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Effects of vegetarian versus Mediterranean diet on kidney function: Findings from the CARDIVEG study.
Dinu, M, Colombini, B, Pagliai, G, Giangrandi, I, Cesari, F, Gori, A, Giusti, B, Marcucci, R, Sofi, F
European journal of clinical investigation. 2021;(9):e13576
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Abstract
BACKGROUND The aim of the present study was to assess the effects of a lacto-ovo-vegetarian diet (VD), compared to a Mediterranean diet (MD), on kidney function in a group of subjects with medium-to-low cardiovascular risk profile. METHODS We analysed 107 subjects (82 women, 25 men; median age 52) who followed a VD (n = 54) and a MD (n = 53) for 3 months in the CARDIVEG study, a randomized, open, crossover trial that compared the effects of these 2 diets on cardiovascular disease risk. RESULTS The effect of the two diets on kidney function markers was evaluated by conducting a general linear model for repeated measurements adjusted for possible confounding factors such as age, sex, physical activity, alcohol, smoking, hypertension, LDL cholesterol, glucose and body weight change. A significant reduction in creatinine (-5.3%; P < .001), urea nitrogen levels (-9%; P = .001), blood urea nitrogen (BUN) (-8.7%; P = .001) and BUN/creatinine ratio (-5.8%; P < .001), and an increase in estimated glomerular filtration rate (eGFR) (+3.5%; P = .001) was observed during the VD period. On the contrary, no significant changes were noted in the MD group. Variations obtained in the two dietary interventions were significantly different (P < .0001) for creatinine levels, BUN/creatinine and eGFR, for which opposite trends were observed in the VD and MD groups. CONCLUSIONS In a selected group of subjects with medium-to-low cardiovascular risk profile, a 3 month VD period determined significant improvements in kidney function markers. Further trials are needed to confirm these results.
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Comparison of renin-angiotensin-aldosterone system inhibitors with other antihypertensives in association with coronavirus disease-19 clinical outcomes.
Bezabih, YM, Bezabih, A, Alamneh, E, Peterson, GM, Bezabhe, W
BMC infectious diseases. 2021;(1):527
Abstract
BACKGROUND Reports on the effects of renin-angiotensin-aldosterone system (RAAS) inhibitors on the clinical outcomes of coronavirus disease-19 (COVID-19) have been conflicting. We performed this meta-analysis to find conclusive evidence. METHODS We searched published articles through PubMed, EMBASE and medRxiv from 5 January 2020 to 3 August 2020. Studies that reported clinical outcomes of patients with COVID-19, stratified by the class of antihypertensives, were included. Random and fixed-effects models were used to estimate pooled odds ratio (OR). RESULTS A total 36 studies involving 30,795 patients with COVID-19 were included. The overall risk of poor patient outcomes (severe COVID-19 or death) was lower in patients taking RAAS inhibitors (OR = 0.79, 95% CI: [0.67, 0.95]) compared with those receiving non-RAAS inhibitor antihypertensives. However, further sub-meta-analysis showed that specific RAAS inhibitors did not show a reduction of poor COVID-19 outcomes when compared with any class of antihypertensive except beta-blockers (BBs). For example, compared to calcium channel blockers (CCBs), neither angiotensin-I-converting enzyme inhibitors (ACEIs) (OR = 0.91, 95% CI: [0.67, 1.23]) nor angiotensin-II receptor blockers (ARBs) (OR = 0.90, 95% CI: [0.62, 1.33]) showed a reduction of poor COVID-19 outcomes. When compared with BBs, however, both ACEIs (OR = 0.85, 95% CI: [0.73, 0.99) and ARBs (OR = 0.72, 95% CI: [0.55, 0.94]) showed an apparent decrease in poor COVID-19 outcomes. CONCLUSIONS RAAS inhibitors did not increase the risk of mortality or severity of COVID-19. Differences in COVID-19 clinical outcomes between different class of antihypertensive drugs were likely due to the underlying comorbidities for which the antihypertensive drugs were prescribed, although adverse effects of drugs such as BBs could not be excluded.
