External validation of the Oakland Score to assess safe hospital discharge among adult patients with acute lower gastrointestinal bleeding in a single New Zealand Centre.

BACKGROUND: Acute lower gastrointestinal bleeding (LGIB) is a common reason for hospital admission. However, the majority resolve spontaneously and only a minority require inpatient intervention. We aimed to describe the epidemiology and aetiology of acute LGIB admissions in our institution. We also aimed to validate the Oakland Score, which can identify patients at low risk of adverse outcome from LGIB, in our population and determine the proportion who could have safely avoided admission. METHODS: Using the prospective, validated Otago Clinical Audit database (DIVA), we searched for adult patients admitted to Dunedin Hospital with a primary diagnosis of LGIB between January 2013 and December 2020. We retrieved data to calculate the Oakland Score and details of inpatient treatment from the electronic patient record. We excluded patients admitted electively, admissions related to inflammatory bowel disease, and those with upper gastrointestinal bleeding. RESULTS: We identified 761 patients of which 501 met inclusion criteria (56% male, median age 76 years, 82% NZ European). Overall, 72% were managed with observation or diagnostic endoscopy, 32% received blood products, and 7% required haemostatic intervention to control bleeding. The area under the receiver operating characteristic curve for the Oakland Score was 0.85 (95% CI, 0.81-0.89). A cut-off score of ≤10 predicted a 95% probability of safely avoiding admission. This equates to saving 30 bed-days annually. CONCLUSION: The majority of patients admitted with LGIB are managed conservatively. The Oakland Score could be used as a stratification tool to safely reduce the admission rate.

Lack of anti-TNF drugs levels in fistula tissue - a reason for nonresponse in Crohn's perianal fistulating disease?

INTRODUCTION: Anti-TNF therapy is recommended as treatment for patients with Crohn´s perianal fistulas. However, a significant proportion of patients have a sub-optimal response to anti-TNF therapy. Higher serum levels of anti-TNF agents have been associated with improved outcomes in perianal Crohn's disease. Currently, it is unknown whether anti-TNF agent levels can be detected in tissue from fistula tracts themselves and whether this is associated with response. AIMS AND METHODS: We undertook a pilot study to measure fistula tissue levels of anti-TNF medication (infliximab and adalimumab). We used a previously validated targeted proteomic technique, employing ultraperformance liquid chromatography-mass spectrometry, to detect/quantify anti-TNF drugs. Biopsies were obtained from fistula tracts of patients with Crohn's disease on maintenance treatment; with idiopathic (cryptoglandular) fistula tissues used as negative controls as well as positive controls (by spiking the latter tissues with anti-TNF drugs). RESULTS: Tissue was sampled from the fistula tracts of seven patients with Crohn's perianal disease (five patients were on adalimumab and two patients were on infliximab). The anti-TNF drugs, infliximab and adalimumab, were not detected in fistula samples from any of the Crohn's patients despite detection in 'spiked' positive control samples. CONCLUSION: Absence of detection of the anti-TNF drugs in fistula tissue raises the question on the role of tissue penetrance of anti-TNF drugs in response to therapy. Further work is required in a larger number of patients to validate the findings observed and investigate if any correlation exists between tissue and serum levels of anti-TNF and clinical outcome. SUMMARY: Predicting response in Crohn's fistula patients on biologic therapy is difficult with no reliable biomarkers. This pilot study uses targeted proteomics to investigate the potential role of tissue drug levels in acting as a biomarker of treatment response.

Comparison of cytokine and phosphoprotein profiles in idiopathic and Crohn's disease-related perianal fistula.

BACKGROUND: Perianal fistulae are either primary (idiopathic) or secondary [commonly associated with Crohn's disease, (CD)]. It is assumed, although not proven, that the pathophysiology differs. AIM: To systematically compare the clinical phenotypes, cytokine and phosphoprotein profiles of idiopathic and CD-related perianal fistulae. METHODS: Sixty-one patients undergoing surgery for perianal fistula were prospectively recruited (48 idiopathic, 13 CD) into a cohort study. Clinical data, including the Perineal Disease Activity Index (PDAI) and EQ-5D-5L were collected. Biopsies of the fistula tract, granulation tissue, internal opening mucosa and rectal mucosa were obtained at surgery. Concentrations of 30 cytokines and 39 phosphoproteins were measured in each biopsy using a magnetic bead multiplexing instrument and a chemiluminescent antibody array respectively. Over 12000 clinical and 23500 laboratory measurements were made. RESULTS: The PDAI was significantly higher (indicating more active disease) in the CD group with a mean difference of 2.40 (95%CI: 0.52-4.28, P = 0.01). Complex pathoanatomy was more prevalent in the CD group, namely more multiple fistulae, supralevator extensions, collections and rectal thickening. The IL-12p70 concentration at the internal opening specimen site was significantly higher (median difference 19.7 pg/mL, 99%CI: 0.2-40.4, P = 0.008) and the IL-1RA/IL-1ß ratio was significantly lower in the CD group at the internal opening specimen site (median difference 15.0, 99%CI = 0.4-50.5, P = 0.008). However in the remaining 27 cytokines and all 39 of the phosphoproteins across the four biopsy sites, no significant differences were found between the groups. CONCLUSION: CD-related perianal fistulae are more clinically severe and anatomically complex than idiopathic perianal fistulae. However, overall there are no major differences in cytokine and phosphoprotein profiles.

