Population attributable fractions of modifiable risk factors for dementia: a systematic review and meta-analysis.

BACKGROUND: More than 57 million people have dementia worldwide. Evidence indicates a change in dementia prevalence and incidence in high-income countries, which is likely to be due to improved life-course population health. Identifying key modifiable risk factors for dementia is essential for informing risk reduction and prevention strategies. We therefore aimed to estimate the population attributable fraction (PAF) for dementia associated with modifiable risk factors. METHODS: In this systematic review and meta-analysis, we searched Embase, MEDLINE, and PsycINFO, via Ovid, from database inception up to June 29, 2023, for population-derived or community-based studies and reviews reporting a PAF value for one or more modifiable risk factor for later-life dementia (prevalent or incident dementia in people aged ≥60 years), with no restrictions on dementia subtype, the sex or baseline age of participants, or the period of study. Articles were independently screened for inclusion by four authors, with disagreements resolved through consensus. Data including unweighted and weighted PAF values (weighted to account for communality or overlap in risk) were independently extracted into a predefined template by two authors and checked by two other authors. When five or more unique studies investigated a given risk factor or combination of the same factors, random-effects meta-analyses were used to calculate a pooled PAF percentage estimate for the factor or combination of factors. The review protocol was registered on PROSPERO, CRD42022323429. FINDINGS: 4024 articles were identified, and 74 were included in our narrative synthesis. Overall, PAFs were reported for 61 modifiable risk factors, with sufficient data available for meta-analysis of 12 factors (n=48 studies). In meta-analyses, the highest pooled unweighted PAF values were estimated for low education (17·2% [95% CI 14·4-20·0], p<0·0001), hypertension (15·8% [14·7-17·1], p<0·0001), hearing loss (15·6% [10·3-20·9], p<0·0001), physical inactivity (15·2% [12·8-17·7], p<0·0001), and obesity (9·4% [7·3-11·7], p<0·0001). According to weighted PAF values, low education (9·3% [6·9-11·7], p<0·0001), physical inactivity (7·3% [3·9-11·2], p=0·0021), hearing loss (7·2% [5·2-9·7], p<0·0001), hypertension (7·1% [5·4-8·8], p<0·0001), and obesity (5·3% [3·2-7·4], p=0·0001) had the highest pooled estimates. When low education, midlife hypertension, midlife obesity, smoking, physical inactivity, depression, and diabetes were combined (Barnes and Yaffe seven-factor model; n=9 studies), the pooled unweighted and weighted PAF values were 55·0% (46·5-63·5; p<0·0001) and 32·0% (26·6-37·5; p<0·0001), respectively. The pooled PAF values for most individual risk factors were higher in low-income and middle-income countries (LMICs) versus high-income countries. INTERPRETATION: Governments need to invest in a life-course approach to dementia prevention, including policies that enable quality education, health-promoting environments, and improved health. This investment is particularly important in LMICs, where the potential for prevention is high, but resources, infrastructure, budgets, and research focused on ageing and dementia are limited. FUNDING: UK Research and Innovation (Medical Research Council).

Penetrating hypopharyngeal foreign body impalement of the thyroid gland: A case report of rare complication of ingested fish bone.

INTRODUCTION AND IMPORTANCE: Foreign body ingestion complicated by hypopharyngeal perforation is an uncommon but potentially life-threatening condition. Early recognition and appropriate management are crucial to prevent serious complications. We present an extremely rare case highlighting the importance of this clinical entity. CASE PRESENTATION: A 60-year-old female presented with odynophagia 10 days after ingesting fish and chicken. Imaging revealed a linear foreign body penetrating through the left lateral hypopharyngeal wall into the left thyroid lobe, with surrounding inflammatory changes. The patient underwent neck exploration, which identified a sharp fishbone lodged in the postero-medial aspect of the left thyroid lobe, necessitating a left hemithyroidectomy for removal. CLINICAL DISCUSSION: To our knowledge, this is the first reported case of hypopharyngeal perforation by an ingested foreign body penetrating the thyroid gland itself. Despite its rarity, early recognition is crucial to prevent complications like abscess, mediastinitis, and mortality. A high index of suspicion is needed in patients with odynophagia or neck pain after ingesting fish. Advanced imaging and surgical intervention may be required for the management of larger perforations or those involving surrounding structures. CONCLUSION: This unique case highlights an extremely rare presentation of hypopharyngeal perforation with extension into the thyroid gland caused by an ingested fish bone. Prompt diagnosis through appropriate imaging and treatment with surgical exploration and foreign body removal was key to ensuring a positive outcome. Increased awareness of this potential complication is essential among clinicians.

