Is Early Menopause a Different Entity From Premature Ovarian Insufficiency?

Premature ovarian insufficiency (POI, defined as age at menopause < 40 years) affects 1%-3% of postmenopausal women. It is positively associated with an increased risk of diabetes mellitus, arterial hypertension, cardiovascular disease, osteoporosis, fractures, cognitive impairment, and depression. Early menopause (EM, defined as age at menopause < 45 years) is also associated with these adverse health consequences, in most cases to the same degree as in POI. Therefore, a unifying term for EM and POI, such as 'premature menopause', may be proposed, using the age threshold of < 45 years. This could provide broader coverage of these women, substantiating the need for prompt administration of menopausal hormone therapy (in this case, 'hormone replacement therapy'). However, the benefits of this approach, which precludes a higher oestrogen dose up to the normal age of menopause, need to be proven in well-designed randomized controlled trials.

The association of vasomotor symptoms with fracture risk and bone mineral density in postmenopausal women: a systematic review and meta-analysis of observational studies.

BACKGROUND/AIMS: Vasomotor symptoms (VMS) adversely affect postmenopausal quality of life. However, their association with bone health has not been elucidated. This study aimed to systematically review and meta-analyze the evidence regarding the association of VMS with fracture risk and bone mineral density (BMD) in peri- and postmenopausal women. METHODS: A literature search was conducted in PubMed, Scopus and Cochrane databases until 31 August 2023. Fracture, low BMD (osteoporosis/osteopenia) and mean change in lumbar spine (LS) and femoral neck (FN) BMD were assessed. The results are presented as odds ratio (OR) and mean difference (MD), respectively, with a 95% confidence interval (95% CI). The I2 index quantified heterogeneity. RESULTS: Twenty studies were included in the qualitative and 12 in the quantitative analysis (n=49,659). No difference in fractures between women with and without VMS was found (n=5, OR 1.04, 95% CI 0.93-1.16, I2 16%). However, VMS were associated with low BMD (n=5, OR 1.54, 95% CI 1.42-1.67, I2 0%). This difference was evident for LS (MD -0.019 g/cm2, 95% CI -0.03 to -0.008, I2 85.2%), but not for FN BMD (MD -0.010 g/cm2, 95% CI -0.021 to 0.001, I2 78.2%). These results were independent of VMS severity, age and study design. When the analysis was confined to studies that excluded menopausal hormone therapy use, the association with BMD remained significant. CONCLUSIONS: The presence of VMS is associated with low BMD in postmenopausal women, although it does not seem to increase fracture risk.

Burosumab Efficacy and Safety in Patients with X-Linked Hypophosphatemia: Systematic Review and Meta-analysis of Real-World Data.

To assess the efficacy and safety of burosumab in children and adults with X-linked hypophosphatemia based on real-world evidence. MEDLINE (via PubMed) and Cochrane Library were searched until 18 October 2023 for single-arm (before-after) studies. Registries including Clinicaltrials.gov, EU Clinical Trials, WHO International Clinical Trials Registry Platform, and conference abstracts. The outcomes were a change in serum phosphorus concentrations and change in RSS, a change in serum ALP, bone-specific ALP, a change in the ratio of Tubular maximum reabsorption of Phosphate to Glomerular Filtrate rate, a change in serum 1,25(OH)2D and 25(OH)2D concentrations, change in height Z-score, McMaster Universities Osteoarthritis Index (WOMAC) and safety outcomes. An inverse variance random-effects meta-analysis was applied for data synthesis. Fifteen studies (289 participants) were included. Burosumab treatment improved serum phosphate concentrations [mean difference 0.88 mg/dl, 95% confidence interval 0.70 to 1.07, I2 = 92%), Rickets Severity score (mean difference - 1.86, 95% confidence interval - 2.5 to - 1.21, I2 = 71%), serum alkaline phosphate concentrations (mean difference - 1.86, 95% confidence interval - 2.5 to - 1.21, I2 = 71%), serum 1,25(OH)2D concentrations (mean difference 18.91 pg/ml, 95% confidence interval 6.39 to 31.43, I2 = 96%) and renal phosphate reabsorption (mean difference 1.22 mg/dl, 95% confidence interval 0.70 to 1.74, I2 93%). Burosumab treatment improved overall clinical and laboratory findings in patients with X-linked hypophosphatemia.

Circulating lipoprotein(a) in patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis.

