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Epidemiological trends and trajectories of MAFLD-associated hepatocellular carcinoma 2002-2033: the ITA.LI.CA database

Gut. 2021 Dec 21:gutjnl-2021-324915. doi: 10.1136/gutjnl-2021-324915. Online ahead of print.

ABSTRACT

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a new inclusive definition of the whole spectrum of liver diseases associated to metabolic disorders. The main objective of this study was to compare patients with MAFLD and non-MAFLD with hepatocellular carcinoma (HCC) included in a nationally representative cohort.

METHODS: We analysed 6882 consecutive patients with HCC enrolled from 2002 to 2019 by 23 Italian Liver Cancer centres to compare epidemiological and future trends in three subgroups: pure, single aetiology MAFLD (S-MAFLD); mixed aetiology MAFLD (metabolic and others, M-MAFLD); and non-MAFLD HCC.

RESULTS: MAFLD was diagnosed in the majority of patients with HCC (68.4%). The proportion of both total MAFLD and S-MAFLD HCC significantly increased over time (from 50.4% and 3.6% in 2002-2003, to 77.3% and 28.9% in 2018-2019, respectively, p<0.001). In Italy S-MAFLD HCC is expected to overcome M-MAFLD HCC in about 6 years. Patients with S-MAFLD HCC were older, more frequently men and less frequently cirrhotic with clinically relevant portal hypertension and a surveillance-related diagnosis. They had more frequently large tumours and extrahepatic metastases. After weighting, and compared with patients with non-MAFLD, S-MAFLD and M-MAFLD HCC showed a significantly lower overall (p=0.026, p=0.004) and HCC-related (p<0.001, for both) risk of death. Patients with S-MAFLD HCC showed a significantly higher risk of non-HCC-related death (p=0.006).

CONCLUSIONS: The prevalence of MAFLD HCC in Italy is rapidly increasing to cover the majority of patients with HCC. Despite a less favourable cancer stage at diagnosis, patients with MAFLD HCC have a lower risk of HCC-related death, suggesting reduced cancer aggressiveness.

PMID:34933916 | DOI:10.1136/gutjnl-2021-324915

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Global and Regional Variations in Transthyretin Cardiac Amyloidosis: A Comparison of Longitudinal Strain and 99mTechnetium Pyrophosphate Imaging

J Nucl Med Technol. 2021 Dec 21:jnmt.120.261893. doi: 10.2967/jnmt.120.261893. Online ahead of print.

ABSTRACT

Background: There is limited data on the head-to-head comparison of 99mTc-pyrophosphate (PYP) and echocardiographic strain imaging in the assessment of transthyretin (TTR) cardiac amyloidosis. Methods: At Mayo Clinic Arizona, patients that had undergone both a 99mTc-PYP scan and transthoracic echocardiogram (TTE) within a 90-day period were retrospectively identified for chart review and strain imaging analysis. Patients were divided into two groups according to their 99mTc-PYP results (PYP+ and PYP -) for the comparison. A standard 17-segment model was used for segmental, regional and global longitudinal strain comparison. A p-value of <0.05 was deemed as significant. Results: A total of 64 patients were included, the mean age was 75.1 ± 13.0 years and 57(89.1%) were male. Comparing the PYP+ to the PYP- group, the left ventricular global longitudinal strain was significantly worse (PYP+ vs. PYP-: -10.5 ± 2.6 vs. -13.1 ± 4.1, P = 0.003). PYP+ patients also had worse regional basal strain (-4.6 ± 2.6 vs. -8.8±4.0, p<0.001) and a trend of worse mid-ventricular strain (-9.6 ± 4.0 vs. -11.7± 4.4, P = 0.07), however, no statistical difference in apical region (-17.6 ± 4.73 vs. -19.0 ± 6.46, P = 0.35). This is consistent with an apical sparing pattern shown by the relative apical longitudinal strain index (1.3 ±0.5 vs. 1.0 ± 0.3, P = 0.008). Segment to segment analysis demonstrated significant difference in strain between PYP+ and PYP- segments in 4 segments: basal inferior (P = 0.006), basal anterolateral (P = 0.01), apical septal (P = 0.002) and apical inferior (P = 0.001). Left ventricular diastolic dysfunction was significantly different with 17 (77.3%) patients in group PYP+ versus 15 (36.6%) in PYP- participants (P = 0.002). Conclusion: Our study suggested that PYP uptake is related to overall worse LV segmental, regional and global longitudinal strain function, as well as diastolic function compared to patients without PYP uptake. This provides important data for clinicians to know the echocardiographic function features related to 99mTc-PYP uptake and can serve as a hypothesis-generating study for future investigators.

