Alterations in coagulation following major liver resection.

The international normalised ratio is frequently raised in patients who have undergone major liver resection, and is assumed to represent a potential bleeding risk. However, these patients have an increased risk of venous thromboembolic events, despite conventional coagulation tests indicating hypocoagulability. This prospective, observational study of patients undergoing major hepatic resection analysed the serial changes in coagulation in the early postoperative period. Thrombin generation parameters and viscoelastic tests of coagulation (thromboelastometry) remained within normal ranges throughout the study period. Levels of the procoagulant factors II, V, VII and X initially fell, but V and X returned to or exceeded normal range by postoperative day five. Levels of factor VIII and Von Willebrand factor were significantly elevated from postoperative day one (p < 0.01). Levels of the anticoagulants, protein C and antithrombin remained significantly depressed on postoperative day five (p = 0.01). Overall, the imbalance between pro- and anticoagulant factors suggested a prothrombotic environment in the early postoperative period.

Using molecular tools to identify the geographical origin of a case of human brucellosis.

Although Malta is historically linked with the zoonosis brucellosis, there had not been a case of the disease in either the human or livestock population for several years. However, in July 2013 a case of human brucellosis was identified on the island. To determine whether this recent case originated in Malta, four isolates from this case were subjected to molecular analysis. Molecular profiles generated using multilocus sequence analysis and multilocus variable number tandem repeat for the recent human case isolates and 11 Brucella melitensis strains of known Maltese origin were compared with others held on in-house and global databases. While the 11 isolates of Maltese origin formed a distinct cluster, the recent human isolation was not associated with these strains but instead clustered with isolates originating from the Horn of Africa. These data was congruent with epidemiological trace-back showed that the individual had travelled to Malta from Eritrea. This work highlights the potential of using molecular typing data to aid in epidemiological trace-back of Brucella isolations and assist in monitoring of the effectiveness of brucellosis control schemes.

Patients with liver cirrhosis suffer from primary haemostatic defects? Fact or fiction?

Patients with cirrhosis can have abnormalities in laboratory tests reflecting changes in primary haemostasis, including bleeding time, platelet function tests, markers of platelet activation, and platelet count. Such changes have been considered particularly relevant in the bleeding complications that occur in cirrhosis. However, several studies have shown that routine diagnostic tests, such as platelet count, bleeding time, PFA-100, thromboelastography are not clinically useful to stratify bleeding risk in patients with cirrhosis. Moreover, treatments used to increase platelet count or to modulate platelet function could potentially do harm. Consequently the optimal management of bleeding complications is still a matter of discussion. Moreover, in the last two decades there has been an increased recognition that not only bleeding but also thrombosis complicates the clinical course of cirrhosis. Thus, we performed a literature search looking at publications studying both qualitative and quantitative aspects of platelet function to verify which primary haemostasis defects occur in cirrhosis. In addition, we evaluated the contribution of qualitative and quantitative aspects of platelet function to the clinical outcome in cirrhosis and their therapeutic management according to the data available in the literature. From the detailed analysis of the literature, it appears clear that primary haemostasis may not be defective in cirrhosis, and a low platelet count should not necessarily be considered as an automatic index of an increased risk of bleeding. Conversely, caution should be observed in patients with severe thrombocytopenia where its correction is advised if bleeding occurs and before invasive diagnostic and therapeutic procedures.

Superficial Tissue Swabs Versus Deep Tissue Samples in the Detection of Microbiological Profile of Infected Diabetic Foot Ulcerations.

This study aimed to determine the most accurate microbiological test for the detection of micro-organisms in infected diabetic foot ulcerations in people living with type-2 Diabetes. For 20 eligible patients, a superficial tissue swab and a deep tissue sample were taken during a regular appointment at a Diabetes out-patient's Podiatry Clinic. Two specimens were collected from each wound for microbial culturing after debridement. Infected foot ulcerations were graded according to the Wagner's classification as per clinical protocol. This study found a significant difference [p = 0.028] between the two different samples. The deep tissue sample was found to be more accurate in identifying micro-organisms than the superficial swabs, although the latter is more widely used in clinical practice. Further studies are warranted to provide more evidence to clinicians on the best method to adopt when swabbing different types of diabetic foot ulcerations with different wound classification since, it is clearly still a matter of debate how to detect wound infection.

