence of invasive melanoma under 40 years of age, beginning with the birth cohort born around the mid-1960s, with steepest falls for those born around 1980 and later. Age-specific incidence was stable between 40-59 years of age from the 1945 birth cohort onwards. Melanoma mortality over the period was stable or decreased in all groups except in men aged 60 or over. These findings are evidence of real advances in the prevention and early detection of invasive melanoma in this very high-risk population. They make a compelling case for continued public health efforts to reduce the burden of melanoma in susceptible populations. This article is protected by copyright. All rights reserved.

http://ift.tt/2hJJvrq

Five-year relative survival for human papillomavirus-associated cancer sites

BACKGROUND

Human papillomavirus (HPV) vaccines can potentially prevent greater than 90% of cervical and anal cancers as well as a substantial proportion of vulvar, vaginal, penile, and oropharyngeal cancers caused by certain HPV types. Because more than 38,000 HPV-associated cancers are diagnosed annually in the United States, current studies are needed to understand how relative survival varies for each of these cancers by certain demographic characteristics, such as race and age.

METHODS

The authors examined high-quality data from 27 population-based cancer registries covering approximately 59% of the US population. The analyses were limited to invasive cancers that were diagnosed during 2001 through 2011 and followed through 2011 and met specified histologic criteria for HPV-associated cancers. Five-year relative survival was calculated from diagnosis until death for these cancers by age, race, and sex.

RESULTS

The 5-year age-standardized relative survival rate was 64.2% for cervical carcinomas, 52.8% for vaginal squamous cell carcinomas (SCCs), 66% for vulvar SCCs, 47.4% for penile SCCs, 65.9% for anal SCCs, 56.2% for rectal SCCs, and 51.2% for oropharyngeal SCCs. Five-year relative survival was consistently higher among white patients compared with black patients for all HPV-associated cancers across all age groups; the greatest differences by race were observed for oropharyngeal SCCs among those aged <60 years and for penile SCCs among those ages 40 to 49 years compared with other age groups.

CONCLUSIONS

There are large disparities in relative survival among patients with HPV-associated cancers by sex, race, and age. HPV vaccination and improved access to screening (of cancers for which screening tests are available) and treatment, especially among groups that experience higher incidence and lower survival, may reduce disparities in survival from HPV-associated cancers. Cancer 2017. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

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Survival of human papillomavirus-associated cancers: Filling in the gaps

Human papillomavirus-associated cancers contribute to the total cancer burden in the United States. Although they are mostly preventable, 5-year relative survival rates can be as low as 47% for penile cancer and as high as 66% for vulvar cancer. See also pages 000-000.

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What’s New in Imaging for Gynecologic Cancer?

Abstract

Magnetic resonance imaging (MRI) is the optimal modality for local staging of gynecological tumors. Advances in functional MRI with diffusion-weighted and dynamic contrast-enhanced sequences provide more detailed information regarding tumor cellularity, vascularity, and viability. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) now has an established role in imaging for gynecological cancers, particularly staging of locally advanced cervical cancers and pre-salvage exenterative therapy in relapsed gynecologic tumors. Novel PET tracers, targeting other aspects of tumor biology, are being evaluated although none are currently in routine clinical use. New PET/MR scanners have the potential to combine the strengths of both modalities in one sitting. This review covers advances in gynecologic imaging concentrating on cervical, endometrial, and ovarian cancers.

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Correction to: Preliminary use of Polygonum minus Linn. leaf extract on growth performance, feed utilization, and some hematological indices of Anabas testudineus (Bloch, 1792)

Abstract

The original version of this paper unfortunately captured the equation incorrectly and is corrected in this article.

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Adaptation and Molecular Characterization of Two Malaysian Very Virulent Infectious Bursal Disease Virus Isolates Adapted in BGM-70 Cell Line