PMID:34933921 | DOI:10.2967/jnmt.120.261893

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Human intrinsic choroidal neurons do not alter the expression of intrinsic markers in response to pressure

Br J Ophthalmol. 2021 Dec 21:bjophthalmol-2021-320211. doi: 10.1136/bjophthalmol-2021-320211. Online ahead of print.

ABSTRACT

BACKGROUND: The choroid is densely innervated by all parts of the autonomic nervous system and further harbours a network of local nerve cells, the intrinsic choroidal neurons (ICN). Their function in ocular control is currently unknown. While morphological data assume a role in intraocular pressure regulation, we here test if increased pressure on isolated choroids may activate ICN.

METHODS: Donor tissue was transferred into a pressurisable tissue culture chamber, and nasal and temporal choroid halves incubated for 1 or 4 hours, with pressures set to 15 or 50 mm Hg, followed by qRT-PCR expression analysis of the ICN-specific markers VIP, UCN, NOS1, UCH-L1. POL2-normalised data in the different pressure settings, incubation times and localisations were statistically analysed.

RESULTS: The presence of the ICN-specific markers VIP, UCN, NOS1, UCH-L1 was confirmed using immunohistochemistry, and mRNA of all markers was detected in all experimental conditions. Marker analysis revealed no significant changes of mRNA expression levels between 15 and 50 mm Hg in the different incubation times. When comparing all samples over all experimental conditions, a significant increase of VIP and NOS1 mRNA was detected in temporal versus nasal choroids.

CONCLUSION: In this functional analysis of human ICN in vitro, higher amounts of VIP and NOS1 mRNA were detected in the temporal choroid, that is, the choroidal site with ICN accumulation. Further, our data indicate that elevated pressure is apparently not able to trigger ICN responses via the investigated markers. Alternative markers and stimuli need to be investigated in upcoming studies in order to unravel ICN function.

PMID:34933896 | DOI:10.1136/bjophthalmol-2021-320211

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Impact of New York State’s Health Home program on access to care among patients with diabetes

BMJ Open Diabetes Res Care. 2021 Dec;9(Suppl 1):e002204. doi: 10.1136/bmjdrc-2021-002204.

ABSTRACT

INTRODUCTION: Access to care is essential for patients with diabetes to maintain health and prevent complications, and is important for health equity. New York State’s Health Homes (HHs) provide care management services to Medicaid-insured patients with chronic conditions, including diabetes, and aim to improve quality of care and outcomes. There is inconsistent evidence on the impact of HHs, and care management programs more broadly, on access to care.

RESEARCH DESIGN AND METHODS: Using a cohort of patients with diabetes derived from electronic health records from the INSIGHT Clinical Research Network, we analyzed Medicaid data for HH enrollees and a matched comparison group of HH non-enrollees. We estimated HH impacts on several access measures using natural experiment methods.

