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BackgroundThe incidence of acute kidney injury requiring dialysis (AKI-D) is increasing globally and it is usually associated to chronic kidney disease (CKD) and high mortality. Literature is lacking in short- and intermediate-term data on recovery of renal function after acute kidney injury (AKI).ObjectivesThe objective was to evaluate the overall survival and renal recovery after an episode of AKI requiring dialysis out of intensive care units (ICUs).Materials and methodsRetrospective study including patients admitted in two nephrology units along a period of 2 years. Patients admitted to ICUs and renal transplant patients were excluded. Baseline renal function, mortality and glomerular filtration rate (GFR) improvement were evaluated.Results151 consecutive adult patients with AKI requiring renal replacement therapy (RRT) were included. Mean age was 70.5 ± 15.2 years, 60.3% were males. Median baseline creatinine (bCr) and baseline GFR (bGFR) were 1.4 mg/dL and 46 mL/min/1.73 m2, respectively. After 1 year of follow-up, we completed the monitoring of 94 patients: 64.9% had died, 10.6% were alive on dialysis and 24.5% were alive without need for RRT. Patients with bGFR > 60 mL/min/1.73 m2 prior to AKI episode had a slower but sustained GFR improvement through the follow-up in comparison with patients with bGFR < 60 mL/min/1.73 m2 whose recovery was incomplete.ConclusionsPatients with AKI requiring RRT have high short- and intermediate-term mortality and some require maintenance dialysis. Patients with GFR > 60 mL/min/1.73 m2 prior to AKI had a renal recovery closer to the basal renal function than in patients with a previously diminished GFR.

Background: Refractory congestive heart failure (RCHF) is associated with a high mortality rate and is a major contributor to hospital admissions. Peritoneal dialysis (PD) is an option to control volume overload and perhaps improve outcomes in this challenging patient population. The aim of this systematic review is to describe the relative risk-benefit ratio based on data reported regarding the use of PD in RCHF. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. An electronic search of PubMed, Embase, and the Cochrane Library was performed to identify relevant studies published from January 1951 to February 2014. Eligible studies selected were prospective or retrospective adult population studies on PD in the setting of RCHF. The following clinical outcomes were used to assess PD therapy: (1) hospitalization rates; (2) heart function; (3) renal function; (4) fluid overload, and (5) adverse clinical outcomes. Summary: Of 864 citations, we excluded 843 citations and included 21 studies (n = 673 patients). After PD, hospitalization days declined significantly (p = 0.0001), and heart function improved significantly (left ventricular ejection fraction: p = 0.0013; New York Heart Association classification: p = 0.0000). There were no statistically significant differences in glomerular filtration rate after PD treatment in non-chronic kidney disease stage 5D patients (p = 0.1065). Among patients treated with PD, body weight decreased significantly (p = 0.0006). The yearly average peritonitis rate was 14.5%, and the average yearly mortality was 20.3%. Key Messages: This systematic review suggests that PD may be an effective and safe therapeutic tool for patients with RCHF.

Background Immune-inflammatory biomarkers (IIBs) showed a prognostic relevance in patients with metastatic CRC (mCRC). We aimed at evaluating the prognostic power of a new comprehensive biomarker, the Pan-Immune-Inflammation Value (PIV), in patients with mCRC receiving first-line therapy. Methods In the present pooled-analysis, we included patients enrolled in the Valentino and TRIBE trials. PIV was calculated as: (neutrophil count × platelet count × monocyte count)/lymphocyte count. A cut-off was determined using the maximally selected rank statistics method. Generalised boosted regression (GBR), the Kaplan–Meier method and Cox hazards regression models were used for survival analyses. Results A total of 438 patients were included. Overall, 208 patients (47%) had a low-baseline PIV and 230 (53%) had a high-baseline PIV. Patients with high PIV experienced a worse PFS (HR, 1.66; 95% CI, 1.36–2.03, P  < 0.001) and worse OS (HR, 2.01; 95% CI, 1.57–2.57; P  < 0.001) compared to patients with low PIV. PIV outperformed the other IIBs in the GBR model and in the multivariable models. Conclusion PIV is a strong predictor of survival outcomes with better performance than other well-known IIBs in patients with mCRC treated with first-line therapy. PIV should be prospectively validated to better stratify mCRC patients undergoing first-line therapy.

In patients with metastatic colon cancer, fluorouracil, oxaliplatin, and irinotecan plus bevacizumab, as compared with fluorouracil and irinotecan plus bevacizumab, improved progression-free and overall survival, with an increase in some side effects.

