Frequency and Nature of Genomic Alterations in ERBB2-Altered Urothelial Bladder Cancer.

BACKGROUND: Human epidermal growth factor-2 (HER2) overexpression is an oncogenic driver in many solid tumors, including urothelial bladder cancer (UBC). In addition, activating mutations in the ERBB2 gene have been shown to play an oncogenic role similar to ERBB2 amplification. OBJECTIVE: To describe and compare the frequency and nature of genomic alterations (GA) of ERBB2-altered (mutations, amplification) and ERBB2 wild-type UBC. PATIENTS AND METHODS: Using a hybrid capture-based comprehensive profiling assay, 9518 UBC cases were grouped by ERBB2 alteration and evaluated for all classes of genomic alterations (GA), tumor mutational burden (TMB), microsatellite instability (MSI), genome-wide loss of heterozygosity (gLOH), and genomic mutational signature. PD-L1 expression was measured by immunohistochemistry (Dako 22C3). Categorical statistical comparisons were performed using Fisher's exact tests. RESULTS: A total of 602 (6.3%) UBC cases featured ERBB2 extracellular domain short variant (SV) GA (ECDmut+), 253 (2.7%) cases featured ERBB2 kinase domain SV GA (KDmut+), 866 (9.1%) cases had ERBB2 amplification (amp+), and 7797 (81.9%) cases were ERBB2 wild-type (wt). European genetic ancestry of ECDmut+ was higher than ERBB2wt. Numerous significant associations were observed when comparing GA by group. Notably among these, CDKN2A/MTAP loss were more frequent in ERBB2wt versus ECDmut+ and amp+. ERBB3 GA were more frequent in ECDmut+ and KDmut+ than ERBB2wt. TERT GA were more frequent in ECDmut+, KDmut+, and amp+ versus ERBB2wt. TOP2A amplification was significantly more common in ECDmut+ and amp+ versus ERBB2wt, and TP53 SV GA were significantly higher in ERBB2 amp+ versus ERBB2wt. Mean TMB levels were significantly higher in ECDmut+, KDmut+, and amp+ than in ERBB2wt. Apolipoprotein B mRNA-editing enzyme, catalytic polypeptides (APOBEC) signature was more frequent in ECDmut+, KDmut+, and amp+ versus ERBB2wt. No significant differences were observed in PD-L1 status between groups, while gLOH-high status was more common in amp+ versus ERBB2wt. MSI-high status was more frequent in KDmut+ versus ERBB2wt, and in ERBB2wt than in amp+. CONCLUSIONS: We noted important differences in co-occurring GA in ERBB2-altered (ECDmut+, KDmut+, amp+) versus ERBB2wt UBC, as well as higher mean TMB and higher APOBEC mutational signature in the ERBB2-altered groups. Our results can help refine future clinical trial designs and elucidate possible response and resistance mechanisms for ERBB2-altered UBC.

Is cognitive behavioral therapy more effective than pharmacotherapy for binge spectrum disorders? A systematic review and meta-analysis.

OBJECTIVES: Binge spectrum disorders are prevalent worldwide. Psychiatric and medical comorbidities are common, and societal costs are significant. Evidence-based treatment remains underutilized. Cognitive behavioral therapy is the recommended first-line treatment, but pharmacotherapy may be easier to access. INTERVENTIONS: Meta-analytic evidence directly comparing cognitive behavioral therapy with pharmacotherapy is lacking. We aimed to compare the effects of cognitive behavioral therapy interventions with any pharmacological treatment for binge spectrum disorders. We searched PubMed, Embase, CENTRAL, ClinicalTrials.gov and reference lists for randomized controlled trials comparing cognitive behavioral therapy with any pharmacotherapy for bulimia nervosa/binge eating disorder and performed pairwise meta-analytic evaluations. PRIMARY OUTCOMES: Primary outcomes are remission and frequency of binges. Secondary outcomes are frequency of purges, response, eating disorder psychopathology, weight/body mass index, depression, anxiety, quality of life and dropouts. RESULTS: Eleven randomized controlled trials comparing cognitive behavioral therapy with fluoxetine/imipramine/desipramine/methylphenidate/sibutramine were identified (N = 531). Cognitive behavioral therapy was superior to antidepressants in terms of remission, frequency of binges and eating disorder psychopathology. There were no statistically significant differences for any of the individual cognitive behavioral therapy vs drug comparisons in terms of response/depression/anxiety/weight/quality of life/dropouts. Cognitive behavioral therapy was not superior to sibutramine/methylphenidate for the primary outcomes. CONCLUSIONS: Data are scarce, comparisons underpowered and, considering the inherent methodological limitations of psychotherapy trials, questions arise regarding the presumed superiority of cognitive behavioral therapy. Further research is needed.

