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Background Serum procalcitonin and high-sensitivity C-reactive protein (hs-CRP) elevations have been associated with pneumonia in adults. Our aim was to establish their diagnostic usefulness in a cohort of hospitalized multimorbid patients ≥65 years old admitted to hospital with acute respiratory symptoms. Methods With a retrospective cohort study design, all multimorbid patients ≥65 years-old with acute respiratory symptoms admitted to an internal medicine hospital ward in Italy from January to August 2013 were evaluated. Pneumonia diagnosis, comorbidities expressed through Cumulative Illness Rating Scale (CIRS), setting of living, length of stay, serum hs-CRP and procalcitonin at admission were collected for each patient. Data were analyzed with Mann-Whitney’s U test and multivariate Cox logistic regression analysis. A Receiver Operating Characteristic (ROC) curve was used to verify each biomarker’s association with pneumonia diagnosis. Results Four hundred fifty five patients (227 M) were included in the study, of whom 239 with pneumonia (138 M, mean age 80 ± 13) and 216 without pneumonia (89 M, mean age 80 ± 14). After adjustment for age and sex, median levels of hs-CRP were significantly higher in patients with pneumonia (116 mg/L, IQR 46.5–179.0, vs 22.5 mg/dl, IQR 6.9–84.4, p 61 mg/L were independently associated with a 3.59-fold increased risk of pneumonia (OR 3.59, 95 % CI 2.35–5.48, p < 0.0001). Conclusion In elderly multimorbid patients who require hospital admission for respiratory symptoms, serum hs-CRP testing seems to be more useful than procalcitonin for guiding the diagnostic process when clinical suspicion of pneumonia is present. Procalcitonin testing might hence be not recommended in this setting.

To evaluate the safety of laparoscopic radical nephrectomy (LRN) for renal cell carcinoma (RCC)7 cm, addressing the issue of modality and risk factors for complications and open conversion, and to assess the oncologic outcome.The data of 222 patients undergoing LRN for RCC7 cm prospectively enrolled from 2002 to 2010 at 5 urologic centers were reviewed. Transperitoneal LRN was performed by 5 experienced laparoscopic surgeons. The Clavien-Dindo classification was used to assess complications. Multivariable analysis of factors predictive of conversions was performed. Oncologic outcomes for survival were estimated using the Kaplan-Meier method.Median tumor size was 8.5 cm, operative time was 180 minutes, and blood loss was 280 mL. Forty-two patients (19%) received a blood transfusion. Six (2.7%) patients had grade III-IV complications: 2 with postoperative bleeding requiring abdominal re-exploration and 1 each with adrenal injury, splenic injury, wound diastasis, and respiratory insufficiency. Twelve patients (5.4%) were converted to open surgery. The diameter was 11.9 in converted groups and 8.5 cm in nonconverted groups (P = .001). Multivariable analysis revealed that pathologic stage was the only independent predictor of conversion (P = .002). The 5-year overall (OS), cancer-specific (CSS), and progression-free (PFS) survival was 74%, 78%, and 66%, respectively. The 5-year stage-adjusted CSS was 89% in pT2 and 40% in pT3 patients (P .0001). Limitations of this study were its retrospective nature and the relatively short follow-up period for oncologic outcome.LRN for large RCC is a safe operation. Stage pT3 is a risk factor for open conversion and is associated to significantly lower cancer-specific survival compared with pT2 stage.

Cardioplegic arrest is a model of ischemia/reperfusion injury and results in the death of irreplaceable cardiac myocytes by a programmed cell death or apoptosis. Signal transducers and activators of transcription (STAT) signaling pathways play an important role in the modulation of apoptosis after ischemia and reperfusion. Angiotensin II type 1 (AT1) receptor antagonist added to cardioplegia could represent an additional modality for enhancing myocardial protection during cardioplegic arrest. To test that hypothesis, we studied the effect of AT1 receptor antagonism and cardioplegia temperature perfusion on STATs modulation during cardioplegic arrest in neonatal rat hearts. Isolated, nonworking hearts (n = 4 per group) from neonatal rats were perfused aerobically in the Langendorff mode according to the following scheme: Dulbecco's Modified Eagle's Medium solution (Group 1); cold (4°C) modified St. Thomas' Hospital no. 2 (MSTH2) cardioplegic solution (Group 2); cold (4°C) MSTH2 cardioplegic solution plus AT1 antagonist (Valsartan) (Group 3); and warm (34°C) MSTH2 cardioplegic solution (Group 4). Thus, myocytes were isolated by enzymatic digestion, and STAT1, STAT2, STAT3, and STAT5 were investigated in Western blot studies. Times to arrest after cardioplegia were 6-10 s for all groups with the exception of Group 1 (spontaneous arrest after 12-16 s). Total cardioplegia delivery volume was about 300 mL in 15 min. Perfusion with cold MSTH2 supplemented with AT1 receptor antagonist (Group 3) induced a significant reduction in STAT1, STAT2, and STAT5 tyrosine phosphorylation versus other groups (P 0.05). The decreased activation of STAT1, STAT2, and STAT5 observed in Group 3 was accompanied by reduction of interleukin-1β (P 0.05). On the other hand, STAT3 activation was significantly reduced in Groups 1 and 4 (P 0.05). Only perfusion with AT1 receptor antagonist supplemented with cold MSTH2 significantly decreases the inflammatory response of the neonatal rat cardiomyocytes without affecting antiapoptotic influence provided by activation of STAT3. Therefore, AT1 receptor antagonist could play a pivotal role in cytoprotective effect and cardiac recovery in neonates and infants.