Probabilistic tsunami hazard analysis (PTHA) introduces potential biases in tsunami risk assessment if it assumes static coastlines. Global warming, in addition to geological and local factors, may affect sea-level rise in the next few decades. Here, we provide a method that integrates the expected sea-level rise into existing PTHA, updating regional models without further tsunami simulations. We perform the tsunami hazard analysis at the densely populated Mediterranean coasts, which are highly exposed to tsunami inundations, as reported by historical and instrumental evidence. PTHA and related epistemic uncertainties significantly change when we include the time-dependent components, such as: (1) vertical land movements along the coasts, and (2) future sea-level changes based on the expected climate scenarios described by the IPCC AR6 Report. Probability maps show that the mean probability of exceeding the 1 m and 2 m maximum inundation heights in 2070 has a general increase differentiating locally, with percent variations mainly in the range 10–30% of the updated time-dependent PTHA compared with the current PTHA.

Understanding the formation of trust is a key issue because of the impact of trust on economic performance. Earlier attempts to measure the strength of intergenerational transmission of trust relied on the cross-sectional regression of children’s trust on the contemporaneous trust of parents. In this paper, we take an original approach to the analysis of the transmission process by introducing the distinction between permanent trust (the long-lasting belief on whether one trusts people) and transient trust (capturing, e.g., random errors in the reported trust), and argue that only permanent trust is relevant for the transmission process. Using data from the German Socio-Economic Panel, we show that 2/3 of the observed variability in children’s trust is due to the transient component. The remaining variability due to the permanent component is only moderately determined by the permanent trust of the parents, with mothers being much more relevant than fathers. Focusing on the subsample of families with more than one child, we show that most of the variability in children’s permanent trust is due to unobservable family-specific features of the environment shared by siblings. We conclude that while the family environment in which children grew up determines most of their permanent trust, the direct role of intergenerational transmission is small.

We conducted a large, multicenter, retrospective survey aimed to explore the impact of tumor bone involvement in Non-Small Cell Lung Cancer.Data on clinical-pathology, skeletal outcomes and bone-directed therapies for 661 deceased patients with evidence of bone metastasis were collected and statistically analyzed. Bone metastases were evident at diagnosis in 57.5% of patients. In the remaining cases median time to bone metastases appearance was 9 months. Biphosphonates were administered in 59.6% of patients. Skeletal-related events were experienced by 57.7% of patients; the most common was the need for radiotherapy. Median time to first skeletal-related event was 6 months. Median survival after bone metastases diagnosis was 9.5 months and after the first skeletal-related event was 7 months. We created a score based on four factors used to predict the overall survival from the diagnosis of bone metastases: age >65 years, non-adenocarcinoma histology, ECOG Performance Status >2, concomitant presence of visceral metastases at the bone metastases diagnosis. The presence of more than two of these factors is associated with a worse prognosis.This study demonstrates that patients affected by Non-Small Cell Lung Cancer with bone metastases represent a heterogeneous population in terms of risk of skeletal events and survival.

We conducted a retrospective analysis in our center (Umberto I Polyclinic) in collaboration with Campus Biomedico Polyclinic to assess the results of the REFLECT study, which was the first study that demonstrated the non-inferiority of Lenvatinib to Sorafenib. We identified 21 patients affected by advanced hepatocellular carcinoma during the last 3 years who were treated in our centers. They were subdivided according to the treatment administered (Lenvatinib or Sorafenib). Progression-free survival (PFS) and overall survival (OS) were calculated, and subgroups were compared using the log-rank test. Specific predictive and prognostic factors were identified. The safety profile of the two drugs and the collateral effects were evaluated. The OS in patients in the Lenvatinib arm was 19 (months and 12.5 months in the Sorafenib arm. PFS in patients in the Lenvatinib arm was 6 months and 2.5 months in the Sorafenib arm. OS and PFS in patients treated with Lenvatinib were higher in any subcategory analyzed whereas no positive predictors of response to Sorafenib were found. Based on data from literature, the albumin bilirubin index (ALBI) grade was found to be a key prognostic factor. Patients treated with Sorafenib had more adverse events than those treated with Lenvatinib (100% versus 81.8%, respectively). Patients treated with Sorafenib had more frequently hand-foot syndromes, diarrhea, and nausea whereas patients treated with Lenvatinib commonly had hypertension, proteinuria, and weight loss. Lenvatinib was found to be better than Sorafenib in terms of both survival and toxicity, in advanced hepatic cell carcinoma patients.