Association of the Streptococcus bovis/Streptococcus equinus Complex With Colorectal Neoplasia: A Systematic Review and Meta-analysis.

Background: Invasive infection with Streptococcus bovis/Streptococcus equinus complex (SBSEC) bacteria is associated with underlying colorectal neoplasia. However, the link between intestinal or fecal colonization with SBSEC isolates or antibody responses to SBSEC members and colorectal cancer is not thoroughly investigated in the literature. Methods: We searched the PubMed, EMBASE, and Web of Science databases for case-control studies as well as retrospective or prospective cohort studies reporting an association between SBSEC bacteria and colorectal neoplasia. Results: We identified 22 studies (15 case-control and 7 cohort) that met our inclusion criteria. Among the cohort studies, patients with SBSEC bacteremia were 3.73 times more likely to have underlying colorectal cancer compared with individuals with no bacteremia (relative risk [RR], 3.73; 95% CI, 2.79-5.01), whereas the risk of underlying colorectal adenoma in patients with SBSEC bacteremia was not significantly increased (RR, 5.00; 95% CI, 0.83-30.03). In case-control studies, patients with colorectal cancer were 2.27 times more likely to have evidence of intestinal or fecal colonization with SBSEC isolates (odds ratio [OR], 2.27; 95% CI, 1.11-4.62) and immunoglobulin G (IgG) antibody responses to SBSEC antigens (OR, 2.27; 95% CI, 1.06-4.86) compared with controls. Patients with colorectal adenoma were not more likely to be colonized with SBSEC isolates compared with controls (OR, 1.12; 95% CI, 0.55-2.25). Conclusions: Apart from the well-established association of SBSEC bacteremia and underlying colorectal cancer, intestinal or fecal colonization with SBSEC isolates and IgG antibody responses to SBSEC antigens were higher in patients with colorectal cancer compared with controls. Neither bacteremia from SBSEC isolates nor colonization with SBSEC bacteria was associated with underlying colorectal adenoma.

Pharmacotherapy compared to placebo for people with Bulimia Nervosa: A systematic review and meta-analysis.

Bulimia Nervosa is a disorder with high rates of psychiatric and medical comorbidity and substantial societal costs. Cognitive Behavioural Therapy is considered the preferred treatment, but access can be problematic. Pharmacotherapy is more accessible but remains significantly underutilised. We aimed to assess the efficacy, tolerability, and safety of all available forms of pharmacotherapy for the treatment of bulimia nervosa. We conducted a comprehensive search of PubMed, EMBASE, CENTRAL, ClinicalTrials.gov, and reference lists of relevant articles up until April 2023. The primary outcomes were remission and binge frequency. 52 randomised controlled trials (RCTs) involving 3313 participants were included in the meta-analysis. Overall, no significant difference was observed between drugs and placebo in terms of remission; however, the available data were limited. Notably, drugs, particularly antidepressants, demonstrated a significant reduction in the frequency of binge episodes compared to placebo. Antidepressants were also found to be more effective than placebo in terms of treatment response and other clinically meaningful outcomes. An important limitation is that few RCTs were available for individual drugs. Our findings provide evidence supporting the increased utilisation of pharmacotherapy in clinical practice and underscore the need for further research involving larger populations and a broader range of outcomes.

Response and Outcomes of Maintenance Avelumab After Platinum-Based Chemotherapy (PBC) in Patients With Advanced Urothelial Carcinoma (aUC): "Real World" Experience.