Spondylodiscitis following perforated acute appendicitis in a 14-year-old female: A case report.

INTRODUCTION AND IMPORTANCE: Acute appendicitis is a common surgical emergency, often resulting in perforation and increased morbidity. Up to 55 % of children with complicated appendicitis may experience a complication such as infection, bowel obstruction, or unplanned hospital re-admission (Blakely et al., 2011 [23]). However, the development of infectious spondylodiscitis following appendectomy is an extremely rare complication, particularly in pediatric patients. We present the first reported case of lumbar spondylodiscitis occurring post-perforated appendicitis in a 14-year-old female, highlighting the importance of recognizing and managing uncommon complications. CASE PRESENTATION: A previously healthy 14-year-old female underwent urgent appendectomy for perforated appendicitis. Postoperatively, she developed severe back pain and immobility. Imaging revealed early lumbar discitis, and Pseudomonas aeruginosa was isolated from the surgical site. The patient received multiple antibiotic regimens, including vancomycin, ceftazidime, and meropenem, resulting in clinical improvement. CLINICAL DISCUSSION: Infectious spondylodiscitis is typically hematogenously spread or due to direct inoculation. In this case, the spread from a contiguous focus of infection without vascular insufficiency is suspected. The coexistence of appendicitis and spondylodiscitis poses diagnostic challenges, requiring a multidisciplinary approach for accurate diagnosis and appropriate treatment. CONCLUSION: This unique case highlights the need for vigilance in recognizing rare complications of appendicitis, such as infectious spondylodiscitis. Early diagnosis and tailored antibiotic therapy are crucial for optimal outcomes. Further research is needed to explore the underlying mechanisms and risk factors associated with this rare complication.

Novel Therapeutic Agents for Management of Diabetes Mellitus: A Hope for Drug Designing against Diabetes Mellitus.

Diabetes mellitus (DM) is characterized by an absolute decline in insulin secretion and peripheral resistance and is the most prevalent metabolic and endocrine disorder. However, the pathogenesis of DM also includes adipocyte insulin resistance, increased glucagon secretion, increased renal glomerular glucose absorption, and neurotransmitter dysfunction. Although there is a wide spectrum of therapeutics available for glycemic control, owing to the identification of various pathogenic determinants of DM, management of DM remains challenging and complex. Current therapeutic interventions against DM focus mostly on glycemic control without considering the other pathological determinants that eventually lead to treatment failure and the progression of DM. Furthermore, long-term use of these conventionally available anti-diabetic drugs leads to various side effects, henceforth development of novel drugs against DM remains an unending search strategy for researchers. Various studies conducted in various parts of the world have proposed that these novel therapeutic interventions target multiple and alternate pathogenic hotspots involved in DM. The current review article discusses novel therapeutic options that hold particular promise to support their safety and discuss the side effects resulting from their use so that these novel candidate drugs can be effectively fabricated into potential drugs for the treatment of DM.

Frontal Meningoencephalocele With Cerebrospinal Fluid Rhinorrhea: A Case Report.

Traumatic brain injuries are a significant public health concern often associated with immediate consequences. However, delayed complications can manifest, including rare congenital neural tube defects such as encephaloceles. We present a case of a 45-year-old male with a history of traumatic brain injuries who developed a posttraumatic frontal meningoencephalocele associated with cerebrospinal fluid rhinorrhea. This case emphasizes the need for vigilance in assessing patients with a history of head trauma for delayed complications, even years after the initial injury. Early diagnosis and intervention can significantly impact outcomes.

