Altered intestinal microbiota has been reported in pancreatic disorders, however, it remains unclear whether these changes alter the course of disease in patients with acute (AP) and chronic ...pancreatitis (CP), or whether these disease states alter the environment to enable pathogenic microbial composition changes to occur. We undertook a systematic review to characterize the gut microbiome in pancreatitis patients.
MEDLINE and EMBASE were searched for studies on microbiota in pancreatitis published from January 1, 2000 to June 5, 2020. Animal studies, reviews, case reports, and non-English articles were excluded. A frequency analysis was performed for outcomes reported in ≥2 studies and studies were analyzed for risk of bias and quality of evidence.
22 papers met inclusion criteria; 15 included AP, 7 included CP. No studies were appropriately designed to assess whether alterations in the gut microbiome exacerbate pancreatitis or develop as a result of pancreatitis. We did identify several patterns of microbiome changes that are associated with pancreatitis. The gut microbiome demonstrated decreased alpha diversity in 3/3 A P studies and 3/3 C P studies. Beta diversity analysis revealed differences in bacterial community composition in the gut microbiome in 2/2 A P studies and 3/3 C P studies. Functionally, gut microbiome changes were associated with infectious pathways in AP and CP. Several studies suffered from high risk of bias and inadequate quality.
Detecting differences in microbial composition associated with AP and CP may represent a diagnostic tool. Appropriately controlled longitudinal studies are needed to determine whether microbiome changes are causative or reactive in pancreatitis.
Older patients with advanced chronic kidney disease are at increased risk for a severe course of the coronavirus disease-2019 (COVID-19) and vulnerable to mental health problems. We aimed to ...investigate prevalence and associated patient (demographic and clinical) characteristics of mental wellbeing (health-related quality of life HRQoL and symptoms of depression and anxiety) before and during the COVID-19 pandemic in older patients with advanced chronic kidney disease.
An ongoing Dutch multicentre prospective cohort study enrols patients of ≥70 years with an eGFR < 20 mL/min/1.73m
from October 2018 onward. With additional questionnaires during the pandemic (May-June 2020), disease-related concerns about COVID-19 and general anxiety symptoms were assessed cross-sectionally, and depressive symptoms, HRQoL, and emotional symptoms longitudinally.
The 82 included patients had a median age of 77.5 years (interquartile range 73.9-82.1), 77% were male and none had tested positive for COVID-19. Cross-sectionally, 67% of the patients reported to be more anxious about COVID-19 because of their kidney disease, and 43% of the patients stated that their quality of life was reduced due to the COVID-19 pandemic. Compared to pre-COVID-19, the presence of depressive symptoms had increased (11 to 22%; p = .022) and physical HRQoL declined (M = 40.4, SD = 10.1 to M = 36.1, SD = 10.4; p < .001), particularly in males. Mental HRQoL (M = 50.3, SD = 9.6 to M = 50.4, SD = 9.9; p = .913) and emotional symptoms remained similar.
Older patients with advanced chronic kidney disease suffered from disease-related anxiety about COVID-19, increased depressive symptoms and reduced physical HRQoL during the COVID-19 pandemic. The impact of the pandemic on this vulnerable patient group extends beyond increased mortality risk, and awareness of mental wellbeing is important.
The study is registered at the Netherlands Trial Register (NTR), trial number NL7104. Date of registration: 06-06-2018.
Risk of Cardiovascular Events After COVID-19 Tereshchenko, Larisa G.; Bishop, Adam; Fisher-Campbell, Nora ...