Maternal BMI, Peripheral Deiodinase Activity, and Plasma Glucose: Relationships Between White Women in the HAPO Study.

OBJECTIVES: Explore the maternal body mass index (BMI) relationship with peripheral deiodinase activity further. Examine associations between deiodinase activity, glucose, and C-peptide. Consider findings in the historical context of related existing literature. DESIGN: Identify fasting plasma samples and selected demographic, biophysical, and biochemical data from a subset of 600 randomly selected non-Hispanic white women recruited in the Hyperglycemia Adverse Pregnancy Outcomes (HAPO) study, all with glucose tolerance testing [545 samples sufficient to measure TSH, free T4 (fT4), and T3]. Exclude highest and lowest 1% TSH values (535 available for analysis). Assess deiodinase activity by using T3/fT4 ratios. Among women with and without gestational diabetes mellitus (GDM), compare thyroid measurements, C-peptide, and other selected data. Examine relationships independent of GDM status between BMI and thyroid hormones and between thyroid hormones and glucose and C-peptide. RESULTS: Levels of BMI, T3/fT4 ratio, and T3 were significantly higher among women with GDM (P = 0.01, 0.005, and 0.001, respectively). Irrespective of GDM status, maternal BMI was associated directly with both T3/fT4 ratio (r = 0.40, P < 0.001) and T3 (r = 0.34, P < 0.001) but inversely with fT4 (r = -0.21, P < 0.001). In turn, fasting thyroid hormone levels (most notably T3/fT4 ratio) were directly associated with maternal glucose [z score sum (fasting, 1, 2 hours); r = 0.24, P < 0.001] and with C-peptide [z score sum (fasting, 1 hour); r = 0.27, P < 0.001]. CONCLUSIONS: Higher BMI was associated with increased deiodinase activity, consistent with reports from elsewhere. Increased deiodinase activity, in turn, was associated with higher glucose. Deiodinase activity accounts for a small percentage of z score sum glucose.

Peripheral deiodinase activity: A potential explanation for the association between maternal weight and gestational hyperglycemia.

BACKGROUND: High maternal weight is known to associate with both low free thyroxine and gestational diabetes mellitus. We explore a deiodinase-related mechanism that may help explain these associations. METHODS: Among 108 women receiving routine oral glucose tolerance testing for gestational diabetes mellitus, we collected biophysical data and measured free thyroxine and total triiodothyronine, using residual plasma samples. RESULTS: Fasting triiodothyronine/free thyroxine ratio and triiodothyronine were higher among women with gestational diabetes mellitus (p = 0.02; p = 0.04). The triiodothyronine/free thyroxine ratio and triiodothyronine measurements at 2 h were associated with weight (r = 0.20, p = 0.04; r = 0.22, p = 0.02); free thyroxine showed a non-significant inverse weight relationship (r = -0.06, p = 0.55). Glucose at all four intervals was associated with triiodothyronine/free thyroxine ratios, and triiodothyronine at 2 h. In stepwise regression, triiodothyronine/free thyroxine ratio predicted glucose more strongly than did weight. CONCLUSION: These relationships may be explained by higher maternal weight inducing peripheral deiodinase activity, resulting in higher plasma glucose (via triiodothyronine stimulation) and thereby increasing gestational diabetes mellitus risk.

Remote ischemic preconditioning for cardioprotection in elective inpatient abdominal surgery - a randomized controlled trial.