The Charcot Foot: An Emerging Public Health Problem for African Diabetes Patients.

Background: Although the awareness, diagnosis, management of the complications associated with diabetes have improved in African countries over the past decade, surveillance activities in Tanzania and anecdotal reports from other African countries have suggested an increased prevalence of Charcot Neuroarthropathy (CN) over the past few years. Aim: To characterize the epidemiology and the clinical burden of CN in a large diabetes population in Tanzania, and to evaluate outcomes of persons with the condition. Methods: This was a prospective analytic cohort study conducted between January 2013 through December 2015. Following informed consent, patients were followed at the outpatient clinic. Detailed clinical assessments and documented presence of diabetic peripheral neuropathy (DPN), macrovascular disease and microvascular disease were recorded. Education and counseling were part of the follow-up program. Results: 3271 ulcerations were presented at the clinic during the 3-year study period. 571 (18%) met the case definition for CN; all patients had Type 2 diabetes. The prevalence for each of the years 2013, 2014, and 2015 was 19/1192 (1.6%), 209/1044 (20%), and 343/1035 (34%), respectively; the increases in the slope of the trendline was statistically significant (P < .001). Conclusion: The prevalence of CN is increasing in the Tanzanian diabetes patient population, and is strongly associated with neuropathy. CN can lead to severe deformity, disability, and amputation. Due to the risk of limb amputation, patients with diabetes must seek immediate care if signs or symptoms appear and avoid delay in seeking medical attention. Early diagnosis of CN by caregivers is extremely important for successful outcomes.

Peripheral vascular changes in the lower limbs following cocaine abuse.

Background: Worldwide, substance use disorder is on the rise, especially amongst the young generation. Although cocaine-induced cardiovascular and cerebrovascular events are well documented, knowledge about the relationship of cocaine use and its effect on arterial perfusion in the lower limbs is scarce.Objective: This study sought to investigate the relationship between cocaine use and peripheral arterial disease.Methods: The study population comprised 30 subjects' dependent on cocaine, smoking and alcohol [Group A] and another 30 subjects dependent on smoking and alcohol only [Group B]. A comprehensive lower limb vascular assessment was conducted utilizing pulse palpation, Doppler spectral waveform analysis, Ankle brachial pressure index (ABPI) and Toe brachial pressure index (TBPI) to determine the arterial perfusion status in the lower limbs.Results: Group A had lower ABPIs and TBPIs than Group B suggesting poorer vascular perfusion in lower limbs. Furthermore, a larger percentage of Group A had monophasic/continuous waveforms of all three pedal pulses compared to Group B. Conversely there was a higher percentage in Group B with biphasic/triphasic waveforms compared to Group A implying better vascular perfusion.Conclusion: In this study, cocaine use was associated with diminished arterial perfusion of the lower limbs suggesting that cocaine use has the potential to increase the risk of peripheral arterial disease. Regular vascular foot screening is warranted if foot complications are to be avoided.

Outbreak of norovirus infection in a nursing home for the elderly in Malta, November-December 2008.

In norovirus outbreak in a nursing home in Malta in November and December 2008, 44 people were affected. 35 of 91 residents and nine of 44 employees were symptomatic. The overall attack rate among residents was 38.5% [corrected]. The outbreak lasted 17 days and the symptoms were mild.

Coagulation and fibrosis in chronic liver disease.

