Potassium status of patients with cirrhosis.

Whole body potassium measurements were performed on 55 cirrhotic patients in different stages of the disease. They included 34 with alcoholic cirrhosis, 10 with cryptogenic cirrhosis, eight with chronic active hepatitis, and three with haemochromatosis. Serial measurements were carried out in 21 patients. The findings of this study indicate that: (1) the aetiology of the cirrhosis is important in determining the potassium status of cirrhotics, most alcoholics being depleted; (2) ascites and decompensation are usually associated with potassium depletion but compensated cirrhotics may also be depleted even when not receiving diuretics; (3) the initial potassium status, whether a cirrhotic be decompensated or not, is difficult to alter in the short term (six months). Marked changes in potassium status can occur in alcoholic patients studied over longer periods.     

1 Versus 2-cm Excision Margins for pT2-pT4 Primary Cutaneous Melanoma (MelMarT): A Feasibility Study

Background

There is a lack of consensus regarding optimal surgical excision margins for primary cutaneous melanoma?>?1 mm in Breslow thickness (BT). A narrower surgical margin is expected to be associated with lower morbidity, improved quality of life (QoL), and reduced cost. We report the results of a pilot international study (MelMarT) comparing a 1 versus 2-cm surgical margin for patients with primary melanoma?>?1 mm in BT.

Methods

This phase III, multicentre trial [NCT02385214] administered by the Australia & New Zealand Medical Trials Group (ANZMTG 03.12) randomised patients with a primary cutaneous melanoma?>?1 mm in BT to a 1 versus 2-cm wide excision margin to be performed with sentinel lymph node biopsy. Surgical closure technique was at the discretion of the treating surgeon. Patients’ QoL was measured (FACT-M questionnaire) at baseline, 3, 6, and 12 months after randomisation.

Results

Between January 2015 and June 2016, 400 patients were randomised from 17 centres in 5 countries. A total of 377 patients were available for analysis. Primary melanomas were located on the trunk (56.9%), extremities (35.6%), and head and neck (7.4%). More patients in the 2-cm margin group required reconstruction (34.9 vs. 13.6%; p?<?0.0001). There was an increased wound necrosis rate in the 2-cm arm (0.5 vs. 3.6%; p?=?0.036). After 12 months’ follow-up, no differences were noted in QoL between groups.

Discussion

This pilot study demonstrates the feasibility of a large international RCT to provide a definitive answer to the optimal excision margin for patients with intermediate- to high-risk primary cutaneous melanoma.

     

Extended interval for retrieval of vena cava filters is safe and may maximize protection against pulmonary embolism

BACKGROUND: Retrieval of optional vena cava filters (VCF) has been demonstrated to be safe and feasible in injured patients in 4 recent studies. However, 2 pulmonary emboli PE were reported in these studies with mean implant durations less than 19 days. In light of these occurrences, we changed our practice for VCF retrieval when patients had recovered from their injuries and at least 30 days after their discharge, or had been stable on therapeutic anticoagulation for deep venous thrombosis (DVT) or PE for at least 2 weeks. The aim of the current study was to assess the safety of this approach. METHODS: A review of prospectively collected data on optional VCF over a 16-month period. The filters were inserted prophylactically per an institutional practice guideline or for the presence of DVT or PE with a contraindication and/or complication to anticoagulation. All patients underwent duplex imaging of the lower extremities and had pre- and post- retrieval cavagrams. Demographics, duration of implantation, and complications were recorded. RESULTS: Eighty-three patients had optional VCF inserted since the change in our clinical practice. Indications included prophylaxis for high-risk trauma patients (n = 58), DVT or PE with acute contraindication to therapeutic anticoagulation (n = 22), or complications of anticoagulation (n = 3). Two patients developed lower extremity DVT after filter insertion and 1 patient developed a vena cava thrombosis. Retrieval was successful in 47 of 54 cases (87%) attempted. Median implantation duration was 142 days (range 17-475). A filter strut fracture occurred during retrieval without further consequences. No post-insertion or post-retrieval PE occurred in this study. CONCLUSION: Extended intervals for retrieval of VCF are safe and may maximize protection against pulmonary embolism.     