BACKGROUND: Perioperative myocardial injury (PMI) is common in elective inpatient abdominal surgery and correlates with mortality risk. Simple measures for reducing PMI in this cohort are needed. This study evaluated whether remote ischemic preconditioning (RIPC) could reduce PMI in elective inpatient abdominal surgery. METHODS: This was a double-blind, sham-controlled trial with 1:1 parallel randomization. PMI was defined as any post-operative serum troponin T (hs-TNT) > 14 ng/L. Eighty-four participants were randomized to receiving RIPC (5 min of upper arm ischemia followed by 5 min reperfusion, for three cycles) or a sham-treatment immediately prior to surgery. The primary outcome was mean peak post-operative troponin in patients with PMI, and secondary outcomes included mean hs-TnT at individual timepoints, post-operative hs-TnT area under the curve (AUC), cardiovascular events and mortality. Predictors of PMI were also collected. Follow up was to 1 year. RESULTS: PMI was observed in 21% of participants. RIPC did not significantly influence the mean peak post-operative hs-TnT concentration in these patients (RIPC 25.65 ng/L [SD 9.33], sham-RIPC 23.91 [SD 13.2], mean difference 1.73 ng/L, 95% confidence interval - 9.7 to 13.1 ng/L, P = 0.753). The treatment did not influence any secondary outcome with the pre-determined definition of PMI. Redefining PMI as > 5 ng/L in line with recent data revealed a non-significant lower incidence in the RIPC cohort (68% vs 81%, P = 0.211), and significantly lower early hs-TnT release (12 h time-point, RIPC 5.5 ng/L [SD 5.5] vs sham 9.1 ng/L [SD 8.2], P = 0.03). CONCLUSIONS: RIPC did not at reduce the incidence or severity of PMI in these general surgical patients using pre-determined definitions. PMI is nonetheless common and effective cardioprotective strategies are required. TRIAL REGISTRATION: This trial was registered with Clinicaltrials.gov, NCT01850927 , 5th July 2013.

Tiroides y neurodesarrollo fetal / Thyroid hormones and fetal neurodevelopment

No disponible

Current margin practice and effect on re-excision rates following the publication of the SSO-ASTRO consensus and ABS consensus guidelines: a national prospective study of 2858 women undergoing breast-conserving therapy in the UK and Ireland.

INTRODUCTION: There is variation in margin policy for breast conserving therapy (BCT) in the UK and Ireland. In response to the Society of Surgical Oncology and American Society for Radiation Oncology (SSO-ASTRO) margin consensus ('no ink on tumour' for invasive and 2 mm for ductal carcinoma in situ [DCIS]) and the Association of Breast Surgery (ABS) consensus (1 mm for invasive and DCIS), we report on current margin practice and unit infrastructure in the UK and Ireland and describe how these factors impact on re-excision rates. METHODS: A trainee collaborative-led multicentre prospective study was conducted in the UK and Ireland between 1st February and 31st May 2016. Data were collected on consecutive BCT patients and on local infrastructure and policies. RESULTS: A total of 79 sites participated in the data collection (75% screening units; average 372 cancers annually, range 70-900). For DCIS, 53.2% of units accept 1 mm and 38% accept 2-mm margins. For invasive disease 77.2% accept 1 mm and 13.9% accept 'no ink on tumour'. A total of 2858 patients underwent BCT with a mean re-excision rate of 17.2% across units (range 0-41%). The re-excision rate would be reduced to 15% if all units applied SSO-ASTRO guidelines and to 14.8% if all units followed ABS guidelines. Of those who required re-operation, 65% had disease present at margin. CONCLUSION: There continues to be large variation in margin policy and re-excision rates across units. Altering margin policies to follow either SSO-ASTRO or ABS guidelines would result in a modest reduction in the national re-excision rate. Most re-excisions are for involved margins rather than close margins.

Antimüllerian Hormone Levels Are Not Altered by Glucose Challenge or a Meal.

BACKGROUND: Measurement of antimüllerian hormone (AMH) is used to assess ovarian reserve. Circulating levels of AMH correlate with antral follicle count, with relatively high levels indicating an ample reserve of primary and preantral follicles in the ovary. AMH levels are stable with dilution and freezer storage, and are not altered by hemolysis or menstrual cycle day in young women of reproductive age. We sought to examine whether glucose challenge or food intake modifies AMH levels compared with fasting. METHODS: Residual plasma samples were available from 54 pregnant women under fasting conditions and then 1, 2, and 3 h after ingestion of a 100-g glucose challenge. These samples were collected as part of routine clinical care to identify gestational diabetes (GDM) at 24-28 weeks of gestation. Twelve of these women met criteria for GDM based on an increased glucose level at a minimum of 2 time points. A second set consisted of serum samples collected from 8 nonpregnant women at fasting and 1 h after a meal. Levels of AMH were measured using an ultrasensitive assay (Ansh Labs, Webster, TX). A 2-way ANOVA (sample timing and GDM status) or matched t-test was performed. AMH measurements were subject to a logarithmic transformation before analysis. RESULTS: Median AMH levels in pregnant women at 1, 2, or 3 h after glucose challenge did not differ compared with AMH levels at fasting or by diagnosis of GDM. Similarly, there was no difference in median AMH levels in nonpregnant women of reproductive age at fasting and after a meal. CONCLUSION: AMH levels are not altered by glucose or food intake.

