ABSTRACT TheBrazilian Dietary Guidelines provide crucial recommendations for a healthy diet, aiming at promoting health and preventing non-communicable chronic diseases. The core principle is the preference for natural or minimally processed foods and freshly prepared dishes over ultra-processed foods. Despite their growing recognition, healthcare professionals struggle to integrate these guidelines into clinical practice. This article aims to present two innovative strategies for incorporating the Brazilian Dietary Guidelines into healthcare. The Protocols based on the Brazilian Dietary Guidelines for Individual Dietary Advice are standardized clinical tools to support healthcare professionals (nutritionists or not) in giving nutritional advice during individual appointments to various life stages. The Protocols operationalize the assessment of individuals’ dietary patterns using the Food Consumption Markers Questionnaire and support the delivery of personalized and priority recommendations through a stepwise flowchart. Conversely, Brazilian Dietary Guidelines-based Meal Plans consist of personalized dietary prescriptions comprising structured daily menus that, unlike conventional plans primarily focusing on nutrient goals, prioritize overall eating patterns guided by the Brazilian Dietary Guidelines. The proposal encourages, in the first place, the selection of a variety of culinary preparations based on natural or minimally processed foods, emphasizing tasteful, accessible, and culturally appropriate choices as the initial step. In a second step, these plans can be customized to individual energy requirements, and adjustments made based on strategic nutrient needs. This article aims to support the enhancement of healthcare professionals’ skills in promoting healthy eating practices, thereby contributing to improved health and a reduced disease burden among the Brazilian population.

ABSTRACT Objective: To explore the diagnostic value of the TUIAS (SW_TH01/II) computer-aided diagnosis (CAD) software system for the ultrasound Thyroid Imaging Reporting and Data System (TI-RADS) features in thyroid nodules. Materials and methods: This retrospective study enrolled patients with thyroid nodules in Shanghai East Hospital between January 2017 and October 2021. The novel CAD software (SW_TH01/II) and three sonographers performed a qualitative analysis of the ultrasound TI-RADS features in aspect ratio, margin irregularity, margin smoothness, calcification, and echogenicity of the thyroid nodules. Results: A total of 225 patients were enrolled. The accuracy, sensitivity, and specificity of the CAD software in “aspect ratio” were 95.6%, 96.2%, and 95.4%, in “margin irregularity” were 90.7%, 90.5%, and 90.9%, in “margin smoothness” were 85.8%, 88.5%, and 83.0%, in “calcification” were 83.6%, 81.7%, and 82.0%, in “homogeneity” were 88.9%, 90.6%, and 82.2%, in “major echo” were 85.3%, 88.0%, and 85.4%, and in “contains very hypoechoic echo” were 92.0%, 90.0%, and 92.4%. The analysis time of the CAD software was significantly shorter than for the sonographers (2.7 ± 1.6 vs. 29.7 ± 12.7 s, P < 0.001). Conclusion: The CAD system achieved high accuracy in describing thyroid nodule features. It might assist in clinical thyroid nodule analysis.

ABSTRACT FGF21 is a hormone produced primarily by the liver with several metabolic functions, such as induction of heat production, control of glucose homeostasis, and regulation of blood lipid levels. Due to these actions, several laboratories have developed FGF21 analogs to treat patients with metabolic disorders such as obesity and diabetes. Here, we performed a systematic review and meta-analysis of randomized controlled trials that used FGF21 analogs and analyzed metabolic outcomes. Our search yielded 236 articles, and we included eight randomized clinical trials in the meta-analysis. The use of FGF21 analogs exhibited no effect on fasting blood glucose, glycated hemoglobin, HOMA index, blood free fatty acids or systolic blood pressure. However, the treatment significantly reduced fasting insulinemia, body weight and total cholesterolemia. None of the included studies were at high risk of bias. The quality of the evidence ranged from moderate to very low, especially due to imprecision and indirection issues. These results indicate that FGF21 analogs can potentially treat metabolic syndrome. However, more clinical trials are needed to increase the quality of evidence and confirm the effects seen thus far.