BACKGROUND: Platinum-based chemotherapy (PBC) followed by avelumab switch maintenance in nonprogressors is standard first line (1L) treatment for advanced urothelial carcinoma (aUC). We describe clinical features and outcomes in a "real-world' cohort treated with avelumab maintenance for aUC. MATERIALS AND METHODS: This was a retrospective cohort study of patients (pts) who received 1L switch maintenance avelumab after no progression on PBC for aUC. We calculated progression-free survival (PFS) and overall survival (OS) from initiation of maintenance avelumab. We also described OS and PFS for specific subsets using Cox regression and observed response rate (ORR). RESULTS: A total of 108 pts with aUC from 14 sites treated with maintenance avelumab were included. There was a median of 6 weeks1-30 from end of PBC to avelumab initiation; median follow-up time from avelumab initiation was 8.8 months (1-42.7). Median [m]PFS was 9.6 months (95%CI 7.5-12.1) and estimated 1-year OS was 72.5%. CR/PR (vs. SD) to 1L PBC (HR = 0.33, 95% CI 0.13-0.87) and ECOG PS 0 (vs. ≥1), (HR = 0.15, 95% CI 0.05-0.47) were associated with longer OS. The presence of liver metastases was associated with shorter PFS (HR = 2.32, 95% CI 1.17-4.59). ORR with avelumab maintenance was 28.7% (complete response 17.6%, partial response 11.1%), 29.6% stable disease, 26.9% progressive disease as best response (14.8% best response unknown). CONCLUSIONS: Results seem relatively consistent with findings from JAVELIN Bladder100 trial and recent "real world" studies. Prior response to platinum-based chemotherapy, ECOG PS 0, and absence of liver metastases were favorable prognostic factors. Limitations include the retrospective design, lack of randomization and central scan review, and possible selection/confounding biases.

High Versus Low Adherence to the Mediterranean Diet for Prevention of Diabetes Mellitus Type 2: A Systematic Review and Meta-Analysis.

Diabetes mellitus type 2 (DMT-2) presents with a growing incidence, and its complications contribute mainly to cardiovascular disease and overall mortality. DMT-2 prevention and early stage management include lifestyle modification by adopting healthy eating patterns and increasing physical activity levels. The Mediterranean diet (MD) is associated with beneficial effects on human health and has been found effective for preventing and managing DMT-2. The purpose of this meta-analysis is to investigate whether the level of MD adherence plays a role in DMT-2 prevention and to what extent. A systematic literature search in PubMed, EMBASE, Web of Science Core Collection, Scopus, and Google Scholar databases was conducted until November 2022, and related observational studies fulfilling the eligibility criteria were included. The literature search concluded with 24 studies in the qualitative analysis and 23 studies in the quantitative analysis. Of those, 18 cohort studies were eligible for meta-analysis with hazard ratio as effect size and five studies providing odds ratio as effect size. The cohort studies included 248,140 participants with a mean follow-up of 10.8 years (3 to 22 years). Individuals with high adherence to MD presented an 11% and 18% decrease in risk and odds, respectively, of developing DMT-2 compared to those with low MD adherence (HR 0.89, 95%CI 0.83 to 0.95) and (OR 0.82, 95%CI 0.72 to 0.93). In studies where the follow-up was longer than 10 years, the 12% decrease in the risk of developing DMT-2 remained (HR 0.88 95%CI 0.84 to 0.92), whereas in studies where follow-up was less than 10 years, no difference between groups with different levels of adherence was found. Long-term high MD adherence is associated with a reduced risk of developing DMT-2, but further studies are needed to confirm these results.

Impact of COVID-19 lockdown on smoking and vaping: systematic review and meta-analysis.