Two Malaysian very virulent infectious bursal disease virus (vvIBDV) strains UPM0081 and UPM190 (also known as UPMB00/81 and UPM04/190, respectively) isolated from local IBD outbreaks were serially passaged 12 times (EP12) in specific pathogen free (SPF) chicken embryonated eggs (CEE) by chorioallantoic membrane (CAM) route. The EP12 isolate was further adapted and serially propagated in BGM-70 cell line up to 20 passages (P20). Characteristic cytopathic effects (CPEs) were subtly observed at P1 in both isolates 72 hours postinoculation (pi). The CPE became prominent at P5 with cell rounding, cytoplasmic vacuoles, granulation, and detachment from flask starting from day 3 pi, up to 7 days pi with titers of 109.50 TCID50/mL and  TCID50/mL for UPM0081 and UPM190, respectively. The CPE became subtle at P17 and disappeared by P18 and P19 for UPM0081 and UPM190, respectively. However, the presence of IBDV was confirmed by immunoperoxidase, immunofluorescence, and RT-PCR techniques. Phylogenetic analysis showed that these two isolates were of the vvIBDV. It appears that a single mutation of UPM190 and UPM0081 IBDV isolates at D279N could facilitate vvIBDV strain adaptability in CEE and BGM-70 cultures.

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Measuring the impact of medicines regulatory interventions – systematic review and methodological considerations

Summary

Aim

Evaluating the public health impact of regulatory interventions is important but there is currently no common methodological approach to guide this evaluation. This systematic review provides a descriptive overview of the analytical methods for impact research.

Methods

We searched MEDLINE and EMBASE for articles with an empirical analysis evaluating the impact of European Union or non-European Union regulatory actions to safeguard public health published until March 2017. References from systematic reviews and articles from other known sources were added. Regulatory interventions, data sources, outcomes of interest, methodology and key findings were extracted.

Results

From 1,246 screened articles, 229 were eligible for full-text review and 153 articles in English language were included in the descriptive analysis. Over a third of articles studied analgesics and antidepressants. Interventions most frequently evaluated are regulatory safety communications (28.8%), black box warnings (23.5%) and direct healthcare professional communications (10.5%). 55% of studies measured changes in drug utilisation patterns, 27% evaluated health outcomes and 18% targeted knowledge, behaviour, or changes in clinical practice. Unintended consequences like switching therapies or spill-over effects were rarely evaluated. Two thirds used before-after time series and 15.7% before-after cross-sectional study designs. Various analytical approaches were applied including interrupted time series regression (31.4%), simple descriptive analysis (28.8%) and descriptive analysis with significance tests (23.5%).

Conclusion

Whilst impact evaluation of pharmacovigilance and product-specific regulatory interventions is increasing, the marked heterogeneity in study conduct and reporting highlights the need for scientific guidance to ensure robust methodologies are applied and systematic dissemination of results occurs.

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Metabolic Alterations of Thyroid Cancer as Potential Therapeutic Targets

Thyroid cancer (TC) is the most frequent endocrine tumor with a growing incidence worldwide. Besides the improvement of diagnosis, TC increasing incidence is probably due to environmental factors and lifestyle modifications. The actual diagnostic criteria for TC classification are based on fine needle biopsy (FNAB) and histological examination following thyroidectomy. Since in some cases it is not possible to make a proper diagnosis, classical approach needs to be supported by additional biomarkers. Recently, new emphasis has been given to the altered cellular metabolism of proliferating cancer cells which require high amount of glucose for energy production and macromolecules biosynthesis. Also TC displays alteration of energy metabolism orchestrated by oncogenes activation and tumor suppressors inactivation leading to abnormal proliferation. Furthermore, TC shows significant metabolic heterogeneity within the tumor microenvironment and metabolic coupling between cancer and stromal cells. In this review we focus on the current knowledge of metabolic alterations of TC and speculate that targeting TC metabolism may improve current therapeutic protocols for poorly differentiated TC. Future studies will further deepen the actual understandings of the metabolic phenotype of TC cells and will give the chance to provide novel prognostic biomarkers and therapeutic targets in tumors with a more aggressive behavior.