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MOMENTUM: momelotinib vs danazol in patients with myelofibrosis previously treated with JAKi who are symptomatic and anemic.
Verstovsek, S, Chen, CC, Egyed, M, Ellis, M, Fox, L, Goh, YT, Gupta, V, Harrison, C, Kiladjian, JJ, Lazaroiu, MC, et al
Future oncology (London, England). 2021;(12):1449-1458
Abstract
Hallmark features of myelofibrosis (MF) are cytopenias, constitutional symptoms and splenomegaly. Anemia and transfusion dependency are among the most important negative prognostic factors and are exacerbated by many JAK inhibitors (JAKi). Momelotinib (MMB) has been investigated in over 820 patients with MF and possesses a pharmacological and clinical profile differentiated from other JAKi by inhibition of JAK1, JAK2 and ACVR1. MMB is designed to address the complex drivers of iron-restricted anemia and chronic inflammation in MF and should improve constitutional symptoms and splenomegaly while maintaining or improving hemoglobin in JAKi-naive and previously JAKi-treated patients. The MOMENTUM Phase III study is designed to confirm and extend observations of safety and clinical activity of MMB.
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Differences in outcomes of hospitalizations for heart failure after SGLT2 inhibitor treatment: effect modification by atherosclerotic cardiovascular disease.
Shao, SC, Chang, KC, Lin, SJ, Chang, SH, Hung, MJ, Chan, YY, Lai, EC
Cardiovascular diabetology. 2021;(1):213
Abstract
BACKGROUND The treatment effects on hospitalization for heart failure (hHF) from sodium-glucose cotransporter 2 (SGLT2) inhibitors may vary among type 2 diabetes (T2D) patients depending on whether or not they have established atherosclerotic cardiovascular diseases (ASCVD). We aimed to examine differences in hHF outcomes after dapagliflozin or empagliflozin use between T2D patients with and without a history of established ASCVD. METHODS We conducted a retrospective multi-institutional cohort study in Taiwan. We included T2D patients newly receiving dapagliflozin or empagliflozin during 2016-2019, and followed them up until December 31, 2020. We implemented 1:1 propensity score matching to create homogenous groups for comparisons. We generated Cox proportional hazard models to compare the risk of hHF between dapagliflozin and empagliflozin (reference group). We included interaction terms of SGLT2 inhibitor and ASCVD history in the regression models to examine effect modification by ASCVD. RESULTS We included a total cohort of 9,586 dapagliflozin new users and 9,586 matched empagliflozin new users. The overall hHF risks were similar for dapagliflozin and empagliflozin (HR: 0.90, 95% CI 0.74-1.09). However, differential hHF risks between dapagliflozin and empagliflozin were observed only in the subgroup without ASCVD (HR: 0.67, 95% CI 0.49-0.90), while not in the subgroup with ASCVD (HR: 1.12, 95% 0.87-1.45), and the p-value for examining interaction was 0.0097. CONCLUSION In this study, history of established ASCVD was associated with different hHF risks among SGLT2 inhibitors. For T2D patients without ASCVD, dapagliflozin may offer a more favorable hHF reduction effect, compared to empagliflozin, in clinical practice. Future prospective studies should be conducted to validate our findings.
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The effect of type of fluid on disease severity in acute pancreatitis treatment.