ABSTRACT Objective: To study associations between polymorphisms in the angiotensin converting enzyme (ACE I/D), actinin 3 (ACTN3 R577X) and paraoxonase 1 (PON1 T(-107)C) genes and chronic diseases (diabetes and hypertension) in women. Materials and methods: Genomic DNA was extracted from saliva samples of 78 women between 18 and 59 years old used for genetic polymorphism screening. Biochemical data were collected from the medical records in Basic Health Units from Southern Brazil. Questionnaires about food consumption, physical activity level and socioeconomic status were applied. Results: The XX genotype of ACTN3 was associated with low HDL levels and high triglycerides, total cholesterol and glucose levels. Additionally, high triglycerides and LDL levels were observed in carriers of the TT genotype of PON1, and lower total cholesterol levels were associated to the CC genotype. As expected, women with diabetes/hypertense had increased body weight, BMI (p = 0.02), waist circumference (p = 0.01), body fat percentage, blood pressure (p = 0.02), cholesterol, triglycerides (p = 0.02), and blood glucose (p = 0.01), when compared to the control group. Conclusion: Both ACTN3 R577X and PON1 T(-107)C polymorphisms are associated with nutritional status and blood glucose and lipid levels in women with diabetes/hypertense. These results contribute to genetic knowledge about predisposition to obesity-related diseases.

ABSTRACT Bisphosphonates (BPs) are medications widely used in clinical practice to treat osteoporosis and reduce fragility fractures. Its beneficial effects on bone tissue have been consolidated in the literature for the last decades. They have a high affinity for bone hydroxyapatite crystals, and most bisphosphonates remain on the bone surface for a long period of time. Benefits of long-term use of BPs: Large and important trials (Fracture Intervention Trial Long-term Extension and Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial) with extended use of alendronate (up to 10 years) and zoledronate (up to 6 years) evidenced significant gain of bone mineral density (BMD) and vertebral fracture risk reduction. Risks of long-term use of BPs: The extended use of antiresorptive therapy has drawn attention to two extremely rare, although severe, adverse events. That is, atypical femoral fracture and medication-related osteonecrosis of the jaw are more common in patients with high cumulative doses and longer duration of therapy. BPs have demonstrated safety and effectiveness throughout the years and evidenced increased BMD and reduced fracture risks, resulting in reduced morbimortality, and improved quality of life. These benefits overweight the risks of rare adverse events.

ABSTRACT Objective: COVID-19 is a multisystem immunoinflammatory disorder, and the hypothalamo–pituitary-adrenal (HPA) axis may be affected by SARS-CoV-2 as well as by steroid treatment during the illness. Information on the HPA axis after recovering from COVID-19, especially in those treated with steroids, is sparse. Hence, this study was performed to evaluate the hypothalamo-pituitary-adrenal axis during the post-COVID-19 period in patients treated with steroids during the illness. Subject and methods: This prospective study involved 60 patients aged 18-60 years who had recovered from moderate or severe COVID-19 and had received steroid treatment during the illness. The HPA axis was assessed with a low-dose (1 mcg) adrenocorticotropic hormone stimulation test at 3, 6 and 9 months in the post-COVID period. Results: The HPA axis was suppressed in 31.66% of the patients at 3 months and 5% at 6 months; however, all patients recovered at 9 months. Cumulative steroid use during the illness was inversely correlated with stimulated cortisol at 3 months in the post-COVID period. Fatigue was present in 58.33% of the patients at 3 months and was more prevalent in those with HPA axis suppression. Conclusion: Nearly one-third of the patients with moderate to severe COVID-19 who were treated with steroids had suppressed HPA axis at 3 months, with gradual recovery over a period of 9 months. Cumulative steroid equivalent dose, but not disease severity, was predictive of HPA axis suppression at 3 months.

ABSTRACT Objective: Congenital hypopituitarism (CH) is a rare disease characterized by one or more hormone deficiencies of the pituitary gland. To date, many genes have been associated with CH. In this study, we identified the allelic variant spectrum of 11 causative genes in Turkish patients with CH. Materials and methods: This study included 47 patients [21 girls (44.6%) and 26 boys (55.4%)] from 45 families. To identify the genetic etiology, we screened 11 candidate genes associated with CH using next-generation sequencing. To confirm and detect the status of the specific familial variant in relatives, Sanger sequencing was also performed. Results: We identified 12 possible pathogenic variants in GHRHR, GH1, GLI2, PROP-1, POU1F1, and LHX4 in 11 patients (23.4%), of which six were novel variants: two in GHRHR, two in POU1F1, one in GLI2, and one in LHX4. In all patients, these variants were most frequently found in GLI2, followed by PROP-1 and GHRHR. Conclusion: Genetic causes were determined in only 23.4% of all patients with CH and 63% of molecularly diagnosed patients (7/11) from consanguineous families. Despite advances in genetics, we were unable to identify the genetic etiology of most patients with CH, suggesting the effect of unknown genes or environmental factors. More genetic studies are necessary to understand the etiology of CH.

