Correlation of frailty assessment metrics in one-year follow-up of aged care residents: a sub-study of a randomised controlled trial.

INTRODUCTION: Frailty is increasingly recognised as a dynamic syndrome, with multiple causes, dimensions and consequences. There is little understanding of how those frailty assessment metrics interact over time. The aim of this study was to describe the longitudinal correlation between five frailty metrics, namely multimorbidity, muscular strength, mood alterations, cognitive capacity, and functional capacity in a cohort study of aged care (nursing home) residents. METHODS: 248 aged care residents with Frailty Index at baseline of < 0.4 and no dementia were followed for 12 months. A multimorbidity score and an activity of daily living limitation score were created using individual items of the Frailty Index. Muscular strength was measured by grip strength. Cognitive capacity was measured using the Montreal Cognitive Assessment (MoCA) test. Mood alterations were measured using the anxiety/depression screening question from EQ-5D. We analysed the inter-individual correlation at baseline, association between baseline and future change, and within-individual correlation at baseline, 6 and 12 months. RESULTS: Population analysis shows that metrics were not associated at baseline. All of the studied metrics at baseline were associated with change in 12 months, with the exception of anxiety/depression scores. Pairwise within-individual correlation was strong between MoCA and grip strength (0.13, p = 0.02) and activity of daily living (- 0.48, p < 0.001), and between activities of daily living and multimorbidity index (0.28, p < 0.001). No within-individual correlation was found between anxiety depression score and other metrics. CONCLUSION: The results suggest an interdependence between comorbidities, physical capacity, cognition and activities of daily living in aged care residents. Comprehensive measurement of frailty-related metrics may provide improved understanding of frailty progression at later life stages.

Three-year epidemiology of hospitalised paediatric burn patients in a Malaysian Tertiary Hospital 2016 - 2018.

INTRODUCTION: Burn injuries incur not just significant morbidity but also long-term psychosocial impact. This study aims to identify the clinico-demographics of children hospitalised for burns and factors associated with prolonged hospitalisation. MATERIALS AND METHODS: Written medical records of burn patients admitted to the Sultanah Aminah Hospital paediatric surgical ward, from January 2016 to December 2018, were retrospectively reviewed. Details on the patients' socio-demographic background, burn injuries, management and outcomes were recorded and analysed with logistic regression. RESULTS AND CONCLUSION: Of the 255 children included in the study, the majority were males (62.7%), children aged between 1 to 3 years (43.1%), and of the Malay ethnic group (83.1%). The commonest injury mechanism was scalds burns (81.2%). Staphylococcus aureus remained the commonest organism cultured from paediatric burn wounds. Most patients (66.4%) were hospitalised for less than 1 week. A significant number of patients experienced complications from their injuries. Multivariate analysis showed burns affecting total body surface area > 10% (adjusted OR, 13.45 [95% CI 6.25 - 28.96]; p = < 0.001) and non-scald burns (adjusted OR, 2.70 [95% CI 1.12 - 6.50]; p = 0.027) were the two main factors associated with prolonged hospitalisation of more than 1 week. These findings describing the epidemiology and outcomes of paediatric burn cases in a tertiary centre in Malaysia may inform future practice. More importantly, the information may contribute to the identification of at-risk populations and advise the development of effective prevention strategies to reduce the incidence and morbidity associated with paediatric burns in this region.

Properties of Deiters' neurons and inhibitory synaptic transmission in the mouse lateral vestibular nucleus.