OBJECTIVES: COVID-19 and the implementation of lockdowns have impacted daily lives worldwide. This systematic review and meta-analysis aimed to investigate the impact of lockdowns on the smoking and vaping behaviours of adults during the pandemic. STUDY DESIGN: This was a systematic review and meta-analysis. METHODS: A systematic literature search was conducted up to 28 April 2022 in the following databases: PubMed, Embase and Web of Science. RESULTS: In total, 77 studies met the inclusion criteria for this review. In 34 studies, an increase in smoking behaviour was reported for the majority of participants; however, in 21 and 18 studies, 'no change' and 'decrease' in smoking were the predominant responses, respectively. The results from the meta-analysis, which examined the change in the number of cigarettes smoked per day, showed no difference between the pre- and post-lockdown periods: 0.81 weighted mean difference (95% confidence interval, -0.59 to 2.21). Regarding vaping, three of seven studies reported an increase in smoking for the majority of participants, whereas 'no change' and 'decrease' were the predominant answers in the other four studies. CONCLUSIONS: The results show that lockdowns led most participants to increase smoking/vaping, whereas a decrease or cessation of smoking/vaping was only reported in the minority of participants. Attention should be given to the non-communicable diseases that could arise as a result of the increase in smoking/vaping during lockdowns, and further research in this area is needed.

Phase Angle and Handgrip Strength as Predictors of Clinical Outcomes in Hospitalized COVID-19 Patients.

Phase angle (PhA) and muscle strength are predictors of clinical outcomes in critically ill patients. Malnutrition may affect body composition measurements. The aim of this prospective study was to investigate the association between PhA and handgrip strength (HGS), and clinical outcomes in hospitalized COVID-19 patients. The study included a total of 102 patients. Both PhA and HGS were measured twice, within 48 h of hospital admission and on the 7th day of hospitalization. The primary outcome was the clinical status on the 28th day of hospitalization. Secondary outcomes included the hospital length of stay (LOS), the concentrations of ferritin, C-reactive protein and albumin, oxygen requirements and the severity of pneumonia. A one-way analysis of variance (ANOVA) test and Spearman rS correlation coefficient were used for statistical analysis. No differences were found for PhA [on day 1 (p = 0.769) and day 7 (p = 0.807)] and the primary outcome. A difference was found between HGS on day 1 and the primary outcome (p = 0.008), while no difference was found for HGS on day 7 (p = 0.476). Body mass index was found to be associated with the oxygen requirement on day 7 (p = 0.005). LOS was correlated neither with PhA (rs = -0.081, p = 0.422) nor with HGS (rs = 0.137, p = 0.177) on the first day. HGS could be a useful indicator of clinical outcomes in COVID-19 patients, while PhA does not seem to have a clinical impact. However, further research is needed to validate the results of our study.

Critical evaluation and comparison of nutritional clinical practice guidelines for cancer patients.

BACKGROUND: The growing incidence of cancer globally, and the importance of nutrition support for these patients, emphasize the need for the development of nutritional clinical practice guidelines and consensus papers (CPGs) in the field. Numerous relevant CPGs have been published by several organizations worldwide. The aim of this systematic review was to compare the content of the existing CPGs and evaluate the quality of their development using the AGREE-II tool. METHODS: A systematic literature search in PubMed, Embase and Web of Science databases was conducted for the identification of relevant CPGs and consensus papers. Eligible CPGs was blindly evaluated by four appraisers according to the Appraisal of Guidelines for Research and Evaluation ΙΙ (AGREE-II) tool. RESULTS: In total 15 CPGs were identified and were evaluated. All but one set of CPGs underlined the importance of nutritional screening and assessment, whereas recommendations on nutritional interventions, supplements, management of complications and nutritional follow-up were also reported by several organizations. AGREE-II results showed that two CPGs were characterized as high, eight as moderate and five as low regarding their quality of development. CONCLUSIONS: Variety on recommendations could be observed between CPGs that should be considered when applied into clinical practice. Limitations of the existing CPGs could be the fact that they are non-specific and only a minority of them are focused to specific cancer types. Frequent updates for CPGs and inclusion of more nutritional topics should be considered for some CPGs. Improvement of the quality of the CPGs development should also be pursued in future.

Demand for Water-Soluble Vitamins in a Group of Patients with CKD versus Interventions and Supplementation-A Systematic Review.

