Quality of care and clinical inertia in the management of cardiovascular risk factors in patients with type 1 and type 2 diabetes: data from AMD annals.

BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality among patients with diabetes, and for this reason, all guidelines for CV risk management provide the same targets in controlling traditional CV risk factors in patients with type 1 or type 2 diabetes at equal CV risk class. Aim of our study was to evaluate and compare CV risk management in patients with type 1 and type 2 diabetes included in AMD Annals Database paying particular attention to indicators of clinical inertia. METHODS: This was a multicenter, observational, retrospective study of AMD Annals Database during year 2022. Patients with diabetes were stratified on the basis of their cardiovascular risk, according to ESC-EASD guidelines. The proportion of patients not treated with lipid-lowering despite LDL cholesterol > to 100 mg/dl or the proportion of patients not treated with antihypertensive drug despite BP > 140/90 mmhg and proportion of patients with proteinuria not treated with angiotensin converting enzyme inhibitors or angiotensinogen receptor blockers (ACE/ARBs) were considered indicators of clinical inertia. The proportion of patients reaching at the same time HbA1c < 7% LDL < 70 mg/dl and BP < 130/80 mmhg were considered to have good multifactorial control. Overall quality of health care was evaluated by the Q-score. RESULTS: Using the inclusion criteria and stratifying patients by ESC/EASD Cardiovascular Risk categories, we included in the analysis 118.442 patients at High Cardiovascular risk and 416.246 patients at Very High Cardiovascular risk. The proportion of patients with good multifactorial risk factor control was extremely low in both T1D and T2D patients in each risk class. At equal risk class, the patients with T1D had lower proportion of subjects reaching HbA1c, LDL, or Blood Pressure targets. Indicators of clinical inertia were significantly higher compared with patients with T2D at equal risk class. Data regarding patients with albuminuria not treated with RAAS inhibitors were available only for those at Very High risk and showed that the proportion of patients not treated was again significantly higher in patients with T1DM. CONCLUSIONS: In conclusion, this study provides evidence of wide undertreatment of traditional cardiovascular risk factors among patients with diabetes included in AMD Annals Database. Undertreatment seems to be more pronounced in individuals with T1D compared to those with T2D and is frequently due to clinical inertia.

Evaluation of a large set of patients with Autoimmune Polyglandular Syndrome from a single reference centre in context of different classifications.

PURPOSE: To characterize patients with APS and to propose a new approach for their follow-up. Query ID="Q1" Text="Please check the given names and familynames." METHODS: Monocentric observational retrospective study enrolling patients referred to the Outpatients clinic of the Units of Endocrinology, Diabetology, Gastroenterology, Rheumatology and Clinical Immunology of our Hospital for Autoimmune diseases. RESULTS: Among 9852 patients, 1174 (11.9%) [869 (73.9%) female] were diagnosed with APS. In 254 subjects, the diagnosis was made at first clinical evaluation (Group 1), all the other patients were diagnosed with a mean latency of 11.3 ± 10.6 years (Group 2). Group 1 and 2 were comparable for age at diagnosis (35.7 ± 16.3 vs. 40.4 ± 16.6 yrs, p = .698), but different in male/female ratio (81/173 vs 226/696, p = .019). In Group 2, 50% of patients developed the syndrome within 8 years of follow-up. A significant difference was found after subdividing the first clinical manifestation into the different outpatient clinic to which they referred (8.7 ± 8.0 vs. 13.4 ± 11.6 vs. 19.8 ± 8.7 vs. 7.4 ± 8.1 for endocrine, diabetic, rheumatologic, and gastroenterological diseases, respectively, p < .001). CONCLUSIONS: We described a large series of patients affected by APS according to splitters and lumpers. We propose a flowchart tailored for each specialist outpatient clinic taking care of the patients. Finally, we recommend regular reproductive system assessment due to the non-negligible risk of developing premature ovarian failure.

Pharmacological treatment and prevention of chronic venous ulcers: a review.

