Thresholds for hypoglycaemic screening-a cause for concern?

The new Framework for Practice highlights the limited evidence for our current clinical practice (1). It is helpful in emphasising the importance of accurate measurement of glucose concentrations, listening to the concerns of parents and acknowledging that untreated hypoglycaemia can have devastating longterm consequences. However we have the following concerns: Screening thresholds The Framework recommends lowering a commonly accepted screening threshold in infants considered to be at risk of hypoglycaemia to a level that at any other time of life would be considered harmful. It fails to acknowledge the differences between screening and diagnostic thresholds; something neonatologists are very familiar with in the management of babies with jaundice. Phototherapy is provided to many babies with bilirubin levels well below a harmful level to prevent a harmful level being reached. Screening interventions are intended to prevent harmful events. Such thresholds will inevitably mean many individuals are treated ‘unnecessarily’ to avoid the risk of significant harm. In 2000 Cornblath et al published guidance on ‘operational thresholds’ in keeping with the current BAPM framework (2). However, and possibly reflecting concerns about the lack of evidence for the safety of this lower operational threshold, in 2017 in the UK, >80% of neonatal units still used <2.6mmol/ as their defined hypoglycaemic threshold (3). A threshold of <2.6mmol/l provides an opportunity for intervention before damaging neuroglycopaenia occurs

Sepsis biomarkers in unselected patients on admission to intensive or high-dependency care

Although many sepsis biomarkers have shown promise in selected patient groups, only C-reactive protein and procalcitonin (PCT) have entered clinical practice. The aim of this study was to evaluate three promising novel sepsis biomarkers in unselected patients at admission to intensive care. We assessed the performance of pancreatic stone protein (PSP), soluble CD25 (sCD25) and heparin binding protein (HBP) in distinguishing patients with sepsis from those with a non-infective systemic inflammatory response and the ability of these markers to indicate severity of illness. METHODS: Plasma levels of the biomarkers, PCT and selected inflammatory cytokines were measured in samples taken from 219 patients during the first six hours of admission to intensive or high dependency care. Patients with a systemic inflammatory response were categorized as having sepsis or a non-infective aetiology, with or without markers of severity, using standard diagnostic criteria. RESULTS: Both PSP and sCD25 performed well as biomarkers of sepsis irrespective of severity of illness. For both markers the area under the receiver operating curve (AUC) was greater than 0.9; PSP 0.927 (0.887 to 0.968) and sCD25 0.902 (0.854 to 0.949). Procalcitonin and IL6 also performed well as markers of sepsis whilst in this intensive care unit (ICU) population, HBP did not: PCT 0.840 (0.778 to 0.901), IL6 0.805 (0.739 to 0.870) and HBP 0.607 (0.519 to 0.694). Levels of both PSP and PCT reflected severity of illness and both markers performed well in differentiating patients with severe sepsis from severely ill patients with a non-infective systemic inflammatory response: AUCs 0.955 (0.909 to 1) and 0.837 (0.732 to 0.941) respectively. Although levels of sCD25 did not correlate with severity, the addition of sCD25 to either PCT or PSP in a multivariate model improved the diagnostic accuracy of either marker alone. CONCLUSIONS: PSP and sCD25 perform well as sepsis biomarkers in patients with suspected sepsis at the time of admission to intensive or high dependency care. These markers warrant further assessment of their prognostic value. Whereas previously published data indicate HBP has clinical utility in the emergency department, it did not perform well in an intensive-care population

Elevated plasma levels of TIMP-3 are associated with a higher risk of acute respiratory distress syndrome and death following severe isolated traumatic brain injury.