Idiopathic Orbital Pseudotumor: A Rare Case Report.

Orbital pseudotumor is a rare inflammatory condition affecting the orbit of the eye. It has diverse clinical manifestations. Although its exact etiology remains unknown, it is believed to involve an immune-mediated response. A 42-year-old male presented to the ophthalmology clinic with progressively worsening symptoms in his left eye, including pain, swelling, and blurry vision. He had no history of trauma or recent illness. Initial discomfort had escalated over three weeks. The patient had controlled hypertension but no known allergies. Examination showed eyelid edema, erythema, and mild anterior chamber cell, and flare in the left eye. Magnetic resonance imaging revealed orbital soft tissue enhancement, extraocular muscle thickening, and optic nerve involvement. Laboratory results showed elevated inflammatory markers. A diagnosis of orbital pseudotumor was made. The patient was treated with oral corticosteroids, resulting in symptom improvement and regression of inflammatory changes on follow-up. Orbital pseudotumor is a complex condition with diverse clinical manifestations. Its diagnosis requires a comprehensive approach involving clinical evaluation, imaging studies, and laboratory investigations.

Effects of dietary-based weight loss interventions on biomarkers of endothelial function: a systematic review and meta-analysis.

Endothelial dysfunction is closely linked to the development of atherosclerosis. This systematic review and meta-analysis reviewed the evidence on the effect of weight loss, achieved by dietary-based interventions, on biomarkers of endothelial function (EF). Two databases (Medline, Embase) were searched from inception until November 2022 for studies that met the following criteria: 1) adult subjects (≥ 18 years) without exclusion for health status, 2) dietary interventions for weight loss, and 3) measurements of changes in EF biomarkers. Random-effect meta-analysis and meta-regression were performed. Thirty-seven articles including 1449 participants were included in the systematic review. Study duration ranged from 3-52 weeks. Overall, weight loss significantly improved biomarkers of EF [standardised mean difference (SMD):0.65; 95%CI:0.49,0.81; P < 0.001;I2 = 91.9%]. Subgroup analyses showed weight loss significantly improved levels of E-selectin (P < 0.001), intercellular adhesion molecule-1 (ICAM-1) (P < 0.001), vascular cell adhesion molecule-1 (VCAM-1) (P < 0.001), nitrite/nitrate (NOx) (P < 0.001) and vascular endothelial growth factor (VEGF) (P < 0.001). Conversely, there was no significant improvement for von Willebrand Factor (vWF). Meta-regression analysis revealed that changes in EF biomarkers were not affected by age, BMI, quality of the studies or the amount of weight lost. A significant heterogeneity was observed for the effects of weight loss on changes in EF biomarkers. Dietary-induced weight loss may be associated with biomarkers changes indicating an improvement of EF, and it may represent a potential strategy to reduce atherosclerotic risk.

A Rare Case of Trigeminal Neuralgia Caused by an Aneurysmal Bone Cyst in the Temporal Bone.

Trigeminal neuralgia is a rare and debilitating condition characterized by severe facial pain, often caused by the compression or irritation of the trigeminal nerve. Although trigeminal neuralgia caused by petrous bone lesions is uncommon, it can significantly impact a patient's quality of life. In this case report, we describe a 40-year-old female with a five-year history of severe facial pain diagnosed as trigeminal neuralgia. Imaging revealed an aneurysmal bone cyst in the petrous part of the left temporal bone, located near the trigeminal nerve's root entry zone. The patient underwent a successful left retrosigmoid craniotomy with the resection of the lesion, resulting in a significant improvement in her symptoms. At the six-month follow-up, the patient reported no recurrence of her symptoms and a considerable improvement in her quality of life. Although trigeminal neuralgia caused by an aneurysmal bone cyst in the left temporal bone is rare, surgery is the most effective treatment. Long-term outcomes are generally favorable with close follow-up. This case report highlights the importance of early diagnosis and timely surgical intervention in the management of this debilitating condition.

Real-World Efficacy of Tafamidis in Patients With Transthyretin Amyloidosis and Heart Failure.