Deiters' neurons, located exclusively in the lateral vestibular nucleus (LVN), are involved in vestibulospinal reflexes, innervate extensor motoneurons that drive antigravity muscles, and receive inhibitory inputs from the cerebellum. We investigated intrinsic membrane properties, short-term plasticity, and inhibitory synaptic inputs of mouse Deiters' and non-Deiters' neurons within the LVN. Deiters' neurons are distinguished from non-Deiters' neurons by their very low input resistance (105.8 vs. 521.8 MΩ, respectively), long axons that project as far as the ipsilateral lumbar spinal cord, and expression of the cytostructural protein nonphosphorylated neurofilament protein (NPNFP). Whole cell patch-clamp recordings in brain stem slices show that most Deiters' and non-Deiters' neurons were tonically active (>92%). Short-term plasticity was studied by examining discharge rate modulation following release from hyperpolarization [postinhibitory rebound firing (PRF)] and depolarization [firing rate adaptation (FRA)]. PRF and FRA gain were similar in Deiters' and non-Deiters' neurons (PRF 24.9 vs. 20.2 Hz and FRA gain 231.5 vs. 287.8 spikes/s/nA, respectively). Inhibitory synaptic input to both populations showed that GABAergic rather than glycinergic inhibition dominated. However, GABAA miniature inhibitory postsynaptic current (mIPSC) frequency was much higher in Deiters' neurons compared with non-Deiters' neurons (∼15.9 vs. 1.4 Hz, respectively). Our data suggest that Deiters' neurons can be reliably identified by their intrinsic membrane and synaptic properties. They are tonically active and glutamatergic, have low sensitivity or "gain," exhibit little adaptation, and receive strong GABAergic input. Deiters' neurons also have minimal short-term plasticity, and together these features suggest they are well suited to a role in encoding tonic signals for the vestibulospinal reflex.NEW & NOTEWORTHY Deiters' neurons within the lateral vestibular nucleus project the length of the spinal cord and activate antigravity extensor muscles. Deiters' neurons were characterized anatomically and physiologically in mice. Deiters' neurons are tonically active, have homogeneous intrinsic membrane properties, including low input resistance, and receive significant GABAAergic synaptic inputs. Deiters' neurons show little modulation in response to current injection. These features are consistent with Deiters' neurons responding to perturbations to maintain posture and balance.

Fewer losses in the cascade of care for latent tuberculosis with solo interferon-gamma release assay screening compared to sequential screening.

BACKGROUND: Refugees are at increased risk of developing tuberculosis (TB) soon after resettlement. Targeting high-risk populations for latent tuberculosis infection (LTBI) screening and treatment is an important measure towards eliminating TB in low incidence countries, however, there are low rates of screening and treatment completion in the LTBI cascade of care. The authors hypothesized that an interferon-gamma release assay (IGRA) screening strategy would lead to a higher proportion of refugees completing LTBI screening and treatment, compared to sequential screening with tuberculin skin test (TST) and confirmatory IGRA. METHODS: This retrospective cohort study included eligible refugees screened with a sequential strategy versus a solo-IGRA strategy at different time periods from a centralized refugee clinic. The primary outcome was the proportion completing LTBI screening in each cohort. RESULTS: A total of 471 subjects were included (240 in sequential screening, 231 in solo-IGRA screening). 54% of refugees completed LTBI screening with sequential testing, compared to 85% of those screened with a solo-IGRA. Time to completing screening was also shorter in the solo-QFT group (difference 16.5 days, p < 0.01, 95% confidence interval 9.3, 23.7). There was a higher incidence of LTBI diagnosis in the solo-IGRA group (41 versus 20, p = 0.002). Screening completion was predicted by solo-IGRA screening (aOR 3.74, 95% confidence interval 2.30, 6.09; p < 0.001) and if refugees were privately-sponsored (aOR 2.81, 95% confidence interval 1.53, 5.15; p = 0.001). Treatment completion rates did not differ between groups. CONCLUSION: This study has identified fewer dropouts in the LTBI cascade of care if a solo-IGRA strategy is used for screening. An IGRA should be strongly considered as the screening method for refugees arriving in low-incidence settings if resources are available.

Palliative care in Malaysia: the need to do much more.

No abstract provided.

A review of efferent cholinergic synaptic transmission in the vestibular periphery and its functional implications.