In the hepatic tissue repair mechanism, hepatic stellate cells (HSCs) are recruited at the site of injury and their changes reflect paracrine stimulation by all neighbouring cell types, including sinusoidal endothelial cells, Kupffer cells, hepatocytes, platelets and leucocytes. Thrombin converts circulating fibrinogen to fibrin, promotes platelet aggregation, is a potent activator of endothelial cells, acts as a chemoattractant for inflammatory cells and is a mitogen and chemoattractant for fibroblasts and vascular smooth muscle cells. Most of the cellular effects elicited by thrombin are mediated via a family of widely expressed G-protein-coupled receptors termed protease activated receptors (PARs). All known members of the PAR family stimulate cell proliferation/activation in a rat HSC line. Thrombin receptors are constitutively expressed in the liver, and their expression increases in parallel with the severity and/or the duration of liver disease. In human studies, thrombotic risk factors were found to be independently associated with the extent of fibrosis; severity of hepatitis C virus (HCV)-associated liver disease appears to be less in patients with haemophilia when compared with those with HCV alone. Several studies, based mostly on rat models, demonstrate that anticoagulants or antiplatelet agents prevent hepatic necrosis and fibrosis by acting on HSCs. These drugs could be therapeutic agents in patients with chronic liver disease and specific studies should be initiated.

Diabetes foot screening: Challenges and future strategies.

BACKGROUND: Healthcare options for people with diabetes is still not uniform both within and between countries. This is particularly evident for diabetic foot disease. The number of existing documents/guidelines, together with discrepancies which exist between different organizations or countries can lead to confusion for both practicing health care professionals and new countries or organizations who are in the process of developing local clinical guidelines. This study was aimed at exploring different stakeholder perspectives with a view to develop and introduce culturally competent foot screening guidelines. METHODS: A phenomenological study which incorporated non-structured interviews with eleven local stakeholders and experts related to the field were conducted to explore interviewees' perspectives regarding foot screening guidelines in Malta. FINDINGS: Qualitative analysis identified 3 key themes from the data highlighting barriers to the implementation of diabetes foot screening guidelines. These focused on organizational factors, healthcare professional factors and patient factors. CONCLUSION: Current procedures related to diabetes foot screening has shortcomings. The findings of this study clearly highlight the need for change in current practices if effective diabetic foot screening is to be offered. Recommendations from this study are relevant to other countries especially those who share same cultures and practices. Making changes today and implementing them in the appropriate manner could make a world of difference in diabetes foot care.

Thrombin generation testing in routine clinical practice: are we there yet?

Thrombin is the central enzyme in the coagulation cascade. Estimation of an individual's potential to generate thrombin may correlate more closely with a hyper- or hypo-coagulable phenotype, compared to traditional coagulation tests. The possible correlation and recent technical advances in thrombin generation measurement has caused a significant interest in the method and the development of commercial assays. Several variations of the assay exist depending on the defect to be investigated. Fluorogenic thrombin generation assays have acceptable intra-laboratory variation but a higher inter-laboratory variation. Variation in preanalytical variables makes comparisons between studies difficult. Thrombin generation is highly variable between individuals and there are suggestions that this may allow individualized treatment based on global haemostatic response in patients with bleeding disorders or on anticoagulant therapy. In patients with thrombotic disorders it may be possible to identify those at higher risk of recurrent thrombosis. For both scenarios, however, data from large prospective studies are lacking or inconclusive and a good relationship between thrombin generation and phenotype remains to be established. Further standardization of the assay is needed before large multicentre studies can be conducted and until then thrombin generation in routine clinical practice is not yet a reality.

Wide variation in thrombin generation in patients with atrial fibrillation and therapeutic International Normalized Ratio is not due to inflammation.