Tafamidis was associated with a reduction in cardiovascular hospitalizations and all-cause mortality in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) in the ATTR-ACT trial. However, real-world data on the efficacy of tafamidis are limited. We conducted a retrospective, observational cohort study using the TriNetX research network. Patients with wild-type TTR amyloidosis and heart failure (HF) were divided into 2 groups based on treatment with tafamidis. Propensity score matching (PSM) was performed, and rates of heart failure exacerbations (HFE) and all-cause mortality at 12 months were compared. After PSM, 421 patients were in each group (tafamidis vs nontafamidis). During the 12-month follow-up period, patients treated with tafamidis experienced significantly less HFE and all-cause mortality. A higher probability of event-free survival for HFE and all-cause mortality was noted with tafamidis. This real-world analysis supports that tafamidis use is associated with reduced HFE and all-cause mortality in patients with wild-type TTR amyloidosis and HF. Longer-term follow-up is needed to better understand the utility of tafamidis, given the increasing recognition of ATTR-CM and the high cost of tafamidis.

Double-blind controlled dietary cross-over intervention with differentially fertilised intact lettuce leaves shows acute reduction in blood pressure in young adults, associated with faster uptake of nitrate than of phenolics.

PURPOSE: To compare acute effects on blood pressure (BP) of ingestion of visually similar lettuce with controlled high and low content of either nitrate or phenolic compounds. METHODS: In a randomised cross-over design, 19 healthy participants (22-31 years) received 50 g of lettuce containing either 530 mg (8.4 mmol) nitrate + 11 mg (0.03 mmol) phenolic compounds (HNLP); or 3 mg nitrate (0.05 mmol) + 77 mg (0.2 mmol) phenolic compounds (LNHP), obtained by differential fertilisation. Ambulatory BP was recorded along with plasma, salivary and urinary nitrate and nitrite and plasma concentrations of cyclic guanosine monophosphate (cGMP), phenolic metabolites, Trolox equivalent antioxidant capacity (TEAC) and ferric reducing antioxidant power (FRAP). RESULTS: Compared with LNHP, 3 h post ingestion of HNLP, plasma nitrate increased 0.31 ± (95%CI) 0.12 mM (+ 240%), and salivary nitrate 5.5 ± 1.4 mM (+ 910%); accumulated urinary nitrate excretion increased 188 ± 72 mg (+ 296%) (all P < 0.001). Systolic BP was reduced 4.9 ± 4.2 mmHg (P = 0.031) between 3 and 6 h after ingestion of HNLP compared with LNHP; systolic BP differences were negatively correlated (P = 0.004) with differences in saliva nitrate concentrations. LNHP increased plasma phenolics at 6 h, predominantly 3'-methoxycinnamic acid-4'-glucuronide (ferulic acid-4'-glucuronide), 116%, 204 ± 138 nM more than HNLP (P = 0.001); increased cGMP 14% (P = 0.019); and reduced FRAP 3.1% (P = 0.009). CONCLUSION: The acute BP difference within 6 h of consumption matched the plasma/saliva nitrate peak, not the slower changes of plasma phenolics. This is the first double-blind controlled dietary intervention demonstrating differential effects on human physiology by consumption of an intact plant food, where compositional differences were obtained by controlling growing conditions, indicating potential opportunities for health claims relating to precision/vertical farming. CLINICAL TRIAL REGISTRATION: The trial was retrospectively registered on ClinicalTrials.gov, with identifier NCT02701959, on March 8, 2016.

Mediterranean diet and the hallmarks of ageing.

Ageing is a multifactorial process associated with reduced function and increased risk of morbidity and mortality. Recently, nine cellular and molecular hallmarks of ageing have been identified, which characterise the ageing process, and collectively, may be key determinants of the ageing trajectory. These include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intercellular communication. Healthier dietary patterns reduce the risk of age-related diseases and increase longevity and may influence positively one or more of these hallmarks. The Mediterranean dietary pattern (MedDiet) is a plant-based eating pattern that was typical of countries such as Greece, Spain, and Italy pre-globalisation of the food system and which is associated with better health during ageing. Here we review the potential effects of a MedDiet on each of the nine hallmarks of ageing, and provide evidence that the MedDiet as a whole, or individual elements of this dietary pattern, may influence each hallmark positively-effects which may contribute to the beneficial effects of this dietary pattern on age-related disease risk and longevity. We also highlight potential avenues for future research.