Primary lymphedema is a rare inherited condition characterized by swelling of body tissues caused by accumulation of fluid, especially in the lower limbs. In many patients, primary lymphedema has been associated with variations in a number of genes involved in the development and maintenance of the lymphatic system. In this study, we performed a genetic screening in patients affected by primary lymphedema using a next generation sequencing (NGS) approach. With this technology, based on a custom-made oligonucleotide probe library, we were able to analyze simultaneously in each patient all the coding exons of 10 genes (FLT4, FOXC2, CCBE1, GJC2, MET, HGF, GATA2, SOX18, VEGFC, KIF11) associated with primary lymphedema. In the study population, composed of 45 familial and 71 sporadic cases, we identified the presence of rare variants with a potential pathogenic effect in 33% of subjects. Overall, we found a total of 36 different rare nucleotidic alterations, 30 of which had not been previously described. Among these, we identified 23 mutations that we considered most likely to be disease causing. Patients with an FLT4 or FOXC2 alteration accounted for the largest percentage of the sample, followed by MET, HGF, KIK11, GJC2 and GATA2. No alterations were identified in SOX18, VEGFC, and CCBE1 genes. In conclusion, we showed that NGS technology can be successfully applied to perform molecular screening of lymphedema-associated genes in large cohort of patients with a reasonable effort in terms of cost, work, and time.

Abstract While classical nodal mantle cell lymphoma (cMCL) is often associated with involvement of multiple extranodal sites, isolated extranodal disease (ED) at the time of diagnosis is a rare event; data on the outcome of these forms are lacking. On behalf of the European MCL Network, we conducted a retrospective analysis on the clinical characteristics and outcomes of MCL presenting with isolated or predominant ED (MALT MCL). We collected data on 127 patients with MALT MCL diagnosed from 1998 to 2015: 78 patients (61%) were male with a median age of 65 years. The involved sites include: upper airways + Waldeyer ring (40; 32%), gastrointestinal tract (32; 25%), ocular adnexa (17; 13%), oral cavity and salivary glands (17; 13%) and others (13; 1%); 7 patients showed multiple extranodal sites. The median follow-up was 80 months (range: 6–182), 5-year progression-free survival (PFS) was 45% (95% CI: 35–54) and 5-year overall survival (OS) was 71% (95% CI: 62–79). In an explorative setting, we compared MALT MCL with a group of 128 cMCL patients: MALT MCL patients showed a significantly longer PFS and OS compared with nodal cMCL; with a median PFS of 4.5 years vs 2.8 years (p = 0.001) and median OS of 9.8 years vs 6.9 years (p = 0.018), respectively. Patients with MALT MCL at diagnosis showed a more favorable prognosis and indolent course than classical nodal type. This clinical variant of MCL should be acknowledged to avoid possible over-treatment. Supplemental Digital Content is available in the text

Aims To investigate the Oenococcus oeni population occurring during spontaneous malolactic fermentation (MLF) of Amarone wine, a peculiar and hostile environment for malolactic bacteria. Methods and Results Pulsed-field gel electrophoresis (PFGE) analysis showed a high level of genetic heterogeneity within the O. oeni population involved in MLF throughout an industrial vinification of Amarone wine. The 13 strains with distinct PFGE profile displayed different capability to hydrolyse esters and glycosides, as well as great variability to growth under stress parameters, such as high ethanol content (15% v/v), low pH (3·0) and temperature (15°C), and presence of SO2. Moreover, polymorphism in the gene sacB involved in exopolysaccharide production was observed among the strains. The strains showed differences to convert l-malic acid into l-lactic acid in wine. Conclusions The occurrence of spontaneous MLF in stressful ecosystems such as Amarone wine is related to the heterogeneity of O. oeni community; biodiversity indexes and strain evolution analyses suggested that its success depends on its initial strain evenness. Significance and Impact of the Study Remarkable intraspecies complexity within the O. oeni natural population could explain the great versatility of this species as key of successful adaptation to harsh winemaking conditions.