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Pharmacokinetics of Quercetin-Loaded Methoxy Poly(ethylene glycol)-b-poly(L-lactic acid) Micelle after Oral Administration in Rats

The purpose of this study was to evaluate the potential of micelle to change the pharmacokinetics of quercetin (QUT), with a primary goal of enhancing its oral bioavailability. QUT-loaded methoxy poly(ethylene glycol)--poly(L-lactic acid) micelle (QUT-loaded MPEG--PLLA micelle) was prepared by a thin-film hydration method, resulting in a particle size of 88.5 nm. A liquid chromatography tandem-mass spectrometry (LC-MS/MS) method was developed and validated for determination of QUT in rat plasma. The chromatographic separation was performed on an Agilent Eclipse-C18 (4.6 mm 50 mm, 3.5 m) with an isocratic mobile phase system consisting of water and methanol (, ) at a flow rate of 0.4 mL/min. Calibration curves were linear over the concentration ranges of 2.5–2000 ng/mL for QUT. The micelle was orally administered at a single does in rats, and the pharmacokinetic parameters were evaluated and compared with that administered with the QUT aqueous suspension. The results show that the micelle was able to increase the QUT's oral bioavailability 9-fold compared to the QUT aqueous suspension. These results suggest that methoxy poly(ethylene glycol)--poly(L-lactic acid) is a potential carrier for the oral delivery of QUT.

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Chemical Compositions, Somatic Embryogenesis, and Somaclonal Variation in Cumin

This is the first report evaluating the relationship between the chemical compositions of cumin seeds (based on the analysis of the content of catalase, ascorbate peroxidase, proline, protein, terpenic compounds, alcohol/phenols, aldehydes, and epoxides) and the induction efficiency of somatic embryogenesis in two Iranian superior cumin landraces (Golestan and North Khorasan). Cotyledons isolated from Golestan landrace seeds cultivated on MS medium supplemented with 0.1 mg/L kinetin proved to be the best primary explant for the induction of somatic embryogenesis as well as the regeneration of the whole plantlet. Results indicated that different developmental stages of somatic embryos were simultaneously observed on a callus with embryogenic potential. The high content of catalase, ascorbate peroxidase, proline, and terpenic hydrocarbons and low content of alcoholic and phenolic compositions had a stimulatory effect on somatic embryogenesis. Band patterns of RAPD markers in regenerated plants were different from those of the mother plants. This may be related to somaclonal variations or pollination system of cumin. Generally, measurement of chemical compositions can be used as a marker for evaluating the occurrence of somatic embryogenesis in cumin. Also, somaclonal variations of regenerated plants can be applied by the plant breeders in breeding programs.

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“Microdialysis as a tool to determine the local tissue concentration of dicloxacillin in man”

Summary

Aim

The most common pathogen in Denmark, to cause postoperative infections, is Staphylococcus (S.) aureus (1). Despite using prophylactic antibiotics, infections are still seen. Whether the tissue concentration is above the minimal inhibitory concentration (MIC) for the pathogen is unknown. Thus, the concentration of dicloxacillin in muscle and adipose tissue was measured after intravenous administration, in healthy men.

Methods

MIC for dicloxacillin against S. aureus was determined using the broth macrodilution method. A microdialysis (MD) catheter was placed in the subcutaneous tissue of the abdomen and in the lateral vastus muscle of the thigh of six healthy male volunteers. They were given 2 g dicloxacillin intravenously. Samples from blood and MD fluid were collected. The unbound dicloxacillin was isolated from plasma. Samples were analyzed with High Performance Liquid Chromatography.

Results

The maximum concentration was reached in muscle tissue after 0.5 hours and in adipose tissue after 0.8 hours. AUC_0-6h for the dicloxacillin concentration in adipose tissue was significantly lower when compared to the unbound dicloxacillin concentration in plasma. The dicloxacillin concentration was above the MIC for sensitive S. aureus for a minimum of 2.3 and a median of 4.1 hours in muscle tissue and a minimum of 1.8 and a median of 3.2 hours in adipose tissue.

Conclusions

The unbound dicloxacillin concentration in adipose and muscle tissue remained above the MIC for sensitive S. aureus, for a period sufficient for many orthopedic procedures. Whether this is true in patients with compromised circulation this remains to be investigated.

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FDA Warns Companies Marketing Unproven Products, Derived From Marijuana, that Claim to Treat or Cure Cancer

November 1, 2017 -- As part of the U.S. Food and Drug Administration's ongoing efforts to protect consumers from health fraud, the agency today issued warning letters to four companies illegally selling products online that claim to prevent,...

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Ground State Depletion Super-resolution Imaging in Mammalian Cells

This article outlines a protocol for the detection of one or more plasma and/or intracellular membrane proteins using Ground State Depletion (GSD) super-resolution microscopy in mammalian cells. Here, we discuss the benefits and considerations of using such approaches for the visualization and quantification of cellular proteins.