ABSTRACT Objective: To investigate nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) and hepatic fibrosis in biopsies of people with obesity who underwent bariatric surgery and examine the possible association of different variables with a diagnosis of NAFLD and NASH. Materials and methods: Epidemiological, clinical and laboratory data from 574 individuals with obesity of both genders seen by the same physician between 2003 and 2009 who had a liver biopsy during bariatric surgery were examined. Results: Of the 437 patients included, 39.8% had some degree of liver fibrosis, 95% had a histologic diagnosis of NAFLD, and the risk factors were age ≥ 28 years and Homeostatic Model Assessment (HOMA) ≥ 2.5 (p = 0.001 and p = 0.016, respectively). In the NAFLD group, NASH was present in 26% of patients and the associated factors were aspartate aminotransferase and alanine aminotransferase index (AST/ALT) > 1, high-density lipoprotein cholesterol (HDL-c) < 40 mg/dL, total cholesterol (TC) ≥ 200 mg/dL, gamma-glutamyl transferase (GGT) > 38 U/L and triglycerides (TG) levels > 150 mg/dL. The independent risk factors were low HDL-c, elevated AST/ALT and high TG. Conclusion: The variables associated with a diagnosis of NAFLD were HOMA ≥ 2.5 and age ≥ 28 years. NASH was associated with low HDL-c, high TG and AST/ALT ≤ 1.

ABSTRACT Objective: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and a growing global epidemic. In NAFLD, liver fat surpasses 5% of hepatocytes without the secondary causes of lipid accumulation or excessive alcohol consumption. Given the link between NAFLD and insulin resistance, the possible association between the rs2854744 (−202 G>T) promoter polymorphism of insulin-like growth factor binding protein 3 (IGFBP3) gene and NAFLD was investigated in this study. Materials and methods: In this genetic case-control association study, the IGFBP3 rs2854744 genotypes of 315 unrelated individuals, including 156 patients with biopsy-proven NAFLD and 159 controls, were determined using polymerase chain reaction/restriction fragment length polymorphism analyses. Results: The “GT+TT” genotype of the IGFBP3 rs2854744 polymorphism, compared with the “GG” genotype, was associated with a 2.7-fold increased risk of NAFLD after adjustment for confounding factors (P = 0.009; odds ratio [OR] = 2.71; 95% confidence interval [CI] = 1.19-3.18). Additionally, the IGFBP3 rs2854744 “T” allele, in comparison with the “G” allele, was significantly overrepresented in NAFLD patients than the controls (P = 0.008; OR = 1.85; 95%CI = 1.23-2.94). Conclusion: Our findings first indicated that the IGFBP3 rs2854744 “GT+TT” genotype is a marker of increased NAFLD susceptibility; however, it needs to be supported by further investigations in other populations.