Atrial fibrillation (AF) is a common cardiac arrhythmia with a 5-20% annual risk of stroke. Warfarin reduces this risk by at least 60%. Despite adequate anticoagulation within the target International Normalized Ratio (INR) range of 2.0-3.0, some patients still experience thrombotic and bleeding events. It is now possible to assess the intensity of anticoagulation with automated thrombin generation (TG) tests, such as the calibrated automated thrombogram (CAT). These tests were compared and an inverse relationship was found between the INR and CAT in 143 elderly AF patients. There was equally good correlation between the concentration of factors II, VII, IX and X and the INR and TG parameters. The peak thrombin was most strongly associated with the concentration of prothrombin fragment 1 + 2 in plasma. There was wide variability in TG parameters in patients with identical INR values, sometimes up to a fourfold difference. This TG variability in individuals with the same INR is not due to inflammation, at least when the latter is measured as the concentration of factor VIII coagulant activity, von Willebrand factor antigen, high sensitivity C-reactive protein and fibrinogen. It was concluded that, although the TG and INR were closely correlated there was wide variability in peak thrombin and endogenous thrombin potential in patients within the INR therapeutic range, the cause of which remains unclear.

Management of surgical patients receiving anticoagulation and antiplatelet agents.

BACKGROUND: Temporary interruption of long-term anticoagulation and antiplatelet therapy during surgical procedures exposes patients to thrombotic risk. Continuation of these agents, however, is associated with an increased risk of bleeding. Managing anticoagulation can be a particular challenge in the emergency setting. METHODS: A literature review of published articles sourced using the keywords heparin, warfarin, perioperative, antiplatelet, aspirin and surgery was undertaken. A management plan for all likely situations was developed. RESULTS AND CONCLUSION: Based on an individual assessment of risk factors for arterial or venous thromboembolism and the risk of perioperative bleeding, it is possible to form an anticoagulant and antiplatelet management plan likely to achieve a low incidence of bleeding and thrombosis. A multidisciplinary approach is desirable.

The rarest aortic arch anomaly a case report of asymptomatic isolation of the subclavian artery.

We present a rare case of isolated right subclavian artery arising from a right-sided patent arterial duct in a patient with DiGeorge syndrome, diagnosed on cardiac CT, along with potential complications and management approaches.

Comparison of in vivo vs. frozen vs. Thiel cadaver specimens in visualisation of anatomical structures of the ankle on proton density Magnetic Resonance Imaging (MRI) through a visual grading analysis (VGA) study.

PURPOSE: The use of cadavers for medical education purposes and for radiology research methodologies which involve subjective image quality evaluation of anatomical criteria is well documented. The aim of this study was to quantify the impact of cadaver tissue preservation in producing MR images that are representative of living tissue by comparing the visualisation of anatomical structures of the ankle obtained from live and cadaver (fresh frozen and Thiel embalmed) specimens through a visual grading analysis (VGA) study. METHODS: A VGA study was conducted on an image data set consisting of 4 coronal proton density weighted (PDw) sequences obtained from ankles of a live patient and those of a cadaveric specimen, of which the right ankle was frozen and the left Thiel embalmed. RESULTS: Comparison of the image quality scores obtained from: the live patient vs. the Thiel specimen indicate a significant difference (p ≤ 0.05) between the scores in favour of the Thiel specimen; between the live patient vs. the frozen specimen indicate a significant difference (p ≤ 0.05) in favour of the frozen specimen and between the frozen vs. the Thiel specimen indicate a significant difference (p ≤ 0.05) in favour of the Thiel specimen. CONCLUSIONS: The advantages of the use of cadavers (frozen or Thiel embalmed) has been shown to also apply for use with proton density (PD) MR imaging. The preservation of cadavers especially using Thiel is a suitable alternative for MRI optimisation and protocol development purposes.

A comparative study using thrombin generation and three different INR methods in patients on Vitamin K antagonist treatment.

