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Pharmacogenomics studies how genes influence a person's response to treatment. When complex phenotypes are influenced by multiple genetic variations with little effect, a single piece of genetic information is often insufficient to explain this variability. The application of machine learning (ML) in pharmacogenomics holds great potential — namely, it can be used to unravel complicated genetic relationships that could explain response to therapy. In this study, ML techniques were used to investigate the relationship between genetic variations affecting more than 60 candidate genes and carboplatin‐induced, taxane‐induced, and bevacizumab‐induced toxicities in 171 patients with ovarian cancer enrolled in the MITO‐16A/MaNGO‐OV2A trial. Single‐nucleotide variation (SNV, formerly SNP) profiles were examined using ML to find and prioritize those associated with drug‐induced toxicities, specifically hypertension, hematological toxicity, nonhematological toxicity, and proteinuria. The Boruta algorithm was used in cross‐validation to determine the significance of SNVs in predicting toxicities. Important SNVs were then used to train eXtreme gradient boosting models. During cross‐validation, the models achieved reliable performance with a Matthews correlation coefficient ranging from 0.375 to 0.410. A total of 43 SNVs critical for predicting toxicity were identified. For each toxicity, key SNVs were used to create a polygenic toxicity risk score that effectively divided individuals into high‐risk and low‐risk categories. In particular, compared with low‐risk individuals, high‐risk patients were 28‐fold more likely to develop hypertension. The proposed method provided insightful data to improve precision medicine for patients with ovarian cancer, which may be useful for reducing toxicities and improving toxicity management. [ABSTRACT FROM AUTHOR]

Background: Renal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology. Materials & Methods: We investigated associations of age at menarche and age at menopause, pregnancy‐related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Results: During 15 years of follow‐up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. <20 years HR = 0.53, 95% CI 0.34, 0.82). Additionally, we identified a positive association for hysterectomy (HR = 1.43 95% CI 1.09, 1.86) and bilateral ovariectomy (HR = 1.67, 95% CI 1.13, 2.47), but not unilateral ovariectomy (HR = 0.99, 95% CI 0.61, 1.62) with RCC risk. No clear associations were found for age at menarche, age at menopause or exogenous hormone use. Conclusion: Our results suggest that parity and reproductive organ surgeries may play a role in RCC aetiology. [ABSTRACT FROM AUTHOR]

Experimental evidence suggests that alcohol induces cutaneous carcinogenesis, yet epidemiological studies on the link between alcohol intake and skin cancer have been inconsistent. The European Prospective Investigation into Cancer and Nutrition (EPIC) is a prospective cohort initiated in 1992 in 10 European countries. Alcohol intake at baseline and average lifetime alcohol intake were assessed using validated country‐specific dietary and lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in Cox models. A total of 14 037 skin cancer cases (melanoma: n = 2457; basal‐cell carcinoma (BCC): n = 8711; squamous‐cell carcinoma (SCC): n = 1928; unknown: n = 941) were identified among 450 112 participants (average follow‐up: 15 years). Baseline alcohol intake was positively associated with SCC (>15 vs 0.1‐4.9 g/day: HR = 1.44, 95% CI = 1.17‐1.77; Ptrend =.001), BCC (HR = 1.12, 95% CI = 1.01‐1.23; Ptrend =.04), and melanoma risks in men (HR = 1.17, 95% CI = 0.95‐1.44; Ptrend =.17), while associations were more modest in women (SCC: HR = 1.09, 95% CI = 0.90‐1.30; Ptrend =.13; BCC: HR = 1.08, 95% CI = 1.00‐1.17, Ptrend =.03; melanoma: HR = 0.93, 95% CI = 0.80‐1.08, Ptrend =.13). Associations were similar for lifetime alcohol intake, with an attenuated linear trend. Lifetime liquor/spirit intake was positively associated with melanoma (fourth vs first quartile: HR = 1.47, 95% CI = 1.08‐1.99; Ptrend =.0009) and BCC risks in men (HR = 1.17, 95% CI = 1.04‐1.31; Ptrend =.14). Baseline and lifetime intakes of wine were associated with BCC risk (HR = 1.25 in men; HR = 1.11‐1.12; in women). No statistically significant associations were found between beverage types and SCC risk. Intake of beer was not associated with skin cancer risk. Our study suggests positive relationships between alcohol intake and skin cancer risk, which may have important implications for the primary prevention of skin cancer. What's new? Drinking alcohol can make the skin more sensitive to sunlight and vulnerable to skin cancer. Here, the authors conducted a large prospective cohort study to evaluate whether alcohol consumption correlates with skin cancer risk. Among the 450 112 participants, there were 2457 cases of melanoma, 8711 of basal cell carcinoma, and 1928 of squamous cell carcinoma. There was a positive association between alcohol and all three cancer types, stronger in men than in women. The association varied somewhat by beverage type. [ABSTRACT FROM AUTHOR]