Chronic venous insufficiency and chronic venous ulcers represent an important medical problem, because of the high incidence and prevalence in the general population, and need to be considered as a lifelong degenerative condition, with socioeconomic consequences. Ulceration is a severe complication of the post-thrombotic syndrome, often precipitated by minor trauma. The rate of post-thrombotic syndrome varies between 20% and 100% of patients with deep vein thrombosis, mostly occurring within two years of an initial thrombotic event. This syndrome is difficult to treat, causes significant disability and reduces the quality of life. To date, there are no effective therapies of chronic venous ulcers and no definite strategies for identifying patients at risk for the development of ulceration. The role of adequate compression with elastic stockings is well recognized. Several systemic drugs have been tested for a possible effect on chronic venous ulcer healing, but none has been widely accepted as standard therapy in this setting. It has been suggested that extended oral anticoagulation should be investigated as a possible preventative measure. Waiting for the results in this field, an adequate management of anticoagulation in terms of anticoagulant intensity and duration should be recommended for the prevention of recurrent deep vein thrombosis, post-thrombotic syndrome and chronic venous ulcers.

Diabetes mellitus and cardiovascular prevention: the role and the limitations of currently available antiplatelet drugs.

Diabetes mellitus (DM) is associated with macrovascular and microvascular complications. Platelets have a "key role" in atherogenesis and its thrombotic complications in subjects with DM. Moreover, the concomitant presence of multiple "classical" cardiovascular risk factors in diabetic subjects contributes to enhanced atherothrombotic risk. Antiplatelet agents are effective in primary and secondary prevention of arterial thrombosis (cardiovascular events, ischaemic stroke, and peripheral arterial occlusive disease). The role of chronic administration of antiplatelet drugs in primary prevention of arterial vascular events is known to be less clear than in secondary prevention, and, also in diabetic patients, the decision to give primary prophylaxis should be taken on an individual-patient basis, after a careful evaluation of the balance between the expected benefits and the risk of major bleedings. Although, currently, treatment has proven useful in reducing vascular events, diabetic patients continue to have a higher risk of adverse cardiovascular events compared with those in nondiabetic patients. This paper reviews the role of currently available antiplatelet drugs in primary and secondary prevention of vascular events in diabetic patients and the limitations of these drugs, and it discusses the role of novel and more potent antiplatelets and of new agents currently under clinical development.

Longer-acting factor VIII to overcome limitations in haemophilia management: the PEGylated liposomes formulation issue.

Injected factor VIII (FVIII), the current treatment for haemophilia A, leads to major improvements in the quality of life and life expectancy of individuals with this disorder. However, because injected FVIII has a short half-life in vivo, this strategy has major limitations for highly demanding regimens (e.g. prophylaxis, immune tolerance induction, surgery). Newer formulations of longer-acting FVIII are presently under investigation. The use of low molecular weight polyethylene glycol (PEG)-containing liposomes as carriers for recombinant FVIII (rFVIII) results in the prolongation of haemostatic efficacy. Data from preclinical experiments in mice, early clinical evaluations, and pharmacokinetics and pharmacodynamics results indicate that an rFVIII pegylated liposomal formulation may provide potential clinical benefit to patients with severe haemophilia A by prolonging the protection from bleeding. In light of this potential clinical benefit, a multicentre, randomized, active-controlled, non-inferiority phase II trial with two parallel treatment arms and equal randomization after stratification for the presence or absence of target joints in patients and for ages >/=18 years vs. <18 years is currently being conducted. The study will test the hypothesis that rFVIII-Lip once-weekly prophylaxis is not inferior to rFVIII-water for injection thrice-weekly prophylaxis. A total of 250 patients will be enrolled with severe haemophilia A (<1% FVIII) on on-demand or secondary prophylaxis treatment and with documented bleeds or injections during the 6 months before study entry. Sixty-four centres in 14 different countries are involved in the study; recruitment is underway. In Italy, six centres have already included 15 patients (no screening failure). Eight of these patients have completed the run-in phase and have begun the home treatment. No unexpected serious adverse events have been reported thus far. Data emerging from this phase II study will help collect relevant data to overcome current limitations in haemophilia management by employing treatment with longer-acting rFVIII.

Can serum TGF-beta 1 be used to evaluate the response to antiviral therapy of haemophilic patients with HCV-related chronic hepatitis?

