EXPERIMENTAL INDUCTION OF TYPE 2 DIABETES MELLITUS AND THE EFFICIENCY OF BARIATRIC SURGERY IN ITS REVERSAL IN RATS.

BACKGROUND: Following recent years, there is an increased body of literature on the connections that might exist between type 2 diabetes mellitus and the efficiency of bariatric surgery in its reversal compared to other medical approaches such as dieting. AIM: To induce experimentally type 2 diabetes mellitus in rats in order to observe the effects of bariatric surgery in the recovery as well as the reestablishment of normal insulin levels in order to extend the findings in house animals. MATERIALS AND METHODS: This study was conducted in three stages: the first consisted in inducing type 2 diabetes mellitus (T2DM) in 40 young Wistar male rats, by initially feeding them human food high in vegetal fats, oleaginous seeds, simple and complex carbohydrates, sugars, lipids, fats, proteins and fructose for a period of 8 weeks followed by a single low dose of streptozotocin (STZ), administered through intraperitoneal injection. The second stage of the study started when the rats became obese and therefore qualified for the bariatric procedure and the third stage consisted of post-operation supervision and care. The surgical procedure, performed on 10 obese rats, consisted in reducing the size of the stomach by partial gastrectomy of a 1.5 - 2.0 cm wide and 6.5 - 7.5 cm long area on the large curvature. RESULTS: Showed rapid improvements in body weight and blood sugar control after 9 days. CONCLUSION: After putting the rats on a diet high in carbohydrates, sugars, lipids and fats and administering them STZ, the induction of type 2 diabetes was successful and the partial gastrectomy led to a better blood sugar control. The bariatric procedure provides a faster therapeutic response than conventional diets.

Combined use of antifibrinolytics and activated prothrombin complex concentrate (aPCC) is not related to thromboembolic events in patients with acquired haemophilia A: data from FAIR Registry.

Antifibrinolytics combined with aPCC are not routinely administered to patients with acquired hemophilia A due to increased thrombotic risk. This association normalizes clot stability, and improves the efficacy of therapy, but can increase the risk of severe side effects. Due to these premises it has always raised doubts and perplexities in the clinics. We now report the data of the "FEIBA® on acquired haemophilia A Italian Registry (FAIR Registry)", a retrospective-prospective study that included 56 patients. This is the first study that assessed the clinical response of the combination of aPCC and antifibrinolytic agents in patients with acquired haemophilia A. A total of 101 acute bleeds were treated with aPCC. Antifibrinolytic agents were used in the treatment of 39.6% of total bleeds, based on both, a clinical assessment and an evaluation of bleeding. Twenty-five of the 30 patients (57.1%) treated with antifibrinolytic drugs showed serious co-morbidity. Among them, 40% presented severe cardiovascular diseases. All bleeds treated with combined therapy had a shorter duration of treatment (mean reduction 16.3%). All the treated patients presented a good tolerability and no arterial or venous thromboembolic events were reported. In our retrospective registry the combination of antifibrinolytics and aPCC appears safe and effective in the treatment of patients with AHA, especially in the case of severe and life-threatening bleeding, but this hypothesis needs to be confirmed in adequate, larger clinical trials.

Low dose of aPCC after the initial treatment in acquired haemophilia A is useful to reduce bleeding relapses: Data from the FAIR registry.

BACKGROUND: Bypassing agents are the first line therapy in patients with acquired haemophilia A (AHA). Activated prothrombin complex concentrate (aPCC) proved to be effective as initial treatment, but 20% of patients (pts) had relapses. aPCC as short-term prophylaxis to reduce subsequent bleeds is still not clear. AIM: To evaluate whether a short-term prophylaxis with low dose of aPCC can reduce bleeding relapses after initial AHA treatment, maintaining safety. METHODS: The FAIR Registry is a retrospective-prospective study started on December 2012, that collected data on all pts with AHA treated with aPCC in 12 Italian Haemophilia Centers. All statistical analyses were carried out in the 56 pts included in the registry. RESULTS: 31 retrospective and 25 prospective pts were evaluated.101 bleeds requiring treatment were reported, 84.1% spontaneous, 71.3% involving muscles or skin. Major bleeds were 38,6%. Low-dose aPCC as short-term prophylaxis was started after the first resolved episode in 15/56 pts, 58% of whom prospective, in a mean dose of 54.2 ±â€¯23.0 IU/kg, higher (61.4 ±â€¯23.4 IU/kg) in the prospective group than in the retrospective one (44.3 ±â€¯19.7 IU/kg) and it was continued up to a mean of 20.5 ±â€¯17.6 days, similar in both groups. A total of 32 bleeding relapses were reported, 87.5% in the retrospective group. Only 9.4% occurred during short-term prophylaxis (p < 0.05). In our Registry no thromboembolic events were found. CONCLUSION: Initial AHA treatment with aPCC proved to be highly effective, but a consecutive low dose as short-term prophylaxis seems to demonstrate a significant reduction in bleeding relapses maintaining safety.