Data regarding early predictors of clinical deterioration in patients with infection of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) is still scarce. The aim of the study is to identify early symptoms or signs that may be associated with severe coronavirus disease 2019 (COVID‐19). We conducted a multicentre prospective cohort study on a cohort of patients with COVID‐19 in home isolation from March 2020 to April 2021. We assessed longitudinal clinical data (fever, dyspnea, need for hospitalization) through video calls at three specific time points: the beginning of symptoms or the day of the first positivity of the nasopharyngeal swab for SARS‐CoV‐2‐RNA (t0), and 3 (t3) and 7 (t7) days after the onset of symptoms. We included 329 patients with COVID‐19: 182 (55.3%) males, mean age 53.4 ± 17.4 years, median Charlson comorbidity index (CCI) of 1 (0–3). Of the 329 patients enrolled, 171 (51.98%) had a mild, 81 (24.6%) a moderate, and 77 (23.4%) a severe illness; 151 (45.9%) were hospitalized. Compared to patients with mild COVID‐19, moderate and severe patients were older (p < 0.001) and had more comorbidities, especially hypertension (p < 0.001) and cardiovascular diseases (p = 0.01). At t3 and t7, we found a significant higher rate of persisting fever (≥37°C) among patients with moderate (91.4% and 58.0% at t3 and t7, respectively; p < 0.001) and severe outcome (75.3% and 63.6%, respectively; p < 0.001) compared to mild COVID‐19 outcome (27.5% and 11.7%, respectively; p < 0.001). Factors independently associated with a more severe outcome were persisting fever at t3 and t7, increasing age, and CCI above 2 points. Persisting fever at t3 and t7 seems to be related to a more severe COVID‐19. This data may be useful to assess hospitalization criteria and optimize the use of resources in the outpatient setting. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that components of one‐carbon metabolism, particularly circulating vitamin B6, have an etiological role in renal cell carcinoma (RCC). Vitamin B6 is a cofactor in the transsulfuration pathway. We sought to holistically investigate the role of the transsulfuration pathway in RCC risk. We conducted a nested case‐control study (455 RCC cases and 455 matched controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Plasma samples from the baseline visit were analyzed for metabolites of the transsulfuration pathway, including pyridoxal 5′‐phosphate (PLP, the biologically active form of vitamin B6), homocysteine, serine, cystathionine, and cysteine, in addition to folate. Bayesian conditional logistic regression was used to estimate associations of metabolites with RCC risk as well as interactions with established RCC risk factors. Circulating PLP and cysteine were inversely associated with RCC risk, and these associations were not attenuated after adjustment for other transsulfuration metabolites (odds ratio (OR) and 90% credible interval (CrI) per 1 SD increase in log concentration: 0.76 [0.66, 0.87]; 0.81 [0.66, 0.96], respectively). A comparison of joint metabolite profiles suggested substantially greater RCC risk for the profile representative of low overall transsulfuration function compared to high function (OR 2.70 [90% CrI 1.26, 5.70]). We found some statistical evidence of interactions of cysteine with body mass index, and PLP and homocysteine with smoking status, on their associations with RCC risk. In conclusion, we found evidence suggesting that the transsulfuration pathway may play a role in metabolic dysregulation leading to RCC development. [ABSTRACT FROM AUTHOR]