BACKGROUND AND AIM: Although nonalcoholic fatty liver disease (NAFLD) and lipoprotein(a) [Lp(a)] are associated with cardiovascular diseases, existing data on Lp(a) in NAFLD are conflicting. The aim of this systematic review and meta-analysis was to summarize and compare data on circulating Lp(a) between NAFLD patients and non-NAFLD controls. METHODS: A systematic literature search was performed in PubMed, Scopus, and Cochrane Library. This meta-analysis included 18 studies containing data on 74 691 individuals (20 220 patients with NAFLD and 54 471 controls). RESULTS: Circulating Lp(a) was similar between patients with NAFLD and controls (standardized mean difference [SMD] 0.09; 95% confidence interval [95% CI] -0.21, 0.38). The heterogeneity among studies was high (I2 = 100%); no publication bias was detected (Egger's test P = 0.941). However, in subgroup analysis, Lp(a) was lower in NAFLD patients than controls, when Lp(a) was measured with nephelometry (SMD -0.26; 95% CI -0.46, -0.06), but not turbidimetry; this analysis also resulted in mild reduction of heterogeneity within the subgroup of nephelometry (I2 = 87%). The sensitivity analyses, based on the exclusion of studies with Newcastle-Ottawa Scale score ≤6 (n = 5), studies in which liver biopsy was used for NAFLD diagnosis (n = 4) or studies that adopted the criteria of metabolic dysfunction-associated fatty liver disease (n = 2), and meta-regression analysis did not explain the high heterogeneity among studies. CONCLUSIONS: Overall, circulating Lp(a) was similar between NAFLD patients and non-NAFLD controls; however, patients with NAFLD had lower circulating Lp(a) compared with controls, when Lp(a) was measured with nephelometry. These results should be cautiously interpreted, because of the high heterogeneity among studies.

Proteomics in Patients with Fibromyalgia Syndrome: A Systematic Review of Observational Studies.

PURPOSE OF REVIEW: Fibromyalgia syndrome (FMS) is a disease of unknown pathophysiology, with the diagnosis being based on a set of clinical criteria. Proteomic analysis can provide significant biological information for the pathophysiology of the disease but may also reveal biomarkers for diagnosis or therapeutic targets. The present systematic review aims to synthesize the evidence regarding the proteome of adult patients with FMS using data from observational studies. RECENT FINDINGS: An extensive literature search was conducted in MEDLINE/PubMed, CENTRAL, and clinicaltrials.gov from inception until November 2022. The study protocol was published in OSF. Two independent reviewers evaluated the studies and extracted data. The quality of studies was assessed using the modified Newcastle-Ottawa scale adjusted for proteomic research. Ten studies fulfilled the protocol criteria, identifying 3328 proteins, 145 of which were differentially expressed among patients with FMS against controls. The proteins were identified in plasma, serum, cerebrospinal fluid, and saliva samples. The control groups included healthy individuals and patients with pain (inflammatory and non-inflammatory). The most important proteins identified involved transferrin, α-, ß-, and γ-fibrinogen chains, profilin-1, transaldolase, PGAM1, apolipoprotein-C3, complement C4A and C1QC, immunoglobin parts, and acute phase reactants. Weak correlations were observed between proteins and pain sensation, or quality of life scales, apart from the association of transferrin and a2-macroglobulin with moderate-to-severe pain sensation. The quality of included studies was moderate-to-good. FMS appears to be related to protein dysregulation in the complement and coagulation cascades and the metabolism of iron. Several proteins may be dysregulated due to the excessive oxidative stress response.

Higher live birth rate following transdermal testosterone pretreatment in poor responders: a systematic review and meta-analysis.

A systematic review and meta-analysis was performed aiming to identify good-quality randomized controlled trials (RCT) evaluating testosterone pretreatment in poor responders. Eight RCTs were analysed, evaluating 797 women. Transdermal testosterone gel was used in all studies, with a dose ranging from 10 to 12.5 mg/day for 10-56 days. The main outcome measure was achievement of pregnancy, expressed as clinical pregnancy or live birth. Testosterone pretreatment was associated with a significantly higher live birth (risk ratio [RR] 2.07, 95% confidence interval [CI] 1.09-3.92) and clinical pregnancy rate (RR 2.25, 95% CI 1.54-3.30), as well as a significant increase in the number of cumulus-oocyte complexes retrieved. Significantly fewer days to complete ovarian stimulation, a lower total dose of gonadotrophins, a lower cancellation rate due to poor ovarian response and a thicker endometrium on the day of triggering of final oocyte maturation were observed. No significant differences were observed in oestradiol concentration, the numbers of follicles ≥17 mm, metaphase II oocytes, two-pronuclear oocytes and embryos transferred, and the proportion of patients with embryo transfer. The current study suggests that the probability of pregnancy is increased in poor responders pretreated with transdermal testosterone who are undergoing ovarian stimulation for IVF.