The American journal of cardiology,
09/2022, Letnik:
179
Journal Article
Recenzirano
Odprti dostop
We aimed to determine absolute and relative risks of either symptomatic or asymptomatic SARS-CoV-2 infection for late cardiovascular (CV) events and all-cause mortality. We conducted a retrospective ...double cohort study of patients with either symptomatic or asymptomatic SARS-CoV-2 infection (COVID-19+ cohort) and its documented absence (COVID-19− cohort). The study investigators drew a simple random sample of records from all patients under the Oregon Health & Science University Healthcare (n = 65,585), with available COVID-19 test results, performed March 1, 2020 to September 13, 2020. Exclusion criteria were age <18 years and no established Oregon Health & Science University care. The primary outcome was a composite of CV morbidity and mortality. All-cause mortality was the secondary outcome. The study population included 1,355 patients (mean age 48.7 ± 20.5 years; 770 women 57%, 977 White non-Hispanic 72%; 1,072 ensured 79%; 563 with CV disease history 42%). During a median 6 months at risk, the primary composite outcome was observed in 38 of 319 patients who were COVID-19+ (12%) and 65 of 1,036 patients who were COVID-19− (6%). In the Cox regression, adjusted for demographics, health insurance, and reason for COVID-19 testing, SARS-CoV-2 infection was associated with the risk for primary composite outcome (hazard ratio 1.71, 95% confidence interval 1.06 to 2.78, p = 0.029). Inverse probability-weighted estimation, conditioned for 31 covariates, showed that for every patient who was COVID-19+, the average time to all-cause death was 65.5 days less than when all these patients were COVID-19−: average treatment effect on the treated −65.5 (95% confidence interval −125.4 to −5.61) days, p = 0.032. In conclusion, either symptomatic or asymptomatic SARS-CoV-2 infection is associated with an increased risk for late CV outcomes and has a causal effect on all-cause mortality in a late post-COVID-19 period.
Background Phosphate binders are the cornerstone of hyperphosphatemia management in dialysis patients. Ferric citrate is an iron-based oral phosphate binder that effectively lowers serum phosphorus ...levels. Study Design 52-week, open-label, phase 3, randomized, controlled trial for safety-profile assessment. Setting & Participants Maintenance dialysis patients with serum phosphorus levels ≥6.0 mg/dL after washout of prior phosphate binders. Intervention 2:1 randomization to ferric citrate or active control (sevelamer carbonate and/or calcium acetate). Outcomes Changes in mineral bone disease, protein-energy wasting/inflammation, and occurrence of adverse events after 1 year. Measurements Serum calcium, intact parathyroid hormone, phosphorus, aluminum, white blood cell count, percentage of lymphocytes, serum urea nitrogen, and bicarbonate. Results There were 292 participants randomly assigned to ferric citrate, and 149, to active control. Groups were well matched. For mean changes from baseline, phosphorus levels decreased similarly in the ferric citrate and active control groups (−2.04 ± 1.99 SD vs −2.18 ± 2.25 mg/dL, respectively; P = 0.9); serum calcium levels increased similarly in the ferric citrate and active control groups (0.22 ± 0.90 vs 0.31 ± 0.95 mg/dL; P = 0.2). Hypercalcemia occurred in 4 participants receiving calcium acetate. Parathyroid hormone levels decreased similarly in the ferric citrate and active control groups (−167.1 ± 399.8 vs −152.7 ± 392.1 pg/mL; P = 0.8). Serum albumin, bicarbonate, serum urea nitrogen, white blood cell count and percentage of lymphocytes, and aluminum values were similar between ferric citrate and active control. Total and low-density lipoprotein cholesterol levels were lower in participants receiving sevelamer than those receiving ferric citrate and calcium acetate. Fewer participants randomly assigned to ferric citrate had serious adverse events compared with active control. Limitations Open-label study, few peritoneal dialysis patients. Conclusions Ferric citrate was associated with similar phosphorus control compared to active control, with similar effects on markers of bone and mineral metabolism in dialysis patients. There was no evidence of protein-energy wasting/inflammation or aluminum toxicity, and fewer participants randomly assigned to ferric citrate had serious adverse events. Ferric citrate is an effective phosphate binder with a safety profile comparable to sevelamer and calcium acetate.