Background: Topical azelaic acid (AzA) is a common treatment for mild/moderate inflammatory rosacea. Aims: To assess the efficacy and tolerability of a novel formulation cream containing 15% AzA (anti‐inflammatory/anti‐oxidant/anti‐microbial agent) combined with 1% dihydroavenanthramide D (anti‐inflammatory/anti‐itch) in inflammatory rosacea using clinical/instrumental evaluation. Methods: In this multicentre, prospective, open‐label trial, 45 patients with mild/moderate inflammatory rosacea enrolled at the Dermatology Clinic of the University of Catania, Naples, and Rome (Italy) were instructed to apply the cream twice daily for 8 weeks. Clinical evaluation was performed at baseline (T0) and at 8 weeks (T1) by (1) Investigator Global Assessment (IGA) score based on a 5‐point scale (from 0 = clear/no erythema/papules/pustules to 4 = severe erythema/several papules/pustules) and (2) inflammatory lesions count. Instrumental evaluation of erythema degree was performed by erythema‐directed digital photography (EDDP) by a 5‐point scale (from 0 = no redness to 4 = severe redness) at all time points. Tolerability was assessed by a self‐administered questionnaire at 8 weeks. Statistical analysis was performed using SAS version 9. Results: Forty‐four patients completed the study. At week 8, a significant decrease in baseline of IGA scores [median from 3 (T0) to 1 (T1)] and inflammatory lesions count [median from 8 (T0) to 1 (T1)] was recorded along with a significant reduction of erythema scores [median from 2 (T0) to 1 (T1)]. No relevant side effects were recorded. Conclusions: Our results suggest that this new non‐irritating product represents a valid therapeutic option for mild/moderate inflammatory rosacea, and EDDP is able to provide a more defined evaluation of erythema changes. [ABSTRACT FROM AUTHOR]

Summary: Background: Chronic use of proton pump inhibitors (PPIs) in patients with impaired liver function may worsen cytochrome P450 (CYP450) activity, predisposing them to clinically relevant drug–drug interactions. The 13C‐aminopyrine breath test (13C‐ABT) is a non‐invasive tool to study CYP450‐dependent liver function. Aims: To assess 13C‐ABT modifications with different PPIs in patients with cirrhosis Methods: Sixty consecutive patients with HCV‐related cirrhosis and indication to start PPI therapy were randomised to receive omeprazole 20 mg/day, esomeprazole 20 mg/day, lansoprazole 15 mg/day, pantoprazole 40 mg/day or rabeprazole 20 mg/day. 13C‐ABT was performed at baseline and on the 15th day of PPI therapy. Results: At baseline, mean values of max 13C% dose/h and 13C% cum dose at 120 minutes did not differ significantly among groups. On the 15th day of therapy, max 13C% dose/h and 13C% cum dose at 120 minutes did not significantly differ with respect to baseline for pantoprazole (P = 0.184 and P = 0.309, respectively) or rabeprazole (P = 0.536 and P = 0.286, respectively), but were significantly decreased on omeprazole (P = 0.013 and P = 0.015, respectively), esomeprazole (P = 0.009 and P = 0.001, respectively), and lansoprazole (P = 0.033 and P = 0.035, respectively). Conclusions: In patients with cirrhosis, omeprazole, esomeprazole and lansoprazole inhibit microsomal activity while pantoprazole and rabeprazole do not have a significant impact. Should our data be confirmed in larger cohort studies, pantoprazole and rabeprazole could be safely recommended for patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Aim: In order to disclose relations between reduction of haemoglobin A1c (HbA1c) levels and risk of major cardiovascular events (MACE), we performed a meta‐analysis with metaregression of all cardiovascular outcome trials (CVOTs) so far published in patients with type 2 diabetes (T2D). Materials and Methods: An electronic search up to February 10, 2020 was conducted to determine eligible trials. Pooled summary estimates and 95% confidence intervals (CI) were calculated according to the random effects model using the Paule‐Mandel method; restricted maximum likelihood estimators were used to estimate model parameters in the metaregression. Results: The 15 CVOTs included evaluated 138,250 patients. In the pooled analysis, the risk of MACE was significantly reduced by 9% (hazard ratio, HR = 0.91, 0.87–0.95, P <0.001) as compared with placebo, with significant heterogeneity between trials (I2 = 44%, P = 0.060) There was a robust relation between the reduction in achieved HbA1c at the end of the trial and the HR reduction for MACE (beta = −0.3169, P = 0.029), explaining most (78%) of the between‐study variance; this relation was totally driven by the risk reduction of non‐fatal stroke only, which explained 100% of between‐study variance, and apparently restricted to the class of glucagon‐like peptide 1 receptor agonists (GLP−1RAs). There was no relation between the reduction in achieved HbA1c and the HR for heart failure (variance explained = 0%) or all‐cause mortality (variance explained = 6%). Conclusion: The blood glucose reduction observed in CVOTs may play some role in reducing the risk of non‐fatal stroke, at least during treatment with GLP‐1RAs, without affecting the other two components of MACE. [ABSTRACT FROM AUTHOR]