Serum Concentrations and Dietary Intake of Vitamin B12 in Children and Adolescents on Metformin: A Case-Control Study.

The International Society of Pediatric and Adolescent Diabetes (ISPAD) recommends metformin (MET) use for metabolic disturbances and hyperglycemia, either in combination with insulin therapy or alone. A caveat of MET therapy has been suggested to be biochemical vitamin B12 deficiency, as seen mainly in studies conducted in adults. In the present case-control study, children and adolescents of different weight status tiers on MET therapy for a median of 17 months formed the cases group (n = 23) and were compared with their peers not taking MET (n = 46). Anthropometry, dietary intake, and blood assays were recorded for both groups. MET group members were older, heavier, and taller compared with the controls, although BMI z-scores did not differ. In parallel, blood phosphorus and alkaline phosphatase (ALP) concentrations were lower in the MET group, whereas MCV, Δ4-androstenedione, and DHEA-S were higher. No differences were observed in the HOMA-IR, SHBG, hemoglobin, HbA1c, vitamin B12, or serum 25(OH)D3 concentrations between groups. Among those on MET, 17.4% exhibited vitamin B12 deficiency, whereas none of the controls had low vitamin B12 concentrations. Participants on MET therapy consumed less energy concerning their requirements, less vitamin B12, more carbohydrates (as a percentage of the energy intake), and fewer fats (including saturated and trans fats) compared with their peers not on MET. None of the children received oral nutrient supplements with vitamin B12. The results suggest that, in children and adolescents on MET therapy, the dietary intake of vitamin B12 is suboptimal, with the median coverage reaching 54% of the age- and sex-specific recommended daily allowance. This low dietary intake, paired with MET, may act synergistically in reducing the circulating vitamin B12 concentrations. Thus, caution is required when prescribing MET in children and adolescents, and replacement is warranted.

Nonalcoholic fatty liver disease and osteoporosis: A potential association with therapeutic implications.

Nonalcoholic fatty liver disease (NAFLD) and osteoporosis are two highly prevalent metabolic diseases. Increasing experimental evidence supports a pathophysiological link between NAFLD and osteoporosis. A key feature could be chronic, low-grade inflammation, which characterizes NAFLD and possibly affects bone metabolism. In this context, several factors, including but not limited to receptor activator of nuclear factor kappa-B ligand, osteoprotegerin, osteopontin and osteocalcin, may serve as mediators. In the clinical setting, most but not all epidemiological evidence indicates that NAFLD is associated with lower bone mineral density or osteoporosis in adults. Although an association between NAFLD and osteoporosis has not yet been established, and thus remains speculative, pharmacological considerations already exist. Some of the current and emerging pharmacological options for NAFLD have shown possible anti-osteoporotic properties (eg, vitamin E, obeticholic acid, semaglutide), while others (eg, pioglitazone, canagliflozin) have been associated with increased risk of fractures and may be avoided in patients with NAFLD and concomitant osteoporosis, especially those at high fracture risk. Conversely, some anti-osteoporotic medications (denosumab) might benefit NAFLD, while others (raloxifene) might adversely affect it and, consequently, may be avoided in patients with osteoporosis and NAFLD. If an association between NAFLD and osteoporosis is established, a medication that could target both diseases would be a great advancement. This review summarizes the main experimental and clinical evidence on the potential association between NAFLD and osteoporosis and focuses on treatment considerations derived from this potential association.

Circulating adiponectin in patients with nonalcoholic fatty liver disease-related liver fibrosis: A systematic review and a meta-analysis.