Congenital coagulation disorders limit the use of liver biopsy, especially when repeated assessment is needed. TGF-beta 1 plays a pivotal role in inducing fibrosis and has been proposed as its surrogate marker. Aiming at validating the clinical utility of this cytokine, fifteen haemophilic patients suffering from HCV-related chronic hepatitis were treated with Peg-IFN alpha2beta plus Ribavirin. Serum TGFbeta 1, viral load and liver enzymes were analyzed at baseline and at six, twelve, and eighteen months. As expected, patients initially showed significantly higher TGF-beta 1 levels than age-matched controls (43.8 ng/mL, 28.7-46.4 vs. 26.9 ng/mL, 23.0-34.0, median and 95% CI; p=0.004). The end of therapy response rate was 67%. The main finding was a significant drop in TGF-beta 1 at six months compared to baseline values; this drop de facto predicted the levels reached in the following six months, which were fixed at lower concentrations (37.0 ng/mL, 21.9-43.8 and 27.0 ng/mL, 24.1-44.0 respectively; p<0.009), independently of treatment outcome (three patients were breakthrough, twelve were sustained virological responders (SVRs). During the treatment period none had clinical or biochemical signs of inflammation in other areas. Treatment was followed by a six-month follow-up, at the end of which TGF-beta 1 was increased compared to the previous values, reaching the initial levels in ten SVRs (45 ng/mL, 24.5-52.9). Interestingly, at a longer follow-up, two out of ten SVRs, who displayed the highest values of TGF-beta 1, relapsed. Serum TGF-beta 1 could be used to assess therapeutic outcome and short-term prognosis of HCV-related chronic hepatitis.

Assessment of right ventricular function by strain rate imaging in chronic obstructive pulmonary disease.

The purpose of the current study was to compare right ventricular (RV) myocardial wall velocities (tissue Doppler imaging) and strain rate imaging (SRI) parameters with conventional echocardiographic indices evaluating RV function in chronic obstructive pulmonary disease (COPD) patients. In total, 39 patients with COPD and 22 healthy subjects were included in the current study. Seventeen patients had pulmonary artery pressure <35 mmHg (group I) and 22 patients had pulmonary artery pressure >35 mmHg (group II). Tissue Doppler imaging, strain and strain rate (SR) values were obtained from RV free wall (FW) and interventricular septum. Respiratory function tests were performed (forced expiratory volume in one second/vital capacity (FEV(1)/VC) and carbon monoxide diffusion lung capacity per unit of alveolar volume (D(L,CO)/V(A))). Strain/SR values were reduced in all segments of group II patients compared with group I patients and controls with lowest values at basal FW site. A significant relationship was shown between peak systolic SR at basal FW site and radionuclide RV ejection fraction. A significant relationship was shown between peak systolic SR at basal FW site and D(L,CO)/V(A) and FEV(1)/VC. In conclusion, in chronic obstructive pulmonary disease patients, strain rate imaging parameters can determine right ventricular dysfunction that is complementary to conventional echocardiographic indices and is correlated with pulmonary hypertension and respiratory function tests.

Long-term prophylaxis with intermediate-purity factor VIII concentrate (Haemate P) in a patient with type 3 von Willebrand disease and recurrent gastrointestinal bleeding.

Prophylaxis with von Willebrand factor (VWF)-containing concentrates is considered to be a potential approach for patients with von Willebrand disease (VWD) and severe bleeding tendency. We report the case of a 57-year-old man with type 3 VWD and a history of recurrent melaena. Bleeding frequency and severity had progressively increased and the patient showed chronic anaemia and persistent haemoglobin in the stools. Endoscopic examinations revealed multiple vascular mucosal abnormalities (MVA) of the stomach and large bowel. Photocoagulation of some actively bleeding lesions and octreotide did not significantly affect his clinical conditions: six red cell transfusions and >400 000 IU of intermediate-purity factor VIII (FVIII) concentrate (Haemate P) on-demand were needed during 2002. Prophylaxis with Haemate P 40 IU kg(-1) (102 IU kg(-1) VWF:RCo) thrice weekly was associated with improvement of his mean haemoglobin levels, cessation of clear-cut melaena and red cell transfusions and reduction of total Haemate P requirements (-20% over 2003-04). Prophylaxis with Haemate P is still ongoing without any adverse event over a 30-month period. Clinical course and pharmacokinetic evaluations led to administer Haemate P each 72-96 h. Possible vascular complications were excluded by a careful clinical follow up, as the patient suffered from arterial hypertension and diabetes mellitus; thrombophilic abnormalities were previously excluded and no signs of abnormal coagulation activation or FVIII:C levels >150% were detected thereafter. Long-term prophylaxis with Haemate P has been shown to be safe, effective (also in terms of quality of life) and cost saving in this patient with severe gastrointestinal bleeding due to MVA and VWD.