BackgroundComplications after injury, such as acute respiratory distress syndrome (ARDS), are common after traumatic brain injury (TBI) and associated with poor clinical outcomes. The mechanisms driving non-neurologic organ dysfunction after TBI are not well understood. Tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) is a regulator of matrix metalloproteinase activity, inflammation, and vascular permeability, and hence has plausibility as a biomarker for the systemic response to TBI.MethodsIn a retrospective study of 182 patients with severe isolated TBI, we measured TIMP-3 in plasma obtained on emergency department arrival. We used non-parametric tests and logistic regression analyses to test the association of TIMP-3 with the incidence of ARDS within 8 days of admission and in-hospital mortality.ResultsTIMP-3 was significantly higher among subjects who developed ARDS compared with those who did not (median 2810 pg/mL vs. 2260 pg/mL, p=0.008), and significantly higher among subjects who died than among those who survived to discharge (median 2960 pg/mL vs. 2080 pg/mL, p&lt;0.001). In an unadjusted logistic regression model, for each SD increase in plasma TIMP-3, the odds of ARDS increased significantly, OR 1.5 (95% CI 1.1 to 2.1). This association was only attenuated in multivariate models, OR 1.4 (95% CI 1.0 to 2.0). In an unadjusted logistic regression model, for each SD increase in plasma TIMP-3, the odds of death increased significantly, OR 1.7 (95% CI 1.2 to 2.3). The magnitude of this association was greater in a multivariate model adjusted for markers of injury severity, OR 1.9 (95% CI 1.2 to 2.8).DiscussionTIMP-3 may play an important role in the biology of the systemic response to brain injury in humans. Along with clinical and demographic data, early measurements of plasma biomarkers such as TIMP-3 may help identify patients at higher risk of ARDS and death after severe isolated TBI.Level of evidenceIII

Most incompetent calf perforating veins are found in association with superficial venous reflux

AbstractPurpose: The indications for surgical perforator interruption remain undefined. Previous work has demonstrated an association between clinical status and the number of incompetent perforating veins (IPVs). Other studies have demonstrated that correction of IPV physiology results from abolition of saphenous system reflux. The purpose of this study was to identify which, if any, patterns of venous reflux and obstruction are particularly associated with IPV. Patients and Methods: Two hundred thirty patients and subjects (103 men, 127 women, 308 limbs) with varying grades of venous disease were examined both clinically and with duplex ultrasound scan. The odds ratios (ORs) for the presence of IPVs were calculated for different anatomical distributions of main-stem venous reflux and obstruction. The base group are those with no main-stem venous disease. Results: There were no significant associations between the proportions of limbs demonstrating IPVs and patient age or sex. The ORs for the presence of IPVs in association with other venous disease are as follows (age/sex adjusted): long saphenous vein reflux, OR = 1.86, range = 1.32-2.63; short saphenous vein reflux, OR = 1.36, range = 1.02-1.82; deep system venous reflux, OR = 1.61, range = 1.2-2.15; superficial system reflux, OR = 3.17, range = 1.87-5.4; and deep system obstruction, OR = 1.09, range = 0.51-2.33. The ORs for combinations of venous disorders were calculated. Combinations of disease produced higher odds for the presence of IPVs than those above, the highest being long saphenous vein, short saphenous vein, and deep reflux combined, OR = 6.85 (95% CI, 2.97-15.83; P =.0001). Conclusions: Although the presence of IPVs is associated with venous ulceration, the highest ORs for the presence of IPVs were found in patients with superficial disease alone or in combination with deep reflux. Many of these may be corrected by saphenous surgery alone. (J Vasc Surg 2001;34:774-8.

Gastro oesophageal reflux disease (GORD)-related symptoms and its association with mood and anxiety disorders and psychological symptomology: a population-based study in women