Kayhan, S, Selcan Akyol, B, Ergul, M, Baysan, C
European review for medical and pharmacological sciences. 2021;(23):7460-7467
Abstract
OBJECTIVE In this study, we aimed to investigate the effect of type of fluid (Normal Saline solution: NSS or Lactated Ringer's solution: LRS) to be selected in fluid replacement in acute pancreatitis (AP) treatment on disease severity. SUBJECTS AND METHODS This study is a prospective, single-center study. Patients diagnosed with acute pancreatitis in emergency service were included in the study and randomized to receive LRS or NSS. The severity of AP was determined regarding Revised Atlanta Classification. C-reactive protein (CRP) levels and serum pH and bicarbonate (HCO3) levels were measured to evaluate the systemic inflammatory response and to detect changes in acid-base balance, respectively. RESULTS Sixty-five and seventy-seven patients receiving NSS and LRS, respectively, were analyzed. Eighty-nine (67.4%) and 43 (32.6%) patients were with mild and moderate AP, respectively; however, there was no patient with severe AP. The frequency of moderate AP was significantly lower in the LRS group than the NSS group in terms of the severity of AP (p=0.011). Subjects that were randomized to receive LRS had lower CRP levels when compared to the participants in the NSS treatment arm 48 hours after resuscitation (p=0.010). In addition to these results, serum pH and HCO3 level in patients resuscitated with NSS reduced in comparison to LRS (p<0.001). CONCLUSIONS Resuscitation with LRS is associated with decreased severity of AP in patients with AP. It may derive from how it causes lower CRP levels.
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The Bioequivalence of Two Peficitinib Formulations, and the Effect of Food on the Pharmacokinetics of Peficitinib: Two-Way Crossover Studies of a Single Dose of 150 mg Peficitinib in Healthy Volunteers.
Shibata, M, Toyoshima, J, Kaneko, Y, Oda, K, Kiyota, T, Kambayashi, A, Nishimura, T
Clinical pharmacology in drug development. 2021;(3):283-290
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Abstract
The marketed tablet formulation of peficitinib differs from the tablet used during the clinical trials. The bioequivalence of the marketed formulation and developmental tablet, and the food effect on the marketed formulation, were analyzed in 2 Japanese open-label, randomized, 2-way crossover studies in healthy male volunteers. Volunteers received a single oral dose of the marketed 150-mg peficitinib tablet under fasted conditions (bioequivalence), and under fed or fasted conditions (food effect). Bioequivalence was compared with the developmental 150-mg tablet. Samples for pharmacokinetic analysis were collected before dose and ≤72 hours after dose. Safety assessments included adverse events, vital signs, and laboratory variables. In total, 40 and 18 subjects were randomized to the bioequivalence and food effect studies, respectively. The 2 peficitinib formulations were bioequivalent (90% confidence intervals of the geometric mean ratios for Cmax and AUCt of peficitinib were within predefined limits of 0.8 to 1.25). The AUClast and the Cmax of the marketed tablet were 36.8% and 56.4% higher, respectively, under fed versus fasted conditions. Peficitinib was well tolerated. The marketed 150-mg tablet formulation of peficitinib was bioequivalent to the developmental 150-mg formulation, with no discernible safety differences. Bioavailability increased under fed conditions with the marketed tablet formulation.
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Increasing disparity between Society for Vascular Surgery guidelines for infrarenal abdominal aortic aneurysm repair and real-world practice.