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High-throughput Analysis of Locomotor Behavior in the Drosophila Island Assay

The island assay is a relatively new, cost-effective assay that can be used to evaluate the basic locomotor behavior of Drosophila melanogaster. This manuscript describes algorithms for automatic data processing and objective quantification of island assay data, making this assay a sensitive, high-throughput readout for large genetic or pharmacological screens.

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Fla. county residents can text 9-1-1 now

The feature came just before Senator Bill Nelson introduced legislation that calls for the expansion of federal grants to assist with next-generation 911 systems

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Primary Esophageal Melanoma with Aberrant CD56 Expression: A Potential Diagnostic Pitfall

Primary esophageal malignant melanoma (MM) is rare and extremely aggressive. For pathologists, it can be challenging to diagnose and differentiate from other poorly differentiated malignant neoplasms in the esophagus. Complicating this fact, MM can have divergent differentiation and express nonmelanocytic immunohistochemical markers including epithelial markers (cytokeratins) and rarely neuroendocrine markers. Lack of awareness of this fact by a pathologist can lead to an erroneous diagnosis and delay treatment for an already aggressive disease. Herein, we report a case of primary esophageal malignant melanoma with aberrant CD56 expression without accompanying synaptophysin or chromogranin expression.

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Relationship of Obstructive Sleep Apnoea with Diabetic Retinopathy: A Meta-Analysis

Until now, the relationship of obstructive sleep apnoea (OSA) with diabetic retinopathy (DR) was controversial. This meta-analysis was performed to obtain definitive conclusion on this topic. Relevant articles were searched on databases of Pubmed, Google Scholar, and Chinese National Knowledge Infrastructure (CNKI). The articles were selected according to inclusion and exclusion criteria. Odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the relationship of OSA with risk of DR. and value were used to assess the presence of heterogeneity. ≥ 50% or indicated significant heterogeneity. Sensitivity analysis was performed to evaluate the robustness of pooled results. Begg's funnel plot and Egger's regression analysis were adopted to assess publication bias. 6 eligible studies were selected in the present meta-analysis. The pooled results indicated that OSA was significantly associated with increased risk of DR (OR = 2.01, 95% CI = 1.49–2.72). Subgroup analysis based on type of diabetes mellitus suggested that OSA was related to DR in both Type 1 and Type 2 diabetes mellitus. Sensitivity analysis demonstrated that pooled results were robust. No significant publication bias was observed (). The results indicate that OSA is related to increased risk of DR.

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Variability of Chemical Compositions and Antimicrobial and Antioxidant Activities of Ruta chalepensis Leaf Essential Oils from Three Palestinian Regions

Introduction. Interest in essential oils was recently revived with their popularity increasing in medicine, pharmacy, and aromatherapy. This study was performed to identify the chemical compositions of the essential oil of Ruta chalepensis growing wildly in three regions in Palestine and to assess and compare their antimicrobial and antioxidant activities. Methods. Identification of the essential oil was performed by gas chromatography coupled with mass spectrometry (GC-MS). Antimicrobial activity was tested against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Methicillin-Resistant Staphylococcus aureus, and Candida albicans by using minimum inhibitory concentration (MIC) assay, while antioxidant activity was analyzed by using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method. Results. The essential oils of R. chalepensis from Jerusalem and Hebron regions have almost identical components; the major compounds identified were linalyl acetate and β-linalool; these essential oils exerted potential antioxidant and antibacterial activities. On the other hand, the major components of the plant essential oil from Jenin region were 2-undecanone and 2-nonanone, which exhibited potential antifungal activity. Conclusions. The phytoconstituents and antioxidant and antimicrobial properties of the essential oil of R. chalepensis from different regions in Palestine were established in this study. The obtained results indicate possible applications for R. chalepensis in the treatment of various infectious and noninfectious diseases.