INTRODUCTION: Vitamin K antagonist (VKA) treatment requires routine monitoring using the international normalized ratio (INR). However, different INR assays may vary in their results. The aim of this study was to assess the agreement of three different INR methods, compared with thrombin generation, in patients on VKA treatment. METHODS: Sixty patients attending the Anticoagulation Clinic at Mater Dei Hospital (Msida, Malta) for VKA monitoring between August and September 2015 were enrolled. The INR was tested using a point-of-care (POC) device (CoaguChek XS Plus, Roche Diagnostics) for both capillary and venous blood samples, a photo-optical (Sysmex CS-2100i/CA-1500, Siemens) and a mechanical clot detection system (Thrombolyzer XRC, Behnk Elektronik). All assays used human recombinant thromboplastin as reagent. Thrombin generation was performed using the calibrated automated thrombogram. RESULTS: There was a negative curvilinear correlation between the endogenous thrombin potential and different INR assays (r≤-.75) and a strong positive linear correlation between the CoaguChek XS Plus on capillary samples and the other INR methodologies (r≥.96). CONCLUSION: All different INR assays showed good correlation with the thrombin generation potential. The POC INR showed one of the highest correlation coefficients with thrombin generation, confirming the POC devices as an accurate, valid alternative to laboratory INR in VKA patients.

Effect of temperature on kainic acid-induced seizures.

The effects of body temperature on kainic acid-induced seizures and seizure-related brain damage were examined in rats. In rats with status epilepticus induced by intraperitoneal injection of 12 mg/kg of kainic acid (KA), ictal discharges were decreased by 50% when body temperature was lowered to 28 degrees C and nearly abolished when body temperature was lowered to 23 degrees C. In rats with mild hypothermia (28 degrees C), the duration of ictal discharges following KA injection was significantly lower than in rats with normal body temperature. No detectable hippocampal cell loss was observed in rats with hypothermia to 28 degrees C whereas gross cell loss in the hippocampus was observed in all rats with KA injection at normal body temperature. In contract to hypothermia, hyperthermia markedly aggravated the seizures and hippocampal damage induced by KA. Following elevation of body temperature to 42 degrees C KA (12 mg/kg) resulted in severe seizures and all rats died of tonic seizures within 2 h. Furthermore, 6 mg/kg of KA administered to rats with a body temperature of 41-42 degrees C, resulted in up to 4 h of continuous ictal discharges whereas no continuous ictal discharges were observed after the same injections in rats with normal body temperature. Histological examination in rats receiving 6 mg/kg of KA revealed severe cell loss in the hippocampus in rats with hyperthermia but not in rats with normal temperature. These results demonstrate that body temperature plays an important role in the control of epileptic seizures and seizure-related brain damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuroprotective effect of chronic infusion of basic fibroblast growth factor on seizure-associated hippocampal damage.

Basic fibroblast growth factor (bFGF) has been shown to have neuroprotective effects in animal models of ischemia. To determine whether bFGF is protective against seizure-induced brain damage, we administered bFGF through osmotic pumps prior to, and after treatment with kainic acid (KA). Recombinant bFGF, CS23, a modified human bFGF, was infused into the lateral ventricles in rats for 2 days before and 5 days after the injection of KA. Control rats received equal volumes of phosphated saline over the same period of time. Infusion of 5 micrograms/ml of bFGF (0.5 microliter/h) did not modify the latency and duration of seizures induced by intraperitoneal injections of KA. However, bFGF prevented cell loss in the hippocampus in 80% of the rats. In control rats, cell loss in the hippocampus was found in all rats. These results indicate that bFGF has a substantial neuroprotective effect.

Effects of quisqualic acid and glutamate on subsequent learning, emotionality, and seizure susceptibility in the immature and mature animal.

To compare the long-term behavioral effects of chronic administration of excitatory amino acids in the mature and immature brain quisqualic acid (QA) and glutamate (GLU) were administered intraventricularly by osmotic pumps over 7 days in 20- and 60-day-old rats. Both age groups received identical dosages of QA or GLU. At age 90 days, all animals were assessed for abnormalities of learning and memory using the Morris water maze, emotionality using the handling test, and seizure threshold using flurothyl inhalation. No significant differences were found in either the water maze or handling test. However, 60-day-old rats receiving QA or GLU had more spontaneous seizures than the 20-day-old rats. In both age groups histological damage following QA and GLU was limited to the ipsilateral hippocampus, was maximum at the site of the catheter tube, and was similar in the two age groups studied. The adverse effects of long-term effects of chronic exposure to excitatory amino acids are similar in the immature and mature brain.