It has been over 60 years since peripheral efferent vestibular terminals were first identified in mammals, and yet the function of the efferent vestibular system remains obscure. One reason for the lack of progress may be due to our deficient understanding of the peripheral efferent synapse. Although vestibular efferent terminals were identified as cholinergic less than a decade after their anatomical characterization, the cellular mechanisms that underlie the properties of these synapses have had to be inferred. In this review we examine how recent mammalian studies have begun to reveal both nicotinic and muscarinic effects at these terminals and therefore provide a context for fast and slow responses observed in classic electrophysiological studies of the mammalian efferent vestibular system, nearly 40 years ago. Although incomplete, these new results together with those of recent behavioral studies are helping to unravel the mysterious and perplexing action of the efferent vestibular system. Armed with this information, we may finally appreciate the behavioral framework in which the efferent vestibular system operates.

Association of blood mercury levels with nonmelanoma skin cancer in the U.S.A. using National Health and Nutrition Examination Survey data (2003-2016).

BACKGROUND: Some studies have reported increased incidence or mortality of lung and brain cancers associated with occupations involving potential mercury exposure. Epidemiological evidence related to skin cancer is also limited. OBJECTIVES: To investigate the association between blood mercury (Hg) levels and nonmelanoma skin cancer (NMSC). METHODS: We used National Health and Nutrition Examination Survey data from 2003 to 2016. The exposures were blood total (tHg), inorganic (iHg) and methylmercury (MeHg). The outcome was a self-reported diagnosis of NMSC. We included participants aged ≥ 20 years who had information on blood mercury and sociodemographic factors. We conducted a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of NMSC associated with quartiles of blood Hg, after adjusting for the sociodemographic factors and survey year. RESULTS: The number of participants was 29 413; mean age was 49 years and 52% were female. Compared with those with a tHg ≤ 0·47 µg L-1 (Q1), those with a tHg > 1·74 µg L-1 (Q4) had nearly double the odds of NMSC (OR 1·79, 95% CI 1·19-2·71; Ptrend = 0·004). Similarly, those in the highest quartile of MeHg (> 1·44 µg L-1 ) had 1·7 times greater odds of NMSC (OR 1·74, 95% CI 1·13-2·70; Ptrend = 0·01) than those in the lowest quartile (≤ 0·21 µg L-1 ). iHg levels were nonsignificantly positively associated with NMSC (Ptrend = 0·08). CONCLUSIONS: We found that higher blood tHg and MeHg levels were associated with a higher prevalence of NMSC. Linked Comment: Taylor. Br J Dermatol 2020; 183:413-414.

Lactococcus lactis harbouring Ara h 2.02 alleviates allergen-specific Th2-associated responses in sensitized mice.

AIM: To study the prophylactic effect of recombinant Lactococcus lactis (rLl) harbouring Ara h 2.02 peanut allergen, in sensitized and challenged mice. METHODS AND RESULTS: Ara h 2.02 cDNA was cloned into pNZ8048 for heterologous expression in L. lactis. The purified recombinant allergen showed IgE binding comparable with native Ara h 2. Balb/c mice were fed with either recombinant (rLl), nonrecombinant L. lactis (Ll) or NaHCO3 (Sham) prior to sensitization and challenged with rAra h 2.02, whereas the baseline group was only fed with Ll. Allergen-specific immunoglobulin and splenocyte cytokines responses were determined for each mouse. Mice fed with either Ll or rLl showed significant alleviation of IgE and IgG1 compared to the Sham group. Despite no significant decrease in Th2 (IL-4, IL-13, IL-6) or increase in Th1 (IFN-γ) cytokines, both groups showed lower IL-10 level, while the IL-4 : IFN-γ ratio was significantly lower for rLl compared to Ll group. CONCLUSIONS: Oral administration of rLl harbouring Ara h 2.02 demonstrated alleviation of Th2-associated responses in allergen-challenged mice and a possible added allergen-specific prophylactic effect. SIGNIFICANCE AND IMPACT OF THE STUDY: Ara h 2.02 coupled with the intrinsic properties of probiotic L. lactis as a delivery vehicle can be explored for the development of a commercially scalable vaccine.

Expression and function of macrophage-inducible C-type lectin (Mincle) in inflammation driven parturition in fetal membranes and myometrium.

