Prediction of 8-year cardiovascular outcomes in patients with systemic arterial hypertension: Value of stress Tc-99m-tetrofosmin myocardial perfusion imaging in a high-risk cohort

Systemic arterial hypertension is a strong and prevalent cardiovascular risk factor. Currently, information on the very long-term prognostic value of single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in patients with systemic arterial hypertension is lacking. The aim of this study was to assess the value of stress Tc-99m-tetrofosmin MPI for the prediction of very long-term outcome in these patients. The study population consisted of 608 patients with systemic arterial hypertension who underwent exercise or dobutamine stress Tc-99m-tetrofosmin MPI for the assessment of known or suspected coronary artery disease. Follow-up was successful in 600 (99%) patients. The endpoints were all-cause mortality, cardiac death, nonfatal infarction, and coronary revascularization. Kaplan-Meier survival cures were constructed and univariate and multivariate analyses were performed to identify predictors of v The mean age of the patients was 59 +/- A 10 years, and 65% of them were male. MPI findings were normal in 301 patients (50%). Myocardial perfusion abnormalities were fixed in 162 (27%) and reversible in 137 (23%) patients. During a median 8.1-year follow-up, 241 (40%) patients died (121 cardiac deaths), 52 (9%) had a nonfatal myocardial infarction, and 128 (21%) underwent coronary revascularization. Survival curves in patients with a low vs a high summed difference score diverged up to 5 years Stress Tc-99m-tetrofosmin MPI provides incremental prognostic information for the prediction of cardiovascular outcome in patients with systemic arterial hypertension. Patients with normal stress MPI have a significantly better prognosis as compared with those with an abnormal study, up to 5 years after the test is performed

Effect of Preventive Supplementation with Zinc and other Micronutrients on Non-Malarial Morbidity in Tanzanian Pre-School Children: A Randomized Trial.

The efficacy of preventive zinc supplementation against diarrhea and respiratory illness may depend on simultaneous supplementation with other micronutrients. We aimed to assess the effect of supplementation with zinc and multiple micronutrients on diarrhea and other causes of non-malarial morbidity. Rural Tanzanian children (n = 612) aged 6-60 months and with height-for-age z-score < -1.5 SD were randomized to daily supplementation with zinc (10 mg) alone, multi-nutrients without zinc, multi-nutrients with zinc, or placebo. Children were followed for an average of 45 weeks. During follow-up, we recorded morbidity episodes. We found no evidence that concurrent supplementation with multi-nutrients influenced the magnitude of the effect of zinc on rates of diarrhea, respiratory illness, fever without localizing signs, or other illness (guardian-reported illness with symptoms involving skin, ears, eyes and abscesses, but excluding trauma or burns). Zinc supplementation reduced the hazard rate of diarrhea by 24% (4%-40%). By contrast, multi-nutrients seemed to increase this rate (HR; 95% CI: 1.19; 0.94-1.50), particularly in children with asymptomatic Giardia infection at baseline (2.03; 1.24-3.32). Zinc also protected against episodes of fever without localizing signs (0.75; 0.57-0.96), but we found no evidence that it reduced the overall number of clinic visits. We found no evidence that the efficacy of zinc supplements in reducing diarrhea rates is enhanced by concurrent supplementation with other micronutrients. By reducing rates of fever without localizing signs, supplementation with zinc may reduce inappropriate drug use with anti-malarial medications and antibiotics. ClinicalTrials.gov NCT00623857