Summary: Background: Candidaemia remains associated with high mortality and increased costs worldwide. Objective: To assess the changes over time in the relative prevalence of non‐albicans candidaemia (NAC). Methods: A systematic review, meta‐analysis and meta‐regression were performed. Observational studies investigating the epidemiology of consecutive, non‐selected, candidaemia episodes were included. Two separated analyses were conducted: (a) whole hospital analysis and (b) intensive care unit (ICU) analysis. Results: Starting from an initial total of 7726 records, 220 studies fulfilled inclusion criteria. The pooled prevalence of NAC in whole hospital analysis was 49.5% (95% confidence intervals [CI] 48.0‐51.1, I2 93.1%), while the pooled prevalence in ICU analysis was 50.6% (95% CI 46.6‐54.6; I2 86.7%). In meta‐regression, a progressive increase in NAC prevalence was observed in whole hospital analysis, although it explained only a small portion of between‐study variance (estimated yearly prevalence change +0.3%, 95% CI from +0.1% to +0.5%, P =.003; adjusted R2 3.42%) and was observed only in some continents in subgroup analyses. No relevant changes over time were observed in NAC prevalence for ICU studies. Conclusions: We registered an increasing trend in the relative prevalence of NAC, which, nonetheless, seems to be limited to some continents and to contribute only minimally to explain the observed differences in NAC prevalence across studies. [ABSTRACT FROM AUTHOR]

Data on the prevalence of occult HBV infection (OBI) in Western Europe and in Northern America are few; hence, we conducted a systematic review and meta‐analysis. All studies included had to fulfil the following inclusion criteria: (a) they investigated the prevalence of OBI (HBV DNA in liver tissue in HBsAg‐negative subjects), (b) were carried out in Western Europe and in Northern America; (c) were available as a full‐text manuscript, (d) written in English and (e) published up to December 2018. The exclusion criteria were as follows: (a) meta‐analyses, letters, reviews, meeting abstracts or editorial comments; (b) studies investigating HBsAg‐positive patients; (c) those investigating OBI outside Western Europe and in Northern America; and (d) to avoid small sample bias in the random‐effects model, those enrolling less than five subjects. Thirty‐four studies met the inclusion criteria, allowing a meta‐analysis on 2729 patients. The overall prevalence of OBI was 34% (95% CI = 26%‐42%), 28% (CI 95%: 12%‐48%) in 329 subjects without chronic liver disease and 35% (95% CI 26%‐44%) in 2400 patients with chronic liver disease. The prevalence of OBI was 51% (95% CI 40%‐62%) in the 823 anti‐HBc‐positive subjects and 19% (95% CI 10%‐30%) in the 1,041 anti‐HBc‐negative subjects. Evaluating the data from 17 studies comparing anti‐HBc‐positive and negative subjects, the prevalence of OBI was higher in the 641 anti‐HBc‐positive subjects than in the 1041 anti‐HBc‐negative (prevalence ratio = 2.29; 95% CI = 1.61‐3.26, P <.001). This meta‐analysis showed that in HBsAg‐negative subjects the prevalence of OBI was high and was associated with anti‐HBc positivity. [ABSTRACT FROM AUTHOR]