The pivotal role of inflammatory processes in human parturition is well known, but not completely understood. We have performed a study to examine the role of macrophage-inducible C-type lectin (Mincle) in inflammation-associated parturition. Using human samples, we show that spontaneous labour is associated with up-regulated Mincle expression in the myometrium and fetal membranes. Mincle expression was also increased in fetal membranes and myometrium in the presence of pro-labour mediators, the proinflammatory cytokines interleukin (IL)-1B and tumour necrosis factor (TNF), and Toll-like receptor (TLR) ligands fsl-1, poly(I:C), lipopolysaccharide (LPS) and flagellin. These clinical studies are supported by mouse studies, where an inflammatory challenge in a mouse model of preterm birth increased Mincle expression in the uterus. Importantly, elimination of Mincle decreased the effectiveness of proinflammatory cytokines and TLR ligands to induce the expression of pro-labour mediators; namely, proinflammatory cytokines and chemokines, contraction-associated proteins and prostaglandins, and extracellular matrix remodelling enzymes, matrix metalloproteinases. The data presented in this study suggest that Mincle is required when inflammatory activation precipitates parturition.

STAT-3 regulation of CXCR4 is necessary for the prenylflavonoid Icaritin to enhance mesenchymal stem cell proliferation, migration and osteogenic differentiation.

Mesenchymal stem cell (MSC) dysfunction has been implicated in the pathogenesis of osteoporosis. MSCs derived from osteoporotic subjects demonstrate significant impairment in proliferation, adhesion and chemotaxis, and osteogenic differentiation, leading to reduced functional bone-forming osteoblasts and ultimately nett bone loss and osteoporosis. Epimedium herbs and its active compound Icaritin (ICT) have been used in Chinese ethnopharmacology for the treatment of metabolic bone diseases. Using an in-vitro cell culture model, we investigated the benefits of ICT treatment in enhancing MSC proliferation, migration and osteogenic differentiation, and provide novel data to describe its mechanism of action. ICT enhances MSC proliferation, chemotaxis to stromal cell-derived factor-1 (SDF-1) and osteogenic differentiation through the activation of signal transduction activator transcription factor 3 (STAT-3), with a consequential up-regulation in the expression and activity of cysteine (C)-X-C motif chemokine receptor 4 (CXCR4). These findings provide a strong basis for future clinical studies to confirm the therapeutic potential of ICT for the prevention and treatment of osteoporosis and fragility fractures.

The SAGES Fundamental Use of Surgical Energy program (FUSE): history, development, and purpose.

BACKGROUND: Adverse events due to energy device use in surgical operating rooms are a daily occurrence. These occur at a rate of approximately 1-2 per 1000 operations. Hundreds of operating room fires occur each year in the United States, some causing severe injury and even mortality. The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) therefore created the first comprehensive educational curriculum on the safe use of surgical energy devices, called Fundamental Use of Surgical Energy (FUSE). This paper describes the history, development, and purpose of this important training program for all members of the operating room team. METHODS: The databases of SAGES and the FUSE committee as well as personal photographs and documents of members of the FUSE task force were used to establish a brief history of the FUSE program from its inception to its current status. RESULTS: The authors were able to detail all aspects of the history, development, and national as well as global implementation of the third SAGES Fundamentals Program FUSE. CONCLUSIONS: The written documentation of the making of FUSE is an important contribution to the history and mission of SAGES and allows the reader to understand the idea, concept, realization, and implementation of the only free online educational tool for physicians on energy devices available today. FUSE is the culmination of the SAGES efforts to recognize gaps in patient safety and develop state-of-the-art educational programs to address those gaps. It is the goal of the FUSE task force to ensure that general FUSE implementation becomes multinational, involving as many countries as possible.

Is there an association between dietary intake and academic achievement: a systematic review.