Incidence of septicemia. Etiology and antimicrobial susceptibility testing among patients admitted to tertiary care hospital.

INTRODUCTION: Septicemia is considered as an important cause of life-threating infections. The study was aimed at determining the incidence of septicemia considering different age groups and gender among suspected patients admitted to a tertiary care hospital in Iraq. METHODOLOGY: A total of 168 blood samples were collected and cultured using BacT/Alert 3D automated system. The isolated pathogens were identified and subjected to antimicrobial susceptibility testing using automated Vitek 2 Compact system. RESULTS: Out of 168 blood samples, 53 (31.5%) gave positive microbial growth. Thirty-three samples (62.3%) came from male patients and 20 (37.7%) from female ones, both gender and microbial growth were significantly related (P < 0.05). Age group (21 year - 30 year) was found to have the highest percentage of positive growth (26.4%) while age group (51 year - 60 year) the lowest percentage (5.7%) of positive growth. Both microbial growth and age group were found to be associated to a significant level (P < 0.05). 36 isolates (67.9%) were Gram negative, 15 isolates (28.3%) were Gram-positive and 2 isolates (3.8%) were fungi. Salmonella typhi (41.7%) represented the most common pathogen isolated followed by Acinetobacter baumannii (22.2%). An isolate of Pseudomonas aeruginosa showed resistance to all antibiotics used. CONCLUSION: Community-acquired septicemia occurred mainly in male than female. Salmonella typhi and Acinetobacter baumannii represented the most frequent causative agents of community-acquired septicemia. Antimicrobial susceptibility testing should be performed to detect the antibiotic of choice for each pathogen causing community-acquired septicemia.

Disease burden of osteoporosis and other non-communicable diseases in Lebanon.

Osteoporosis is more common than most feared non-communicable diseases in the Middle East. This justifies the need to place osteoporosis as a health priority in the region. INTRODUCTION: Osteoporosis is a common disease associated with severe debilitating consequences. The objective of this study is To evaluate and compare disease burden from osteoporosis and other non-communicable diseases (NCDs) in Lebanon. METHODS: We assessed the prevalence of osteoporosis and other NCDs, such as obesity, diabetes, hypertension, dyslipidemia, and cardiovascular diseases, based on a published population-based study of Lebanese ≥ 65 years. We compared incidence rates of hip fractures and major osteoporotic fractures (MOF) (spine, hip, humerus, and forearm) to the five commonest cancers in women ≥ 50 years. Rates were based on the national hip fracture and cancer registry data, provided by the Lebanese Ministry of Public Health. MOF incidence rates were derived from national hip fracture incidence rates and MOF/hip fractures incidence rate ratios from the literature. RESULTS: Over 70% of elderly Lebanese had osteoporosis defined by densitometric criteria or prevalent morphometric vertebral fractures. This by far exceeded the prevalence of other NCDs, such as hypertension (53%), diabetes (21%), dyslipidemia (31%), and cardiovascular diseases (30%). Morphometric vertebral fractures (grades 2 and 3) were present in 19% of women and 12% of men. The incidence rates for MOF were 1.6 times greater than those for breast cancer, and 7.4-9.9 folds higher than those for the next commonest cancers of the lungs, colon, and ovaries. Hip fracture incidence rates were lower than those of breast cancer but were 2.1-2.8 folds higher than those of the above-mentioned cancers. CONCLUSION: This first of its kind study in the Middle East demonstrates that osteoporosis is a common disease, more common than most feared NCDs. Our findings are comparable to those in western populations and justify placing osteoporosis on the top of NCDs' priority list in our country and possibly the region.