Background: Psychopathology seems to play a role in reflux pathogenesis and vice versa, yet few population based studies have systematically investigated the association between gastro-oesophageal reflux disease (GORD) and psychopathology. We thus aimed to investigate the relationship between GORD-related symptoms and psychological symptomatology, as well as clinically diagnosed mood and anxiety disorders in a randomly selected, population-based sample of adult women.&nbsp;Methods:&nbsp;This study examined data collected from 1084 women aged 20-93 yr participating in the Geelong&nbsp;Osteoporosis Study. Mood and anxiety disorders were identified using the Structured Clinical Interview for DSM-IVTR Research Version, Non-patient edition (SCID-I/NP), and psychological symptomatology was assessed using the&nbsp;General Health Questionnaire (GHQ-12). GORD-related symptoms were self-reported and confirmed by medication&nbsp;use where possible and lifestyle factors were documented.Results: Current psychological symptomatology and mood disorder were associated with increased odds of&nbsp;concurrent GORD-related symptoms (adjusted OR 2.1, 95% CI 1.3-3.5, and OR 3.0, 95% CI 1.7-5.6, respectively). Current&nbsp;anxiety disorder also tended to be associated with increased odds of current GORD-related symptoms (p=0.1).&nbsp;Lifetime mood disorder was associated with a 1.6-fold increased odds of lifetime GORD-related symptoms (adjusted OR&nbsp;1.6, 95% CI 1.1-2.4) and lifetime anxiety disorder was associated with a 4-fold increased odds of lifetime GORD- related&nbsp;symptoms in obese but not non-obese participants (obese, age-adjusted OR 4.0, 95% CI 1.8-9.0).Conclusions: These results indicate that psychological symptomatology, mood and anxiety disorders are positively&nbsp;associated with GORD-related symptoms. Acknowledging this common comorbidity may facilitate recognition and&nbsp;treatment, and opens new questions as to the pathways and mechanisms of the association.</div

Diversity in fall characteristics hampers effective prevention: the precipitants, the environment, the fall and the injury

Summary Falls among the elderly are common and characteristics may differ between injurious and non-injurious falls. Among 887 older Australian women followed for 1.6 years, 32% fell annually. Only 8.5% resulted in fracture and/or hospital admission. The characteristics of those falls are indistinguishable from those not coming to medical attention. Introduction The precipitants and environment of all falls occurring among a large cohort of older Caucasian women were categorised by injury status to determine if the characteristics differed between injurious and non-injurious falls. Methods Among 887 Australian women (70+ years), falls were ascertained using monthly postcard calendars and a questionnaire was administered for each fall. Hospital admissions and fractures were independently confirmed. Results All falls were reported for a mean observation time of 577 (IQR 546–607) days per participant, equating to a total 1400 person-years. Thirty-two percent fell at least once per year. The most common features of a fall were that the faller was walking (61%) at home (61%) during the day (88%) and lost balance (32%). Only 12% of all falls occurred at night. Despite no difference in the type of injury between day and night, the likelihood of being hospitalised from a fall at night was 4.5 times greater than that of a daytime fall with adjustment for injury type and participant age (OR 4.5, 95% CI 2.1, 9.5; p < 0.001). Of all falls, approximately one third were associated with no injury to the faller (31%), one third reported a single injury (37%) and one third reported more than one injury (32%). In 95% of falls, the faller was not admitted to hospital. Only 5% of falls resulted in fracture(s). Conclusions Our findings demonstrate the significant diversity of precipitants and environment where falls commonly occur among older community-dwelling women. Falls resulting in fracture and/or hospital admission collectively represent 8.5% of all falls and their characteristics are indistinguishable from falls not coming to medical attention and incurring no apparent cost to the health system

Fibrillin-1 regulates the bioavailability of TGFβ1

We have discovered that fibrillin-1, which forms extracellular microfibrils, can regulate the bioavailability of transforming growth factor (TGF) β1, a powerful cytokine that modulates cell survival and phenotype. Altered TGFβ signaling is a major contributor to the pathology of Marfan syndrome (MFS) and related diseases. In the presence of cell layer extracellular matrix, a fibrillin-1 sequence encoded by exons 44–49 releases endogenous TGFβ1, thereby stimulating TGFβ receptor–mediated Smad2 signaling. This altered TGFβ1 bioavailability does not require intact cells, proteolysis, or the altered expression of TGFβ1 or its receptors. Mass spectrometry revealed that a fibrillin-1 fragment containing the TGFβ1-releasing sequence specifically associates with full-length fibrillin-1 in cell layers. Solid-phase and BIAcore binding studies showed that this fragment interacts strongly and specifically with N-terminal fibrillin-1, thereby inhibiting the association of C-terminal latent TGFβ-binding protein 1 (a component of the large latent complex [LLC]) with N-terminal fibrillin-1. By releasing LLC from microfibrils, the fibrillin-1 sequence encoded by exons 44–49 can contribute to MFS and related diseases