Levosimendan has an inhibitory effect on platelet function

Levosimendan enhances cardiac contractility by increasing myocyte sensitivity to calcium, and induces vasodilatation. Although studies have evaluated the efficacy of levosimendan in heart failure, it is not clear whether it might produce functional influence on platelet response. In this study, the effect of levosimendan on platelet aggregation was investigated. Platelet function tests were performed in 12 healthy male volunteers. Three concentrations of levosimendan solution were prepared that would result in 10, 25, and 45 ng/ml levosimendan concentrations in the blood similar to that observed after clinical therapeutic intravenous application of 0.05-0.1 microg/kg/min. Each concentration of levosimendan solution and a control diluent without levosimendan were incubated with whole blood at 37 degrees C. After incubation for 15 min, aggregation responses were evaluated with adenosine diphosphate (ADP) (5 and 10 microM) and collagen (2 and 5 microg/ml) in platelet-rich plasma. Preincubation with all dilutions of levosimendan inhibited aggregation of platelets induced by ADP and collagen significantly. Levosimendan also inhibited significantly the secondary wave of platelet aggregation induced by ADP. The results showed that there was a relationship between levosimendan concentration and inhibition of platelet aggregation. In conclusion, this study with an in vitro model showed that levosimendan had a significant inhibitory effect on platelets in clinically relevant doses.     

Intraosseous carcinoma of the jaws—A clinicopathologic review. Part I: Metastatic and salivary‐type carcinomas

This is the first part of a 3‐part comprehensive review of intraosseous carcinoma of the jaws. We have outlined 4 groups of intraosseous carcinoma of the jaws (metastatic, salivary‐type, odontogenic, and primary intraosseous carcinoma), emphasizing the need for accurate diagnosis and the problems associated with changing classification systems, standardization of diagnostic criteria and nomenclature, and the accuracy of existing literature. In this first part, the features of metastatic and the very rare salivary‐type carcinomas of the jaws are examined with particular emphasis on histologic and immunohistochemical characteristics, diagnostic difficulties, and uncertainties. © 2012 Wiley Periodicals, Inc. Head Neck, 2012     

Suicide risk among adults with epilepsy in Kaduna,Nigeria

Objective

There is paucity of information on epilepsy and suicide in Nigeria. The objective of this study therefore was to assess the prevalence and determinants of suicide risk among adults with epilepsy (AWE) in Kaduna, Nigeria.

Method

We administered the suicidality module of the Mini International Neuropsychiatric Interview, the three-item Oslo Social Support Scale and the Hospital Anxiety and Depression Scale to 170 consecutive AWE attending the outpatient clinic of Federal Neuropsychiatric Hospital, Kaduna, between January and June 2011 to determine the prevalence of suicide risk, the level of social support and the psychological symptoms, respectively. We also recorded the sociodemographic and clinical characteristics of the subjects.

Results

There are 99 males and 71 females. The subject’s mean age was 28.7±12.1 years. The prevalence of suicide risk was 20.0%. Short seizure-free periods (χ²= 4.658, P= .031), previous suicide attempts (χ²= 12.216, P< .001), anxiety symptoms (χ²= 5.075, P= .024) and depressive symptoms (χ²= 5.093, P= .016) were significantly associated with suicidal tendencies. However, after a logistic regression analysis, none of the above variables predicted suicide risk.

Conclusion

Suicide risk is common among AWE. Poor seizure control, previous suicidal attempts and emotional distress are associated factors.     

Evaluation of reporting quality for observational studies using routinely collected health data in pharmacovigilance

Objectives: To appraise the reporting quality of studies which concerned linezolid-related thrombocytopenia referring to REporting of studies Conducted using Observational Routinely collected health Data (RECORD) statement.

Methods: Medline, Embase, Cochrane library and clinicaltrial.gov were searched for observational studies concerning linezolid-related thrombocytopenia using routinely collected health data from 2000 to 2017. Two reviewers screened potential eligible articles and extracted data independently. Finally, reporting quality assessment was performed by two senior researchers using RECORD statement.

