Plasma insulin-like growth factor-II (IGF-II) and IGF-II/IGF-I ratio in a chilean case of Doege-Potter Syndrome.

INTRODUCTION: Doege-Potter syndrome is a rare clinical entity characterized by recurrent hypoglycemic events caused by non-pancreatic tumors secreting an incompletely processed high-molecular-weight form of Insulin-like Growth factor-II (IGF-II). AIM: To report IGF-II and IGF-I circulating levels in a Chilean case of Doege-Potter syndrome and control individuals, and to identify the high-molecular-weight form of IGF-II. METHODS: We measured IGF-II and IGF-I plasma levels using enzyme-linked immunoassays (ELISA) in the patient and ten controls. We identified the high-molecular-weight form of IGF-II performed by Western blot. RESULTS: The plasma concentration of IGF-II in the patient was 868.9 ng/mL, which is only slightly > 80th percentile of controls (681,4 ± 212,8 ng/mL; mean ± standard deviation). In contrast, IGF-I plasma concentration in the patient was 17.6 ng/mL, which is notoriously lower than the corresponding levels in controls (109.1 ± 19.1 ng/mL). The IGF-II/IGF-I ratio in the patient was 49.4 (normal value < 10), which is 7.8 times higher compared to the average ratio of controls (6.3 ± 1.5). The high-molecular form of IGF-II presence in samples was confirmed through Western blot. CONCLUSIONS: The plasma IGF-II/IGF-I ratio better indicates the Doege-Potter syndrome's metabolic impairment than isolated measurements of circulating IGF-II or IGF-I levels.

Identification and functional analysis of missense mutations in the lecithin cholesterol acyltransferase gene in a Chilean patient with hypoalphalipoproteinemia.

BACKGROUND: Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme that esterifies cholesterol in high- and low-density lipoproteins (HDL and LDL). Mutations in LCAT gene causes familial LCAT deficiency, which is characterized by very low plasma HDL-cholesterol levels (Hypoalphalipoproteinemia), corneal opacity and anemia, among other lipid-related traits. Our aim is to evaluate clinical/biochemical features of a Chilean family with a proband showing clinical signs of familial LCAT deficiency, as well as to identify and assess the functional effects of LCAT mutations. METHODS: An adult female proband with hypoalphalipoproteinemia, corneal opacity and mild anemia, as well as her first-degree relatives, were recruited for clinical, biochemical, genetic, in-silico and in-vitro LCAT analysis. Sequencing of exons and intron-exon boundaries was performed to identify mutations. Site-directed mutagenesis was carried out to generate plasmids containing cDNA with wild type or mutant sequences. Such expression vectors were transfected to HEK-239 T cells to asses the effect of LCAT variants in expression, synthesis, secretion and enzyme activity. In-silico prediction analysis and molecular modeling was also used to evaluate the effect of LCAT variants. RESULTS: LCAT sequencing identified rare p.V333 M and p.M404 V missense mutations in compound heterozygous state in the proband, as well the common synonymous p.L363 L variant. LCAT protein was detected in proband's plasma, but with undetectable enzyme activity compared to control relatives. HEK-293 T transfected cells with vector expression plasmids containing either p.M404 V or p.V333 M cDNA showed detectable LCAT protein expression both in supernatants and lysates from cultured cells, but with much lower enzyme activity compared to cells transfected with the wild-type sequence. Bioinformatic analyses also supported a causal role of such rare variations in LCAT lack of function. Additionally, the proband carried the minor allele of the synonymous p.L363 L variant. However, this variant is unlikely to affect the clinical phenotype of the proband given its relatively high frequency in the Chilean population (4%) and its small putative effect on plasma HDL-cholesterol levels. CONCLUSION: Genetic, biochemical, in vitro and in silico analyses indicate that the rare mutations p.M404 V and p.V333 M in LCAT gene lead to suppression of LCAT enzyme activity and cause clinical features of familial LCAT deficiency.

[Auto-expandable metal stent in the management of distal stomach cancer]. / Experiencia con los stents metálicos autoexpandibles para el manejo de cáncer gástrico distal.