Schlieder, I, Kontopidis, I, Blackwood, S, Krol, E, Dietzek, AM
Journal of vascular surgery. 2021;(4):1227-1233.e1
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Abstract
OBJECTIVE The current Society for Vascular Surgery (SVS) guidelines, based on randomized controlled trials published more than a decade ago, recommend a minimum threshold diameter of 5.5 cm for infrarenal abdominal aortic aneurysm (iAAA) repair. It is unknown whether practice patterns with respect to size of repair have changed since the publication of these guidelines. We aimed to evaluate the real-world practice of vascular surgeons in our region with respect to iAAA size at the time of repair, whether this has changed over the past 12 years and if any changes were associated with the repair type, open vs endovascular. METHODS The Vascular Study Group of New England (VSGNE) database was used to identify all patients who received iAAA repair between 2003 and 2015. The primary end point was to quantify the annual percentage of iAAAs repaired in different size categories (≥5.5 cm; <5.5 cm but ≥5.0 cm; <5.0 cm) over the study time period and by type of repair. The secondary end points were morbidity and mortality in these groups. We excluded nonelective cases (ruptured or symptomatic), patients with coexisting iliac artery aneurysms, and those missing critical data. RESULTS A total of 5314 patients with iAAA repairs (1538 open, 3776 endovascular) were identified in the VSGNE database during the study period. In 40% (2110 of 5314) of patients, repair was performed for aneurysms <5.5 cm, with endovascular aneurysm repair (EVAR) comprising 75% (1581 of 2110) and open 25% (529 of 2110). More EVARs were performed for <5.5 cm in 2015 (46%) compared with 2003 (33%) (P < .05, n - 1 χ2) with an average increase of 1.1%/y. There was also a non-statistically significant increase in open repair of small aneurysms (0.7%/y; P = .759). Overall, 30-day mortality was 1.11% in the EVAR group (0.54% in <5.0 cm, 0.91% in ≥5.0 but <5.5 cm, and 1.55% in ≥5.5 cm), compared with 3% in the open group (2.88%, 1.79%, and 3.77%, respectively) with no significant change in mortality in either group over time. CONCLUSIONS Despite the SVS guidelines suggesting surveillance rather than repair of iAAA <5.5 cm, an increasing proportion of repairs in the VSGNE database were performed below that threshold. The reasons for this are likely multifactorial and might include a lesser complexity and lower operative mortality for smaller aneurysms and markedly improved third- and fourth-generation stent graft technology with possibly better long-term survival. As such, it may be time to re-examine the current guidelines for iAAA repair.
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Dravet syndrome and Dravet syndrome-like phenotype: a systematic review of the SCN1A and PCDH19 variants.
Rampazzo, ACM, Dos Santos, RRP, Maluf, FA, Simm, RF, Marson, FAL, Ortega, MM, de Aguiar, PHP
Neurogenetics. 2021;(2):105-115
Abstract
Dravet syndrome (DS) is a rare and severe epileptic syndrome of childhood with prevalence between 1/22,000 and 1/49,900 of live births. Approximately 80% of patients with this syndrome present SCN1A pathogenic variants, which encodes an alpha subunit of a neural voltage-dependent sodium channel. There is a correlation between PCDH19 pathogenic variants, encodes the protocadherin 19, and a similar disease to DS known as DS-like phenotype. The present review aims to clarify the differences between DS and DS-like phenotype according to the SCN1A and PCDH19 variants. A systematic review was conducted in PubMed and Virtual Health Library (VHL) databases, using "Dravet Syndrome" and "Severe Myoclonic Epilepsy in Infancy (SMEI)" search words, selecting cohort of studies published in journal with impact factor of two or greater. The systematic review was according to the Preferred Reporting Items for Systematic Review and Meta-Analysis recommendations. Nineteen studies were included in the present review, and a significant proportion of patients with DS-carrying SCN1A was greater than patients with DS-like phenotype-harboring PCDH19 variants (76.6% versus 23.4%). When clinical and genetic data were correlated, autism was predominantly observed in patients with DS-like-carrying PCDH19 variants compared to SCN1A variant carriers (62.5% versus 37.5%, respectively, P-value = 0.044, P-value corrected = 0.198). In addition, it was noticed a significant predisposition to hyperthermia during epilepsy crisis in individuals carrying PCDH19 variants (P-value = 0.003; P-value corrected = 0.027). The present review is the first to point out differences between the DS and DS-like phenotype according to the SCN1A and PCDH19 variants.
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Transarterial chemoembolization plus sorafenib versus sorafenib for intermediate-advanced hepatocellular carcinoma: A meta-analysis comparing clinical outcomes.