Dementia with Lewy bodies: a review.

The dementia with Lewy bodies (DLB) is the second major type of senile, degenerative dementia, after the Alzheimer disease (AD). It is characterized by the presence of cytoplasmic inclusions of alpha-synuclein in the cerebral cortex and in the nuclei of the brain stem. DLB patients frequently have complex visual hallucinations, depressive symptoms, Parkinsonian manifestations and cognitive deficits, showing important associations with the Parkinson disease and the AD. The DLB should be differentiated from atypical Parkinsonisms, but the differential diagnosis often remains difficult and unsafe. Clinical and neuropathological findings, as well as neuroimaging are valuable tools in establishing specific diagnosis of DLB. Acetylcholinesterase inhibitors, dopamine-agonists, benzodiazepines of short or medium half-life, and antidepressants may be useful in the treatment of DLB, depending on the dominant symptoms of the given patients.

Assessment of severity of mechanical prosthetic mitral regurgitation by transoesophageal echocardiography.

OBJECTIVE: To evaluate the ability of colour Doppler transoesophageal echocardiography (TOE) to assess quantitatively prosthetic mitral valve insufficiency. METHODS: 47 patients were studied with multiplane TOE and cardiac catheterisation. Proximal jet diameter was measured as the largest diameter of the vena contracta. Regurgitant area was measured by planimetry of the largest turbulent jet during systole. Flow convergence zone was considered to be present when a localised area of increased systolic velocities was apparent on the left ventricular side of the valve prosthesis. Pulmonary vein flow velocity was measured at peak systole and diastole. RESULTS: Mean (SD) proximal jet diameter was 0.63 (0.16) cm, with good correlation with angiographic grades (r = 0.83). Mean (SD) maximum colour jet area was 7.9 (2.5) cm2 (r = 0.69) with worse correlation if a single imaging plane was used for measurements (r = 0.62). The ratio of systolic to diastolic peak pulmonary flow velocity averaged 0.7 (1.3) cm (r = -0.66) with better correlation (r = -0.71) if patients with atrial fibrillation were excluded. Mean (SD) regurgitant flow rate was 168 (135) ml/s and regurgitant orifice area was 0.56 (0.43) cm2, with good correlation with angiography (r = 0.77 and r = 0.78, respectively). CONCLUSIONS: TOE correctly identified angiographically severe prosthetic mitral regurgitation, mainly by the assessment of the flow convergence region and the proximal diameter of the regurgitant jet.

Transesophageal dobutamine stress echocardiography with tissue Doppler imaging for detection and assessment of coronary artery disease.

BACKGROUND: Transesophageal dobutamine stress echocardiography (T-DSE) has been shown to be a sensitive and specific technique for the detection of myocardial ischemia. A major limitation of echocardiographic study interpretation, however, is the subjective visual analysis of endocardial motion and wall thickening, which is only semiquantitative. METHODS: To analyze whether T-DSE with the use or tissue Doppler imaging (TDI) during graded dobutamine infusion may be useful to detect and quantify stress-induced myocardial ischemia by changes in myocardial velocities, 70 patients undergoing coronary arteriography were studied with T-DSE and TDI. Midesophageal and transgastric short- and long-axis images were obtained at each level of dobutamine infusion. T-DSE was successful in 67 patients (96%). Baseline resting pulsed and color peak systolic (S) and early diastolic (E) velocities of the anterior, septal, lateral, and inferior walls were examined. RESULTS: Pulsed and color TDI correlated well at rest and after stress. Fifteen patients had a normal response to dobutamine, and 52 patients had inducible ischemia by two-dimensional criteria. In the normal group, there was a significant dose-dependent increase in S and E velocities. Compared with those in the normal group, patients with coronary artery disease (CAD) had lower resting S and E velocities and blunted S wave increase or E wave decrease during DSE. CONCLUSIONS: T-DSE with TDI is a feasible and accurate test for the quantitative assessment of patients with CAD who have impaired augmentation of systolic and diastolic myocardial velocities during dobutamine infusion.