RESULTS: We identified and matched 11 646 HH enrollees; patients were largely non-Hispanic Black (29.9%) and Hispanic (48.7%), and had high rates of dual eligibility (33.0%), Supplemental Security Income disability enrollment (49.1%), and multiple comorbidities. In the 12 months following HH enrollment, HH enrollees had one more month of Medicaid coverage (p<0.001) and 4.6 more outpatient visits than expected (p<0.001, evenly distributed between primary and specialty care). There were also positive impacts on the proportions of patients with follow-up visits within 7 days (4 percentage points (pp), p<0.001) and 30 days (6pp, p<0.001) after inpatient care, and on the proportion of patients with follow-up visits within 30 days after emergency department (ED) care (4pp, p<0.001). We did not find meaningful differences in continuity of care. We found small positive impacts on the proportion of patients with an inpatient visit and the proportion with an ED visit.

CONCLUSIONS: New York State’s HH program improved access to care for Medicaid recipients with diabetes. These findings have implications for New York State Medicaid as well as other providers and care management programs.

PMID:34933873 | DOI:10.1136/bmjdrc-2021-002204

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The effect of interventions targeting gut microbiota on depressive symptoms: a systematic review and meta-analysis

CMAJ Open. 2021 Dec 21;9(4):E1195-E1204. doi: 10.9778/cmajo.20200283. Print 2021 Oct-Dec.

ABSTRACT

BACKGROUND: Despite their popularity, the efficacy of interventions targeting gut microbiota to improve depressive symptoms is unknown. Our objective is to summarize the effect of microbiome-targeting interventions on depressive symptoms.

METHODS: We conducted a systematic review and meta-analysis. We searched MEDLINE, Embase, PsycINFO, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews and the Cochrane Controlled Register of Trials from inception to Mar. 5, 2021. We included studies that evaluated probiotic, prebiotic, synbiotic, paraprobiotic or fecal microbiota transplant interventions in an adult population (age ≥ 18 yr) with an inactive or placebo comparator (defined by the absence of active intervention). Studies must have measured depressive symptoms with a validated scale, and used a randomized controlled trial study design. We conducted a random effects meta-analysis of change scores, using standardized mean difference as the measure of effect.

RESULTS: Sixty-two studies formed the final data set, with 50 included in the meta-analysis. Probiotic, prebiotic, and synbiotic interventions on depressive symptoms showed statistically significant benefits. In the single studies evaluating each of fecal microbiota transplant and paraprobiotic interventions, neither showed a statistically significant benefit.

INTERPRETATION: Despite promising findings of benefit of probiotic, prebiotic and synbiotic interventions for depressive symptoms in study populations, there is not yet strong enough evidence to favour inclusion of these interventions in treatment guidelines for depression. Critical questions about species administered, dosage and timing relative to other antidepressant medications remain to be answered.

STUDY REGISTRATION: PROSPERO no. 143178.

PMID:34933877 | DOI:10.9778/cmajo.20200283

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Evaluation of pathological complete response as surrogate endpoint in neoadjuvant randomised clinical trials of early stage breast cancer: systematic review and meta-analysis

BMJ. 2021 Dec 21;375:e066381. doi: 10.1136/bmj-2021-066381.

ABSTRACT

OBJECTIVE: To evaluate pathological complete response as a surrogate endpoint for disease-free survival and overall survival in regulatory neoadjuvant trials of early stage breast cancer.

DESIGN: Systematic review and meta-analysis.

DATA SOURCES: Medline, Embase, and Scopus to 1 December 2020.

ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised clinical trials that tested neoadjuvant chemotherapy given alone or combined with other treatments, including anti-human epidermal growth factor 2 (anti-HER2) drugs, targeted treatments, antivascular agents, bisphosphonates, and immune checkpoint inhibitors.

DATA EXTRACTION AND SYNTHESIS: Trial level associations between the surrogate endpoint pathological complete response and disease-free survival and overall survival.