OBJECTIVES: To establish the efficacy and safety of antroduodenal metal stents for the treatment of pyloric syndrome in patients with distal gastric cancer. MATERIALS AND METHODS: Data were obtained from 31 patients older than 18 years who had a diagnosis of distal gastric cancer between 2009 and 2017, who presented pyloric syndrome associated with antroduodenal stenosis documented by endoscopy or X-ray of upper digestive tract, being managed with an antroduodenal auto-expandable metal stent in the gastroenterology unit of the San Ignacio University Hospital (HUSI) in Bogotá DC, Colombia. RESULTS: The main documented symptom that led to consultation was the presence of vomiting in 45.1%, followed by weight loss 16.13% and upper digestive tract bleeding 19.35%, the diagnosis being made in 74.19 % of cases with endoscopy of upper digestive tract. 96.7% of the patients presented metastases at the time of diagnosis of pyloric syndrome. 100% of patients had technical success in relation to stenting with subsequent resolution of symptoms in 96.77%, the most frequent complication being displacement in 16.13%. CONCLUSIONS: Auto-expandable metal stents for the management of gastric outlet tract obstruction secondary to distal gastric cancer is a safe and effective method as a palliative treatment, improving morbidity and mortality compared to surgical management.

Minimally Disruptive Medicine for Patients with Diabetes.

PURPOSE OF REVIEW: Patients with diabetes must deal with the burden of symptoms and complications (burden of illness). Simultaneously, diabetes care demands practical and emotional work from patients and their families, work to access and use healthcare and to enact self-care (burden of treatment). Patient work must compete with the demands of family, job, and community life. Overwhelmed patients may not have the capacity to access care or enact self-care and will thus experience suboptimal diabetes outcomes. RECENT FINDINGS: Minimally disruptive medicine (MDM) is a patient-centered approach to healthcare that prioritizes patients' goals for life and health while minimizing the healthcare disruption on patients' lives. In patients with diabetes, particularly in those with complex lives and multimorbidity, MDM coordinates healthcare and community responses to improve outcomes, reduce treatment burden, and enable patients to pursue their life's hopes and dreams.

[Shared decision making in patients with diabetes mellitus]. / Toma de decisiones compartidas en la atención de pacientes con diabetes mellitus: un desafío para Latinoamérica.

Patients with diabetes mellitus often have several medical problems and carry a burden imposed by their illness and treatment. Health care often ignores the values, preferences and context of patients, leading to treatments that do not fit into patients’ overwhelmed lives. Shared Decision Making (SDM) emerges as a way to answer the question: “What’s best for the patient?”. SDM promotes an empathic conversation between patients and clinicians that integrates the best evidence available with their values, preferences and context. We discuss three SDM approaches for patients with diabetes: one focused on sharing information, another on making choices, and a third one on helping patients and clinicians to talk about how to address the problems of living with diabetes and its comorbidities. Despite the benefits demonstrated in studies conducted in the U.S. and Europe, the implementation of SDM continues to be a challenge. In Latin America, healthcare and socio-economic conditions render the implementation of SDM more challenging. Research aimed to respond to this challenge is necessary. Meanwhile, clinicians can practice SDM by sharing evidence-based information, giving voice to patients’ values and preferences in making choices, and creating empathic conversations aimed at decisions aligned with patients’ context, dreams, goals, and life expectations.

Oxytocin for preventing postpartum haemorrhage (PPH) in non-facility birth settings.