BACKGROUND: Increasingly, chronic kidney disease (CKD) is becoming an inevitable consequence of obesity, metabolic syndrome, and diabetes. As the disease progresses, and through dialysis, the need for and loss of water-soluble vitamins both increase. This review article looks at the benefits and possible risks of supplementing these vitamins with the treatment of CKD. METHODS: Data in the PubMed and Embase databases were analyzed. The keywords "chronic kidney disease", in various combinations, are associated with thiamin, riboflavin, pyridoxine, pantothenic acid, folates, niacin, cobalamin, and vitamin C. This review focuses on the possible use of water-soluble vitamin supplementation to improve pharmacological responses and the overall clinical condition of patients. RESULTS: The mechanism of supportive supplementation is based on reducing oxidative stress, covering the increased demand and losses resulting from the treatment method. In the initial period of failure (G2-G3a), it does not require intervention, but later, especially in the case of inadequate nutrition, the inclusion of supplementation with folate and cobalamin may bring benefits. Such supplementation seems to be a necessity in patients with stage G4 or G5 (uremia). Conversely, the inclusion of additional B6 supplementation to reduce CV risk may be considered. At stage 3b and beyond (stages 4-5), the inclusion of niacin at a dose of 400-1000 mg, depending on the patient's tolerance, is required to lower the phosphate level. The inclusion of supplementation with thiamine and other water-soluble vitamins, especially in peritoneal dialysis and hemodialysis patients, is necessary for reducing dialysis losses. Allowing hemodialysis patients to take low doses of oral vitamin C effectively reduces erythropoietin dose requirements and improves anemia in functional iron-deficient patients. However, it should be considered that doses of B vitamins that are several times higher than the recommended dietary allowance of consumption may exacerbate left ventricular diastolic dysfunction in CKD patients. CONCLUSIONS: Taking into account the research conducted so far, it seems that the use of vitamin supplementation in CKD patients may have a positive impact on the treatment process and maintaining a disease-free condition.

Treatment Rechallenge With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma.

OBJECTIVES: To examine patient and disease characteristics, toxicity, and clinical outcomes for patients with advanced urothelial carcinoma (aUC) who are rechallenged with immune checkpoint inhibitor (ICI)-based therapy. PATIENTS AND METHODS: In this retrospective cohort, we included patients treated with ICI for aUC after having prior ICI treatment. Endpoints included the evaluation of radiographic response and disease control rates with first and second ICI courses, outcomes based on whether there was a change in ICI class (anti-PD-1 vs. anti-PD-L1), and assessment of the reasons for ICI discontinuation. RESULTS: We identified 25 patients with aUC from 9 institutions who received 2 separate ICI courses. ORR with first ICI and second ICI were 39% and 13%, respectively. Most patients discontinued first ICI due to progression (n = 19) or treatment-related toxicity (n = 4). Thirteen patients received non-ICI treatment between the first and second ICI, and 12 patients changed ICI class (anti-PD-1 vs. anti-PD-L1) at rechallenge. Among 10 patients who changed ICI class, 8 (80%) had progressive disease as best response with second ICI, while among 12 patients re-treated with the same ICI class, only 3 (25%) had progressive disease as best response at the time of rechallenge. With second ICI, most patients discontinued treatment due to progression (n = 18) or patient preference (n = 2). CONCLUSIONS: A proportion of patients with aUC rechallenged with ICI-based regimens may achieve disease control, supporting clinical trials in that setting, especially with ICI-based combinations. Future studies are needed to validate our results and should also focus on identifying biomarkers predictive of benefit with ICI rechallenge.

Can omega-3 fatty acids be beneficial in pediatric NAFLD? A systematic review and meta-analysis.

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children and no medications or supplements are currently recommended. The role of omega-3 (n-3) fatty acids has been investigated in clinical trials with promising results. The aim of this study is to provide a detailed summary of the evidence about the efficacy of n-3 in the treatment of pediatric NAFLD. A systematic literature search was performed through major electronic databases up to September 20, 2021 for randomized placebo-controlled trials, investigating the efficacy of n-3 fatty acids in children with NAFLD. The primary outcomes were changes in serum transaminases concentration, Body Mass Index (BMI) and improvement of ultrasonographic liver steatosis. The secondary outcomes were changes in the patients' serum lipid profile, γ-glutamyl transferase (GGT), fasting blood glucose (FBG), homeostatic model assessment of insulin resistance (ΗΟΜΑ-ΙR) and waist circumference (WC). Results were expressed as mean differences for continuous outcomes and odds ratios for dichotomous outcomes with 95% confidence intervals. Six RCTs (n = 378 patients) were included. Treatment with n-3, compared to placebo, resulted in a statistically significant reduction in transaminases concentration. In addition, a significant improvement in liver steatosis assessed by ultrasonography and a decrease in BMI were observed. N-3 fatty acids supplementation seems to be an effective alternative treatment in pediatric NAFLD by improving liver biochemistry, ultrasonographic steatosis and BMI. Further research is required concerning the effect of n-3 fatty acids in liver histology.