METHODS: A weighted regression analysis was performed on log transformed treatment effect estimates (hazard ratio for disease-free survival and overall survival and relative risk for pathological complete response), and the coefficient of determination (R2) was used to quantify the association. The secondary objective was to explore heterogeneity of results in preplanned subgroups analysis, stratifying trials according treatment type in the experimental arm, definition used for pathological complete response (breast and lymph nodes v breast only), and biological features of the disease (HER2 positive or triple negative breast cancer). The surrogate threshold effect was also evaluated, indicating the minimum value of the relative risk for pathological complete response necessary to confidently predict a non-null effect on hazard ratio for disease-free survival or overall survival.

RESULTS: 54 randomised clinical trials comprising a total of 32 611 patients were included in the analysis. A weak association was observed between the log(relative risk) for pathological complete response and log(hazard ratio) for both disease-free survival (R2=0.14, 95% confidence interval 0.00 to 0.29) and overall survival (R2 =0.08, 0.00 to 0.22). Similar results were found across all subgroups evaluated, independently of the definition used for pathological complete response, treatment type in the experimental arm, and biological features of the disease. The surrogate threshold effect was 5.19 for disease-free survival but was not estimable for overall survival. Consistent results were confirmed in three sensitivity analyses: excluding small trials (<200 patients enrolled), excluding trials with short median follow-up (<24 months), and replacing the relative risk for pathological complete response with the absolute difference of pathological complete response rates between treatment arms.

CONCLUSION: A lack of surrogacy of pathological complete response was identified at trial level for both disease-free survival and overall survival. The findings suggest that pathological complete response should not be used as primary endpoint in regulatory neoadjuvant trials of early stage breast cancer.

PMID:34933868 | DOI:10.1136/bmj-2021-066381

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Pancreatic fat relates to fasting insulin and postprandial lipids but not polycystic ovary syndrome in adolescents with obesity

Obesity (Silver Spring). 2022 Jan;30(1):191-200. doi: 10.1002/oby.23317.

ABSTRACT

OBJECTIVE: Adolescents with polycystic ovary syndrome (PCOS) and obesity can have insulin resistance, dysglycemia, and hepatic steatosis. Excess pancreatic fat may disturb insulin secretion and relate to hepatic fat. Associations between pancreatic fat fraction (PFF) and metabolic measures in PCOS were unknown.

METHODS: This secondary analysis included 113 sedentary, nondiabetic adolescent girls (age = 15.4 [1.9] years), with or without PCOS and BMI ≥ 90th percentile. Participants underwent fasting labs, oral glucose tolerance tests, and magnetic resonance imaging for hepatic fat fraction (HFF) and PFF. Groups were categorized by PFF (above or below the median of 2.18%) and compared.

RESULTS: Visceral fat and HFF were elevated in individuals with PCOS versus control individuals, but PFF was similar. PFF did not correlate with serum androgens. Higher and lower PFF groups had similar HFF, with no correlation between PFF and HFF, although hepatic steatosis was more common in those with higher PFF (≥5.0% HFF; 60% vs. 36%; p = 0.014). The higher PFF group had higher fasting insulin (p = 0.026), fasting insulin resistance (homeostatic model assessment of insulin resistance, p = 0.032; 1/fasting insulin, p = 0.028), free fatty acids (p = 0.034), and triglycerides (p = 0.004) compared with those with lower PFF. β-Cell function and insulin sensitivity were similar between groups.

CONCLUSIONS: Neither PCOS status nor androgens related to PFF. However, fasting insulin and postprandial lipids were worse with higher PFF.

PMID:34932884 | DOI:10.1002/oby.23317

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Home phototherapy of term neonates improves parental bonding and stress: findings from a randomised controlled trial

Acta Paediatr. 2021 Dec 21. doi: 10.1111/apa.16231. Online ahead of print.

ABSTRACT

AIM: We aimed to evaluate whether in-home phototherapy for hyper bilirubinaemia could reduce the poorer parent-infant bonding and increased parental stress associated with neonatal hospital treatment.