Mediterranean Diet Increases Endothelial Function in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The endothelium plays a key role in the maintenance of vascular health and represents a potential physiological target for dietary and other lifestyle interventions designed to reduce the risk of cardiovascular diseases (CVD) including stroke or coronary heart disease. OBJECTIVE: To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the effects of the Mediterranean dietary pattern (MedDiet) on endothelial function. METHODS: Medline, Embase, and Scopus databases were searched from inception until January 2019 for studies that met the following criteria: 1) RCTs including adult participants, 2) interventions promoting the MedDiet, 3) inclusion of a control group, and 4) measurements of endothelial function. A random-effects meta-analysis was conducted. Metaregression and subgroup analyses were performed to identify whether effects were modified by health status (i.e., healthy participants versus participants with existing comorbidities), type of intervention (i.e., MedDiet alone or with a cointervention), study duration, study design (i.e., parallel or crossover), BMI, and age of participants. RESULTS: Fourteen articles reporting data for 1930 participants were included in the meta-analysis. Study duration ranged from 4 wk to 2.3 y. We observed a beneficial effect of the MedDiet on endothelial function [standardized mean difference (SMD): 0.35; 95% CI: 0.17, 0.53; P <0.001; I2 = 73.68%]. MedDiet interventions improved flow-mediated dilation (FMD)-the reference method for noninvasive, clinical measurement of endothelial function-by 1.66% (absolute change; 95% CI: 1.15, 2.17; P <0.001; I2 = 0%). Effects of the MedDiet on endothelial function were not modified by health status, type of intervention, study duration, study design, BMI, or age of participants (P >0.05). CONCLUSIONS: MedDiet interventions improve endothelial function in adults, suggesting that the protective effects of the MedDiet are evident at early stages of the atherosclerotic process with important implications for the early prevention of CVD. This study has the PROSPERO registration number: CRD42018106188.

Effects of inorganic nitrate and vitamin C co-supplementation on blood pressure and vascular function in younger and older healthy adults: A randomised double-blind crossover trial.

BACKGROUND: Vitamin C and inorganic nitrate have been linked to enhanced nitric oxide (NO) production and reduced oxidative stress. Vitamin C may also enhance the conversion of nitrite into NO. AIMS: We investigated the potential acute effects of vitamin C and inorganic nitrate co-supplementation on blood pressure (BP) and peripheral vascular function. The secondary aim was to investigate whether age modified the effects of vitamin C and inorganic nitrate on these vascular outcomes. METHODS: Ten younger (age 18-40 y) and ten older (age 55-70 y) healthy participants were enrolled in a randomised double-blind crossover clinical trial. Participants ingested a solution of potassium nitrate (7 mg/kg body weight) and/or vitamin C (20 mg/kg body weight) or their placebos. Acute changes in resting BP and vascular function (post-occlusion reactive hyperemia [PORH], peripheral pulse wave velocity [PWV]) were monitored over a 3-h period. RESULTS: Vitamin C supplementation reduced PWV significantly (vitamin C: -0.70 ± 0.31 m/s; vitamin C placebo: +0.43 ± 0.30 m/s; P = 0.007). There were significant interactions between age and vitamin C for systolic, diastolic, and mean arterial BP (P = 0.02, P = 0.03, P = 0.02, respectively), with systolic, diastolic and mean BP decreasing in older participants and diastolic BP increasing in younger participants following vitamin C administration. Nitrate supplementation did not influence BP (systolic: P = 0.81; diastolic: P = 0.24; mean BP: P = 0.87) or vascular function (PORH: P = 0.05; PWV: P = 0.44) significantly in both younger and older participants. However, combined supplementation with nitrate and vitamin C reduced mean arterial BP (-2.6 mmHg, P = 0.03) and decreased PWV in older participants (PWV: -2.0 m/s, P = 0.02). CONCLUSIONS: The co-administration of a single dose of inorganic nitrate and vitamin C lowered diastolic BP and improved PVW in older participants. Vitamin C supplementation improved PWV in both age groups but decreased systolic and mean BP in older participants only. CLINICAL TRIAL REGISTRATION: Current Controlled Trials (ISRCTN98942199).

Limited evidence for a beneficial effect of vitamin C supplementation on biomarkers of cardiovascular diseases: an umbrella review of systematic reviews and meta-analyses.