BACKGROUND AND AIM: There are conflicting data on adiponectin concentrations in nonalcoholic fatty liver disease (NAFLD). The main aim was to compare circulating total adiponectin concentrations in NAFLD patients with versus without liver fibrosis. METHODS: A systematic search was performed in PubMed, Scopus, and Cochrane Library. Twenty-two studies comprising 1753 biopsy-proven NAFLD individuals (1290 with and 463 without fibrosis) were included in the meta-analysis. RESULTS: There was no difference in adiponectin concentration between NAFLD patients with versus without fibrosis (standardized mean difference [SMD]: -0.15; 95% confidence interval [95% CI]: -0.35 to 0.05). Heterogeneity was moderate among studies (Ι2 : 60%, P < 0.001); no risk of publication bias was observed (Egger's test; P = 0.37). The sensitivity analysis, performed after the exclusion of studies with (i) children/adolescents and morbidly obese patients (n = 3) and (ii) adiponectin measurement with other methods than enzyme-linked immunosorbent assay (ELISA) (n = 9), revealed significantly lower adiponectin concentrations in NAFLD patients with fibrosis (i) SMD: -0.23, 95% CI: -0.41 to -0.04; (ii) SMD: -0.30, 95% CI: -0.55 to -0.04, respectively). Meta-regression analysis revealed no significant association of adiponectin SMD with age, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl-transferase, homeostasis model assessment insulin resistance and the proportion of men. CONCLUSIONS: Overall, patients with NAFLD and fibrosis had similar adiponectin concentrations with patients with NAFLD without fibrosis. However, adiponectin concentration was lower in NAFLD patients with fibrosis than those without fibrosis within the adult patients without morbid obesity and in studies in which adiponectin was measured with the same method (ELISA).

Delayed intracranial hemorrhage of patients with mild traumatic brain injury under antithrombotics on routine repeat CT scan: a systematic review and meta-analysis.

BACKGROUND: Patients on antithrombotics experiencing mild traumatic brain injury (mTBI) may benefit from a routine repeat CT scan to detect delayed intracranial hemorrhage (dICH). OBJECTIVES: The primary outcome was the incidence of dICH on routine repeat CT scans of mTBI patients on antithrombotics within an intra-hospital observation period of up to 48 hours. The secondary outcomes were potential risk factors, readmissions, neurosurgical interventions, and mortality. METHODS: A systematic review and a meta-analysis of single proportions were performed according to the PRISMA and PRESS guidelines. The risk of bias was assessed using Newcastle-Ottawa Scale. RESULTS: Eighteen studies with 4613 patients were included. The pooled incidence of dICH was 2% [95% CI 1-2%] with similar rates between different antithrombotic regimens, even in combination. Of the 67 patients with dICH reported (1.45%), eleven required surgery (0.24%), while six died (0.13%). Loss of consciousness was a risk factor of dICH (risk ratio 3.04 [95%CI 0.96; 9.58]). A total of 48 patients were reported for readmission without associated death or surgical intervention. CONCLUSION: The contribution of this routine repeat CT scan should be questioned due to the low incidence, the limited clinical significance, and the unsubstantiated clinical benefit of early or systematic detection of dICH.

Improvement in sperm quality by oral antioxidant supplementation in infertile men with varicocele who have not undergone surgical repair: Systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to assess whether oral antioxidant supplementation improves sperm quality in men with infertility and varicocele (VCL) who have not undergone surgical repair. In men with infertility and VCL who had not undergone surgical repair oral antioxidant supplementation significantly increased sperm concentration (WMD +5.86 × 106 /ml 95% CI: +1.47 to +10.24, p < 0.01; random effects model, six studies, 213 patients), total motility (WMD + 3.76%, 95% CI: +0.18 to +7.34, p = 0.04; random effects model, three studies, 93 patients), progressive motility (WMD + 6.38%, 95% CI: +3.04 to +9.71, p < 0.01; random effects model, three studies, 84 patients) and seminal volume (WMD +0.55 ml, 95%CI: +0.06 to +1.04, p = 0.03; random effects model, four studies, 120 patients). On the other hand, no significance difference was observed in sperm morphology (WMD +3.89%, 95% CI: -0.14 to +7.92, p = 0.06; random effects model, five studies, 187 patients). In conclusion, limited evidence suggests that the use of oral antioxidants in men with infertility and VCL, who have not undergone surgical repair improves their seminal volume, sperm concentration, total and progressive motility.

Bone Health in Patients with Dyslipidemias: An Underestimated Aspect.