BACKGROUND: Postpartum haemorrhage (PPH) is the single leading cause of maternal mortality worldwide. Most of the deaths associated with PPH occur in resource-poor settings where effective methods of prevention and treatment - such as oxytocin - are not accessible because many births still occur at home, or in community settings, far from a health facility. Likewise, most of the evidence supporting oxytocin effectiveness comes from hospital settings in high-income countries, mainly because of the need of well-organised care for its administration and monitoring. Easier methods for oxytocin administration have been developed for use in resource-poor settings, but as far as we know, its effectiveness has not been assessed in a systematic review. OBJECTIVES: To assess the effectiveness and safety of oxytocin provided in non-facility birth settings by any way in the third stage of labour to prevent PPH. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, the WHO International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov (12 November 2015), and reference lists of retrieved reports. SELECTION CRITERIA: All published, unpublished or ongoing randomised or quasi-randomised controlled trials comparing the administration of oxytocin with no intervention, or usual/standard care for the management of the third stage of labour in non-facility birth settings were considered for inclusion.Quasi-randomised controlled trials and randomised controlled trials published in abstract form only were eligible for inclusion but none were identified. Cross-over trials were not eligible for inclusion in this review. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility, assessed risk of bias and extracted the data using an agreed data extraction form. Data were checked for accuracy. MAIN RESULTS: We included one cluster-randomised trial conducted in four rural districts in Ghana that randomised 28 community health officers (CHOs) (serving 2404 potentially eligible pregnant women) to the intervention group and 26 CHOs (serving 3515 potentially eligible pregnant women) to the control group. Overall, the trial had a high risk of bias. CHOs delivered the intervention in the experimental group (injection of 10 IU (international units) of oxytocin in the thigh one minute following birth using a prefilled, auto-disposable syringe). In the control group, CHOs did not provide this prophylactic injection to the women they observed. CHOs had no midwifery skills and did not in any way manage the birth. All other CHO activities (outcome measurement, data collection, and early treatment and referral when necessary) were identical across the control and oxytocin CHOs.Although only one of the nine cases of severe PPH (blood loss greater or equal to 1000 mL) occurred in the oxytocin group, the effect estimate for this outcome was very imprecise and it is uncertain whether the intervention prevents severe PPH (risk ratio (RR) 0.16, 95% confidence interval (CI) 0.02 to 1.30; 1570 women (very low-quality evidence)). Similarly, because of the lack of cases of severe maternal morbidity (e.g. uterine rupture) and maternal deaths, it was not possible to obtain effect estimates for those outcomes (both very low-quality evidence).Oxytocin compared with the control group decreased the incidence of PPH (> 500 mL) in both our unadjusted (RR 0.48, 95% CI 0.28 to 0.81; 1569 women) and adjusted (RR 0.49, 95% CI 0.27 to 0.90; 1174 women (both low-quality evidence)) analyses. There was little or no difference between the oxytocin and control groups on the rates of transfer or referral of the mother to a healthcare facility (RR 0.72, 95% CI 0.34 to 1.56; 1586 women (low-quality evidence)), stillbirths (RR 1.27, 95% CI 0.67 to 2.40; 2006 infants (low-quality evidence)); andearly infant deaths (0 to three days) (RR 1.03, 95% CI 0.35 to 3.07; 1969 infants (low-quality evidence)). There were no cases of needle-stick injury or any other maternal major or minor adverse event or unanticipated harmful event. There were no cases of oxytocin use during labour.There were no data reported for some of this review's secondary outcomes: manual removal of placenta, maternal anaemia, neonatal death within 28 days, neonatal transfer to health facility for advanced care, breastfeeding rates. Similarly, the women's or the provider's satisfaction with the intervention was not reported. AUTHORS' CONCLUSIONS: It is uncertain if oxytocin administered by CHO in non-facility settings compared with a control group reduces the incidence of severe PPH (>1000 mL), severe maternal morbidity or maternal deaths. However, the intervention probably decreases the incidence of PPH (> 500 mL).The quality of the one trial included in this review was limited because of the risk of attrition and recruitment biases related to limitations in the follow-up of pregnant women in both arms of the trials and some baseline imbalance on the size of babies at birth. Additionally, there was serious imprecision of the effect estimates for most of the primary outcomes mainly because of the size of the trial, very few or no events and CIs around both relative and absolute estimates of effect that include both appreciable benefit and appreciable harm.Although the trial presented data both for primary and secondary outcomes, it seemed to be underpowered to detect differences in the primary outcomes that are the ones more relevant for making judgments about the potential applicability of the intervention in other settings (especially severe PPH).Therefore, taking into account the extreme setting where the intervention was implemented, the limited role of the CHO in the trial and the lack of power for detecting effects on primary (relevant) outcomes, the applicability of the evidence found seems to be rather limited.Further well-executed and adequately-powered randomised controlled trials assessing the effects of using oxytocin in pre-filled injection devices or other new delivery systems (spray-dried ultrafine formulation of oxytocin) on severe PPH are urgently needed. Likewise, other important outcomes like possible adverse events and acceptability of the intervention by mothers and other community stakeholders should also be assessed.

[Nicotinic acid increases cellular transport of high density lipoprotein cholesterol in patients with hypoalphalipoproteinemia]. / El ácido nicotínico aumenta el transporte celular de colesterol de las lipoproteínas de alta densidad en pacientes con hipoalfalipoproteinemia.