A meta‐analysis of cardiovascular outcome trials (CVOTs) comparing glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) and placebo concerning cardiorenal outcomes in patients with type 2 diabetes (T2D) is presented. An electronic search without language restrictions up to June 15, 2019 was conducted to determine eligible trials. A meta‐analysis of available trial data was undertaken, using a random‐effects model to calculate overall hazard ratios (HRs) and 95% confidence intervals (CIs). Data from seven CVOTs, comprising 56 004 patients (68.9% with established cardiovascular disease) were included. GLP‐1RA reduced major cardiovascular events (MACE) by 13% (HR, 0.87; 95% CI, 0.80–0.96; P = 0.011) with a non‐significant heterogeneity between subgroups of patients with and without cardiovascular disease (CVD) (P = 0.220). GLP‐1RA also reduced the risk of cardiovascular death by 12%, of non‐fatal stroke by 16%, of hospitalization for heart failure by 9%, of all‐cause mortality by 11%, and the broad composite kidney outcome by 17%; the latter appeared to be driven only by a reduction in macroalbuminuria (HR, 0.76 [0.68–0.86]; P = 0.003). GLP‐1RAs have moderate benefits concerning MACE, and also reduce hospitalization for heart failure and all‐cause mortality; they also robustly reduce the incidence of macroalbuminuria, without affecting the progression of diabetic renal disease. [ABSTRACT FROM AUTHOR]

Background: To evaluate whether pre‐emptive skin analgesia using a lidocaine patch 5% would improve the effects of systemic morphine analgesia for controlling acute post‐thoracotomy pain. Methods: This was a double‐blind, placebo controlled, prospective study. Patients were randomly assigned to receive lidocaine 5% patch (lidocaine group) or a placebo (placebo group) three days before thoracotomy. Postoperative analgesia was induced in all cases with intravenous morphine analgesia. The intergroup differences were assessed in order to evaluate whether the lidocaine patch 5% would have effects on pain intensity when at rest and after coughing (primary end‐point) on morphine consumption, on the recovery of respiratory function, and on peripheral painful pathways measured with N2 and P2 laser‐evoked potential (secondary end‐points). Results: A total of 90 patients were randomized, of whom 45 were allocated to the lidocaine group and 45 to the placebo group. Lidocaine compared with the placebo group showed a significant reduction in pain intensity both at rest (P = 0.013) and after coughing (P = 0.015), and in total morphine consumption (P = 0.001); and also showed a better recovery of flow expiratory volume in one second (P = 0.025) and of forced vital capacity (P = 0.037). The placebo group compared with the lidocaine group presented a reduction in amplitude of N2 (P = 0.001) and P2 (P = 0.03), and an increase in the latency of N2 (P = 0.023) and P2 (P = 0.025) laser‐evoked potential. Conclusions: The preventive skin analgesia with lidocaine patch 5% seems to be a valid adjunct to intravenous morphine analgesia for controlling post‐thoracotomy pain. However, our initial results should be corroborated/confirmed by larger studies. [ABSTRACT FROM AUTHOR]