Results: Of 25 included studies, 11 (44.0%) mentioned the type of data in the title and/or abstract. In 38 items derived from RECORD statement, the median number of items reported in the included studies was 22 (inter-quartile range 18–27). Inadequate reporting issues were discovered in the following aspects: validation studies of the codes or algorithms, study size estimation, quantitative variables, subgroup statistical methods, missing data, follow-up/matching or sampling strategy, sensitivity analysis and cleaning methods, funding and role of funders and accessibility of protocol, raw data.

Conclusion: This study provides the evidence that the reporting quality of post-marketing safety evaluation studies conducted using routinely collected health data was often insufficient. Future stakeholders are encouraged to endorse the RECORD guidelines in pharmacovigilance.     

A retrospective study on oral anticoagulant prophylaxis in 103 Italian patients with hereditary thrombophilia and thrombosis

Summary The clinical records of 103 Italian patients with inherited thrombophilia and thrombosis were reviewed to estimate the incidence of thrombotic recurrences and major bleeding complications according to the different duration of oral anticoagulant prophylaxis (OAP). The incidence of the first thrombotic recurrence was 2.9, 7.4 and 10.8×100 patients/year, respectively, in subjects receiving lifelong OAP, stopping OAP after a mean of 9 months (range 1–30 months) or not receiving OAP. The probability to remain free from thrombotic recurrences in patients undergoing lifelong OAP, as estimated by the Kaplan-Meier method, was significantly higher in comparison with untreated patients (p<0.001), but did not reach the statistical significance in comparison with patients who stopped prophylaxis. The incidence of further thrombotic recurrences was 1.2, 21.1 and 22.3×100 patients/year, respectively, in the three groups defined above. The difference between patients who prolonged indefinitely OAPvs those who stopped or did not receive OAP was statistically significant (p=0.003). Two intracranial bleedings, one of which fatal, were observed in patients undergoing lifelong OAP, whereas no major bleeding complications occurred in the other two groups. Our study supports the recommendations to continue indefinitely OAP in patients with inherited thrombophilia and recurrent thrombosis, but suggests caution in starting lifelong prophylaxis soon after the first thrombotic event in all patients. Members of the Study Group: F. Baudo (Milano); M. Berrettini (Perugia); G. Castaman (Vicenza); N. Ciavarella (Bari); S. Coccheri (Bologna); V. De Stefano (Roma); A. G. Dettori (Parma); N. Erba (Merate); G. Leone (Roma); P. M. Mannucci (Milano); C. Manotti (Parma); M. G. Mazzucconi (Roma); G. Palareti (Bologna); F. Panicucci (Pisa); E. Pogliani (Monza); F. Rodeghiero (Vicenza); A. Tripodi (Milano).     

Evaluation of the predictive role of neutrophil/lymphocyte ratio in the diagnosis of lymphoma in patients with asymptomatic and ısolated cervical lymphadenopathy

IntroductionThe diagnostic approach to patients with isolated asymptomatic cervical lymphadenopathy varies between excisional biopsy and follow-up. When the anamnesis, physical examination, laboratory and imaging findings are not sufficient to identify the etiology, an excisional biopsy is performed for the differential diagnosis between early-stage lymphoma and infectious or reactive causes. If the excisional biopsy, which may have some complications, is not performed, it may delay the diagnosis of lymphoma. This diagnostic challenge could be avoided by predictive markers.ObjectivesThis study was planned to determine the predictive value of neutrophil/lymphocyte ratio in the diagnosis of Hodgkin and non-Hodgkin limphoma in patients with asymptomatic, isolated cervical limphadenopathy and underwent excisional biopsy.MethodsA total of 90 patients between the years 2016 ? 2019 admitted to our clinics due to asymptomatic isolated cervical lymphadenopathy, present in at least 4 weeks with lympho nodes in pathological dimensions persisting in the cervical region, were included to our study. An excisional lympho node biopsy was performed in all 90 patients.ResultsOf the 90 patients who underwent excisional biopsy; 34 were diagnosed as reactive lymphadenopathy 30 were non-Hodgkin linphoma, and 26 were Hodgkin linphoma. A total of 56 (62.2%) patients were diagnosed as lymphoma, either Hodgkin or non-Hodgkin, while 34 patients (38.8%) were diagnosed as reactive lymphadenopathy. The median age, total whiteblood count, neutrophil count of the lymphoma groups were significantly higher than reactive lymphadenopathy group, whereas the lymphocyte count was significantly lower in the lymphoma patients. The median neutrophil/ lymphocyte ratio was 1.7 in the reactive lymphadenopathy group, 3.5 in the non-Hodgkin limphoma group, and 3.0 in the Hodgkin limphoma group (p <  0.001).ConclusionAccording to the results of our study, neutrophil/lymphocyte ratio was significantly higher in patients who were admitted with isolated asymptomatic lymphadenopathy and were diagnosed with lymphoma, and who were diagnosed with early-stage Hodgkin and non- Hodgkin lymphoma compared to those who were found to have reactive lymphadenopathy. Neutrophil/lymphocyte ratio, which is a low-cost, fast and easy-to-access test, has a predictive value in the diagnosis of lymphoma in patients with asymptomatic lymphadenopathy.     