BACKGROUND: The majority of literature examining the effect of dietary behaviour on academic achievement has focused on breakfast consumption only. Here, we aim to systematically review the literature investigating the broader effects of dietary intake and behaviours on school-aged children's academic achievement. METHODS: A search was undertaken across seven databases using keywords. For studies to be included, they needed to be conducted in: school-aged children (5-18 years); assess and report: (i) a measure of academic performance; (ii) a measure of dietary intake/behaviour; and (iii) the association between dietary intake/behaviours and academic performance. Forty studies were included in the review. RESULTS: The majority of studies were cross-sectional in design (n = 33) and studied children aged >10 years, with very few reports in younger age groups. More than 30 different dietary assessment tools were used, with only 40% of those using a validated/standardised assessment method. Half the studies collected outcomes of academic achievement objectively from a recognised educational authority, whereas 10 studies used self-reported measures. The dietary outcomes most commonly reported to have positive associations with academic achievement were: breakfast consumption (n = 12) and global diet quality/meal patterns (n = 7), whereas negative associations reported with junk/fast food (n = 9). CONCLUSIONS: This review highlights that moderate associations exist for dietary intakes characterised by regular breakfast consumption, lower intakes of energy-dense, nutrient-poor foods and overall diet quality with respect to outcomes of academic achievement. Future studies should consider the use of validated dietary assessment methods and standardised reporting of academic achievement.

Multidisciplinary retroperitoneal and pelvic soft-tissue sarcoma case conferences: the added value that radiologists can provide.

Clinical Vignette: A 50-year-old woman presents to the emergency department with increasing abdominal pain. Abdominal computed tomography imaging reveals an expanded inferior vena cava-filling defect that is suspicious for a retroperitoneal sarcoma, possibly a primary leiomyosarcoma of the inferior vena cava. The surgery team discusses the case with the radiologist, and all agree that there are multiple challenges with obtaining a tissue diagnosis and determining resectability. Thus, it is decided that this patient should be discussed at a multidisciplinary case conference. In the present article, we feature a case-based scenario focusing on the role of the radiologist in this type of multidisciplinary team.

The risk of internal hernia or volvulus after laparoscopic colorectal surgery: a systematic review.

AIM: To determine the incidence of internal hernias after laparoscopic colorectal surgery and evaluate the risk factors and strategies in the management of this serious complication. METHOD: Two databases (MEDLINE from 1946 and Embase from 1949) were searched to mid-September 2015. The search terms included volvulus or internal hernia and laparoscopic colorectal surgery or colorectal surgery or anterior resection or laparoscopic colectomy. We found 49 and 124 articles on MEDLINE and Embase, respectively, an additional 15 articles were found on reviewing the references. After removal of duplicates, 176 abstracts were reviewed, with 33 full texts reviewed and 15 eligible for qualitative synthesis. RESULTS: The incidence of internal hernia after laparoscopic colorectal surgery is low (0.65%). Thirty-one patients were identified. Five cases were from two prospective studies (5/648, 0.8%), 20 cases were from seven retrospective studies (20/3165, 0.6%) and six patients were from case reports. Of the 31 identified cases, 21 were associated with left-sided resection, four with right sided resection, two with transverse colectomy, one with a subtotal colectomy and in three cases the operation was not specified. The majority of cases (64.3%) were associated with a restorative left sided resection. Nearly all cases occurred within 4 months of surgery. All patients required re-operation and reduction of the internal hernia and 35.7% of cases required a bowel resection. In 52.2% of cases, the mesenteric defect was closed at the second operation and 52.6% of cases were successfully managed laparoscopically. There were three deaths (0.08%). CONCLUSION: Mesenteric hernias are a rare but important complication of laparoscopic colorectal surgery. The evidence does not support routine closure for all cases, but selective closure of the mesenteric defect during left-sided restorative procedures in high-risk patients at the initial surgery may be considered.

Electrical maturation of spinal neurons in the human fetus: comparison of ventral and dorsal horn.