ABSTRACT The aim of this review is to comprehensively assess the association between a gluten-free diet (GFD) and metabolic control of type 1 diabetes mellitus (T1DM) in children and adolescents with T1DM and with T1DM plus coeliac disease (CD). PubMed, Embase, Cochrane Library, and Web of Science were searched until June 19, 2023. Primary outcomes were hemoglobin A1c (HbA1c), insulin dose, insulin dose adjusted A1c (IDAA1c), blood glucose (B-glu) at 90 min during Mixed Meal Tolerance Test (MMTT), C-peptide area under the curve (AUC), and C-peptide. Seven studies involving 355 T1DM patients were included. Three studies involving 141 patients compared a GFD to a standard diet in children and adolescents with T1DM without CD. Additionally, two studies with 164 patients examined the same diet comparison in those with T1DM and concurrent CD. A comparison between T1DM with CD and T1DM alone, using a GFD, was conducted in two studies encompassing 50 patients. Patients with T1DM alone had similar HbA1c [pooled weighted mean difference (WMD) = −0.5, 95% confidence interval (CI): −1.0 to 0.1, P = 0.079] and IDAA1c (pooled WMD = −0.4, 95%CI: −0.9 to 0.1, P = 0.095) levels after a GFD and a standard diet. In children and adolescents with T1DM and CD, a GFD was associated with a significantly lower HbA1c compared with a standard diet (pooled WMD = −0.64, 95%CI: −1.22 to −0.05, P = 0.034). Insulin dose was significantly lower in T1DM combined with CD patients having a GFD vs a standard diet (pooled WMD = −0.34, 95%CI: −0.66 to −0.03, P = 0.032). Our study suggests that a GFD may offer significant benefits for children and adolescents with both T1DM and CD over a standard diet. While the evidence indicates improved glycemic control with a GFD, the quality of this evidence is low, highlighting the need for rigorous, randomized trials to confirm these preliminary findings. In the interim, enhancing dietary awareness and providing tailored nutritional guidance could be pivotal for optimizing glucose management in this patient population. glutenfree gluten free (GFD TDM T DM (T1DM . (CD) PubMed Embase Library 19 2023 Ac c HbA1c, HbAc , HbA (HbA1c) IDAA1c, IDAAc IDAA (IDAA1c) Bglu B glu (B-glu 9 MMTT, MMTT (MMTT) Cpeptide C peptide AUC, AUC (AUC) Cpeptide. peptide. 35 included 14 Additionally 16 5 pooled (WMD 05 0 −0.5 95 CI (CI) 10 −1. 01 0.1 0.079 0079 079 04 4 −0.4 95%CI 95CI 09 −0. 0.095 0095 095 064 64 −0.64 122 22 −1.2 005 −0.05 0.034. 0034 0.034 034 0.034) 34 −0.34 066 66 −0.6 003 03 −0.03 0.032. 0032 0.032 032 0.032) low rigorous findings interim population (CD 202 (HbA1c (IDAA1c (MMTT (AUC 3 (CI −1 0. 0.07 007 07 −0 0.09 009 06 6 12 2 00 −0.0 0.03 −0.3 20 − 0.0

ABSTRACT Type 1 diabetes (TID) is a chronic disease caused by autoimmune destruction of pancreatic β-cells, that progresses in three stages: 1) stage 1: β-cell autoimmunity + normoglycemia; 2) stage 2: β-cell autoimmunity + mild dysglycemia; 3) stage 3: symptomatic disease + hyperglycemia. Interventions to prevent or cure T1D in the various stages of the disease have been pursued and may target the prevention of the destruction of β cells, regression of insulitis, preservation or recovery of β cells residual mass. Some therapies show promising results that might change the natural history and the approach to patients with T1D in the next few years. Teplizumab, a humanized monoclonal antibody that binds to CD3, was recently approved in the USA to delay Stage 3 T1D in individuals ≥ 8 years of age. Other non-cellular immunomodulatory therapies, both antigen-specific and non-specific, have shown interesting results either in patients with stage 2 or recent onset stage 3 T1D. Cell therapies such as non-myeloablative transplantation of autologous hematopoietic stem cells, mesenchymal stem cells, and tolerogenic dendritic cells have been also studied in these individuals, aiming immunomodulation. Stem cell-derived islet replacement therapy is promising for patients with long-standing T1D, especially with asymptomatic hypoglycemia not resolved by technology. This review aimed to provide updated information on the main immunomodulatory agents and cell therapy options for type 1 diabetes. TID (TID βcells, βcells β-cells βcell normoglycemia dysglycemia hyperglycemia TD T D insulitis mass Teplizumab CD3 CD age noncellular non cellular antigenspecific antigen specific nonspecific, nonspecific specific, non-specific nonmyeloablative myeloablative immunomodulation cellderived derived longstanding long standing technology

ABSTRACT The global increase in life expectancy has led to a concomitant rise in diagnoses of sarcopenia. At the same time, the epidemic levels of obesity have given rise to the emergence of a complex condition known as sarcopenic obesity. Characterized by the simultaneous presence of loss of muscle mass and strength along with obesity or excess body fat, sarcopenic obesity represents a concerning health condition. Contrary to prevailing assumptions, sarcopenic obesity is not exclusive to older adults, as it may also manifest in individuals with obesity and chronic diseases and in those who undergo rapid weight loss. This juxtaposition of fat accumulation and muscle depletion epitomizes a harmful combination, especially in healthy adults. A precise definition of sarcopenic obesity and an understanding of how different body composition components affect functional parameters, comorbidities, and mortality rates are crucial for grasping the full extent and significance of this condition. Despite its multifaceted nature, sarcopenic obesity is often undiagnosed and undertreated, posing a considerable challenge to healthcare systems worldwide. In this review, we explore the intricate interplay of factors contributing to the development and consequences of sarcopenic obesity and discuss newly proposed diagnostic guidelines aimed at improved screening. Enhancing awareness and understanding of sarcopenic obesity is imperative for addressing its growing prevalence and mitigating its adverse health effects. sarcopenia time assumptions adults combination parameters comorbidities nature undertreated worldwide review screening effects

