Complete Metabolic Response with Recanalization of Portal Vein Tumor Thrombosis after Sunitinib in a Patient with Advanced Hepatocellular Carcinoma

The prognosis of patients with advanced hepatocellular carcinoma (HCC) is very poor. The outcome of these patients is particularly bleak when the disease is complicated by portal vein tumor thrombosis (PVTT), since the increased portal pressure often causes serious gastrointestinal bleedings. Before the introduction of sorafenib (SOR), a tyrosine kinase inhibitor, no effective treatment was available for patients with advanced disease. SOR is now considered the standard treatment even for patients with tumor thrombosis, although the well-known interference between tyrosine kinase inhibitors and the coagulation pathway calls for caution against their use in this setting. Here, we report the case of a 74-year-old male patient with advanced HCC and PVTT treated with sunitinib (SUN), another multikinase inhibitor. During the third cycle, our patient experienced a life-threatening hematemesis with hemorrhagic shock that required intensive care treatment and SUN discontinuation. However, he completely recovered, and the PET/CT scan performed 1 year after the adverse effect demonstrated no evidence of the tumor together with portal vein recanalization. The short course of SUN causing both tumor response and gastrointestinal bleeding warrants further studies on the effectiveness of SUN in this setting as well as on the duration of treatment with multikinase inhibitors in patients with tumor thrombosis.     

In vitro activities of the lipopeptides palmitoyl (Pal)-Lys-Lys-NH(2) and Pal-Lys-Lys alone and in combination with antimicrobial agents against multiresistant gram-positive cocci

The in vitro activities of the lipopeptides palmitoyl (Pal)-Lys-Lys-NH(2) and Pal-Lys-Lys against gram-positive cocci were investigated. Enterococci and streptococci demonstrated higher susceptibilities than staphylococci and Rhodococcus equi. A positive interaction was shown when the lipopeptides were combined with beta-lactams and vancomycin. These results suggest that lipopeptides are promising candidates for antimicrobial therapy for infections caused by gram-positive organisms.     

Congenital pathology of the pituitary gland and parasellar region

The adenohypophysis and neurohypophysis originate from the combination of 2 events occurring during the fourth week of life, the development of Rathke pouch and of a neuroectodermal evagination of tissue from the floor of the diencephalon. Congenital pathology of the pituitary gland and parasellar regions derives from abnormalities of these coordinated events. In this article, we review the pathogenesis, clinical presentation, and imaging features of common and rare congenital disorders of the region of the sella turcica.     

Immunolocalization of G Protein‐Coupled Estrogen Receptor in the Pig Epididymis

The presence of estrogen in the genital ducts of different mammalian species has been extensively studied and the estrogen influence on the functional activity of the male genital tract has been hypothesized. Conversely, very few data have been reported on pig excurrent ducts: the localization of classical estrogen receptors (ERα and ERβ) is scarcely known, while the expression of the G protein‐coupled receptor (GPER1), a membrane estrogen receptor, is still unknown in pig. The aim of the present study was to evaluate GPER1 expression in the different regions of the mature pig epididymis, using immunohistochemistry, western blot and RT‐PCR analyses. The results showed that GPER1 is mainly expressed in the epithelial cells of the corpus epididymis compared to the caput and the cauda, while muscle cells are moderately immunostained and stromal cells are unstained. The presence of GPER1 was confirmed by Western blot and RT‐PCR analyses. In our study, we have demonstrated for the first time the GPER1 expression in male porcine epididymis, revealing a new mediator of estrogen signaling at this site. In conclusion, these new data suggest that estrogen action via GPER1 may contribute to sperm maturation in the corpus and sperm protection/storage in the cauda. Interestingly, the presence of GPER1 in the muscle layer may be indicative of a possible GPER1 involvement in the estrogen regulation of duct contractility. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.     

Correlation of lipoprotein(a) levels and myocardial stress thallium scintigraphy pattern in different entities of CHD severity

BACKGROUND: Higher levels of lipoprotein(a) confer an increased risk for coronary heart disease (CHD). Apo-E genotype (APO-E) also plays a role, the APO-E epsilon 4 allele being associated with CHD. Furthermore, higher Lp(a) concentrations are correlated with APO-E epsilon 4 allele presence. The study was performed to investigate the relationship of Lp(a) and APO-E with the functional status of coronary arteries as evaluated by myocardial scintigraphy. PATIENTS AND METHODS: We studied 70 patients (27 F and 43 M; mean age: 55 +/- 6 yrs.) consecutively referred for CHD, and 50 normal sex and age-matched controls. Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apo-AI, apo-B, Lp(a) levels (ELISA), Lp(a) isoforms (Immuno Blotting) and APO-E (PCR) were measured in all subjects. Only CHD patients underwent a myocardial tomographic stress thallium scintigraphy (201Tl-SPECT); the SPECT pattern was classified as follows: no perfusion defects (unstable angina group = 1), reversible defects at stress images (ischemia group = 2), fixed defects (infarction group = 3). RESULTS: Lp(a) medians were significantly higher than controls in group 1 (p < 0.05), 2 (p < 0.001) and 3 (p = 0.00). Low molecular weight isoforms (B, S1, S2) were significantly more frequent in all CHD-patients vs. controls (p < 0.05), whereas APO-E genotypes did not differ among controls and patients. Multiple regression analysis showed family history (p < 0.001) to be the only independent predictive variable of CHD severity correlated to the scintigraphic pattern. CONCLUSION: Among the considered biological parameters in our patients only Lp(a) plasma levels are related to the entity of ischemic cardiac wall damage as evaluated by 201Tl-SPECT.     