BACKGROUND: Plasma high density lipoproteins (HDL) are involved in reverse cholesterol transport mediated by the scavenger receptor class B type I (SR-BI). Nicotinic acid increases HDL cholesterol levels, even though its specific impact on SR-BI dependent-cellular cholesterol transport remains unknown. AIM: To determine the effect of nicotinic acid on HDL particle functionality in cholesterol efflux and uptake mediated by SR-BI in cultured cells in hypoalphalipoproteinemic patients. MATERIAL AND METHODS: In a pilot study, eight patients with low HDL (≤ 40 mg/dL) were treated with extended release nicotinic acid. HDL cholesterol and phospholipid levels, HDL2 and HDL3 fractions and HDL particle sizes were measured at baseline and post-therapy. Before and after nicotinic acid treatment, HDL particles were used for cholesterol transport studies in cells transfected with SR-BI. RESULTS: Nicotinic acid treatment raised total HDL cholesterol and phospholipids, HDL2 levels as well as HDL particle size. Nicotinic acid significantly increased HDL cholesterol efflux and uptake capacity mediated by SR-BI in cultured cells. CONCLUSIONS: Nicotinic acid therapy increases SR-BI-dependent HDL cholesterol transport in cultured cells, establishing a new cellular mechanism by which this lipid-lowering drug appears to modulate HDL metabolism in patients with hypoalphalipoproteinemia.

[Treatment of diabetic ketoacidosis using 2009 American Diabetes Association guidelines]. / Cetoacidosis diabética: Casuística 2008-2012, epidemiología y fisiopatología.

BACKGROUND: During 2009, new guidelines for the treatment of diabetic ketoacidosis were published by the American Diabetes Association. AIM: To assess the impact of new treatment guidelines on the evolution of patients treated for diabetic ketoacidosis (KAD). PATIENTS AND METHODS: Anonymous data was obtained from computational medical records of patients treated for KAD at our institution two years before ("Traditional Protocol") and TWO years after ("ADA-2009 Protocol") the publication of the 2009 American Diabetes Association (ADA) KAD guidelines. RESULTS: Twenty three patients aged 36.5 ± 15.1 years were treated with the traditional method and 23 patients aged 44.4 ± 21.1 years were treated following 2009 ADA guidelines. Among patients treated with the traditional protocol and treated following ADA 2009 guidelines, the diabetes type 1/type 2 ratio was 18/5 and 19/16 respectively (p = NS), the glycosylated hemoglobin on admission was 12.6 ± 2.5 and 14.3 ± 2.7% respectively (p = 0.03), minimal blood pH was 7.15 ± 0.14 and 7.19 ± 0.09 respectively (p = NS), bicarbonate was required in seven and no patient respectively (p = 0.01), hypokalemia < 3.5 mEq/L occurred in 78.2 and 48.5% of patients (p = 0.03), the lapse until resolution was 28.7 ± 28.0 and 28.8 ± 20.6 hours (p = NS). Only one patient, treated following ADA 2009 guidelines, died. CONCLUSIONS: Introduction of the ADA-2009 protocol for the treatment of KAD resulted in decrease in the use of intravenous bicarbonate and a reduction in the incidence of hypokalemia. There was no impact neither in the lapse until resolution or lethality.

APOA5 Q97X mutation identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family.

BACKGROUND: Severe hypertriglyceridemia (HTG) has been linked to defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are probably caused by as yet unidentified mutations. Very high triglyceride plasma levels (>112 mmol/L at diagnosis) were found in two sisters of a Chilean consanguineous family, which is strongly suggestive of a recessive highly penetrant mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG in this family. METHODS: We carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel). Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives. RESULTS: A large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster. Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X mutation (p.Gln97Ter) found in both affected sisters but not in non-affected relatives nor in a sample of unrelated controls. CONCLUSION: The Q97X mutation of the APOA5 gene in homozygous status is responsible for the severe hypertriglyceridemia in this family. We have shown that homozygosity mapping correctly pinpointed the genomic region containing the gene responsible for severe hypertriglyceridemia in this consanguineous Chilean family.

Patient Work and Treatment Burden in Type 2 Diabetes: A Mixed-Methods Study.