Comparative efficacy of different treatment modalities in the management of pediatric non-alcoholic fatty liver disease: A systematic review and network meta-analysis.

The incidence of non-alcoholic fatty liver disease (NAFLD) in children is constantly rising. Lifestyle modification is the cornerstone of the management of pediatric NAFLD. Even though several clinical trials have been conducted, there are barely any approved medications or supplements that can be used in the management of pediatric NAFLD. The aim of our study was to systematically review the current literature and perform a network meta-analysis to compare the different treatment interventions in pediatric NAFLD. Pubmed/Medline, Embase and Scopus were searched from inception to 2 December 2021. The primary outcomes were changes in alanine transaminase (`concentrations. Secondary outcomes were changes in aspartate aminotransferase (AST), lipidemic and other biochemical parameters concentrations and body mass index (BMI) values. The evaluation of transitivity was performed by comparing the distribution of potential effect modifiers across the difference comparisons. Our study included 1241 participants from 18 studies. Different interventions such as omega 3 fatty acids and probiotics seem to exert possible beneficial effects in the management of pediatric NAFLD. Vitamin D and vitamin E supplementation alone or in combination with other interventions also seem to be beneficial in specific patient groups. Several interventions such as omega-3 fatty acids, probiotics and vitamin D and E can be combined with lifestyle modification to manage pediatric NAFLD. Decisions should be individualized based on the patient's profile. Future studies with optimal methodology are needed to draw safe and applicable conclusions.

Vitamin D as a chemopreventive agent in colorectal neoplasms. A systematic review and meta-analysis of randomized controlled trials.

Colorectal cancer (CRC) is the third most common cancer in both sexes and the second in terms of mortality. Apart from genetic predisposition, dietary and lifestyle factors have been implicated in the development of CRC. Several studies suggested that vitamin D (VitD) might be a promising strategy in CRC prevention, while other studies did not confirm this finding. The aim of our study was to examine the role of Vit-D supplementation in the prevention of colorectal neoplasms (CRC and polyps). We conducted a systematic search in Pubmed, Embase and Web of Science databases for Randomized Controlled Trials (RCTs) examining the incidence of colorectal neoplasms in patients taking Vit-D supplementation compared to placebo. We synthetized results using Risk Ratio along with 95% Confidence Intervals (CIs). Nine RCTs (N = 71,386) were included. Non-significant correlations were observed between Vit-D supplementation and CRC incidence (RR:1.06, p = 0.52). Similarly, non-significant associations were observed between the use of Vit-D supplements and colorectal adenoma incidence (RR:1.00, p = 0.91). Advanced adenomas (OR:1.05, p = 0.63) and serrated polyps (RR:1.03, p = 0.63) were also not significantly inversely associated with Vit-D supplementation. Our study shows that Vit-D does not seem to have a role in the chemoprevention of colorectal neoplasms. However, additional well-designed studies are needed in order to draw safe conclusions. A potentially beneficial role of Vit-D supplementation in CRC primary prevention in individuals with severe vitamin D deficiency as well in the primary prevention of early-onset CRC, requires further investigation.

The Benefit of Probiotics in Pediatric Nonalcoholic Fatty Liver Disease: A Meta-analysis of Randomized Control Trials.