We present a source solution for the tsunami generated by the Mw 6.6 earthquake that occurred on 2 May 2020, about 80 km offshore south of Crete, in the Cretan Passage, on the shallow portion of the Hellenic Arc subduction zone (HASZ). The tide gauges recorded this local tsunami on the southern coast of Crete and Kasos island. We used Crete tsunami observations to constrain the geometry and orientation of the causative fault, the rupture mechanism, and the slip amount. We first modelled an ensemble of synthetic tsunami waveforms at the tide gauge locations, produced for a range of earthquake parameter values as constrained by some of the available moment tensor solutions. We allow for both a splay and a back-thrust fault, corresponding to the two nodal planes of the moment tensor solution. We then measured the misfit between the synthetic and the Ierapetra observed marigram for each source parameter set. Our results identify the shallow, steeply dipping back-thrust fault as the one producing the lowest misfit to the tsunami data. However, a rupture on a lower angle fault, possibly a splay fault, with a sinistral component due to the oblique convergence on this segment of the HASZ, cannot be completely ruled out. This earthquake reminds us that the uncertainty regarding potential earthquake mechanisms at a specific location remains quite significant. In this case, for example, it is not possible to anticipate if the next event will be one occurring on the subduction interface, on a splay fault, or on a back-thrust, which seems the most likely for the event under investigation. This circumstance bears important consequences because back-thrust and splay faults might enhance the tsunamigenic potential with respect to the subduction interface due to their steeper dip. Then, these results are relevant for tsunami forecasting in the framework of both the long-term hazard assessment and the early warning systems.

Preclinical data have suggested a synergistic effect of cetuximab combined with gemcitabine and cisplatin and clinical data have shown a substantial improvement in response and survival when gemcitabine is combined with a platinum analogue compared with gemcitabine alone. The aim of this study was to assess the activity and feasibility of a combination of cetuximab with gemcitabine and cisplatin compared with use of gemcitabine and cisplatin alone for the treatment of advanced pancreatic cancer. In a multicentre, randomised phase II trial, 84 patients with advanced pancreatic cancer were randomly assigned to either 250 mg/m 2 cetuximab weekly, after a loading dose of 400 mg/m 2, plus 1000 mg/m 2 gemcitabine and 35 mg/m 2 cisplatin on days 1 and 8 of a 21-day cycle or to the same chemotherapeutic regimen without cetuximab. The primary endpoint was objective response (defined as the proportion of patients whose best response was either partial response or complete response). Secondary endpoints included disease control (defined as the proportion of patients whose best response was either partial response, complete response, or stable disease), progression-free survival, and overall survival. All assessments of response at each site were done blindly by a local experienced radiologist who was not directly involved in the trial. Responses were measured according to an intention-to-treat analysis. This trial is registered with the Clinical Trial registry, number NCT00536614. 29 men and 13 women were randomly assigned to cetuximab plus gemcitabine and cisplatin (median age 61 years [range 38–78]) and 22 men and 20 women were randomly assigned to gemcitabine and cisplatin (median age 64 years [range 40–76]). Seven of 40 (17·5%) patients had an objective response in the cetuximab group (95% CI 7·3–32·8) and five of 41 (12·2%) patients had an objective response in the non-cetuximab group (95% CI 4·1–26·2). No significant difference was noted between the groups both for objective response (5·3% higher in the cetuximab group [95% CI −16·5 to 27·1]; χ 2 test=0·360; p=0·549) or for disease control (3·5% higher in the non-cetuximab group [−34·0% to 27·0%]; 0·446; p=0·504). Overall median follow-up was 11·8 months (range 2·5–18·5). No significant differences between the groups were noted in median progression-free survival (hazard ratio 0·96, 95% CI 0·60–1·52, p=0·847) or in median overall survival (0·91, 0·54–1·55, p=0·739): median progression-free survival was 3·4 months (95% CI 2·4–5·1) in the cetuximab group and 4·2 months (2·6–5·4) in the non-cetuximab group; median overall survival was 7·5 months (5·1–8·8) and 7·8 months (5·3–15·0), respectively. 33 patients from both groups had at least one grade 3–4 toxic effect. The addition of cetuximab to a combination of gemcitabine and cisplatin does not increase response or survival for patients with advanced pancreatic cancer. Although toxic effects were not increased by cetuximab, this combination should not be further assessed in phase III trials.