Vitamin C is an essential nutrient with important antioxidant properties. Higher vitamin C intake appears to be associated with positive effects on cardiovascular risk factors in cohort studies, whereas large randomized controlled clinical trials did not confirm the benefits of supplemental vitamin C on cardiovascular disease (CVD) outcomes. In this overview of systematic reviews and meta-analyses, an "umbrella review," we investigated the effects of vitamin C supplementation on biomarkers of cardiovascular risk, that is, arterial stiffness, blood pressure, endothelial function, glycemic control, and lipid profile. In addition, we assessed the strength of the evidence and the methodological qualities of available studies. Two independent investigators searched 4 databases (Medline, Embase, Scopus, and The Cochrane Library databases) from inception until February 2018. After full text examination, 10 systematic reviews and meta-analyses were included in the umbrella review which included 6409 participants. Three systematic reviews investigated the effects of vitamin C on endothelial function with contrasting results (2 reviews reported a significant effect, and all 3 showed a high heterogeneity [I2> 50%]); 1 systematic review reported significant improvement for each of the following risk factors: blood pressure, and blood concentrations of glucose, low-density lipoprotein cholesterol, and triglycerides. There were no overall effects of vitamin C on arterial stiffness and blood concentration of insulin, total cholesterol, and high-density lipoprotein cholesterol, but subgroup analyses revealed some evidence for significant improvements in subpopulations with higher body mass index, higher plasma concentrations of glucose or cholesterol, and low plasma concentration of vitamin C. Results from this umbrella review emphasize the weakness of the current evidence base about effects of vitamin C supplementation on markers of CVD risk. There is limited evidence that some population subgroups (older people, the obese, those with lower vitamin C status at baseline, and those at higher CVD risk) may be more responsive to vitamin C supplementation and offer opportunities for tailored nutritional interventions to improve cardiometabolic health. Future studies should implement a selective recruitment strategy that is informed by evidence-based literature synthesis.

Lycopene and tomato and risk of cardiovascular diseases: A systematic review and meta-analysis of epidemiological evidence.

BACKGROUND AND AIMS: Worldwide, cardiovascular diseases (CVDs) remains as the main cause of mortality. Observational studies supports an association between intake of tomato products or lycopene with a reduced CVDs risk. Our aim was to undertake a systematic review and meta-analysis of the evidence on the topic. METHODS: Medline, Web of Science, and Scopus were searched from inception until July 2017. We included longitudinal and cross-sectional studies reporting associations between lycopene and tomato consumption and cardiovascular morbidity and mortality among adult subjects. Random-effects models were used to determine the pooled effect sizes. RESULTS: Twenty-eight publications met our inclusion criteria and 25 studies provided quantitative data for meta-analysis. Results showed that individuals in the highest consumption category of, or with the highest serum concentration of, lycopene had significantly lower risk of stroke (hazard ratio (HR) 0.74, 0.62-0.89, p = 0.02; I2 = 32) and CVDs (HR 0.86, 0.77-0.95, p = 0.003; I2 = 0). In addition, individuals categorised in the highest serum concentration of lycopene also had significantly lower risk of mortality (HR 0.63, 0.49-0.81, p<0.001; I2 = 46). Lycopene was not significantly associated with myocardial infarction, while scarce evidence on the association of lycopene with atherosclerosis, congestive heart failure, or atrial fibrillation was evident. Evidence from three studies suggested that higher intakes of tomato were associated with non-significantly lower stroke, CVDs and CHD. CONCLUSIONS: This comprehensive meta-analysis suggests that high-intakes or high-serum concentration of lycopene are associated with significant reductions in the risk of stroke (26%), mortality (37%) and CVDs (14%).

Does dietary nitrate say NO to cardiovascular ageing? Current evidence and implications for research.