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Fungicidal, Corrosive, and Mutational Effects of Polyhexamethylene Biguanide Combined with 1-Bromo-3-chloro-5,5-dimethylimidazolidine-2,4-dione

Background. The disinfectants polyhexamethylene biguanide (PHMB) and 1-bromo-3-chloro-5,5-dimethylimidazolidine-2,4-dione (BCDMH) each have limitations. So far, their combined usage has not been examined. In this study, the fungicidal activity of combined disinfectant using PHMB and BCDMH, named PB, against Candida albicans was evaluated. Methods. Suspension quantitative fungicidal test and viable fungi count were used to test fungicidal effects against C. albicans. Coupon corrosion testing was used to evaluate disinfectants' corrosive effects on stainless steel, copper, and aluminum. The mouse lymphoma assay was used to detect mutations induced by PB. Results and Discussion. Fungicidal activity of the combination of 40 mg/L PHMB and 40 mg/L BCDMH was comparable to, or even better than, those of 600 mg/L PHMB or 640 mg/L BCDMH alone. The combination of 400 mg/L PHMB and 400 mg/L BCDMH exhibited good fungicidal effects in field applications. The combination of 100 mg/L PHMB and 100 mg/L BCDMH did not have corrosive effects on stainless steel and no mutagenic effect was observed under the test conditions. Conclusions. The combination of PHMB and BCDMH has strong fungicidal effects and little metal corrosive and mutagenic effect and can be used as one suitable fungicide for wide household and industrial applications, including shipping containers.

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Antidiarrheal Activity of Dissotis multiflora (Sm) Triana (Melastomataceae) Leaf Extract in Wistar Rats and Subacute Toxicity Evaluation

The present work was undertaken to evaluate antidiarrheal activity of ethanolic leaf extract of Dissotis multiflora (Sm) Triana (D. multiflora) on Shigella flexneri-induced diarrhea in Wistar rats and its subacute toxicity. Diarrhea was induced by oral administration of 1.2 × 109 cells/mL S. flexneri to rats. Antidiarrheal activity was investigated in rats with the doses of 111.42 mg/kg, 222.84 mg/kg, and 445.68 mg/kg. The level of biochemical parameters was assessed and organs histology examined by 14 days' subacute toxicity. S. flexneri stool load decreased significantly in dose-dependent manner. The level of ALT increased () in male rats treated with the dose of 445.68 mg/kg while creatinine level increased in rats treated with both doses. In female rats, a significant decrease () of the level of AST and creatinine was noted in rats treated with the dose of 222.84 mg/kg of D. multiflora. Histological exams of kidney and liver of treated rats showed architectural modifications at the dose of 445.68 mg/kg. This finding suggests that D. multiflora leaf extract is efficient against diarrhea caused by S. flexneri but the treatment with doses lower than 222.84 mg/kg is recommended while further study is required to define the exact efficient nontoxic dose.

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The prehospital management of hypothermia — An up-to-date overview

Publication date: Available online 4 November 2017
Source:Injury
Author(s): Frederike J.C. Haverkamp, Gordon G. Giesbrecht, Edward C.T.H. Tan
BackgroundAccidental hypothermia concerns a body core temperature of less than 35°C without a primary defect in the thermoregulatory system. It is a serious threat to prehospital patients and especially injured patients, since it can induce a vicious cycle of the synergistic effects of hypothermia, acidosis and coagulopathy; referred to as the trauma triad of death. To prevent or manage deterioration of a cold patient, treatment of hypothermia should ideally begin prehospital. Little effort has been made to integrate existent literature about prehospital temperature management. The aim of this study is to provide an up-to-date systematic overview of the currently available treatment modalities and their effectiveness for prehospital hypothermia management.Data sourcesDatabases PubMed, EMbase and MEDLINE were searched using the terms: "hypothermia", "accidental hypothermia", "Emergency Medical Services" and "prehospital". Articles with publications dates up to October 2017 were included and selected by the authors based on relevance.ResultsThe literature search produced 903 articles, out of which 51 focused on passive insulation and/or active heating. The most effective insulation systems combined insulation with a vapor barrier. Active external rewarming interventions include chemical, electrical and charcoal-burning heat packs; chemical or electrical heated blankets; and forced air warming. Mildly hypothermic patients, with significant endogenous heat production from shivering, will likely be able to rewarm themselves with only insulation and vapor barrier, although active warming will still provide comfort and an energy-saving benefit. For colder, non-shivering patients, the addition of active warming is indicated as a non-shivering patient will not rewarm spontaneously. All intravenous fluids must be reliably warmed before infusion.ConclusionAlthough it is now accepted that prehospital warming is safe and advantageous, especially for a non-shivering hypothermic patient, this review reveals that no insulation/heating combinations stand significantly above all the others. However, modern designs of hypothermia wraps have shown promise and battery-powered inline fluid warmers are practical devices to warm intravenous fluids prior to infusion. Future research in this field is necessary to assess the effectiveness expressed in patient outcomes.