OBJECTIVE: To use quantitative and qualitative methods to characterize the work patients with type 2 diabetes mellitus (T2DM) enact and explore the interactions between illness, treatment, and life. PATIENTS AND METHODS: In this mixed-methods, descriptive study, adult patients with T2DM seen at the outpatient diabetes clinic at Mayo Clinic in Rochester, Minnesota, from February 1, 2016, through March 31, 2017, were invited to participate. The study had 3 phases. In phase 1, the Patient Experience with Treatment and Self-management (PETS) scale was used to quantify treatment burden. In phase 2, a convenience sample of patients used a smartphone application to describe, in real time, time spent completing diabetes self-management tasks and to upload descriptive digital photographs. In phase 3, these data were explored in qualitative interviews that were analyed by 2 investigators using deductive analysis. RESULTS: Of 162 participants recruited, 160 returned the survey (phase 1); of the 50 participants who used the smartphone application (phase 2), we interviewed 17 (phase 3). The areas in which patients reported highest treatment burden were difficulty with negotiating health services (eg, coordinating medical appointments), medical expenses, and mental/physical exhaustion with self-care. Participants reported that medical appointments required about 2.5 hours per day, and completing administrative tasks related to health care required about 45 minutes. Time spent on health behaviors varied widely-from 2 to 60 minutes in a given 3-hour period. Patients' experience of a task's burden did not always correlate with the time spent on that task. CONCLUSION: The most burdensome tasks to patients with T2DM included negotiating health care services, affording medications, and completing administrative tasks even though they were not the most time-consuming activities. To be minimally disruptive, diabetes care should minimize the delegation of administrative tasks to patients.

Lipid-Lowering Agents in Older Individuals: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: The efficacy of lipid-lowering agents on patient-important outcomes in older individuals is unclear. METHODS: We included randomized trials that enrolled individuals aged 65 years or older and that included at least 1 year of follow-up.Pairs of reviewers selected and appraised the trials. RESULTS: We included 23 trials that enrolled 60,194 elderly patients. For primary prevention, statins reduced the risk of coronary artery disease [CAD; relative risk (RR): 0.79, 95% CI: 0.68 to 0.91] and myocardial infarction (MI; RR: 0.45, 95% CI: 0.31 to 0.66) but not all-cause or cardiovascular mortality or stroke. These effects were imprecise in patients with diabetes, but there was no significant interaction between diabetes status and the intervention effect. For secondary prevention, statins reduced all-cause mortality (RR: 0.80, 95% CI: 0.73 to 0.89), cardiovascular mortality (RR: 0.68, 95% CI: 0.58 to 0.79), CAD (RR: 0.68, 95% CI: 0.61 to 0.77), MI (RR: 0.68, 95% CI: 0.59 to 0.79), and revascularization (RR: 0.68, 95% CI: 0.61 to 0.77). Intensive (vs less-intensive) statin therapy reduced the risk of CAD and heart failure. Niacin did not reduce the risk of revascularization, and fibrates did not reduce the risk of stroke, cardiovascular mortality, or CAD. CONCLUSION: High-certainty evidence supports statin use for secondary prevention in older individuals. Evidence for primary prevention is less certain. Data in older individuals with diabetes are limited; however, no empirical evidence has shown a significant difference based on diabetes status.

Antihypertensive Agents in Older Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: This systematic review summarizes the benefits of treating blood pressure (BP) in individuals 65 years and older. METHODS: We included randomized trials that evaluated BP-lowering medications or BP targets in individuals 65 years and older. Trials were selected and appraised by pairs of independent reviewers. RESULTS: We included 19 trials (42,134 patients). In individuals 65 years or older, antihypertensive therapy was associated with a reduction in all-cause mortality [relative risk: 0.88 (95% CI: 0.81 to 0.94); high certainty evidence; mean follow-up 31 months], cardiovascular mortality, myocardial infarction, heart failure, stroke, and chronic kidney disease. Individuals 75 years or older had a significant reduction in the risk of all-cause and cardiovascular mortality, stroke, and heart failure. Strict systolic BP targets (<120 mm Hg and <130 mm Hg) were associated with a significant reduction in the risk of all-cause and cardiovascular mortality and heart failure, whereas more liberal systolic targets (<150 mm Hg and <160 mm Hg) were associated with lower risk of heart failure and stroke. Older adults with type 2 diabetes mellitus (DM) had lower risk of chronic kidney disease without a significant reduction in other outcomes. However, there was no significant difference in estimates (i.e., interaction) between those with and without DM. CONCLUSIONS: Individuals aged 65 years and older or 75 years and older who receive antihypertensive therapy have statistically significant reduction in the risk of all-cause and cardiovascular mortality, heart failure, and stroke. There was no statistically significant difference in estimates between those with and without DM.

Trends in P Value, Confidence Interval, and Power Analysis Reporting in Health Professions Education Research Reports: A Systematic Appraisal.