Objects: Rapid palatal expansion (RPE) is a widespread orthopaedic procedure used in several clinical situations. The aim of the study was to provide a systematic review and meta-analysis of transverse intercanine and intermolar width changes after RPE and long-term effects.Setting and Sample Population: A systematic literature search was conducted until January 2018 on original studies with RPE treatment.Material and Methods: Intercanine and intermolar distance were measured at the start of RPE (T1, median age 9.2 years) and at the end of treatment (T2). The long-term evaluation was conducted on a subset of articles with 5-year follow-up (T3).Results: Eighteen studies T1-T2 and 5 studies T3 were selected. Regarding the intercanine distance, the RPE resulted in a gain of space T1-T2 of 3.73 mm with a significant heterogeneity (P < 0.0001; I2  = 94.21%) and a relapse T2-T3 of -0.81 mm with a significant heterogeneity (P < 0.0001; I2  = 95.8%); the overall gain of space was 2.91 mm. Regarding the intermolar distance, the RPE resulted in a gain of space T1-T2 of 4.85 mm with a significant heterogeneity (P < 0.0001; I2  = 92.41%) and a relapse T2-T3 of -0.47 mm with a significant heterogeneity (P < 0.0001; I2  = 87.5%); the overall gain of space was 4.38 mm. Meta-regression analysis showed that at younger age, the amount of anterior expansion is similar to posterior. With increasing age, the anterior opening diminishes significantly more than the posterior, being half of the posterior at 15 years.Conclusion: Because long-term results were obtained with simultaneously fixed appliances and long upper retention, RPE should be carefully considered before using. [ABSTRACT FROM AUTHOR]

A meta‐analysis is presented of randomized controlled trials (RCTs) comparing free or fixed combinations of a glucagon‐like peptide‐1 receptor agonist plus basal insulin versus insulin intensification on metabolic control in patients with type 2 diabetes. Electronic databases were searched for RCTs assessing changes in HbA1c, proportion of patients at HbA1c target of <7% (53 mmol/mol), hypoglycaemia and body weight. A random‐effect model was used to calculate the weighted mean difference (WMD) or relative risk (RR) with 95% CI. Eleven RCTs were identified, lasting 24–30 weeks and involving 6176 patients. In the overall analysis, the combination therapy led to a mean HbA1c decrease significantly greater than insulin up‐titration (WMD −0.53%, 95% CI, −0.66, −0.40%, P < 0.001), more patients at HbA1c target (RR 1.69, 95% CI, 1.42, 2.00, P < 0.001), similar hypoglycaemic events (RR 0.97, 95% CI, 0.84, 1.12, P = 0.114), and reduction in body weight (WMD −1.9, 95% CI −2.3, −1.4, P < 0.001), with heterogeneity (I2 > 71%, P < 0.001). Results did not differ in either the free or fixed combination subgroups. Combination strategies, either free or fixed, represent a good option for intensifying basal insulin therapy in patients with type 2 diabetes who need amelioration of glycaemic control. [ABSTRACT FROM AUTHOR]

The perception of pain varies considerably across individuals and is affected by psychological traits. This study aimed to investigate the combined effects of somatosensory amplification and trait anxiety on orthodontic pain. Five-hundred and five adults completed the State Trait Anxiety Inventory ( STAI) and the Somatosensory Amplification Scale ( SSAS). Individuals with combined STAI and SSAS scores below the 20th percentile ( LASA group: five men and 12 women; mean age ± SD = 22.4 ± 1.3 yr) or above the 80th percentile ( HASA group: 13 men and seven women; mean age ± SD = 23.7 ± 1.0 yr) were selected and filled in the Oral Behaviors Checklist ( OBC). Orthodontic separators were placed for 5 d in order to induce experimental pain. Visual analog scales ( VAS) were administered to collect ratings for occlusal discomfort, pain, and perceived stress. Pressure pain thresholds ( PPT) were measured. A mixed regression model was used to evaluate pain and discomfort ratings over the 5-d duration of the study. At baseline, the LASA group had statistically significantly higher PPT values for the masseter muscle than did the HASA group. During the experimental procedure, the HASA group had statistically significantly higher discomfort and pain. A significant difference in pain ratings during the 5 d of the study was found for subjects in the HASA group. Higher OBC values were statistically significantly positively associated with pain. Somatosensory amplification and trait anxiety substantially affect experimentally induced orthodontic pain. [ABSTRACT FROM AUTHOR]