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Good functional outcome in patients suffering fragility fractures of the pelvis treated with percutaneous screw stabilisation: Assessment of complications and factors influencing failure

Publication date: Available online 4 November 2017
Source:Injury
Author(s): Henrik Eckardt, Alexander Egger, Rebecca Hasler, Christoph J. Zech, Werner Vach, Norbert Suhm, Mario Morgenstern, Franziska Saxer
BackgroundLow energy pelvic ring fractures in the elderly have traditionally been treated conservatively, a treatment with potential long-term complications and loss of self-independence. Percutaneous screw stabilisation of the posterior pelvic ring is a new treatment modality that enables immediate mobilisation. The aim of this study was to assess the functional outcome after sacroiliac stabilisation in the elderly.MethodsAll elderly patients with a surgically stabilised low energy pelvic fracture between 2010 and 2015 were included. In 2016 a radiographic follow up and functional test was performed at least one year postoperative.ResultsThe 50 operated patients had a mean age of 79 years and a one-year mortality of 10% (5/50). Only six patients lost independency after the pelvic fracture and moved to nursing home. The mean Timed Up and Go test was 16s at follow-up. The operation of the posterior pelvic ring averaged 63min with a radiation equal to a diagnostic pelvic CT. One intra-foraminally placed screw was immediately removed and 9 patients were later re-operated on due to symptomatic loosening of one or more screws. No loosening of screws was seen in 11 patients where both S1 and S2 were stabilised and out of 23 trans-sacral screws (crossing both sacroiliac joints) only two loosened.DiscussionCT guided stabilisation of the posterior pelvis is safe and most patients resumed good function and independent living. The risk of a revision operation was 20%, but trans-sacral screw stabilisation in both S1 and S2 could reduce the risk of implant loosening.



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Prostate Cancer Germline Variations and Implications for Screening and Treatment.

Related Articles

Prostate Cancer Germline Variations and Implications for Screening and Treatment.

Cold Spring Harb Perspect Med. 2017 Nov 03;:

Authors: Dias A, Kote-Jarai Z, Mikropoulos C, Eeles R

Abstract
Prostate cancer (PCa) is a highly heritable disease, and rapid evolution of sequencing technologies has enabled marked progression of our understanding of its genetic inheritance. A complex polygenic model that involves common low-penetrance susceptibility alleles causing individually small but cumulatively significant risk and rarer genetic variants causing greater risk represent the current most accepted model. Through genome-wide association studies, more than 100 single-nucleotide polymorphisms (SNPs) associated with PCa risk have been identified. Consistent reports have identified germline mutations in the genes BRCA1, BRCA2, MMR, HOXB13, CHEK2, and NBS1 as conferring moderate risks, with some leading to a more aggressive disease behavior. Considering this knowledge, several research strategies have been developed to determine whether targeted prostate screening using genetic information can overcome the limitations of population-based prostate-specific antigen (PSA) screening. Germline DNA-repair mutations are more frequent in men with metastatic disease than previously thought, and these patients have a more favorable response to therapy with poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors. Genomic information is a practical tool that has the potential to enable the concept of precision medicine to become a reality in all steps of PCa patient care.

PMID: 29101112 [PubMed - as supplied by publisher]

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Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease

New England Journal of Medicine, Ahead of Print.


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Tolvaptan and Autosomal Dominant Polycystic Kidney Disease

New England Journal of Medicine, Ahead of Print.


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Modernization Trends of Infertility Treatment of Traditional Korean Medicine

Despite the development of assisted reproductive technology (ART), it is difficult to increase the implantation rate. In Korea, Traditional Korean Medicine, including herbal medicine, is an important component of infertility treatment. Korean medical doctors who are treating infertility often use herbal medicine to promote implantation. In this article, as one of the research works on modernization of Traditional Korean Medicine, we investigated the experimental studies to clarify the effects of herbal medicines that are traditionally used to promote pregnancy. We searched for experimental studies over the past 10 years of improvement of endometrial receptivity in herbal medicine using six domestic and international sites. We analyzed 11 studies that meet the selection criteria. We found that herbal medicines demonstrably improved endometrial receptivity and increased pregnancy rates.