PURPOSE: To characterize reporting of P values, confidence intervals (CIs), and statistical power in health professions education research (HPER) through manual and computerized analysis of published research reports. METHOD: The authors searched PubMed, Embase, and CINAHL in May 2016, for comparative research studies. For manual analysis of abstracts and main texts, they randomly sampled 250 HPER reports published in 1985, 1995, 2005, and 2015, and 100 biomedical research reports published in 1985 and 2015. Automated computerized analysis of abstracts included all HPER reports published 1970-2015. RESULTS: In the 2015 HPER sample, P values were reported in 69/100 abstracts and 94 main texts. CIs were reported in 6 abstracts and 22 main texts. Most P values (≥77%) were ≤.05. Across all years, 60/164 two-group HPER studies had ≥80% power to detect a between-group difference of 0.5 standard deviations. From 1985 to 2015, the proportion of HPER abstracts reporting a CI did not change significantly (odds ratio [OR] 2.87; 95% CI 1.04, 7.88) whereas that of main texts reporting a CI increased (OR 1.96; 95% CI 1.39, 2.78). Comparison with biomedical studies revealed similar reporting of P values, but more frequent use of CIs in biomedicine. Automated analysis of 56,440 HPER abstracts found 14,867 (26.3%) reporting a P value, 3,024 (5.4%) reporting a CI, and increased reporting of P values and CIs from 1970 to 2015. CONCLUSIONS: P values are ubiquitous in HPER, CIs are rarely reported, and most studies are underpowered. Most reported P values would be considered statistically significant.

Correction to: Estrogen-based hormone therapy in women with primary ovarian insufficiency: a systematic review.

In the original publication, the given and family name of the author Mohammad Hassan Murad was incorrect. This has been corrected with this erratum.

The efficacy and adverse events of testosterone replacement therapy in hypogonadal men: A systematic review and meta-analysis of randomized, placebo-controlled trials.

CONTEXT: The efficacy and safety of testosterone replacement therapy (TRT) in hypogonadal men remain incompletely understood. OBJECTIVE: To conduct a systematic review and meta-analysis of randomized clinical trials (RCT) to determine the effects of TRT on patient-important outcomes and adverse events in hypogonadal men. DATA SOURCES: We searched Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Database of Systematic Reviews, Ovid Cochrane Central Register of Controlled Trials, and Scopus from inception to March 2th, 2017. STUDY SELECTION: RCTs that assessed the efficacy and adverse events of TRT of at least 12 weeks compared with placebo in adult men with hypogonadism, defined by morning testosterone ≤300 ng/dL and at least one symptom or sign of hypogonadism. DATA EXTRACTION: Reviewers working independently and in duplicate assessed the quality of the trials and collected data on patient characteristics, interventions, and outcomes. DATA SYNTHESIS: We found 11 publications, reporting on 4 eligible trials (including 1,779 patients) at low risk of bias. Compared to placebo, TRT was associated with a small but significant increase in sexual desire or libido [standardized mean difference (SMD): 0.17, 95% CI 0.01, 0.34] (n=1383), erectile function [SMD: 0.16, 95% CI 0.06, 0.27] (n=1344), and sexual satisfaction [SMD: 0.16, 95% CI 0.01, 0.31] (n=676), but had no effect on energy or mood. TRT was associated with an increased risk of developing erythrocytosis [relative risk: 8.14, 95% CI: 1.87, 35.40] (n=1579) compared to placebo, but had no significant effect on lower urinary tract symptoms (LUTS). CONCLUSION: In hypogonadal men TRT improves sexual desire, erectile function, and sexual satisfaction, however it increases the risk of erythrocytosis.

Does Health Coaching Grow Capacity in Cancer Survivors? A Systematic Review.

Interventions that grow patient capacity to do the work of health care and life are needed to support the health of cancer survivors. Health coaching may grow capacity. This systematic review of health coaching interventions explored coaching's ability to grow capacity of cancer survivors. The authors included randomized trials or quasi-experimental studies comparing coaching to alternative interventions, and adhered to PRISMA reporting guidelines. Data were analyzed using the Theory of Patient Capacity (BREWS: Capacity is affected by factors that influence ability to reframe Biography ["B"], mobilize or recruit Resources ["R"], interact with the Environment of care ["E"], accomplish Work ["W"]), and function Socially ["S"]). The authors reviewed 2210 references and selected 12 studies (6 randomized trials and 6 pre-post). These studies included 1038 cancer survivors, mean age 57.2 years, with various type of cancers: breast, colorectal, prostate, and lung. Health coaching was associated with improved quality of life, mood, and physical activity but not self-efficacy. Classified by potential to support growth in patient capacity, 67% of included studies reported statistically significant outcomes that support "B" (quality of life, acceptance, spirituality), 75% "R" (decreased fatigue, pain), 67% "W" (increased physical activity), and 33% "S" (social deprivation index). None addressed changing the patient's environment of care. In cancer survivors, health coaching improved quality of life and supported patient capacity by several mechanisms, suggesting an important role for "Capacity Coaching." Future interventions that improve self-efficacy and patients' environments of care are needed. Capacity Coaching may improve health and quality of life of cancer survivors.