Cellular tropism and localization in the rodent nervous system of a neuropathogenic variant of Friend murine leukemia virus.

BACKGROUND: We studied PVC-211 murine leukemia virus (MuLV) (1), a neuropathogenic variant of Friend MuLV, to determine its cellular tropism and distribution in the nervous system of infected rats and the factors that affected disease expression. EXPERIMENTAL DESIGN: Rats from five different strains and mice from 3 strains were inoculated intracerebrally or intraperitoneally from birth to 10 days of age and observed for signs of neurologic disease and tumors for 24 weeks. Nervous system pathology, MuLV gp70 expression, and virus production were evaluated weekly for 4 weeks after perinatal infection of Fisher (F344) rats. Blood-brain-barrier integrity and ultrastructure were evaluated in 21-day-old symptomatic infected rats. Microvessel and mixed glial cell cultures were prepared from brains of infected and uninfected 21-day-old F344 rats and evaluated for virus production, MuLV gp70 expression, and the presence of PVC-211 MuLV DNA. RESULTS: Tremor, ataxia, spasticity, and hindlimb weakness occurred in rats and mice as early as 3 weeks after neonatal infection. Severity, latency, and progression varied among mouse and rat strains but exposure to PVC-211 MuLV before 6 days of age was required for disease expression. Rapid PVC-211 MuLV replication in brain capillary endothelial cells (BCEC) early in the perinatal period was followed by widespread astrogliosis, neuropil vacuolation, and finally, neuronal degeneration in the spinal cord, brainstem, cerebellum, and subcortex. MuLV gp70 expression in vivo increased during infection, was restricted to BCEC, but was not associated with perivascular inflammatory infiltrates. BCEC cultured from microvessel preparations but not astrocytes or microglia in mixed glial cell cultures isolated from infected rats contained PVC-211 MuLV DNA, expressed MuLV gp70, and produced infectious virus. CONCLUSIONS: The rapid replication of PVC-211 MuLV that occurs in the nervous system of infected rodents is restricted to BCEC. These infected BCEC appear to play a critical role in initiating the astroglial response in this neurodegenerative process through mechanisms that remain to be defined.

Effects of viral specific cytotoxic lymphocytes on the expression of murine leukemia virus induced neurologic disease.

A dose and time related effect on neurologic disease expression followed transfer of viral specific cytotoxic T lymphocytes (CTL) to recipient NFS/N mice previously infected at 2 days of age with Cas-Br-M murine leukemia virus. Cas-Br-M MuLV gp70 was expressed in spleen and capillary endothelial cells in the brain and spinal cord of CTL recipients, but the progression of gliosis, vacuolation, and cell death that followed endothelial cell MuLV gp70 expression in unprotected Cas-Br-M MuLV infected mice was interrupted in protected CTL recipients. A direct cytotoxic effect of CTL on infected brain capillary endothelial or neural cells could not be demonstrated. Reduced levels of infectious MuLV and MuLV gp70 expression in brain following syngeneic CTL transfer early in the course of disease suggest that CTL may function by preventing a time-limited interaction of Cas-Br-M MuLV with a susceptible target cell or receptor critical for neurologic disease induction during the perinatal period.

Ras gene product expression in blood and marrow smears of patients with acute leukemia: importance of fixation.