Molecular Characterisation of Foot‐and‐Mouth Disease Viruses from Pakistan, 2005–2008

Foot‐and‐mouth disease (FMD), an economically important disease of cloven‐hoofed animals, is endemic in Pakistan where three virus serotypes are present (O, A and Asia 1). Fifty‐eight clinical samples collected between 2005 and 2008 from animals with suspected FMD in various locations in Pakistan were subjected to virus isolation on primary cell culture, antigen ELISA and real‐time RT‐PCR (rRT‐PCR). Viruses were isolated from 32 of these samples and identified as FMDV type O (n = 31) or type A (n = 1). Foot‐and‐mouth disease virus (FMDV) genome was detected in a further 11 samples by real‐time RT‐PCR. Phylogenetic analyses of the VP1 nucleotide sequences showed that all of the type O viruses belonged to the MIDDLE EAST–SOUTH ASIA topotype with the majority belonging to the PanAsia‐2 lineage; a single example of the older PanAsia lineage was identified. The single FMDV type A virus belonged to the ASIA topotype, but did not cluster with known strains that are currently circulating (such as Iran‐05) and was not closely related to other type A viruses from the region. These findings demonstrate the widespread distribution of O‐PanAsia‐2 in Pakistan and the presence of undisclosed novel type A lineages in the region.     

Methods for siting emergency stomas in the absence of a stoma therapist

Introduction

Stomas often have to be sited in emergencies by trainees who may have had little training in this. Emergency stomas and stomas where the site has not been marked preoperatively by a stoma therapist are more prone to complications. These complications may severely affect a patient’s quality of life. Advice in the literature on how to best site stomas is conflicting. We compared two easy anatomical methods of siting stomas to sites chosen by a stoma therapist and looked at how this site was affected by the patients’ body mass index (BMI).

Methods

Patients undergoing elective colorectal surgery were seen either pre or postoperatively. Each patient’s BMI was recorded and the positions of three different potential stoma positions (site G: the gold standard, marked by a stoma therapist; site S: marked using a pair of scissors against the umbilicus; site H: halfway between the umbilicus and anterior superior iliac spine) were compared.

Results

The two fixed anatomical methods described (method S and method H) both gave poor results. The most common reason for poor siting was the proximity of a skin crease. There was a statistically significant correlation between the patient’s BMI and the laterality of the gold standard site.

Conclusions

The two simple anatomical methods described here do not provide a shortcut to effective siting. A more effective method may be calculating the laterality of the site using the patient’s BMI, and then moving up/down to avoid a skin crease and improve the patient’s view for changing the bag. This deserves further study.     

VEGFA From Early Osteoblast Lineage Cells (Osterix+) Is Required in Mice for Fracture Healing

Bone formation via intramembranous and endochondral ossification is necessary for successful healing after a wide range of bone injuries. The pleiotropic cytokine, vascular endothelial growth factor A (VEGFA) has been shown, via nonspecific pharmacologic inhibition, to be indispensable for angiogenesis and ossification following bone fracture and cortical defect repair. However, the importance of VEGFA expression by different cell types during bone healing is not well understood. We sought to determine the role of VEGFA from different osteoblast cell subsets following clinically relevant models of bone fracture and cortical defect. Ubiquitin C (UBC), Osterix (Osx), or Dentin matrix protein 1 (Dmp1) Cre-ERT2 mice (male and female) containing floxed VEGFA alleles (VEGFA^fl/fl) were either given a femur full fracture, ulna stress fracture, or tibia cortical defect at 12 weeks of age. All mice received tamoxifen continuously starting 2 weeks before bone injury and throughout healing. UBC Cre-ERT2 VEGFA^fl/fl (UBC cKO) mice, which were used to mimic nonspecific inhibition, had minimal bone formation and impaired angiogenesis across all bone injury models. UBC cKO mice also exhibited impaired periosteal cell proliferation during full fracture, but not stress fracture repair. Osx Cre-ERT2 VEGFA^fl/fl (Osx cKO) mice, but not Dmp1 Cre-ERT2 VEGFA^fl/fl (Dmp1 cKO) mice, showed impaired periosteal bone formation and angiogenesis in models of full fracture and stress fracture. Neither Osx cKO nor Dmp1 cKO mice demonstrated significant impairments in intramedullary bone formation and angiogenesis following cortical defect. These data suggest that VEGFA from early osteolineage cells (Osx+), but not mature osteoblasts/osteocytes (Dmp1+), is critical at the time of bone injury for rapid periosteal angiogenesis and woven bone formation during fracture repair. Whereas VEGFA from another cell source, not from the osteoblast cell lineage, is necessary at the time of injury for maximum cortical defect intramedullary angiogenesis and osteogenesis. © 2019 American Society for Bone and Mineral Research.     