Plasma insulin-like growth factor-II (IGF-II) and IGF-II/IGF-I ratio in a chilean case of Doege-Potter Syndrome / Factor de crecimiento similar a la insulina-II (IGF-II) y razón IGF-II/ IGF-I en un caso chileno de síndrome de Doege-Potter

INTRODUCTION: Doege-Potter syndrome is a rare clinical entity characterized by recurrent hypoglycemic events caused by non-pancreatic tumors secreting an incompletely processed high-molecular-weight form of Insulin-like Growth factor-II (IGF-II). AIM: To report IGF-II and IGF-I circulating levels in a Chilean case of Doege-Potter syndrome and control individuals, and to identify the high-molecular-weight form of IGF-II. METHODS: We measured IGF-II and IGF-I plasma levels using enzyme-linked immunoassays (ELISA) in the patient and ten controls. We identified the high-molecular-weight form of IGF-II performed by Western blot. RESULTS: The plasma concentration of IGF-II in the patient was 868.9 ng/mL, which is only slightly > 80th percentile of controls (681,4 ± 212,8 ng/mL; mean ± standard deviation). In contrast, IGF-I plasma concentration in the patient was 17.6 ng/mL, which is notoriously lower than the corresponding levels in controls (109.1 ± 19.1 ng/mL). The IGF-II/IGF-I ratio in the patient was 49.4 (normal value < 10), which is 7.8 times higher compared to the average ratio of controls (6.3 ± 1.5). The high-molecular form of IGF-II presence in samples was confirmed through Western blot. CONCLUSIONS: The plasma IGF-II/IGF-I ratio better indicates the Doege-Potter syndrome's metabolic impairment than isolated measurements of circulating IGF-II or IGF-I levels.

INTRODUCCIÓN: El síndrome de Doege-Potter es una rara entidad clínica caracterizada por eventos hipoglicémicos recurrentes causados por tumores no-pancreáticos que secretan una forma incompletamente procesada con alto peso molecular del factor de crecimiento similar a la insulina-II (IGF-II). OBJETIVO: Reportar los niveles circulantes de IGF-II e IGF-I en un caso chileno de síndrome de Doege-Potter y en controles, así como identificar la forma de alto peso molecular de IGF-II. MÉTODOS: Los niveles plasmáticos de IGF-II e IGF-I se determinaron mediante inmunoensayos de tipo ELISA en el caso índice y en 10 controles. La forma de alto peso molecular de IGF-II se identificó mediante western-blot. RESULTADOS: La concentración plasmática de IGF-II en el paciente fue de 868,9 ng/mL, que es sólo ligeramente superior al percentil 80 del grupo control (681,4 ± 212,8 ng/mL; media ± desviación estándar). Sin embargo, la concentración plasmática de IGF-I en el paciente fue de 17,6 ng/ mL, que es notoriamente inferior a la de los controles (109,1 ± 19,1 ng/mL). La razón IGF-II/IGF-I en el paciente fue de 49,4 (valor normal < 10), que es 7,8 veces superior a la media de los controles (6,3 ± 1,5). La presencia de la forma de alto peso molecular de IGF-II se confirmó mediante western-blot. CONCLUSIONES: La razón IGF-II/IGF-I en plasma es un mejor indicador de las alteraciones metabólicas del síndrome de Doege-Potter que las mediciones aisladas de IGF-II o IGF-I circulantes.

Effect of estrogen replacement therapy on bone and cardiovascular outcomes in women with turner syndrome: a systematic review and meta-analysis.

