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.

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.

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.

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.

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.

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.

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.

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.

Enhanced thrombin generation in patients with cirrhosis-induced coagulopathy.

BACKGROUND: Prothrombin time (PT) and the international normalized ratio (INR) are still routinely measured in patients with liver cirrhosis to 'assess' their bleeding risk despite the lack of correlation with the two. Thrombin generation (TG) assays are global assays of coagulation that are showing promise in assessing bleeding and thrombosis risks. AIM: To study the relationship between the INR and TG profiles in cirrhosis-induced coagulopathy. METHODS: Seventy-three patients with cirrhosis were studied. All TG parameters were compared with those from a normal control group. Contact activation was prevented using corn trypsin inhibitor. TG was also assayed in the presence of Protac(®). The endogenous thrombin potential (ETP) ratio was derived by dividing the ETP with Protac® by the ETP without Protac®. RESULTS: The INR (mean 1.7) did not correlate with the ETP and the velocity of TG (P > 0.05). There was no difference between the lag time and ETP of the two groups (P > 0.05). The velocity of TG was increased in cirrhosis (67.95 ± 34.8 vs. 45.05 ± 25.9 nM min⁻¹ ; P = 0.016) especially in patients with INRs between 1.21 and 2.0. Both the ETP with Protac(®) and the ETP ratio were increased in cirrhosis (mean 1074 ± 461.4 vs. 818 ± 357.9 nM min, P = 0.004 and 0.80 ± 0.21 vs. 0.44 ± 0.15, P ≤ 0.0001, respectively). CONCLUSION: Despite a raised INR, TG parameters are consistent with a hypercoagulable profile in cirrhosis-related coagulopathy. This confirms that the PT or INR should not be used to assess bleeding risk in these patients, and other parameters, such as TG, need to be explored as clinical markers of coagulopathy.

Systematic review: portal vein thrombosis in cirrhosis.

BACKGROUND: As current imaging techniques in cirrhosis allow detection of asymptomatic portal vein thrombosis during routine ultrasonography, more patients with cirrhosis are diagnosed with portal vein thrombosis. Although a consensus on noncirrhotic extra-hepatic portal vein thrombosis has been published, no such consensus exists for portal vein thrombosis with cirrhosis. AIM: To perform a systematic review of nonmalignant portal vein thrombosis in cirrhosis in terms of prevalence, pathogenesis, diagnosis, clinical course and management. METHODS: Studies were identified by a search strategy using MEDLINE and EMBASE. RESULTS: Portal vein thrombosis is encountered in 10-25% of cirrhotics. In terms of pathophysiology, cirrhosis is no longer considered a hypocoagulable state; rather than a bleeding risk in cirrhosis, various clinical studies support a thrombotic potential. Clinical findings of portal vein thrombosis in cirrhosis vary from asymptomatic disease to a life-threatening condition at first presentation. Optimal management of portal vein thrombosis in cirrhosis is currently not addressed in any consensus publication. Treatment strategies most often include the use of anticoagulation, while thrombectomy and transjugular intrahepatic portosystemic shunts are considered second-line options. CONCLUSIONS: Portal vein thrombosis in cirrhosis has many unresolved issues, which are often the critical problems clinicians encounter in their everyday practice. We propose a possible research agenda to address these unresolved issues.

Optimizing warfarin reversal--an ex vivo study.

BACKGROUND: Warfarin reversal is a common clinical situation. This is commonly performed using vitamin K and, depending on the urgency, fresh frozen plasma (FFP), prothrombin complex concentrates (PCCs), or activated factor VII. Even though PCCs are widely used, the ideal dosing regimen is far from established. OBJECTIVES: To verify differences in warfarin reversal patterns using FFP, recombinant FVIIa (rFVIIa), and PCC; and to test the hypothesis that supratherapeutic International Normalized Ratios (INRs) might not correlate with thrombin generation (TG) and identify the ideal concentrations of PCC required to reverse various INR thresholds. METHODS: We studied the effects of FFP, rFVIIa and Beriplex P/N on the INR and TG, using the calibrated automated thrombography assay in ex vivo warfarinized plasma. Plasmas with different INRs were spiked with different concentrations of Beriplex P/N. RESULTS: Beriplex P/N was the only agent that completely normalized TG and the INR. The endogenous thrombin potential (ETP) and the peak thrombin showed a significant negative correlation with all INRs. The ETP and velocity of TG reached a plateau at an INR of approximately 4.0. A concentration equivalent to a dose of 30 IU kg(-1) Beriplex P/N normalized the ETP, the INR, FII, FVII, FIX and FX of samples with INRs > or = 4.0. Higher doses resulted in hypercoagulable TG patterns. A concentration equivalent to a dose of 20 IU kg(-1) was sufficient to reverse warfarin at an INR range of 2.0-3.9, as judged by the same tests. CONCLUSIONS: Warfarin reversal algorithms could be simplified with the adoption of this strategy utilizing two doses of PCC, depending on the INR of the patient. This would also lead to cost reductions and, possibly, a reduction in thrombotic risk.

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.

The effect of tissue factor concentration on calibrated automated thrombography in the presence of inhibitor bypass agents.

Thrombin generation has been suggested as a method to monitor treatment with factor eight inhibitor bypassing activity (FEIBA) or recombinant FVIIa (rFVIIa). The sensitivity of the assay for individual coagulation factors is dependent on the tissue factor (TF) concentration. An inverse relation between the rFVIIa concentration needed to shorten the clotting time and TF concentration has been shown but the data on thrombin generation are inconsistent. Information on TF concentration in measurements with FEIBA is limited. We studied the influence of TF concentration (1 and 5 pM) on thrombin generation through spiking experiments with rFVIIa and/or FEIBA in the plasma of severe haemophilia A patients and after four and three treatment episodes, respectively, using the calibrated automated thrombin generation assay (CAT) in platelet poor plasma. Spiking with FEIBA showed a linear relation with the endogenous thrombin potential (ETP)/peak at 1 pM but substrate depletion at 5 pM. Spiking with rFVIIa showed a near linear dose-response relation with the ETP/peak at 1 pm but only a shortening of the initiation phase at 5 pM. Similar effects were present in post-treatment samples. FEIBA acted synergistically with rFVIIa. This suggest a role for CAT in monitoring inhibitor bypass treatment but low TF concentrations are required to avoid substrate depletion with FEIBA and to demonstrate the effect of rFVIIa.

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.

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.