What's known on the subject? and What does the study add? The preoperative and postoperative Karakiewicz models for RCC are considered among the best prognostic tools available for clinical counseling. Nevertheless, their predictive acuracy was externally validated only in two papers: by the same author and in an independent sample of Asian patients. However, these models have not been externally validated in truly independent multicentre series of patients., Our study demonstrated that these models 1) provide robust prognostic information; 2) were robustly built; 3) are useful also in population far from the original series. The present results are the first to show the validity and generalizability of Karakiewicz nomograms, which are based on surgical series from European centres, for large-, mid- and small-volume European and American centres., Objective To assess the accuracy and generalizability of the pre- and postoperative Karakiewicz nomograms for predicting cancer-specific survival ( CSS) in patients with renal cell carcinoma ( RCC)., Patients and Methods This retrospective study included 3231 patients from European and US centres, who were treated by radical or partial nephrectomy for RCC between 1992 and 2010., Prognostic scores for each patient were calculated and the primary endpoint was CSS., Discriminating ability was assessed by Harrell's c-index for censored data. The 'validation by calibration' method proposed by Van Houwelingen was used for checking the calibration of covariate effects. Calibration was graphically explored., Results Local and systemic symptoms were present in 23.2% and 9.1% of the patients, respectively., The median follow-up ( FU) was 49 months. At the last FU, 408 cancer-related deaths were recorded, Kaplan-Meier estimates of CSS (with 95% confidence intervals [ CIs]) at 5 and 10 years were 0.86 (0.84-0.87) and 0.77 (0.75-0.80), respectively., Both nomograms discriminated well. Stratified c-indices for CSS were 0.784 (95% CI 0.753-0.814) for the preoperative nomogram, and 0.842 (95% CI 0.816-0.867) for the postoperative one, with a significant difference between the two values ( P < 0.001)., The covariate-based predictions on our data for both nomograms were valid. The calibration plots showed no relevant departures from ideal predictions., Conclusions The results suggest that the postoperative Karakiewicz nomogram discriminates substantially better than the preoperative one., These nomogram-based predictions may be used as benchmark data for pretreatment and postoperative decision-making in patients at various stages of RCC. [ABSTRACT FROM AUTHOR]

The article reports on the study regarding the University of California at Los Angeles (UCLA) Integrated Staging System (UISS) prognostic score in a European multicenter retrospective research. It states that the study was participated by six European institutions. As a result, it is concluded that UISS score offers good discrimination accuracy, based on an adequately acquired risk function.

Background: Chronic use of proton pump inhibitors (PPIs) in patients with impaired liver function may worsen cytochrome P450 (CYP450) activity, predisposing them to clinically relevant drug-drug interactions. The 13 C-aminopyrine breath test ( 13 C-ABT) is a non-invasive tool to study CYP450-dependent liver function., Aims: To assess 13 C-ABT modifications with different PPIs in patients with cirrhosis METHODS: Sixty consecutive patients with HCV-related cirrhosis and indication to start PPI therapy were randomised to receive omeprazole 20 mg/day, esomeprazole 20 mg/day, lansoprazole 15 mg/day, pantoprazole 40 mg/day or rabeprazole 20 mg/day. 13 C-ABT was performed at baseline and on the 15th day of PPI therapy., Results: At baseline, mean values of max 13 C% dose/h and 13 C% cum dose at 120 minutes did not differ significantly among groups. On the 15th day of therapy, max 13 C% dose/h and 13 C% cum dose at 120 minutes did not significantly differ with respect to baseline for pantoprazole (P = 0.184 and P = 0.309, respectively) or rabeprazole (P = 0.536 and P = 0.286, respectively), but were significantly decreased on omeprazole (P = 0.013 and P = 0.015, respectively), esomeprazole (P = 0.009 and P = 0.001, respectively), and lansoprazole (P = 0.033 and P = 0.035, respectively)., Conclusions: In patients with cirrhosis, omeprazole, esomeprazole and lansoprazole inhibit microsomal activity while pantoprazole and rabeprazole do not have a significant impact. Should our data be confirmed in larger cohort studies, pantoprazole and rabeprazole could be safely recommended for patients with cirrhosis., (© 2020 John Wiley & Sons Ltd.)