The spinal cord is critical for modifying and relaying sensory information to, and motor commands from, higher centers in the central nervous system to initiate and maintain contextually relevant locomotor responses. Our understanding of how spinal sensorimotor circuits are established during in utero development is based largely on studies in rodents. In contrast, there is little functional data on the development of sensory and motor systems in humans. Here, we use patch-clamp electrophysiology to examine the development of neuronal excitability in human fetal spinal cords (10-18 wk gestation; WG). Transverse spinal cord slices (300 µm thick) were prepared, and recordings were made, from visualized neurons in either the ventral (VH) or dorsal horn (DH) at 32°C. Action potentials (APs) could be elicited in VH neurons throughout the period examined, but only after 16 WG in DH neurons. At this age, VH neurons discharged multiple APs, whereas most DH neurons discharged single APs. In addition, at 16-18 WG, VH neurons also displayed larger AP and after-hyperpolarization amplitudes than DH neurons. Between 10 and 18 WG, the intrinsic properties of VH neurons changed markedly, with input resistance decreasing and AP and after-hyperpolarization amplitudes increasing. These findings are consistent with the hypothesis that VH motor circuitry matures more rapidly than the DH circuits that are involved in processing tactile and nociceptive information.

Response to dual HER2 blockade in a patient with HER3-mutant metastatic breast cancer.

BACKGROUND: HER3 activating mutations have been shown in preclinical models to be oncogenic and ligand-independent, but to depend on kinase-active HER2. PATIENTS AND METHODS: Whole-exome sequencing of the primary HER2-negative breast cancer and its HER2-negative synchronous liver metastasis from a 46-year-old female revealed the presence of an activating and clonal HER3 G284R mutation. RESULTS: HER2 dual blockade with trastuzumab and lapatinib as third-line therapy led to complete metabolic response in 2 weeks and confirmed radiological partial response after 8 weeks. Following the resection of the liver metastasis, the patient remains disease-free 40 weeks after initiation of the HER2 dual blockade therapy. Immunohistochemical analysis demonstrated a substantial reduction of phospho-rpS6 and phospho-AKT in the post-therapy biopsy of the liver metastasis. DISCUSSION: This is the first-in-man evidence that anti-HER2 therapies are likely effective in breast cancers harboring HER3 activating mutations.

Venous thromboembolism rates in patients undergoing major hip and knee joint surgery at Waitemata District Health Board: a retrospective audit.

BACKGROUND/AIM: Symptomatic venous thromboembolism (VTE) complicates approximately 4% of major orthopaedic surgical procedures performed without thromboprophylaxis. Randomised clinical trials demonstrate primary thromboprophylaxis reduces VTE rates to <1%, with low rates of clinically important bleeding, using low molecular weight heparin (LMWH), oral FXa inhibitors or thrombin inhibitors. We reviewed the rates of VTE in patients undergoing major hip/knee joint surgery at Waitemata District Health Board (WDHB). METHODS: Cases of VTE within 90 days of orthopaedic surgery were identified by retrospective audit of data from the haematology VTE database. The number of major hip/knee joint surgeries at WDHB from January 2006 to December 2010 was obtained from clinical coding data. RESULTS: The cumulative incidence of VTE within 90 days of surgery was 3.29%. The median time from surgery to diagnosis was 7 days. Deep vein thrombosis comprised 75% of cases, 77.6% distal and 23.2% proximal. Pulmonary embolism comprised 26.5% of VTE; 47.7% had right heart strain on computed tomography/echocardiography. Hip fracture surgery comprised one-third of patients. Of patients developing VTE, 85.5% had chemical thromboprophylaxis - aspirin 73%, LMWH 20 mg 16%, LMWH 40 mg 16%, therapeutic LMWH 3%, unfractionated heparin twice daily 1%, and warfarin 4%; 75.6% received mechanical prophylaxis, while 4% of patients received no prophylaxis. CONCLUSION: VTE incidence after major hip/knee joint surgery at WDHB is high, with pulmonary embolism comprising almost one-third of all VTE in this study, indicating the prophylaxis given is suboptimal. Implementation of appropriate, extended duration prophylaxis as per evidence-based guidelines is required to reduce these rates.

Association of Oesophageal Hypertension with Bradycardia Mediated Deglutition Syncope.

Swallow syncope is a rare form of situational syncope. We report a case of swallow syncope with invasive confirmation of esophageal hypertension (spasm) and invasive confirmation of a bradycardia mechanism. Awareness of this uncommon disorder is important as a treatable cause of syncope.