Xie, Y, Tian, H, Xiang, B, Zhang, Y, Liu, J, Cai, Z, Xiang, H
Medicine. 2021;(33):e26958
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Abstract
BACKGROUND Hepatocellular carcinoma (HCC) ranks as the sixth most common cancer and the second leading cause of cancer-related death worldwide, local and systemic therapies are beneficial for those who have more advanced disease or are not suitable for radical treatment. We aim to investigate the clinical outcomes of transarterial chemoembolization (TACE) plus sorafenib compared with sorafenib monotherapy for intermediate-advanced HCC. METHODS A systematic search according to preferred reporting items for systematic reviews and meta-analyses guidelines in the PubMed database was conducted from inception to December 31, 2020 for published studies comparing survival outcomes and tumor response between TACE + sorafenib and sorafenib alone for intermediate-advanced HCC. RESULTS Five eligible cohort studies and a randomized controlled trial with a total of 3015 patients were identified. We found that the TACE + sorafenib group had a significantly better overall survival (OS) (hazard ratio, 0.77; 95% confidence interval [CI] 0.66-0.88, P < .001) than those treated with sorafenib. Median OS ranged from 7.0 to 22.0 months with TACE + sorafenib and from 5.9 to 18.0 months with sorafenib. The combination of TACE + sorafenib had a significantly better time to progression (hazard ratio, 0.74; 95% CI 0.65-0.82, P < .001) than those treated with sorafenib. Median time to progression ranged from 2.5 to 5.3 months with TACE + sorafenib and from 2.1 to 2.8 months with sorafenib. The results showed the TACE + sorafenib group had a higher disease control rate (log odds ratio, 0.52; 95% CI 0.25-0.80, P = .0002), objective response rate (log odds ratio, 0.85; 95% CI 0.37-1.33, P = .0006) than sorafenib group. Hand-foot skin reaction, diarrhea, fatigue, vomiting, and alanine aminotransferase (ALT) elevation were common adverse events. The adverse events were similar between the 2 groups excluding elevated ALT. CONCLUSION Although the TACE + sorafenib group had a higher elevated ALT, the combination of TACE + sorafenib had an OS benefit compared with sorafenib in the treatment of intermediate-advanced HCC. Further research is necessary to affirm this finding and clarify whether certain subgroups benefit from different combinations between TACE and sorafenib.
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The comparison of nasal irrigation outcome between 3% NaCl and 0.9% NaCl in adults majority with intermittent allergic rhinitis: A randomized double-blind study.
Yata, K, Srivanitchapoom, C
Asian Pacific journal of allergy and immunology. 2021;(1):9-14
Abstract
BACKGROUND Management of allergic rhinitis with oral antihistamine and steroid nasal spray are the standard treatment which is recommended by Allergic Rhinitis and its Impact on Asthma guidelines. In addition, nasal irrigation as an adjuvant therapy also provides a satisfactory result. OBJECTIVE To compare the treatment outcome in adults majority with intermittent allergic rhinitis who receive different concentrations of nasal irrigation. METHODS The prospective randomized double-blind study was performed in 80 patients. All patients were prescribed oral antihistamine and nasal irrigated solution between 3% NaCl and 0.9% NaCl. Nasal congestion and rhinorrhea were evaluated at baseline, first and second weeks after treatment. Assessments were measured by nasal congestion visual analog scale rhinorrhea visual analog scale, inferior turbinate size, and peak nasal expiratory flow rate (PNEFR). A p value of < 0.05 was considered statistically significant. RESULTS There were 40 patients in each group of the study. Patients reported satisfactory experience after using saline irrigation at first and second weeks in both solutions (p value < 0.001). However, when compared between groups, no significant differences for all parameters were reported. PNEFR showed good results after the first week of 3% NaCl irrigation (p value = 0.001), while 0.9% NaCl had good results after the second week (p value < 0.001). CONCLUSIONS Both add-on treatments have a significant improvement of all 4 parameters assessed in the study: nasal congestion, rhinorrhea, inferior turbinate size and PNEFR. Of note, 3% NaCl but not 0.9 NaCl had improved the PNEFR earlier from 1 week of the treatment.