Where have all the trisomies gone?

Providing reliable prenatal screening performance estimates is critical for patient counseling and policy-making. Women who choose prenatal screening for aneuploidy are likely to be concerned not only with the common aneuploidies but with all causes of intellectual disability and serious birth defects. Sequential prenatal screening (combined serum and ultrasound testing) for aneuploidy detection commonly is offered as a primary screening test. Among women identified as screen positive, cell-free (cf)DNA has been added recently as a secondary, noninvasive screening option, before the consideration of invasive diagnostic testing (eg, amniocentesis and karyotype). With the anticipation of lower costs in the future, cfDNA might be an alternative to sequential screening in the general population. Sequential and cfDNA tests are both noninvasive, and both identify common aneuploidies. Screening via cfDNA detects more common chromosome abnormalities (eg, trisomy 21, sex trisomies). Sequential screening can identify other aneuploidies (eg, triploidy), as well as chromosome abnormalities associated with fetal structural abnormalities. When the advantages and disadvantages of routine sequential screening with routine cfDNA screening are compared, one important measure is the proportion and severity of chromosome abnormalities identified. When reporting these detection rates, authors need to carefully consider the impact of multiple well-described biases. For women to make informed choices in situations of this type, determining reliable comparative performance estimates is crucial.

Improving the diagnostic stage of the suspected colorectal cancer pathway: A quality improvement project.

We aimed to improve the lead-time and the patient experience of the diagnostic stage of the suspected colorectal cancer pathway. This project worked within the constraints of limited resources and an austere environment. The core team included a project manager trained in quality improvement methodologies. Senior and Fleming's planned change model was used as the overall framework. Baseline data supported the case for change and highlighted targets for improvement. A stakeholder workshop employed social movement theory, lean thinking, experience-based design and patient stories to engage influential leaders and secure support and commitment. Solutions that arose from the workshop were then researched. A "Genchi Genbutsu" ethos took the team to Northumbria to learn about another unit's pathway innovations. Subsequently, our new pathway employed solutions aimed at increasing the proportion of patients who went straight-to-test. Consensus on the design was achieved using Schein's process consultation theory. Implementation of the new pathway resulted in a significant reduction in the median time from referral to endoscopy from 26 days to 14 days (P<0.001), and a significant increase in the proportion going straight-to-test from 6% to 43%. Changes to improve patient experience were also implemented, however data to evidence this has not yet been collected. Going forward, further standardisation is required and issues around sustainability need to be tackled. This project exemplified, amongst others, the value of working from data from the beginning and a comprehensive early stakeholder engagement.

Free Thyroxine During Early Pregnancy and Risk for Gestational Diabetes.

Several studies have now reported associations between gestational diabetes mellitus (GDM) and low free thyroxine (fT4) during the second and third trimesters, but not in the first trimester. The present study further examines relationships between low fT4, maternal weight, and GDM among women in the FaSTER (First and Second Trimester Evaluation of Risk) trial, in an effort to determine the extent to which thyroid hormones might contribute to causality. The FaSTER cohort includes 9351 singleton, euthyroid women; 272 of these women were subsequently classified as having GDM. Thyrotropin (TSH), fT4, and thyroid antibodies were measured at 11-14 weeks' gestation (first trimester) and 15-18.9 weeks' gestation (second trimester). An earlier report of this cohort documented an inverse relationship between fT4 in the second trimester and maternal weight. In the current analysis, women with GDM were significantly older (32 vs. 28 years) and weighed more (75 vs. 64.5 kg). Maternal weight and age (but not TSH) were significantly associated univariately with fT4 (dependent variable), in the order listed. Second trimester fT4 odds ratios (OR) for GDM were 2.06 [95% CI 1.37-3.09] (unadjusted); and 1.89 [95% CI 1.26-2.84] (adjusted). First trimester odds ratios were not significant: OR 1.45 [95%CI 0.97-2.16] (unadjusted) and 1.11 [95% CI 0.74-1.62] (adjusted). The second trimester fT4/GDM relationship thus appeared to strengthen as gestation progressed. In FaSTER, high maternal weight was associated with both low fT4 and a higher GDM rate in the second trimester. Peripheral deiodinase activity is known to increase with high caloric intake (represented by high weight). We speculate that weight-related low fT4 (the metabolically inactive prohormone) is a marker for deiodinase activity, serving as a substrate for conversion of fT4 to free triiodothyronine (fT3), the active hormone responsible for glucose-related metabolic activity.