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Corrigendum to “Topography Prediction of Helical Transmembrane Proteins by a New Modification of the Sliding Window Method”

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Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease

New England Journal of Medicine, Ahead of Print.


http://ift.tt/2yvHQjN

Tolvaptan and Autosomal Dominant Polycystic Kidney Disease

New England Journal of Medicine, Ahead of Print.


http://ift.tt/2lUcdKG

Erratum to “Automatic Segmentation of Ultrasound Tomography Image”

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An Overview of the Biological Effects of Some Mediterranean Essential Oils on Human Health

Essential oils (EOs), extracted from aromatic plants, are interesting natural products and represent an important part of the traditional pharmacopeia. The use of some EOs as alternative antimicrobial and pharmaceutical agents has attracted considerable interest recently. Most of the EOs and their single constituents have been reported to inhibit several phytopathogens, human pathogens, and insects as well as their effective uses in food and pharmaceutical industries. The current review discussed the chemical composition and bioactivity of some important EOs extracted from some Mediterranean plants and their principal bioactive single constituents. Information has been furnished on the mechanisms, mode of actions, and factors affecting the bioactivity of some single constituents from different Mediterranean plant EOs. The current review gives an insight into some common plant EOs belonging to Lamiaceae, Apiaceae, Rutaceae, and Verbenaceae families commonly growing in Mediterranean region. Further information has been provided about the medical uses of some EOs for several human diseases covering the pharmacological effects (anti-inflammatory, antioxidant, and anticarcinogenic). The antimicrobial effects have been also considered in the current review. Although plant EOs are considered promising natural alternatives for many chemical drugs, they still need more specific research for wide application especially in food and pharmaceutical industries.

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Comparison of the Effect of Low-Frequency Repetitive Transcranial Magnetic Stimulation with That of Theta Burst Stimulation on Upper Limb Motor Function in Poststroke Patients

Background. The purpose of this study was to evaluate the difference between the therapeutic effect of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) and that of continuous theta burst stimulation (cTBS), when each is combined with intensive occupational therapy (OT), in poststroke patients with upper limb hemiparesis. Materials and Methods. The study subjects were 103 poststroke patients with upper limb hemiparesis, who were divided into two groups: the LF-rTMS group () and the cTBS group (three pulse bursts at 50 Hz) (). Each subject received 12 sessions of repetitive transcranial magnetic stimulation of 2,400 pulses applied to the nonlesional hemisphere and 240-min intensive OT (two 60-min one-to-one training sessions and two 60-min self-training exercises) daily for 15 days. Motor function was evaluated using the Fugl-Meyer Assessment (FMA) and the performance time of the Wolf motor function test (WMFT) was determined on the days of admission and discharge. Results. Both groups showed a significant increase in the FMA score and a short log performance time of the WMFT (), but the increase in the FMA score was higher in the LF-rTMS group than the cTBS group (). Conclusion. We recommend the use of 2400 pulses of LF-rTMS/OT for 2 weeks as treatment for hemiparetic patients.

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Establishment and Application of Prostate Cancer Circulating Tumor Cells in the Era of Precision Medicine

Prostate cancer (PC) is the second most common cancer in men and is the fifth leading cause of cancer-related deaths worldwide. Additionally, there is concern for overdiagnosis and overtreatment of PC. Thus, selection of an appropriate candidate for active surveillance as well as more accurate and less invasive tools for monitoring advanced PC is required. Circulating tumor cells (CTCs) have emerged as a liquid biopsy tool; there have been several reports on its role, technologies, and applications to various cancers, including PC. Liquid biopsy using CTCs has been gaining attention as a minimal invasive tool for investigation of biomarkers and for prognosis and assessment of response to therapies in patients with PC. Because of the lower invasiveness of liquid biopsy using CTCs, it can be performed more frequently; accordingly, personalized disease status can be successively determined at serial time points. CTC analysis enables detection of genomic alterations, which is drug-targetable, and it is a potential tool for monitoring response to therapeutic agents in patients with PC. This review focuses on the characteristics, technologies for analysis, and advantages and disadvantages of CTCs as a liquid biopsy tool and their application in PC. Finally, we propose future directions of CTCs.

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