The aim of this study was to identify the bitter receptor(s) that recognize the bitter taste of the soy isoflavone genistein. Screening of all 25 human bitter receptors revealed genistein as agonist ...of hTAS2R14 and hTAS2R39. Genistein displayed threshold values of 4 and 8 μM on hTAS2R14 and hTAS2R39 and EC50 values of 29 and 49 μM, respectively. In addition, the behavior of structurally similar isoflavonoids was investigated. Although the two receptors are not closely related, the results for hTAS2R14 and hTAS2R39 were similar toward most isoflavonoid aglycones. By trend, threshold values were slightly lower on hTAS2R14. Glucosylation of isoflavones seemed to inhibit activation of hTAS2R14, whereas four of five glucosylated isoflavones were agonists of hTAS2R39, namely, glycitin, genistin, acetylgenistin, and malonylgenistin. A total of three hydroxyl substitutions of the A- and B-rings of the isoflavonoids seemed to be more favorable for receptor activation than fewer hydroxyl groups. The concentration of the trihydroxylated genistein in several soy foods exceeds the determined bitter receptor threshold values, whereas those of other soy isoflavones are around or below their respective threshold value. Despite its low concentration, genistein might be one of the main contributors to the bitterness of soy products. Furthermore, the bioactive isoflavonoids equol and coumestrol activated both receptors, indicating that their sensory impact should be considered when used as food ingredients.
Patients with chronic kidney disease (CKD) are at risk for progression to kidney failure. Using data of Canadian CKD patients, Tangri et al. recently developed models to predict the progression of ...CKD stages 3-5 to kidney failure within 5 years. We validated this kidney failure risk equation (KFRE) in European CKD patients.
We selected non-transplanted patients with CKD stages 3-5 who participated in the MASTERPLAN study, a randomized controlled trial in patients with CKD. Kidney failure was defined as the initiation of chronic dialysis or kidney transplantation within 5 years. Patients who died before kidney failure were censored. Patients followed for <5 years, who did not develop kidney failure and did not die, were excluded. The 5-year kidney failure risk was predicted using three different models developed by Tangri et al. and compared with the actual kidney failure rate in MASTERPLAN. Model performance was evaluated using the area under the receiver operating characteristic curve (ROC-AUC), the net reclassification index (NRI) and by comparing the observed and predicted rates of kidney failure.
A total of 595 patients were included; 114 developed kidney failure. (Overall observed kidney failure risk in our cohort was 5% lower than in the Canadian validation cohort.) Discrimination of the eight-variable model including age, sex, estimated glomerular filtration rate (eGFR), albuminuria, calcium, phosphate, bicarbonate, albumin was similar to that of the four-variable model (including age, sex, eGFR, albuminuria) and the three-variable model (including age, sex, eGFR); ROC-AUCs were 0.89 95% confidence interval (CI) 0.86-0.92, 0.88 (95% CI 0.85-0.91) and 0.88 (95% CI 0.85-0.92), respectively. Using the NRI, the eight-variable model slightly outperformed the four-variable model (NRI 6.5%) and the three-variable model (NRI 12.4%). The mean differences between the observed and predicted kidney failure risk were -4.0, -7.1 and -7.4% for the eight-, four-, and three-variable model, respectively.
The KFRE accurately predicted the progression to kidney failure in European CKD patients. Discrimination of the three models was similar. Calibration of the eight-variable model was slightly better than that of the simpler models. We question whether this outweighs its added complexity.
Recent studies are emphasising the importance and putative modes of action of specific flavonoids as bioactive components of the diet in in vivo and in vitro models. Thus, it is important to have a ...clear idea of the major phenolic families of which fruit and vegetables are comprised and the levels contained therein. Regularly consumed fruit and vegetables of mixed varieties available on the UK market were analysed for the composition of the major individual phenolic components. The total phenolic content (applying the Folin assay) and the vitamin C levels were also determined. The antioxidant capacities of aqueous/methanolic extracts were comparatively assessed using the TEAC (Trolox Equivalent Antioxidant Capacity), the FRAP (Ferric Reducing Ability of Plasma) and ORAC (Oxygen Radical Absorbance Capacity) assays, which comprise contributions from polyphenols, simple phenols and the ascorbate component. The results were calculated in terms of 100 u g fresh weight (FW) uncooked portion sizes. Fruit and vegetables rich in anthocyanins (e.g. strawberry, raspberry and red plum) demonstrated the highest antioxidant activities, followed by those rich in flavanones (e.g. orange and grapefruit) and flavonols (e.g. onion, leek, spinach and green cabbage), while the hydroxycinnamate-rich fruit (e.g. apple, tomato, pear and peach) consistently elicited the lower antioxidant activities. The TEAC, FRAP and ORAC values for each extract were relatively similar and well-correlated with the total phenolic and vitamin C contents. The antioxidant activities (TEAC) in terms of 100 u g FW uncooked portion size were in the order: strawberry d raspberry=red plum d red cabbage>>>grapefruit= orange>spinach>broccoli>green grape ; onion> green cabbage>pea>apple> cauliflower ; pear> tomato ; peach=leek>banana ; lettuce.
