Associations between model-predicted rivaroxaban exposure and patient characteristics and efficacy and safety outcomes in the treatment of venous thromboembolism

Journal of Thrombosis and Thrombolysis - Traditional statistical models allow population based inferences and comparisons. Machine learning (ML) explores datasets to develop algorithms that do not...     

Ophthalmologic safety of long-term hydroxychloroquine treatment

Ocular toxicity of long-term hydroxychloroquine treatment was assessed by regular ophthalmologic examinations in 99 patients. No patient developed significant loss of vision or visual field constriction to a white test object. Three patients had evidence of toxicity, but the medication had to be permanently discontinued in only one who subsequently had regression of all abnormalities except visual field constriction to a red test object. Neither duration of treatment nor the diagnosis of systemic lupus erythematosus predisposed patients to toxicity.     

Prognostic impact of blast cell counts in dysplastic bone marrow disorders (MDS and CMML I) with concomitant fibrosis

In a retrospective study, 43 patients with dysplastic neoplasms of the bone marrow (myelodysplastic syndromes and myelodysplastic/myeloproliferative-overlap neoplasms) associated with marked (grades 2–3) fibrosis were examined. Histopathologic and morphologic findings as well as cytogenetic and molecular results were correlated with clinical endpoints. Multilineage dysplasia (34 of 43 patients, 79 %) and hypercellular bone marrow (64 %) were found in most patients. In ten of 35 patients, poor risk karyotypes according to the International Prognostic Scoring System (IPSS) were recorded. The JAK2 V617F mutation was detected in four of 30 patients (13 %), and the KIT D816V mutation was found in two of 30 patients (6 %). Patients were mainly treated with palliative drugs and best supportive care. After an observation time of 1–41 (median 21) months, ten of 43 patients (23 %) had developed a secondary acute leukemia. The median survival of all 43 patients was 21.4 months (range 1.8–88.2 months). Of all prognostic parameters examined, the blast cell count at diagnosis was found to be a most reliable and most predictive marker concerning survival and leukemia progression. This confirms previous studies in dysplastic bone marrow neoplasms without fibrosis.     

Herz und Niere

There is strong interaction between heart and kidneys in human beings. Both organs work together in many regulation mechanisms. Thus, heart failure lead in many cases to renal failure due to hemodynamic or hormonal feed-back mechanisms. Vice versa, chronic kidney disease turned out as a major and independent cardiovascular risk factor. Patients who suffer from both heart disease and chronic kidney disease are threatened from a very high morbidity and mortality. Moreover, the number of affected patients has doubled every 8–10 years – a dramatic trend which is ongoing. In many patients suffering from heart and chronic kidney disease, an under-use of cardiologic diagnostics as well as therapies has to be observed due to fears about adverse effects, which further enhances their worse prognosis.     

Visual acuity measurements by swept spatial frequency visual-evoked-cortical potentials (VECPs): clinical application in children with various visual disorders

Previous studies have indicated that visual acuities of normal infants can be estimated with good accuracy using swept spatial frequency visual-evoked-potentials (VECPs). In this report we describe acuity measurements obtained with this technique from 304 examinations performed on 135 children having various visual disorders. When possible, two or more different stimulation frequencies (8, 12, 15 or 24 contrast reversals/sec) were used in each patient, and three to eight sweep VECPs were obtained from each patient under each simulation and recording condition. High correlation coefficients (0.94 - 0.96) between the acuity estimated on each patient from either the single sweep giving the best visual acuity (BSS) or from vector averages (VeA) of the EEG data obtained from several sweeps confirmed previous findings in normal infants. We also found high correlation coefficients among BSS recorded at different temporal frequencies (0.79-0.97) and among comparisons of BSS or VeA acuity to optotype visual acuity (0.6-0.89). Children with clinically undetectable optokinetic responses showed lower visual acuity estimated by BSS than those who demonstrated optokinetic nystagmus. We conclude that the sweep VECP is a valid method, giving estimates of acuity which correlate well with optotype acuity and correspond well to other clinical findings, and that it can be useful in the clinical management of nonverbal patients.     

Peptidergic innervation of the human and guinea pig uterus

The peptidergic innervation of the human and guinea pig uterus was studied using immunohistochemical methods. Antibodies against several peptides were applied for the PAP-technique to stain peptidergic nerves specifically. These are located in the adventitia of large uterine vessels in the myometrium and smaller vessels of the myometrium and endometrium. A differential distribution of the individual peptides was observed for VIP-IR (vasoactive intestinal polypeptide immunoreactivity), NPY-IR (neuropeptide Y), SP-IR (substance P), SOM-IR (somatostatin) and NT-IR (neurotensin) nerve fibers. Specific functional implications for these neuropeptides can be derived from their histochemical location.     

Dicaffeoyltartaric acid analogues inhibit human immunodeficiency virus type 1 (HIV-1) integrase and HIV-1 replication at nontoxic concentrations

The human immunodeficiency virus type 1 (HIV-1) is a major health problem worldwide. In this study, 17 analogues of L-chicoric acid, a potent inhibitor of HIV integrase, were studied. Of these analogues, five submicromolar inhibitors of integrase were discovered and 13 compounds with activity against integrase at less than 10 microM were identified. Six demonstrated greater than 10-fold selectivity for HIV replication over cellular toxicity. Ten analogues inhibited HIV replication at nontoxic concentrations. Alteration of the linkages between the two bis-catechol rings, including the use of amides, mixed amide esters, cholate, and alkyl bridges, was explored. Amides were as active as esters but were more toxic in tissue culture. Alkyl and cholate bridges were significantly less potent against HIV-1 integrase in vitro and were inactive against HIV-1 replication. Two amino acid derivates and one digalloylderivative of L-chicoric acid (L-CA) showed improved selectivity over L-CA against integration in cell culture. These data suggest that in addition to the bis-catechols and free carboxylic acid groups reported previously, polar linkages are important constituents for optimal activity against HIV-1 integrase and that new derivatives can be developed with increased specificity for integration over HIV entry in vivo.     

Long-term outcome after percutaneous transluminal coronary angioplasty in patients with chronic renal failure with and without diabetic nephropathy

OBJECTIVE: Percutaneous transluminal coronary angioplasty (PTCA) in patients on maintenance hemodialysis leads to high rates of restenosis and postinterventional complications. The additional influence of diabetes mellitus on the results of PTCA in patients with diabetic nephropathy and reduced but sufficient renal function has not been investigated before. METHODS: In a retrospective case-control study, 51 patients with reduced renal function were compared to 71 matched controls. Patients with elevated creatinine values were divided in two subgroups: diabetic nephropathy (diabetes, n = 15) and stable renal insufficiency (renal failure, n = 36). RESULTS: The control group had normal renal function (creatinine: 1.0 +/- 0.01) and a mean survival time of 3.6 +/- 0.8 years. Patients with renal failure showed a mean survival time of 2.7 +/- 0.3 years (p < 0.001), creatinine values of 2.0 +/- 0.2 and elevated fibrinogen values of 401 +/- 28 (p < 0.01). Patients with diabetes (creatinine: 2.2 +/- 0.2) had a significantly higher mortality rate with a reduced mean survival time of 1.25 +/- 0.3 years (p < 0.001), postinterventional acute renal failure (n = 2, p < 0.01) and Re-PTCA (n = 2, p < 0.05). DISCUSSION: Patients with reduced but stable renal function showed a higher mortality than comparable patients from the control group. The group of patients with diabetic nephropathy has a poor prognosis after PTCA even though renal function was only moderately reduced.