OBJECTIVES: We conducted a systematic review and meta-analysis to provide a summary of the current literature about the efficacy of probiotics in pediatric nonalcoholic fatty liver disease (NAFLD). METHODS: A systematic literature search through major electronic databases was carried out for RCTs till September 9, 2021, investigating the efficacy of probiotics in the treatment of pediatric patients with NAFLD. Weighted mean differences (WMD) and Standard Deviations (SD) were used to calculate continuous outcomes and a Risk Ratio with 95% CI was used for dichotomous outcomes. RESULTS: In total, 4 RCTs with 238 pediatric patients with NAFLD were included in the study. Probiotic supplementation revealed a statistically significant difference in transaminases' levels (ALT: WMD = -7.51 IU/L, 95% CI, -11.28 to -3.73, I 2 = 0%, P < 0.0001; AST: WMD = -6.46 IU/L, 95% CI, -9.31 to -3.61, I 2 = 0%, P < 0.00001), anthropometric characteristics, total cholesterol, triglycerides and ultrasonographic steatosis improvement. CONCLUSIONS: According to the data of this meta-analysis, probiotic supplementation, and especially supplementation of Lactobacillus acidophilus in combination with other strains of Bifidobacterium or Lactobacillus may be beneficial in the improvement of transaminases', lipid parameters' levels, ultrasonographic, and anthropometric characteristics in children with NAFLD. Current evidence does not allow specifying the exact beneficial strain of probiotics mentioned above. The possible effect of probiotics on liver histology improvement in pediatric NAFLD should be examined in future studies.

The Impact of Lockdowns on Caffeine Consumption: A Systematic Review of the Evidence.

The Coronavirus disease 2019 (COVID-19) has been characterized by the World Health Organization as a pandemic in March 2020 and the lockdown measures that were implemented in an effort to limit the transmission of the virus affected the daily life of many people in all over the world. The aim of this systematic review was to investigate the changes during/after the lockdowns in caffeine consumption by coffee and energy drinks. A systematic literature search was conducted in three databases (PubMed, Embase, Web of Science) up to 31 December 2021 and out of 19,511 studies found and 12,885 screened, 16 studies were included according to eligibility criteria. Results regarding coffee consumption showed that a significant part of individuals decreased their consumption and in five studies an increase was reported, including women and seniors >60 years old. Energy drinks were also consumed less during the lockdown compared to the pre-lockdown time. Attention should be given for menopausal women where an increase in coffee consumption was found which could impair bone density, but further research is needed in order to make safe conclusions.

Cardiac geometry, function, and remodeling patterns in patients under maintenance hemodialysis and peritoneal dialysis treatment.

Cardiovascular disease is the leading cause of mortality in patients with end-stage-kidney disease. Evidence on the possible echocardiographic differences between hemodialysis and peritoneal dialysis (PD) is scarce. This study aimed to evaluate differences in left (LA) and right atrial (RA), left (LV) and right ventricular (RV) geometry, systolic and diastolic function in hemodialysis, and PD patients. Thirty-eight hemodialysis and 38 PD patients were matched for age, sex, and dialysis vintage. Two-dimensional and tissue-Doppler echocardiography, and lung ultrasound were performed during an interdialytic day in hemodialysis and before a programmed follow-up visit in PD patients. Vena cava diameter (11.09 ± 4.53 vs. 14.91 ± 4.30 mm; p < 0.001) was significantly lower in hemodialysis patients. Indices of LA, RA, LV, and RV dimensions were similar between the two groups. LVMi (116.91 [38.56] vs. 122.83 [52.33] g/m2 ; p = 0.767) was similar, but relative wall thickness was marginally (0.40 [0.14] vs. 0.45 [0.15] cm; p = 0.055) lower in hemodialysis patients. LV hypertrophy prevalence was similar between groups (73.7% vs. 71.1%; p = 0.798), but hemodialysis patients presented eccentric and PD patients concentric LVH. Regarding ventricular systolic function, stroke volume (p = 0.030) and cardiac output (p = 0.036) were higher in hemodialysis, while RV systolic pressure (RVSP) (20.37 [22.54] vs. 27.68 [14.32] mm Hg; p = 0.009) was higher in PD. No significant differences were evidenced in diastolic function indices and lung water excess between the two groups. A moderate association was noted between ultrasound B-lines score and LA volume index (r = 0.465, p < 0.001), RVSP (r = 0.431, p < 0.001), and E/e' ratio (r = 0.304, p = 0.009). Hemodialysis and PD patients present largely similar echocardiographic indices reflecting cardiac geometry, systolic, and diastolic function, but different patterns of abnormal LV remodeling.