Everolimus-Induced Pneumonitis in Patients with Neuroendocrine Neoplasms: Real-World Study on Risk Factors and Outcomes

BackgroundEverolimus-induced pneumonitis (EiP) has been poorly studied in patients with neuroendocrine neoplasms (NEN) outside clinical trials. The aim of this study was to evaluate the incidence, risk factors, and outcomes of EiP in patients with NENs using real-world data.MethodsRetrospective study of everolimus-treated patients with advanced NENs. Imaging reports were systematically reviewed for the presence of pneumonitis. Clinical features and treatment profiles for EiP were summarized. Overall survival (OS) was calculated from the initiation of everolimus to the date of death or last follow-up using the Kaplan-Meier method.ResultsA total of 122 patients were included. Median age at start of everolimus was 62 (19-86) years, 62% (76/122) were male, and half were from pancreatic origin (62, 51%). Twenty-eight patients (23%) developed EiP: 82% grade (G)1 or G2, 14% G3 and 4% G4. The median time to EiP was 3.6 (0.8-51) months. Primary tumor site, concurrent lung disease, smoking history, and prior therapies were not associated with the onset of EiP. Patients who developed EiP had longer time on everolimus treatment (median 18 months vs 6 months; P = .0018) and OS (77 months vs 52 months; P = .093). Everolimus-induced pneumonitis was a predictor of improved OS by multivariable analysis (HR 0.39, 95% CI 0.19-0.82; P = .013).ConclusionEverolimus-induced pneumonitis in the real-world clinical setting is present in one quarter of patients with NENs receiving everolimus and often occurs early. While risk factors for EiP were not identified, patients with EiP had improved survival.     

Using diffusion tensor imaging and mixed-effects models to investigate primary and secondary white matter degeneration in Alzheimer's disease and mild cognitive impairment

White matter (WM) degeneration in Alzheimer's disease (AD) and mild cognitive impairment (MCI) may be a key indicator of early damage in AD. Here, we analyzed WM diffusion tensor data using Tract-Based Spatial Statistics in conjunction with mixed-effects models. Four indices of diffusion were assessed in 61 healthy control, 19 non-amnestic MCIs, 14 amnestic MCIs, and 9 AD patients. The aim of the study was to use advanced mixed-effects models to investigate the retrogenesis hypothesis of AD, which suggests that tracts that are late to myelinate in ontogenetic development are the earliest to be affected in AD. Our results show that a number of late-myelinating pathways, including the parahippocampal region and the inferior longitudinal fasciculus, were predominantly affected by changes in WM volume. Conversely, early-myelinating pathways were found to be affected by a combination of both WM and gray matter (GM) atrophy. A model of the entire WM structure of the brain returned GM models for two indices of diffusion, suggesting that more complex regional landscapes of diffusion lie hidden beneath a global analysis of the entire brain. Our results warn against an explanation of white matter damage that points simply to one of two mechanisms: secondary degeneration or direct damage of myelin. We suggest that tracts may be affected by both mechanisms, with the balance depending on whether tracts are early or late-myelinating. A greater understanding of the pattern of WM changes in AD may prove useful for the early detection of AD.