Clinical course of patients with symptomatic isolated superficial vein thrombosis: the ICARO follow-up study.

Essentials Late sequelae of isolated superficial vein thrombosis (iSVT) have rarely been investigated. We studied 411 consecutive outpatients with acute iSVT with a median follow-up of three years. Male sex and cancer are risk factors for future deep vein thrombosis or pulmonary embolism. Patients without cancer appear to be at a negligible risk for death. SUMMARY: Background Studies of long-term thromboembolic complications and death following acute isolated superficial vein thrombosis (iSVT) of the lower extremities are scarce. Objectives To investigate the course of iSVT in the setting of an observational multicenter study. Methods We collected longitudinal data of 411 consecutive outpatients with acute, symptomatic, objectively diagnosed iSVT who were previously included in the cross-sectional ICARO study. Four patients followed for < 30 days and 79 with concomitant deep vein thrombosis (DVT) or pulmonary embolism (PE) were excluded from the present analysis. The primary outcome was symptomatic DVT or PE. The safety outcomes were major bleeding and all-cause death. Results The median follow-up time was 1026 days (interquartile range 610-1796). Symptomatic DVT/PE occurred in 52 (12.9%) patients, giving annualized rates of 1.3% (95% confidence interval [CI] 0.3-3.9%) on anticoagulant treatment and 4.4% (95% CI 3.2-5.8%) off anticoagulant treatment. Male sex (adjusted hazard ratio [HR] 2.03 [95% CI 1.16-3.54]) and active solid cancer (adjusted HR 3.14 [95% CI 1.11-8.93]) were associated with future DVT/PE, whereas prior DVT/PE failed to show significance, most likely because of bias resulting from prolonged anticoagulant treatment. Three major bleeding events occurred on treatment, giving an annualized rate of 1.4% (95 CI 0.3-4.0%). Death was recorded in 16 patients (annualized rate: 1.1% [95% CI 0.6-1.7%]), and was attributable to cancer (n = 8), PE (n = 1), cardiovascular events (n = 3), or other causes (n = 4). Conclusions The long-term risk of DVT/PE after anticoagulant discontinuation for acute iSVT is clinically relevant, especially in males and in the presence of active cancer. The risk of death appears to be negligible in patients without cancer.

A clinical score to rule out the concomitant presence of deep vein thrombosis in patients presenting with superficial vein thrombosis: The ICARO study.

BACKGROUND: Superficial vein thrombosis (SVT) is commonly encountered in clinical practice. Recent studies have suggested that the concomitant presence of deep vein thrombosis (DVT) or pulmonary embolism (PE) at the time of SVT diagnosis is not uncommon, thus increasing the interest on this disease. Whether this coexistence is predicted by specific risk factors remains unknown. AIM OF THE STUDY: To evaluate potential risk factors for DVT coexistence in patients presenting with acute objectively diagnosed SVT of the lower limbs and to develop a simple score entirely based on clinical variables to define the pre-test probability of DVT in these patients. METHODS: A multicenter, retrospective cohort study on SVT patients was conducted. Information was collected on clinical signs and on risk factors for venous thrombosis. RESULTS: 494 patients (mean age 56.3 ± 17.9 years, 64.2% women) were included. Concomitant DVT was found in 16.0% of patients. After multivariate analysis, we identified 5 independent variables that were used to develop the ICARO score: active malignancy (1.5 points), limb edema (1.5 points), rope-like sign (-1 point), age ≥ 50 years (1 point), unprovoked SVT (-1 point). The prevalence of concomitant DVT was 1.1% in the low-probability category (< 0 points), 12.0% in the intermediate-probability category (0 to 1 points), and 32.3% in the high probability category (≥ 1.5 points). CONCLUSIONS: The concomitant presence of major DVT is not negligible in patients with SVT. Our prediction score entirely based on simple clinical variables may be useful in assessing the risk of concomitant DVT in these patients.

Recurrent venous thromboembolism in anticoagulated patients with cancer: management and short-term prognosis.