Proteins associated with pancreatic cancer survival in patients with resectable pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a dismal prognosis. However, while most patients die within the first year of diagnosis, very rarely, a few patients can survive for &gt;10 years. Better understanding the molecular characteristics of the pancreatic adenocarcinomas from these very-long-term survivors (VLTS) may provide clues for personalized medicine and improve current pancreatic cancer treatment. To extend our previous investigation, we examined the proteomes of individual pancreas tumor tissues from a group of VLTS patients (survival ≥10 years) and short-term survival patients (STS, survival &lt;14 months). With a given analytical sensitivity, the protein profile of each pancreatic tumor tissue was compared to reveal the proteome alterations that may be associated with pancreatic cancer survival. Pathway analysis of the differential proteins identified suggested that MYC, IGF1R and p53 were the top three upstream regulators for the STS-associated proteins, and VEGFA, APOE and TGFβ-1 were the top three upstream regulators for the VLTS-associated proteins. Immunohistochemistry analysis using an independent cohort of 145 PDAC confirmed that the higher abundance of ribosomal protein S8 (RPS8) and prolargin (PRELP) were correlated with STS and VLTS, respectively. Multivariate Cox analysis indicated that 'High-RPS8 and Low-PRELP' was significantly associated with shorter survival time (HR=2.69, 95% CI 1.46-4.92, P=0.001). In addition, galectin-1, a previously identified protein with its abundance aversely associated with pancreatic cancer survival, was further evaluated for its significance in cancer-associated fibroblasts. Knockdown of galectin-1 in pancreatic cancer-associated fibroblasts dramatically reduced cell migration and invasion. The results from our study suggested that PRELP, LGALS1 and RPS8 might be significant prognostic factors, and RPS8 and LGALS1 could be potential therapeutic targets to improve pancreatic cancer survival if further validated

Patterns of Recurrence and Survival After Pelvic Treatment for Locally Advanced Penile Cancer

BACKGROUND: Penile cancer (PeCa) is rare, and the survival of patients with advanced disease remains poor. A better understanding of where treatment fails could aid the development of new treatment strategies. OBJECTIVE: To describe the disease course after pelvic lymph node (LN) treatment for PeCa. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analysed 228 patients who underwent pelvic LN treatment with curative intent from 1969 to 2016. The main treatment modalities were neoadjuvant chemotherapy, chemoradiation, and pelvic LN dissection. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: In the case of multiple recurrence locations, the most distant location was taken and recorded as follows: local (penis), regional (inguinal and pelvic LN), and distant (any other location). A competing risk analysis was used to calculate the time to recurrence per location, and a Kaplan-Meier analysis was used for overall survival (OS). RESULTS AND LIMITATIONS: The median follow-up of the surviving patients was 79 mo. The reason for pelvic treatment was pelvic involvement on imaging (29%), two or more tumour-positive inguinal LNs (61%), or inguinal extranodal extension (52%). More than half of the patients (61%) developed a recurrence. The median recurrence-free survival was 11 mo. The distribution was local in 9%, regional in 27%, and distant in 64% of patients. The infield control rate of nonsystemically treated patients was 61% (113/184). From the start of pelvic treatment, the median OS was 17 mo (95% confidence interval 12–22). After regional or distant recurrence, all but one patient died of PeCa with median OS after a recurrence of 4.4 (regional) and 3.1 (distant) mo. This study is limited by its retrospective nature. CONCLUSIONS: The prognosis of PeCa patients treated on their pelvis who recur despite locoregional treatment is poor. The tendency for systemic spread emphasises the need for more effective systemic treatment strategies. PATIENT SUMMARY: In this report, we looked at the outcomes of penile cancer patients in an expert centre undergoing various treatments on their pelvis. We found that survival is poor after recurrence despite locoregional treatment. Therefore, better systemic treatments are necessary

Clinicopathologic predictors of finding additional inguinal lymph node metastases in penile cancer patients following positive dynamic sentinel node biopsy:a European multicentre evaluation