METHODS: In this multicentre randomised controlled trial we allocated families to either home phototherapy or standard hospital care. The primary outcome was parent-infant bonding measured on the Postpartum Bonding Questionnaire directly after therapy and 4 months later. Secondary outcomes were results on four other instruments measuring parental bonding, quality of life, and mental health.

RESULTS: We randomised 78 of 147 newborn infants to intervention and 69 to the control group. No significant differences were detected in length of stay, mean bilirubin, or weight gain. Parents in the intervention group had better scores on bonding both at discharge (p = 0.034) and at 4 months (p = 0.008; effect size r = 0.2) and lower levels of stress at 4 months (p = 0.024) than controls. No statistically significant outcomes were found for the secondary outcomes.

CONCLUSION: In-home phototherapy improved bonding and reduced parental stress in comparison with usual in-hospital treatment. Caregivers should consider offering home phototherapy to families of non-immunised term infants with hyperbilirubinaemia.

PMID:34932853 | DOI:10.1111/apa.16231

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Microsimulation projections of obesity interventions on cardiometabolic health disparities in the United States

Obesity (Silver Spring). 2022 Jan;30(1):62-74. doi: 10.1002/oby.23297.

ABSTRACT

OBJECTIVE: The aim of this study was to estimate long-term impacts of health education interventions on cardiometabolic health disparities.

METHODS: The model simulates how health education implemented in the United States throughout 2019 to 2049 would lead to changes in adult BMI and consequent hypertension and type 2 diabetes. Health outcome changes by sex, racial/ethnic (non-Hispanic White, non-Hispanic Black, and Hispanic), and weight status (normal: 18.5 ≤ BMI < 25; overweight: 25 ≤ BMI < 30; and obesity: 30 ≤ BMI) subpopulations were compared under a scenario with and one without health education.

RESULTS: By 2049, the intervention would reduce average BMI of women with obesity to 27.7 kg/m2 (CI: 27.4-27.9), which would be 2.9 kg/m2 lower than the expected average BMI without an intervention. Education campaigns would reduce type 2 diabetes prevalence, but it would remain highest among women with obesity at 27.7% (CI: 26.2%-29.2%). The intervention would reduce hypertension prevalence among White women by 4.7 percentage points to 38.0% (CI: 36.4%-39.7%). For Black women in the intervention, the 2049 hypertension prevalence would be 52.6% (CI: 50.7%-54.5%). Results for men and women were similar.

CONCLUSIONS: Long-term health education campaigns can reduce obesity-related disease. All population groups benefit, but they would not substantially narrow cardiometabolic health disparities.

PMID:34932883 | DOI:10.1002/oby.23297

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Effect of Different Energy Densities of 915 nm Low Power Laser on The Biological Behavior of Human Gingival Fibroblast Cells in-vitro

Photochem Photobiol. 2021 Dec 21. doi: 10.1111/php.13577. Online ahead of print.

ABSTRACT

Photobiomodulation is recognized as an effective method for adjunct therapy in periodontal treatments. our purpose in this study was to investigate the effects of different energy densities of 915nm diode laser on the viability and viability capacity of human gingival fibroblast cells. cell samples were examined in 5 groups, including 4 irradiation groups with low-level diode laser 915nm, 1,2,3,4 J/cm2 , and a control group (no Laser irradiation). Cell viability and viability were measured 1, 3 and 5 days after irradiation by MTT and DAPI assay. Statistical differences between groups at any time were analyzed by one-way ANOVA and a post hoc Turkey’s test. The cell viability and viability capacity increased on the third day at an energy density of 3 J/cm2 ; (P-value = 0.007) and the fifth day at energy densities of 2,3 and 4 J/cm2 was recorded compared to the control group (P-value =0.000). Also, a significant decrease in the viability and viability of irradiated cells with an energy density of 1 J/cm2 was found. (P-value =0.033). according to our results, Photobiomodulation with 915nm diode laser has a positive stimulating effect on the viability and viability capacity of human gingival fibroblast cells.

PMID:34932837 | DOI:10.1111/php.13577