Similarities in reflex control of laryngeal and cardiac vagal motor neurones

We sought to test the hypothesis that laryngeal adductor and cardiac vagal motor neurones respond similarly to the activation of certain afferent inputs. Experiments were performed on a working heart-brainstem preparation of rat devoid of pulmonary stretch receptor feedback. Upper airway negative pressure receptors (UANPR), peripheral arterial chemoreceptors and receptors at the junction of the pharynx and oesophagus were stimulated selectively while recording heart rate, recurrent laryngeal, phrenic and hypoglossal motor outflows, subglottic pressure during constant translaryngeal airflow (as an index of laryngeal resistance), and single unit respiratory neurone activity. Stimulation of all three receptor types produced bradycardia, evoked discharges in the recurrent laryngeal and hypoglossal motor outflows during the post-inspiratory period and caused swallowing. Stimulation of pharyngoesophageal receptors and peripheral chemoreceptors evoked an increase in laryngeal resistance during the post-inspiratory phase indicative of laryngeal adductor motoneurone activation. Although this reflex response cannot be evaluated during UANPR stimulation, some post-inspiratory neurones were powerfully activated suggesting that UANPR probably drive laryngeal adductor muscles. Our data show that motor outflows controlling cardiac rate and laryngeal patency are concurrently activated by these sensory inputs. This may constitute the basis for a stereotyped defensive reflex response which maintains end expiratory lung volume, thus conserving oxygen in conditions of upper airway obstruction. Our observations lend further support to models of cardiorespiratory control which propose close coupling and shared central mechanisms for the regulation of the cardiovascular and respiratory systems.     

Health-associated changes in drinking: a period prevalence study of the Atherosclerosis Risk In Communities (ARIC) cohort (1987-1995)

BACKGROUND: Several investigators have suggested that drinking cessation occurs because of poor health which may bias studies on the benefit or risk of alcohol consumption. METHODS: Drinking status, level of alcohol consumption, and two measures of health (perceived health and physician diagnosed chronic disease status) were determined from exams 1 (1987-1989) and 3 (1993-1995) on 12,562 African- and European-American participants, who were aged 45-64 years at exam 1 in the ARIC Study. For those in good health at exam 1, logistic regression analyses were used to model the association between health decline and drinking change at exam 3. RESULTS: Among the total population, drinking cessation was significantly more common among those who reported poor health at exam 3, and nondrinkers were unlikely to begin drinking regardless of exam 3 health. Using different measures of health status resulted in associations whose strength and significance varied with ethnicity and, in some cases, by gender. CONCLUSION: While the current data do not prove that the health decline occurred prior to drinking cessation, our findings support the hypothesis that poor health results in drinking changes which could potentially bias studies of alcohol's benefit and risk even when lifetime abstainers are used as the reference group.     

Assessment of potentially avoidable perinatal mortality in a regionalized program

To obtain data regarding factors that influence perinatal mortality, a comprehensive perinatal mortality review project was prospectively developed and implemented. The resulting data cover a 21-month period and include all perinatal mortality at two perinatal centers and ten community hospitals. For each case an assessment of potential avoidability was made using the following definition: if any factor was identified that might have altered the outcome, the case was judged potentially avoidable. All other mortality was classified as either unavoidable or undetermined (if sufficient data were not available). During the review period there were a total of 26,937 live births and 591 cases of perinatal mortality. We conclude that: (1) meaningful analysis of factors affecting perinatal mortality data can be obtained by review of all deaths using a standardized classification; (2) in 21% of perinatal mortality at least one potentially avoidable factor could be identified that might have altered the outcome, while 74% was unavoidable and 5% undetermined; and (3) implementation of the review process enabled the reviewers to recognize patterns of potentially avoidable perinatal deaths.     

APOE-epsilon4 and APOE -491A polymorphisms in individuals with subjective memory loss

The accurate clinical diagnosis of Alzheimer's disease can only be made with a high degree of certainty in specialized centres. The identification of predictive or diagnostic genetic factors may improve accuracy of disease prediction or diagnosis. One major genetic risk factor, the epsilon4 allele of the apolipoprotein E gene, is universally recognised. We have recently shown that the A allele of the apolipoprotein E, -491A/T promoter polymorphism is also an important risk factor for Alzheimer's disease in an Australian population. We designed the present study to investigate the association between apolipoprotein E genotype, -491A/T polymorphism, plasma apoE levels and the subjective experience of memory decline among 98 subjects and 49 age, gender and education-matched normal controls. An increased frequency of the epsilon4 allele of apolipoprotein E was significantly associated with the 'memory complainers' group (OR = 2.35, P = 0.02) as was the A allele of the -491A/T polymorphism (OR = 2, P = 0.02). Among all subjects, only seven individuals were homozygous for both of these alleles, and six of these seven individuals belonged to the 'memory complainers' group. This sub-group also had relatively elevated plasma apolipoprotein E levels (P < 0.01) and tended to score lower on the Mini-Mental State Examination (MMSE) and Cambridge Cognition Test. These data suggest that the epsilon4 allele of apolipoprotein E and the -491A allele are over-represented among individuals who complain of memory difficulties. Follow-up studies should clarify whether these genotypes and phenotypes are useful in the prediction and/or diagnosis of Alzheimer's disease.