Cardiopulmonary reserve examined with cardiopulmonary exercise testing in individuals with chronic kidney disease: A systematic review and meta-analysis.

BACKGROUND: Patients with chronic kidney disease (CKD) often present reduced physical activity and exercise tolerance due to factors relevant to co-existing disturbances of the cardiac, nervous and muscular systems. Cardiopulmonary exercise testing (CPET) is used for clinical evaluation of exercise limitation and related symptoms (i.e., dyspnea, fatigue) in several medical fields. OBJECTIVES: This is a systematic review and meta-analysis of studies using CPET technology to examine cardiopulmonary reserve in individuals with versus without CKD. METHODS: Literature search involved PubMed, Web of Science and Scopus databases; manual search of article references and of gray literature was also performed. Observational studies and randomized trials that used CPET for patients with CKD stage 1-5 versus controls were eligible. The primary outcome was peak oxygen uptake (VO2peak). The Newcastle-Ottawa Scale was used to evaluate the quality of retrieved studies. RESULTS: From an initial 4944 literature records, we identified 29 studies fulfilling the inclusion criteria; of these, 25 studies (2,213 participants) with complete data were included in the final meta-analysis. VO2peak was significantly lower in CKD patients than controls without CKD [standardized mean difference (SMD) -1.40, 95% confidence interval (CI) -1.68; -1.13)]. Values were lower for CKD than non-CKD individuals for oxygen consumption at anaerobic threshold (SMD -1.06, 95% CI -1.34; -0.79) and maximum workload [weighted mean difference (WMD) -58.26, 95% CI 74.14; -42.38]. In 3 studies, CKD patients had higher VO2peak than controls with heart failure without CKD (WMD 6.60, 95% CI 3.02; 10.18). Sensitivity analyses confirmed the robustness of these findings. CONCLUSIONS: VO2peak and other commonly analyzed CPET variables were lower in patients with CKD than controls, which indicates reduced functional cardiopulmonary reserve in CKD. In contrast, patients with CKD performed better than controls with heart failure without CKD. Overall, rehabilitation programs should be more widely applied to individuals with CKD. PROSPERO REGISTRATION NUMBER: CRD42021227805.

A critical update on the role of mild and serious vitamin D deficiency prevalence and the COVID-19 epidemic in Europe.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) has emerged as a pandemic, affecting nearly 180 million people worldwide as of June 22, 2021. Previous studies have examined the association between the mean vitamin D (Vit D) concentration of each country and COVID-19 infection and mortality rate in European countries. The aim of the present study was to critically evaluate the relationship between prevalence of mild and severe Vit D deficiency in each country and COVID-19 infection, recovery, and mortality using updated data and a different methodological approach. METHODS: Information on Vit D concentration or deficiency for each country was retrieved through a literature search. COVID-19 infections and mortalities per million people and total recoveries, as of June 22, 2021, were obtained. The associations between Vit D deficiency and COVID-19 infection, recovery, and mortality were explored using correlation coefficients and scatterplots. RESULTS: Non-significant correlations were observed between both number of COVID-19 infections (r = 0.363, P = 0.116) and number of recoveries (r = 0.388, P = 0.091) and the prevalence of mild Vit D deficiency (<50 nmol/L). Similarly, non-significant correlations were observed between both infections (r = 0.215, P = 0.392) and recoveries (r = 0.242, P = 0.332) and the prevalence of severe Vit D deficiency (<30 nmol/L). Significant correlations were found between COVID-19 mortality and prevalence of both mild Vit D deficiency (r = 0.634, P = 0.003) and severe Vit D deficiency (r = 0.538, P = 0.021). CONCLUSIONS: The prevalence of neither mild nor severe Vit D deficiency was associated with the number of COVID-19 infections in European countries. Thus, it is an important parameter to consider when implementing preventive measures to face COVID-19.