An Inverse Relationship Between Weight and Free Thyroxine During Early Gestation Among Women Treated for Hypothyroidism.

BACKGROUND: Following treatment sufficient to normalize thyrotropin (TSH), nonpregnant hypothyroid adults display higher free thyroxine (FT(4)) concentrations than a reference population. Our aim is to determine whether FT(4) concentrations are higher during pregnancy among women treated for hypothyroidism and whether their weight is associated with FT(4) levels. Weight/FT(4) relationships have not previously been reported in treated hypothyroid adults (either pregnant or nonpregnant). METHODS: Thyroid-related measurements were available from over 10,000 women at two early pregnancy time periods from the FaSTER (First and Second Trimester Evaluation of Risk for Fetal aneuploidy) trial (1999-2002). All women were receiving routine prenatal care. Present analyses were restricted to 9267 reference women and 306 treated, hypothyroid women with TSH between the 2nd and 98th reference percentiles. We compared FT(4) values between those groups at 11-14 and 15-18 weeks' gestation, using linear regression to estimate FT(4)/maternal weight relationships, after accounting for treatment and other potential covariates. RESULTS: In comparison to reference women, median FT(4) values and percent of FT(4) values ≥95th reference percentile were significantly higher in treated women at both 11-14 and 15-18 weeks' gestation (p<0.001) overall and after stratification by weight into tertiles. Among both treated and reference women, median FT(4) decreased monotonically with increasing weight, regardless of anti-thyroperoxidase antibody status. Maternal age, maternal weight, and treatment status were important predictors of FT(4) levels (p<0.001, defined by partial r(2) values of 1% or higher). Anti-thyroperoxidase antibody status, TSH values (after logarithmic transformation), and all interaction terms were well below an r(2) of 1%. FT(4) levels were 1.45 pmol/L higher in treated than reference women, independent of other factors. Maternal age and weight reduced FT(4) levels by 0.0694 pmol/L/y and 0.0208 pmol/L/kg, respectively. CONCLUSIONS: FT(4) concentrations are higher among treated hypothyroid pregnant women than among reference women, and higher maternal weight is associated with lower FT(4) levels, regardless of treatment status. This inverse relationship is not associated with higher TSH levels. While no immediate clinical implications are attached to the current observations, increased peripheral deiodinase activity in the presence of higher weight might explain these findings. Further investigation appears worthy of attention.

Modeling risk for severe adverse outcomes using angiogenic factor measurements in women with suspected preterm preeclampsia.

INTRODUCTION: Preeclampsia (PE) is a pregnancy-specific syndrome associated with adverse maternal and fetal outcomes. Patient-specific risks based on angiogenic factors might better categorize those who might have a severe adverse outcome. METHODS: Women evaluated for suspected PE at a tertiary hospital (2009-2012) had pregnancy outcomes categorized as 'referent' or 'severe', based solely on maternal/fetal findings. Outcomes that may have been influenced by a PE diagnosis were considered 'unclassified'. Soluble fms-like tyrosine kinase (sFlt1) and placental growth factor (PlGF) were subjected to bivariate discriminant modeling, allowing patient-specific risks to be assigned for severe outcomes. RESULTS: Three hundred twenty-eight singleton pregnancies presented at ≤34.0 weeks' gestation. sFlt1 and PlGF levels were adjusted for gestational age. Risks above 5 : 1 (10-fold over background) occurred in 77% of severe (95% CI 66 to 87%) and 0.7% of referent (95% CI <0.1 to 3.8%) outcomes. Positive likelihood ratios for the modeling and validation datasets were 19 (95% CI 6.2-58) and 15 (95% CI 5.8-40) fold, respectively. CONCLUSIONS: This validated model assigns patient-specific risks of any severe outcome among women attending PE triage. In practice, women with high risks would receive close surveillance with the added potential for reducing unnecessary preterm deliveries among remaining women. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.