Beyond being aging-related diseases, atherosclerosis and osteoporosis share common pathogenetic pathways implicated in bone and vascular mineralization. However, the contributory role of dyslipidemia in this interplay is less documented. The purpose of this narrative review is to provide epidemiological evidence regarding the prevalence of bone disease (osteoporosis, fracture risk) in patients with dyslipidemias and to discuss potential common pathophysiological mechanisms linking osteoporosis and atherosclerosis. The effect of hypolipidemic therapy on bone metabolism is also discussed. Despite the high data heterogeneity and the variable quality of studies, dyslipidemia, mainly elevated total and low-density lipoprotein cholesterol concentrations, is associated with low bone mass and increased fracture risk. This effect may be mediated directly by the increased oxidative stress and systemic inflammation associated with dyslipidemia, leading to increased osteoclastic activity and reduced bone formation. Moreover, factors such as estrogen, vitamin D and K deficiency, and increased concentrations of parathyroid hormone, homocysteine and lipid oxidation products, can also contribute. Regarding the effect of hypolipidemic medications on bone metabolism, statins may slightly increase BMD and reduce fracture risk, although the evidence is not robust, as it is for omega-3 fatty acids. No evidence exists for the effects of ezetimibe, fibrates, and niacin. In any case, more prospective studies are needed further to elucidate the association between lipids and bone strength.

Investigation and management of abnormal uterine bleeding in reproductive-aged women: a descriptive review of national and international recommendations.

PURPOSE: To review and compare the most recently published recommendations on the investigation and management of abnormal uterine bleeding (AUB). MATERIALS AND METHODS: A descriptive review of recommendations from the American College of Obstetricians and Gynaecologists (ACOG), the National Institute for Health and Care Excellence (NICE), the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG), the Society of Obstetricians and Gynaecologists of Canada (SOGC) and the International Federation of Gynaecology and Obstetrics (FIGO) on AUB in reproductive-aged women was carried out. RESULTS: There is a consensus that detailed personal and family history along with physical examination are essential in the investigation of menstrual, intermenstrual or postcoital AUB. All the medical societies recommend transvaginal ultrasound as the first-line imaging modality to determine the AUB cause. Moreover, they agree (except for RANZCOG) that, in women with AUB, endometrial biopsy should only be performed if additional risk factors for endometrial cancer are present. Laboratory tests may be helpful in the AUB investigation; however, there are several discrepancies among the recommendations. Regarding AUB management, NICE, ACOG and SOGC agree that the administration of hormonal or non-hormonal medications should be the first-line treatment modality in bleeding disorders and absent or minor structural pelvic pathology. Surgical management should be preferred in cases of identified polyps, large fibroids or unsuccessful pharmacological treatment. CONCLUSIONS: Since AUB affects a significant proportion of reproductive-aged women, the main objective is to improve the quality of life of these patients without missing cases of malignancy.

Treating Anisomastia and Tuberous Breast with Fat Grafting: Technique and Evaluation of Outcomes Using BREAST-Q Surveys.

BACKGROUND: In the surgical correction of tuberous breast deformity, implants and regional flaps play a prominent role. Lately, fat grafting has been used as an alternative, but there is evidence that patient satisfaction is higher after correction with implants compared with lipofilling. METHODS: We report a tuberous breasts correction series of ten cases, enrolled between 2015 and 2018. Percutaneous fasciotomies and fat grafting were performed by the Body-Jet technique. Analysis of outcomes was undertaken with BREAST-Q surveys. RESULTS: The breast satisfaction scores increased from 0 to 75 (p < 0.01), the psychological well-being scores from 20 to 70 (p < 0.01) and the sexual well-being scores from 18.5 to 58 (p = 0.02), while the physical well-being scores remained stable (from 68 to 63, p = 0.2). The median outcome satisfaction score was 86. CONCLUSION: Scores of patient-reported outcomes after lipofilling can reach and even exceed those of patients corrected with implants, at the cost of more interventions. Fat grafting is beginning to establish itself as a true alternative in the treatment of tuberous breast deformity in patients with the appropriate fat deposits. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266 .

Fat Grafting and Auto-Augmentation Mastopexy After Breast Implant Removal: Technique and Evaluation of Outcomes Using BREAST-Q.