Patients with Turner syndrome have adverse bone and cardiovascular outcomes from chronic estrogen deficiency. Hence, long-term estrogen replacement therapy is the cornerstone treatment. The estimates of its effect and optimal use, however, remain uncertain. We aimed to summarize the benefits and harms of estrogen replacement therapy on bone, cardiovascular, vasomotor and quality of life outcomes in patients with Turner syndrome. A comprehensive search of four databases was performed from inception through January 2016. Randomized clinical trials and observational cohort studies studying the effect of estrogen replacement therapy in patients with Turner syndrome under the age of 40 were included. Independently and in duplicate reviewers selected studies, extracted data and assessed risk of bias. Subgroup analyses were based on route of administration and type of estrogen formulation. Twenty-five studies at moderate to high risk of bias (12 randomized trials, 13 cohort studies) with 771 patients were included. Using random-effects models, estrogen replacement therapy showed an increase in bone mineral density [weighted mean change from baseline 0.09 g/cm2 (0.04-0.14)] that differed by type of estrogen but not route of administration. Oral estrogen replacement therapy showed a higher increase in high density lipoprotein cholesterol levels when compared to transdermal [weighted mean difference 9.33 mg/dl (4.82-13.85)] with no significant effect on other lipid fractions. The current evidence suggests possible benefit of estrogen replacement therapy on bone mineral density and high density lipoprotein cholesterol. Whether this improvement translates into changes in patient important outcomes (cardiovascular events or fractures) remains uncertain. Larger randomized clinical trials with direct comparisons on patient important outcomes are necessary.

Estrogen-based hormone therapy in women with primary ovarian insufficiency: a systematic review.

PURPOSE: Sex hormones play a role in bone density, cardiovascular health, and wellbeing throughout reproductive lifespan. Women with primary ovarian insufficiency (POI) have lower estrogen levels requiring hormone therapy (HT) to manage symptoms and to protect against adverse long-term health outcomes. Yet, the effectiveness of HT in preventing adverse outcomes has not been systematically assessed. We summarize the evidence regarding effects of HT on bone and cardiovascular health in women with POI. METHODS: A comprehensive search of the electronic databases MEDLINE, EMBASE, and Scopus was conducted by a medical reference librarian from database inception to January 2016. Randomized trials and observational cohort studies with an estrogen-based HT intervention in women with POI under the age of 40 were included. Reviewers worked independently and in duplicate to assess eligibility and risk of bias, and extract data of interest from each study. RESULTS: The search identified 1670 articles; 12 met inclusion criteria. Four randomized clinical trials and eight cohort studies at high risk of bias enrolled 806 women with POI. The most common HT formulations were transdermal estradiol and oral conjugated equine estrogen combined with medroxyprogesterone acetate. Bone mineral density was the most frequent outcome, with three out of eight studies showing HT associated increase benefits. Only one study reported effects on fractures or vasomotor symptoms and none on cardiovascular mortality. Results regarding lipid profiles were inconsistent. CONCLUSIONS: Evidence supporting bone and cardiovascular benefits of HT in women with POI is limited by high risk of bias, reliance on surrogate outcomes, and heterogeneity of trials regarding the formulation, dose, route of administration, and regimen of HT. Further research addressing patient important outcomes such as fractures, stroke, and cardiovascular mortality are crucial to optimize benefits of this therapy.

Vólvulo gástrico en una paciente nonagenaria: intervención endoscópica y laparoscópica. Reporte de caso / Gastric volvulus in a nonagenarian patient: endoscopic and laparoscopic intervention. Case report

Resumen El vólvulo gástrico es una entidad rara que puede presentarse de manera aguda o crónica y se acompaña de síntomas inespecíficos. Es fundamental su rápida identificación, ya que tiene alta mortalidad y el tratamiento oportuno de esta patología determina el pronóstico del paciente. A continuación, presentamos el caso de una paciente femenina de 89 años, que consulta por cuadro clínico de dolor torácico atípico, con documentación en radiografía de tórax de vólvulo gástrico organoaxial, en quien se realiza inicialmente devolvulación endoscópica con éxito. Sin embargo, en las imágenes de control se evidencia recurrencia del vólvulo, por lo cual se realizó manejo quirúrgico con hiatoplastia y funduplicatura tipo Toupet, además de gastrostomía percutánea de fijación, procedimiento realizado sin complicaciones, con los que se logró la devolvulación completa sin recurrencia.

Abstract Gastric volvulus is a rare condition that can occur acutely or chronically and is accompanied by nonspecific symptoms. Its rapid identification is critical since it has high mortality rate and timely treatment determines the patient's prognosis. The following is the case of an 89-year-old female patient who presented with atypical chest pain, with organoaxial gastric volvulus on chest X-ray, in whom endoscopic devolvulation was initially performed successfully. However, control imaging scans revealed recurrence. Therefore, surgical management included hiatoplasty and Toupet fundoplication, as well as percutaneous fixation gastrostomy, a procedure that was completed without complications and resulted in complete devolvulation without recurrence.