CVD are characterised by a multi-factorial pathogenesis. Key pathogenetic steps in the development of CVD are the occurrence of endothelial dysfunction and formation of atherosclerotic lesions. Reduced nitric oxide (NO) bioavailability is a primary event in the initiation of the atherosclerotic cascade. NO is a free radical with multiple physiological functions including the regulation of vascular resistance, coagulation, immunity and oxidative metabolism. The synthesis of NO proceeds via two distinct pathways identified as enzymatic and non-enzymatic. The former involves the conversion of arginine into NO by the NO synthases, whilst the latter comprises a two-step reducing process converting inorganic nitrate into nitrite and subsequently NO.Inorganic is present in water and food, particularly beetroot and green leafy vegetables. Several investigations have therefore used the non-enzymatic NO pathway as a target for nutritional supplementation ( salts) or dietary interventions (high- foods) to increase NO bioavailability and impact on cardiovascular outcomes. Some studies have reported positive effects of dietary on systolic blood pressure and endothelial function in patients with hypertension and chronic heart failure. Nevertheless, results have been inconsistent and the size of the effect appears to be declining in older individuals. Additionally, there is a paucity of studies for disorders such as diabetes, CHD and chronic kidney failure. Thus, whilst dietary supplementation could represent an effective and viable strategy for the primary and secondary prevention of age-related cardiovascular and metabolic diseases, more large-scale, robust studies are awaited to confirm or refute this notion.

[Anti-D prophylaxis in fetal-maternal erythrocyte incompatibility in Tunisia]. / Prophylaxie anti-D dans l'incompatibilité fœto-maternelle érythrocytaire en Tunisie.

Generalization of postnatal prophylaxis using anti-D immunoglobulins decreased the incidence of erythrocyte fetal-maternal incompatibility (EFMI) in the Rhesus system. Few recent studies have investigated the situation of anti-D prophylaxis in Tunisia and its effects on maternal and neonatal health. The aim of this study was therefore to analyze the situation of anti-D prophylaxis in Tunisia to detect defects and propose solutions. We conducted a retrospective descriptive study of IFME cases in the rhesus system in the Department of Medicine and Neonatal Resuscitation of the Tunis Maternity and Neonatology Center (CMNT) during an 8-year period from 1 January 2006 to 31 December 2015. We collected 51 cases of IFME. The prevalence of IFME was 3.4 per 10 000 live births; 41 % of the patients were transferred in utero and they were from the northwest of the country (17 %). The rate of women with a history of at least one spontaneous miscarriage (SCF) was 45 %. In 42 % of the cases, pregnancies were monitored at local clinics. The search for irregular agglutinins (RAI) was performed in 86 % of the women studied. RAI was positive in 97 % of the cases. Anti-D prophylaxis was correctly performed in only 27 % of the cases. The systematic prophylaxis of the third trimester and a systematic Kleihauer test must be combined with postpartum prophylaxis to better identify dysfunctions and improve the application of the recommendations.

A phase 2 study of vorinostat in locally advanced, recurrent, or metastatic adenoid cystic carcinoma.

PURPOSE: Vorinostat is a histone deacetylase inhibitor (HDACi). Based on a confirmed partial response (PR) in an adenoid cystic carcinoma (ACC) patient treated with vorinostat in a prior phase 1 trial, we initiated this phase 2 trial. METHODS: Vorinostat was administered orally 400 mg daily, 28 day cycles. The primary objective was to evaluate response rate (RR). Exploratory studies included whole exome sequencing (WES) of selected patients. RESULTS: Thirty patients were enrolled. Median age of patients was 53 years (range 21-73). Median number of cycles was 5 (range 1-66). Lymphopenia (n = 5), hypertension (n = 3), oral pain (n = 2), thromboembolic events (n = 2) and fatigue (n = 2) were the only grade 3 adverse events (AEs) that occurred in more than 1 patient. Eleven patients were dose reduced secondary to drug-related AEs. Two patients had a partial response (PR), with response durations of 53 and 7.2 months. One patient had a minor response with a decrease in ascites (for 19 cycles). Stable disease was the best response in 27 patients. Targeted and WES of 8 patients in this trial identified mutations in chromatin remodeling genes highlighting the role of the epigenome in ACC. CONCLUSION: Vorinostat demonstrated efficacy in patients with ACC supporting the inclusion of HDACi in future studies to treat ACC.