BACKGROUND: Auto-augmentation mastopexy after implant removal has been described as a possible alternative for women who do not opt for implant replacement and decline major reconstructive surgery. OBJECTIVES: This study aimed to evaluate patient satisfaction after auto-augmentation mastopexy relative to the final breast volume and to assess the role of fat grafting on patients' satisfaction and quality of life according to the BREAST-Q questionnaire. METHODS: Forty-seven breasts from 28 patients who underwent implant removal and auto-augmentation mastopexy were reviewed; 9 patients (group 1) were primarily treated with several fat grafting sessions with subsequent auto-augmentation, 5 (group 2) were treated primarily with auto-augmentation, but subsequently expressed a wish for breast augmentation by lipofilling, and 14 patients (group 3, control) had only auto-augmentation. RESULTS: Group 1 patients maintained their breast volume, and showed significant improvements in breast satisfaction, psychosocial well-being, and contentment with breast surgery outcomes (P = 0.01, ˂0.01, and ˂0.01, respectively). However, the physical well-being of this group, as well as response to final cup size or interaction parameters, did not improve (P = 0.06). In group 2, all except 1 patient had breast volume reduction to A cup, as was the case with one-third of the patients in control group 3 (group 3A, n = 5) who scored lower, and thus were less satisfied with the breast auto-augmentation than group 3B, who achieved final bigger cup sizes (P ˂ 0.01). CONCLUSIONS: Auto-augmentation mastopexy resulted in substantial improvements in the parameters measured by BREAST-Q. Thus, combined auto-augmentation mastopexy and lipofilling provided a better alternative treatment after breast implant removal.

Tracing open data in emergencies: The case of the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic constitutes an ongoing, burning Public Health Emergency of International Concern (PHEIC). In 2015, the World Health Organization adopted an open data policy recommendation in such situations. OBJECTIVES: The present cross-sectional meta-research study aimed to assess the availability of open data and metrics of articles pertaining to the COVID-19 outbreak in five high-impact journals. METHODS: All articles regarding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), published in five high-impact journals (Ann Intern Med, BMJ, JAMA, NEJM and Lancet) until March 14, 2020 were retrieved. Metadata (namely the type of article, number of authors, number of patients, citations, errata, news and social media mentions) were extracted for each article in each journal in a systematic way. Google Scholar and Scopus were used for citations and author metrics respectively, and Altmetrics and PlumX were used for news and social media mentions retrieval. The degree of adherence to the PHEIC open data call was also evaluated. RESULTS: A total of 140 articles were published until March 14, 2020, mostly opinion papers. Sixteen errata followed these publications. The number of authors in each article ranged from 1 to 63, whereas the number of patients with a laboratory-confirmed SARS-CoV-2 infection reached 2645. Extensive hyperauthorship was evident among case studies. The impact of these publications reached a total of 4210 cumulative crude citations and 342 790 news and social media mentions. Only one publication (0.7%) provided complete open data, while 32 (22.9%) included patient data. CONCLUSIONS: Even though a large number of manuscripts was produced since the pandemic, availability of open data remains restricted.

Implementation of the Endocrine Society clinical practice guidelines for gestational diabetes mellitus to a knowledge tool.

BACKGROUND: Despite the production of clinical practice guidelines (CPGs) in many medical areas, their use is not sufficiently adopted in clinical practice. Incorporation of CPGs in knowledge tools (KnowT) or decision support systems (DSS) for routine use can improve healthcare providers' compliance to CPGs. MATERIALS AND METHODS: Clinical practice guidelines for gestational diabetes mellitus (GDM) were searched for, collected and compared. The CPG that met pre-specified criteria ([a] published by a European or American organization between 2010 and 2018, [b] being developed a systematic way and [c] having statements of "level of evidence" and "strength of recommendation") was chosen for implementation (Endocrine Society, 2013). Its recommendations were deconstructed, re-organized and reconstructed as an algorithm (in the form of a flowchart), which was integrated into a KnowT. Content completeness and evaluation of CPG by the Guideline Implementability Appraisal tool (GLIA) were performed as well. The primary objective was the development of a clinical algorithm in the field of GDM and its integration into a KnowT. The secondary objective was to demonstrate the completeness of the CPG content and evaluate its implementability in the KnowT. RESULTS: Endocrine Society 2013 CPG was restructured as a flowchart, and a KnowT was constructed with the use of the "Openlabyrinth" software. The completeness of the content was confirmed, and GLIA appraisal demonstrated its implementability. CONCLUSION: Endocrine Society 2013 CPG for GDM is a complete set of recommendations. Its structure makes possible the design of a clinical algorithm and its implementation into a KnowT.