Activation of ras protooncogenes by any of several possible mutations in codons 12, 13 or 61 has been demonstrated in a variety of human malignancies, including acute non-lymphoblastic leukemia (ANLL). In situ staining for the ras gene product, p21, has been demonstrated in carcinomas of several sites. High levels of p21 expression have been associated with histologic anaplasia in prostate cancer and regional lymph node metastasis in breast cancer. We examined 16 marrow aspirates and blood smears from patients with acute leukemia, predominantly ANLL, and eight controls. Marrow aspirates or blood were smeared on glass slides and fixed immediately in 10% buffered formalin. p21 was examined with avidin-biotin linked immunoperoxidase visualization. Particular attention must be paid to antibody selection and fixation protocol to demonstrate p21, owing to its rapid degradation ex vivo. Three of 16 patients exhibited occasional high p21 expression primarily in leukemic blasts, but in no case were more than 10% of blast cells positive. Normal reticuloendothelial and myeloid cells occasionally exhibited mild to moderately heavy staining, but megakaryocytes, erythroid precursors, lymphocytes and plasma cells were consistently negative. Most patients, 5 normal volunteers and 3 patients with non-malignant disease, exhibited no reactivity, or only a faint blush. These data suggest that while point mutation and concomitant activation of c-N-ras occurs regularly in ANLL, high levels of ras p21 expression are rarely found with this technique.

Retrovirus induced motor neuron degeneration.

Neurotropic retroviruses are capable of infecting and altering the function of dividing populations of neuron-like cells such as the PC-12 cell line. However, histological, immunohistochemical, and ultrastructural studies have failed to implicate direct infection of neurons by MuLV as the etiologic mechanism responsible for MuLV induced neurodegenerative disease. Indirect mechanisms such as the physical or biochemical disruption of endothelial cell basement membranes or the production of toxic cytokines by virus infected cells may play a role in the development of retrovirus induced neurodegeneration.

T-cell detection with monoclonal antibody T101 kits.

A solid-phase immunoadsorption procedure (Quantigen T&B cell kit; Bio-Rad Laboratories, Richmond, Calif.) employing monoclonal antibody T101 detected mean percentages of peripheral blood T cells comparable to those obtained by rosetting with sheep erythrocytes, while lower values were obtained with an indirect immunofluorescence procedure (Cytotag T&B cell kit; Hybritech, Inc., San Diego, Calif.) employing the same antibody. Therefore, T101 binding appears to be more easily detected by solid-phase immunoadsorption than by immunofluorescence microscopy.

Persistence of herpes simplex virus type-2 genome in a human leukemic cell line.

To study the nature of virus-cell interaction in persistently infected cells we have examined production of infectious virus, synthesis of viral DNA and DNA polymerase in a human leukemic cell line K562. It was found that only one of three K562 cell lines was permissive for limited growth of HSV-2 and infectious virus was released in a cyclical fashion. Intranuclear inclusions with electron-dense fibrils and particles resembling viral structures were observed in the virus-infected but not control K562 cells. Viral DNA synthesis could not be detected by centrifugation in CsCl density gradients; but was readily identified by Southern blot hydridization of virus-infected intracellular DNA with purified viral DNA. Viral DNa polymerase was synthesized by infected cells during active infectious virus production. In one of the two K562 cell lines that did not produce infectious virus, a few DNA fragments from infected cells were found to hybridize with purified viral DNA. These results suggest that variable lengths of HSV-2 genome can be harbored and propagated by different human leukemic K562 cells.

Postoperative radiation therapy after vaginal surgery for endometrial cancer.

From 1958 to 1978, 88 consecutive patients affected by endometrial cancer were referred to the Radiology Institute of the University of Florence, for radiation therapy after vaginal hysterectomy and bilateral salpingo-oophorectomy. Five and ten-year actuarial survival rates are 71% and 62%. In the evaluable patients, results are analysed according to: extension of the tumor, as assessed by pathological evaluation (60 pats.), histologic grade of differentiation (44 pats.), and neoplastic infiltration of myometrium (32 pats.). When the tumor is limited to the uterine body, a 5-year actuarial survival is achieved in 89% of the cases; when the cervix or the adnexa and other pelvic structures are involved, this percentage decreases to 62.5% and 37.5%. The prognosis is also affected by the histological grade of differentiation and the depth of myometrial infiltration.