Background
Previous studies have demonstrated low first‐time donor return rates (DRR) following catastrophic events. Little is known, however, about the influence of demographic factors on the DRR of ...first‐time donors during the COVID‐19 pandemic, including the unique motivation of COVID‐19 convalescent plasma (CCP) donors as compared to non‐CCP donors.
Study Design and Methods
Thirteen blood collection organizations submitted deidentified data from first‐time CCP and non‐CCP donors returning for regular (non‐CCP) donations during the pandemic. DRR was calculated as frequencies. Demographic factors associated with returning donors: race/ethnicity, gender, and generation (Gen Z: 19–24, Millennial: 25–40, Gen X: 41–56, and Boomer: ≥57 years old), within the CCP and non‐CCP first‐time cohorts were compared using chi‐square test at p < .05 statistical significance.
Results
From March 2020 through December 2021, there were a total of 44,274 first‐time CCP and 980,201 first‐time non‐CCP donors. DRR were 14.6% (range 11.9%–43.3%) and 46.6% (range 10.0%–76.9%) for CCP and non‐CCP cohorts, respectively. Age over 40 years (Gen X and Boomers), female gender, and White race were each associated with higher return in both donor cohorts (p < .001). For the non‐CCP return donor cohort, the Millennial and Boomers were comparable.
Conclusion
The findings demonstrate differences in returning donor trends between the two donor cohorts. The motivation of a first‐time CCP donor may be different than that of a non‐CCP donor. Further study to improve first‐time donor engagement would be worthwhile to expand the donor base with a focus on blood donor diversity emphasizing engagement of underrepresented minorities and younger donors.
Multimodal therapy is recommended for early stage pancreatic cancer, although whether all patients benefit and the optimal timing of chemotherapy remain unclear.
Retrospective cohort study of ...patients aged 18–79 years with stage I-II pancreatic ductal adenocarcinoma in the National Cancer Database (2004–2012). Patients were grouped based on treatment strategy as surgery only, adjuvant, and preoperative. Accuracy of nodal staging and rate of nodal downstaging were ascertained using pretreatment clinical and postresection pathologic nodal status data. Association between overall risk of death and treatment strategy was evaluated with multivariable Cox regression.
Among 19,031 patients, 31.1% underwent surgery only, 59.6% received adjuvant, and 9.3% preoperative therapy. Based on patients receiving upfront surgery, clinical nodal staging bore sensitivity, specificity, positive predictive value, and negative predictive value of 46.2%, 95.7%, 95.1%, and 49.8%, respectively. Preoperative therapy downstaged 38% of cN1 patients to ypN0; 5-year overall survival for this group was 27.2% vs 12.3% for ypN1 patients (P < .001). Relative to surgery only, adjuvant (HR 0.75, 95% CI 0.71–0.78) and preoperative therapy (HR 0.66 0.60–0.73) were associated with lower risk of death among patients with pN1, but not pN0 (adjuvant—HR 1.01 0.94–1.09; preoperative—HR 1.10 0.99–1.22), disease.
Our data provide strong support for preoperative chemotherapy for patients with node-positive pancreatic cancer, one third of whom may be downstaged. Among those with seemingly node-negative disease, half will be understaged with current clinical staging modalities. These results should be considered when planning treatment for patients with early stage pancreatic cancer.