BACKGROUND: Recommendations for management of cancer-related venous thromboembolism (VTE) in patients already receiving anticoagulant therapy are based on low-quality evidence. This international registry sought to provide more information on outcomes after a breakthrough VTE in relation to anticoagulation strategies. METHODS: Patients with cancer and VTE despite anticoagulant therapy were reported to the registry. Data on treatments, VTE events, major bleeding, residual thrombosis symptoms and death were collected for the following 3 months. Breakthrough VTE and subsequent recurrences were objectively verified. Outcomes with different treatment strategies were compared with Cox proportional hazards regression. RESULTS: We registered 212 patients with breakthrough VTE. Of those, 59% had adenocarcinoma and 73% had known metastases. At the time of the breakthrough event, 70% were on low-molecular-weight heparin (LMWH) and 27% on a vitamin K antagonist (VKA); 70% had a therapeutic or supratherapeutic dose. After breakthrough the regimen was: unchanged therapeutic dose in 33%, dose increased in 31%, switched to another drug in 24%; and other management in 11%. During the following 3 months 11% had another VTE, 8% had major bleeding and 27% died. Of the survivors, 74% had residual thrombosis symptoms. Additional VTE recurrence was less common with LMWH than with a VKA (hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.11-0.70) but similar with unchanged or increased anticoagulant intensity (HR, 1.09; 95% CI, 0.45-2.63). The bleeding rate did not increase significantly with dose escalation. CONCLUSION: Morbidity and mortality are high after recurrence of cancer-related VTE despite anticoagulation. Further treatment appears to be more effective with LMWH than with a VKA.

Safety of fondaparinux in the prevention of venous thromboembolism in elderly medical patients: results of a single-center, retrospective study.

AIM: Venous thromboembolism (VTE) is one of the leading causes of morbidity and mortality in acutely ill medical patients. Fondaparinux is recommended for the prevention of VTE in this setting, but little information is available on its safety and effectiveness in unselected, "real world" patients. The aim of this paper was to assess the safety and efficacy of fondaparinux in elderly acutely ill medical patients. METHODS: Single center, retrospective study. All patients >60 years, admitted for acute medical disease, bedridden for at least four days and treated with fondaparinux were evaluated. Occurrence of objectively documented, symptomatic VTE, and of bleeding events during the treatment period and follow-up were reported. RESULTS: Two hundred and ten patients (median age 81 years) were treated with fondaparinux. Seventy patients received fondaparinux 1.5 mg daily, 140 received the 2.5 mg daily dose. However, 29 patients in the first group (with a CrCl≥50 mL/min) and 84 patients in the last group (with a CrCl<50 mL/min) did not receive the correct dose of fondaparinux. During treatment, one episode (0.48%, 95% CI 0.1% to 2.6%) of major bleeding and 6 episodes (2.86%, 95% CI 1.3% to 6.1%) of clinically relevant non major bleeding were recorded. Only one thromboembolic event (0.48%, 95% CI 0.1% to 2.6%) was documented. Thirty-nine patients died; no death was related to VTE, unlike one death was due to major bleeding. Cancer was the only significant predictor of bleeding at statistical analysis. CONCLUSION: In elderly acutely ill hospitalized medical patients, thromboprophylaxis with fondaparinux 2.5 or 1.5mg daily is safe and effective in preventing VTE without increasing bleeding risk.

Vascular, hepatic and renal lesions by Dirofilaria immitis invasion in dogs / Lesões vasculares, hepáticas e renais na invasão por Dirofilaria immitis no cão

Morphological investigations were conducted on four bodies of dogs who died due to severe clinical symptoms following a massive invasion of cardiac and pulmonary Dirofilaria. The subjects were monitored clinically and diagnosed serologically positive for the Heartworm disease. The necropsy examination of the cardiovascular system (right ventricle and pulmonary artery) revealed the presence of 25 adult parasites in one dog with length ranging between 8 and 33cm. Macroscopically, lesions consistently observed were represented by the right ventricular dilatation and the diffuse wall thickening of the pulmonary artery. Parasitic invasion secondary lesions were present in the lungs, liver and kidneys (cardiac and vascular lesions). The histological examination mainly revealed myocardial injury, vascular (dystrophic), pulmonary (circulatory and inflammatory), hepatic (degenerative) and renal (degenerative and inflammatory) damage.

Investigações morfológicas foram realizadas em quatro cadáveres de cães, mortos em razão de graves sintomas clínicos atribuídos à invasão massiva cardíaca e pulmonar por Dirofilaria immitis. Os indivíduos foram acompanhados sob o ponto de vista clínico, sendo diagnosticados serologicamente positivos para dirofilariose. À necropsia do sistema cardiovascular (ventrículo direito e artéria pulmonar,) revelou-se em um indivíduo a presença de 25 parasitas adultos, com comprimento entre 8-33 centímetros. Macroscopicamente, as lesões observadas foram a dilatação do ventrículo direito e o espessamento difuso da parede da artéria pulmonar. Lesões secundárias à invasão parasitária estavam presentes nos pulmões, no fígado e nos rins (lesões cardíacas e vasculares). O exame histológico revelou, principalmente, lesões do miocárdio, lesões vasculares (distróficos) e pulmonares (circulatórias e inflamatórias), mas também no fígado (degenerativas) e nos rins (degenerativas e inflamatórias).