OBJECTIVES: Following tumour positive sentinel lymph node biopsy (+DSNB), completion inguinal lymph node dissection (ILND) is negative in 84-89% of basins. Thus, ILND after +DSNB may be considered overtreatment resulting in substantial morbidity. This study aimed to develop a predictive model for additional inguinal lymph node metastases (LNM) at ILND following +DSNB using DSNB characteristics to identify a patient group in which ILND might be omitted. PATIENTS AND METHODS: A retrospective study of 407 inguinal basins with a +DSNB of penile cancer patients who underwent subsequent ILND from seven European centres. From the histopathology reports, the number of positive and negative lymph nodes, extranodal extension and size of the metastasis were recorded. Using bootstrapped logistic regression, variables were selected for the clinical prediction model based on the optimisation of Akaike's information criterion. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was calculated for the resulting model. Decision curve analysis (DCA) was used to evaluate the clinical utility of the model. RESULTS: 64 (16%) of +DSNB harboured additional LNM at ILND. The number of positive nodes at +DSNB (odds ratio (OR) 2.19; 95% confidence interval (CI) 1.17-4.00; p=0.01) and the largest metastasis size in mm (OR 1.06; 95%CI 1.03-1.10; p=0.001) were selected for the clinical prediction model. The AUC was 0.67 (95%CI 0.60-0.74). The DCA showed no clinical benefit of using the clinical prediction model. CONCLUSION: A small but clinically important group of basins harbour additional LNM at completion ILND following +DSNB. While DSNB characteristics were associated with additional LNM, they did not improve the selection of basins in which ILND could be omitted. Thus, completion ILND remains necessary in all basins with a +DSNB

Tuberculosis causes highly conserved metabolic changes in human patients, mycobacteria‑infected mice and zebrafish larvae

Solid state NMR/Biophysical Organic ChemistryAnimal science

Protection against Diarrhea Associated with Giardia intestinalis Is Lost with Multi-Nutrient Supplementation: A Study in Tanzanian Children

Giardia intestinalis is a well-known cause of diarrhea in industrialized countries. In children in developing countries, asymptomatic infections are common and their role as cause of diarrhea has been questioned. In a cohort of rural Tanzanian pre-school children, we assessed the association between the presence of Giardia at baseline and subsequent diarrhea risk. The study was conducted in the context of a randomised trial assessing the effect of supplementation with zinc and other micro-nutrients on malaria, and half of the children daily received a multi-nutrient supplement. Surprisingly, we found that the presence of Giardia at baseline was associated with a substantial reduction in diarrhea risk. Multivariate statistical analysis showed that this protection could not be explained by differences in age or walking distance to the dispensary between children with and without Giardia. Because we cannot exclude that children differed in other (unmeasured) characteristics, we cannot draw firm conclusions about the causality of the observed association, but our findings support the view that the parasite is not an important cause of diarrhea in highly endemic settings. Striking was that the Giardia-associated protection was lost when children received multi-nutrients. Our data do not provide information about the mechanisms involved, but suggest that multi-nutrients may influence the compositionor pathogenicity of intestinal biota

Precursor lesions of early onset pancreatic cancer

Early onset pancreatic cancer (EOPC) constitutes less than 5% of all newly diagnosed cases of pancreatic cancer (PC). Although histopathological characteristics of EOPC have been described, no detailed reports on precursor lesions of EOPC are available. In the present study, we aimed to describe histopathological picture of extratumoral parenchyma in 23 cases of EOPCs (definition based on the threshold value of 45 years of age) with particular emphasis on two types of precursor lesions of PC: pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasms (IPMNs). The types, grades, and densities of precursor lesions of PC were compared in patients with EOPCs, in young patients with neuroendocrine neoplasms (NENs), and in older (at the age of 46 or more) patients with PC. PanINs were found in 95.6% of cases of EOPCs. PanINs-3 were found in 39.1% of EOPC cases. Densities of all PanIN grades in EOPC cases were larger than in young patients with NENs. Density of PanINs-1A in EOPC cases was larger than in older patients with PC, but densities of PanINs of other grades were comparable. IPMN was found only in a single patient with EOPC but in 20% of older patients with PC. PanINs are the most prevalent precursor lesions of EOPC. IPMNs are rarely precursor lesions of EOPC. Relatively high density of low-grade PanINs-1 in extratumoral parenchyma of patients with EOPC may result from unknown multifocal genetic alterations in pancreatic tissue in patients with EOPCs