Comparing large-scale computational approaches to epidemic modeling: Agent-based versus structured metapopulation models

Background  

In recent years large-scale computational models for the realistic simulation of epidemic outbreaks have been used with increased frequency. Methodologies adapt to the scale of interest and range from very detailed agent-based models to spatially-structured metapopulation models. One major issue thus concerns to what extent the geotemporal spreading pattern found by different modeling approaches may differ and depend on the different approximations and assumptions used.     

Renal artery stenting in patients with chronic ischemic heart disease

Objectives : To investigate the role of renal stenting in selected patients with chronic ischemic heart disease and renal artery stenosis. Methods : Consecutive patients, with chronic ischemic heart disease and severe hypertension and/or impaired renal function undergoing renal stenting, were prospectively enrolled. Mid‐term (at least 2 years) follow‐up was performed to assess both changes in renal function [serum creatinine and estimated glomerular filtrate rate (eGFR)] and blood pressure (BP) control (number of required drugs) and to record the incidence of clinical major adverse events. Moreover, in the first consecutive 24 patients, out‐of‐range pressure values at 24‐hr BP monitoring and GFR at renal scintigraphy were measured at baseline and 1 month after stenting. Results : Seventy patients treated by stenting on 86 renal arteries entered the study. Procedural success rate was 99% and no major complication occurred. At 2‐year follow‐up, both mean serum creatinine (?0.1 ± 0.7 mg/dl at follow‐up compared to baseline, P = 0.6) and eGFR (+3.7 ± 23.5 ml/min/1.73m² at follow‐up compared to baseline, P = 0.2) did not significantly change while the number of drugs required to control BP significantly decreased (2.7 ± 0.8 to 2.2 ± 0.7, P < 0.0001). In the subset of 24 patients evaluated at 1 month, GFR significantly increased (62 ± 20 ml/min to 67 ± 21 ml/min; P = 0.008) and the rate of the out‐of‐range systolic pressure values at 24‐hr monitoring significantly decreased (51–33%, P = 0.005). Elevated baseline creatinine values and the presence of global renal ischemia were identified as predictors of poor outcome at the multivariate analysis. Conclusions : In selected patients with chronic ischemic heart disease and hypertension and/or renal insufficiency, renal stenting may be performed with very low periprocedural complications and results in unchanged renal function and improved BP control. © 2010 Wiley‐Liss, Inc.     

Prevalence, incidence and types of mild anemia in the elderly: the ��Health and Anemia�� population-based study

Background

Hemoglobin concentrations slightly below the lower limit of normal are a common laboratory finding in the elderly, but scant evidence is available on the actual occurrence of mild anemia despite its potential effect on health. The objectives of this study were to estimate the prevalence and incidence of mild grade anemia and to assess the frequency of anemia types in the elderly.

Design and Methods

This was a prospective, population-based study in all residents 65 years or older in Biella, Italy.

Results

Blood test results were available for analysis from 8,744 elderly. Hemoglobin concentration decreased and mild anemia increased steadily with increasing age. Mild anemia (defined as a hemoglobin concentration of 10.0–11.9 g/dL in women and 10.0–12.9 g/dL in men) affected 11.8% of the elderly included in the analysis, while the estimated prevalence in the entire population was 11.1%. Before hemoglobin determination, most mildly anemic individuals perceived themselves as non-anemic. Chronic disease anemia, thalassemia trait, and renal insufficiency were the most frequent types of mild anemia. The underlying cause of mild anemia remained unexplained in 26.4% of the cases, almost one third of which might be accounted for by myelodysplastic syndromes. In a random sample of non-anemic elderly at baseline (n=529), after about 2 years, the annual incidence rate of mild anemia was 22.5 per 1000 person-years and increased with increasing age.

Conclusions

The prevalence and incidence of mild anemia increase with age and mild anemia affects more than one out of ten elderly individuals. Unexplained anemia is common and may be due to myelodysplastic syndromes in some cases.     

The pharmacological chaperone 1-deoxynojirimycin increases the activity and lysosomal trafficking of multiple mutant forms of acid alpha-glucosidase

Pompe disease is a lysosomal storage disorder (LSD) caused by mutations in the gene that encodes acid α-glucosidase (GAA). Recently, small molecule pharmacological chaperones have been shown to increase protein stability and cellular levels for mutant lysosomal enzymes and have emerged as a new therapeutic strategy for the treatment of LSDs. In this study, we characterized the pharmacological chaperone 1-deoxynojirimycin (DNJ) on 76 different mutant forms of GAA identified in Pompe disease. DNJ significantly increased enzyme activity and protein levels for 16 different GAA mutants in patient-derived fibroblasts and in transiently transfected COS-7 cells. Additionally, DNJ increased the processing of these GAA mutants to their mature lysosomal forms, suggesting facilitated trafficking through the secretory pathway. Immunofluorescence microscopy studies showed increased colocalization of GAA with the lysosomal marker LAMP2 after incubation with DNJ, confirming increased lysosomal trafficking. Lastly, a GAA structural model was constructed based on the related eukaryotic glucosidase maltase-glucoamylase. The mutated residues identified in responsive forms of GAA are located throughout most of the structural domains, with half of these residues located in two short regions within the catalytic domain. Taken together, these data support further evaluation of DNJ as a potential treatment for Pompe disease in patients that express responsive forms of GAA. Hum Mutat 30:1–10, 2009. © 2009 Wiley-Liss, Inc.