Vanishing bile duct syndrome in non-Hodgkin lymphoma: a case report.

Non-Hodgkin lymphoma (NHL) related vanishing bile duct syndrome (VBDS) is a rare condition that often leads to liver failure and death. A 64-year-old man with history of rheumatic heart disease complicated by steno-aortic insufficiency, mild mitral stenosis, atrial fibrillation, left kidney damage, bilateral glaucoma, left internal jugular vein thrombosis, bronchopneumonia, NHL type B (stage IV) treated with chemo and radiotherapy was admitted to our department for jaundice with predominantly cholestatic component. Liver biopsy allowed a diagnosis of VBDS and patient was treated with ursodesossicolic acid (UDCA) 20 mg/kg/day associated with prednisone 1 mg/kg/day with a transient decrease of bilirubin and cholestasis, but a rapid worsening of general clinical conditions followed by severe acute liver failure (ALF), unresponsive to pharmacological therapy, leads to death our patient. In our case we supposed that this syndrome represents the paraneoplastic epiphenomenon of NHL with severe duct damage, related to lymphomatous release of toxic cytokines. In our clinical practice we must not forget that VBDS can be related to hepatic damage also induced during NHL. A special attention to abnormal liver function is necessary to diagnose this syndrome, because often the tests are interpreted as disseminated (stage IV) disease and not as a possible expression of VBDS which could, in some cases, be attenuated by UDCA and by steroids therapy.

Practical use of intermittent pneumatic compression as thromboprophylaxis in neurosurgery.

Most patients undergoing neurosurgery are considered at increased risk for venous thromboembolism (VTE). Several studies have demonstrate that intracranial surgery, malignancy, leg weakness, prolonged procedures and advanced age can to increase VTE. Use of thromboprophylaxis is recommended to avoid this risk. Low molecular weight heparin (LMWH), low dose unfractionated heparin (LDUH), intermittent pneumatic compression (IPC) and graduated compression stocking (GCS) are commonly used as VTE prophylaxis. This article wants to show the practical use of IPC in neurosurgery, following the guidelines developed by American College of Chest Physicians (ACCP) and used by the most important medical societies such as American Association of Neurological Surgeons (AANS) and European Association of Neurosurgical Societies (EANS). Several studies have demonstrated that IPC use is effective as LMWH, safe and economic.

PBMCs protein expression profile in relapsing IFN-treated multiple sclerosis: A pilot study on relation to clinical findings and brain atrophy.

This cross-sectional study investigated with two-dimensional gel electrophoresis coupled to MALDI-TOF and MRI the relationship between PBMCs protein expression profile and whole-brain atrophy in 16 unselected RR-MS IFN-treated patients compared with 6 RR IFN-untreated and 12 matched healthy control subjects. Grey/white matter fraction, T1/T2 lesion load and clinical variables were considered too. Twenty six proteins showed significant differential expression among RR IFN-treated patients and control samples. Four of these (IN35, GANAB, PP1B, SEPT2) resulted correlated with clinical and MRI findings in RR IFN-treated MS patients. Future clinical applications remain to be validated by other techniques and confirmed by a larger study.

Neuroelectric procedure does not discriminate between painful and paresthetic diabetic neuropathy.

To investigate whether pain and paresthesias could identify two different subclasses of small-fibre diabetic neuropathy, and to evaluate their relation to the metabolic control, we tested nerve conduction velocity (NCV) of median nerve (sensitive-SM, and motor-MM) and deep peroneal nerve (DP) in 48 diabetics (24 IDDM, 24 NIDDM) reporting pain (group A) or paresthesias (group B) that might be due to diabetic polyneuropathy. Glycated haemoglobin (HbA1c) was also assessed. No difference between group A and group B was found either in NCV, in all nerves tested, or in HbA1c. No relation was observed between NCV of nerves tested and HbA1c, duration of diabetes, age and type of diabetes in both groups.

Trigemino-cervical reflex in pathology of the brain stem and of the first cervical cord segments.

The trigemino-cervical reflex (CR) sensitivity and specificity in the assessment of cervico-bulbar lesions was evaluated in eleven selected subjects (4 multiple sclerosis, 3 tumoural processes and 4 cervical cord spondilogenetic myelopathies). Results were compared with those obtained from others neurophysiological investigations (EMG and blink-reflex) and with neuroimaging findings. Significant abnormal responses of CR were found in all patients varying from absent responses, to delayed or reduced amplitude patterns. These data stress the utility of CR in the check of cervico-bulbar lesions, where it can be considered complementary to other electrophysiological tests.