Type 2 Diabetes Mellitus is Associated with Increased Risk of Sarcopenia: A Systematic Review and Meta-analysis.

Diabetes mellitus (DM) is associated with an increased risk of fractures, mainly due to impaired bone architecture and microvascular complications. Whether DM is also associated with increased risk of sarcopenia is not yet known, with studies yielding inconclusive results. The aim of this study was to systematically review and synthesize the best available evidence regarding the association between DM and sarcopenia risk. A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases. Data are expressed as odds ratio (OR) with 95% confidence intervals (CI). The I2 index was employed for heterogeneity. Only studies which had implemented at least two of the three criteria for sarcopenia diagnosis (low muscle mass, muscle strength and/or muscle performance), as defined by the international studying groups, were included. Fifteen studies fulfilled eligibility criteria, yielding a total of 1832 patients with type 2 DM (T2DM) and 1159 cases of sarcopenia. Patients with T2DM demonstrated a higher risk of sarcopenia compared with euglycemic subjects (OR 1.55, 95% CI 1.25-1.91, p < 0.001; I2 34.6%). This risk remained significant when analysis was restricted to studies matched for age and sex. Sarcopenia risk was independent of disease definition or study design. Notably, T2DM patients presented lower muscle performance and strength compared with euglycemic subjects, whereas no difference in muscle mass was observed between groups. Patients with T2DM have an increased risk of sarcopenia compared with euglycemic subjects.

Obesity, osteoporosis and bone metabolism.

Obesity and osteoporosis have become major global health problems over the last decades as their prevalence is increasing. The interaction between obesity and bone metabolism is complex and not fully understood. Historically, obesity was thought to be protective against osteoporosis;however, several studies have challenged this belief. Even though the majority of the studies suggest that obesity has a favourable effect on bone density, it is unclear what the effect of obesity is on skeletal microarchitecture. Additionally, the effects of obesity on skeletal strength might be site-dependent as obese individuals are at higher risk of certain fractures. Several mechanical, biochemical and hormonal mechanisms have been proposed to explain the association between the adipose tissue and bone. Mechanical loading has positive effects on bone health, but this may not suffice in obesity. Low-grade systemic inflammation is probably harmful to the bone and increased bone marrow adipogenesis may lead to decreased bone mass in obese individuals. Finally, visceral abdominal fat may exert different actions to the bone compared with the subcutaneous fat. Achieving a better understanding of the association between adipose and bone tissue may help to identify new molecular therapeutic targets that will promote osteoblastic activity and/or inhibit adipogenesis and osteoclastic activity.

Does coenzyme Q10 supplementation improve fertility outcomes in women undergoing assisted reproductive technology procedures? A systematic review and meta-analysis of randomized-controlled trials.

OBJECTIVE: Increased oxidative stress has been identified as a pathogenetic mechanism in female infertility. However, the effect of specific antioxidants, such as coenzyme Q10 (CoQ10), on the outcomes after assisted reproductive technologies (ART) has not been clarified. The aim of this study was to systematically review and meta-analyze the best available evidence regarding the effect of CoQ10 supplementation on clinical pregnancy (CPR), live birth (LBR), and miscarriage rates (MR) compared with placebo or no-treatment in women with infertility undergoing ART. METHODS: A comprehensive literature search was conducted in PubMed (MEDLINE), Cochrane, and Scopus, from inception to March 2020. Data were expressed as odds ratio (OR) with 95% confidence intervals (CI). The I2 index was employed for heterogeneity. RESULTS: Five randomized-controlled trials fulfilled eligibility criteria (449 infertile women; 215 in CoQ10 group and 234 in placebo/no treatment group). Oral supplementation of CoQ10 resulted in an increase of CPR when compared with placebo or no-treatment (28.8% vs. 14.1%, respectively; OR 2.44, 95% CI 1.30-4.59, p = 0.006; I2 32%). This effect remained significant when women with poor ovarian response and polycystic ovarian syndrome were analyzed separately. No difference between groups was observed regarding LBR (OR 1.67, 95% CI 0.66-4.25, p = 0.28; I2 34%) and MR (OR 0.61, 95% CI 0.13-2.81, p = 0.52; I2 0%). CONCLUSIONS: Oral supplementation of CoQ10 may increase CPR when compared with placebo or no-treatment, in women with infertility undergoing ART procedures, without an effect on LBR or MR.