SUMMARY Denosumab is a potent antiresorptive medication, commonly used in the treatment of osteoporosis, as well as in a variety of other diseases. Potential adverse rebound effects after its cessation include a loss in bone mineral density and an increased risk of osteoporotic fractures. Hypercalcemia is a less frequently reported rebound phenomenon after denosumab discontinuation, that may pose a diagnostic challenge to physicians as a rare non-parathyroid hormone (PTH) dependent cause of hypercalcemia. In our case, a 47-year-old male presented with rebound hypercalcemia after denosumab cessation during follow-up after surgical treatment for parathyroid carcinoma. This non-PTH-dependent hypercalcemia resolved after re-initiation of denosumab. We performed a systematic literature review on rebound hypercalcemia after denosumab cessation and identified 52 individual patient cases. Children appear to be more prone to developing rebound hypercalcemia, which could be attributed to their higher baseline bone turnover, underlying conditions, or denosumab dosage regimens. In most cases, patients initially presented with acute and often severe symptoms of hypercalcemia that occur from 1.75 to 9 months after denosumab cessation (4 to 9 months in adults). Most effective treatment approaches to sufficiently decrease serum calcium levels were bisphosphonates or re-administration of denosumab. A watch and wait strategy may be sufficient in asymptomatic cases, which are less common and probably underdiagnosed. Subsequent antiresorptive treatment after denosumab cessation, which is a common practice in osteoporosis treatment, may reduce the risk of rebound hypercalcemia. As denosumab is a frequently used drug in patients with advanced malignant diseases and rebound hypercalcemia with low PTH levels may raise the suspicion for skeletal metastases, awareness of this rebound effect may be for particular relevance in such settings. medication fractures discontinuation nonparathyroid non (PTH case 47yearold yearold 47 year old followup follow up carcinoma nonPTHdependent reinitiation re initiation 5 cases turnover conditions regimens 175 1 75 1.7 4 ( adults. adults . adults) readministration administration underdiagnosed metastases settings 17 7 1.

ABSTRACT Objective Subacute thyroiditis is also known as subacute granulomatous thyroiditis, giant cell thyroiditis, painful thyroiditis, and De Quervain’s thyroiditis. Immature granulocytes (IG) and neutrophil-to-lymphocyte ratio (NLR) are new inflammatory markers that are easily detected in routine complete blood count (CBC) tests. The aim of this study was to investigate the role of IG and NLR as markers of treatment response in patients with subacute thyroiditis. Subjects and methods The study included 41 patients with subacute thyroiditis treated and monitored in our outpatient clinic between April 2020 and April 2022. From a retrospective review of medical records, we recorded results of IG, NLR, thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) from blood tests obtained routinely before and after treatment. Results Overall, 31 (75.6%) patients were women and 10 (21.4%) were men. The median age was 41 years (range 22-68 years). The laboratory tests showed the following median (range) results: IG, 0.03 (0.01-0.08); NLR, 3.6 (1.2-5.2); TSH, 0.02 mIU/L (0.01-3.35 mIU/L); fT4, 2.3 ng/dL (1.0-7.0 ng/dL); fT3, 5.6 pmol/L (2.6-15.2 pmol/L); ESR, 49 mm/h (17.0-87 mm/h); and CRP, 73 mg/dL (3.0-188 mg/dL). Conclusion Early diagnosis and treatment of subacute thyroiditis is fundamental. In the present study, the new inflammatory markers IG and NLR, measured routinely on CBC tests, decreased significantly after subacute thyroiditis treatment relative to pretreatment values. After treatment, the NLR change correlated with ESR and CRP changes, while the IG change correlated only with CRP change. These findings suggest that the markers IG and NLR may be used to evaluate treatment response in patients with subacute thyroiditis. Quervains Quervain s (IG neutrophiltolymphocyte neutrophil lymphocyte (NLR (CBC 4 202 2022 records thyroidstimulating thyroid stimulating TSH , (TSH) fT4 fT (fT4) fT3 (fT3) (ESR) Creactive C reactive (CRP Overall 3 75.6% 756 75 6 (75.6% 1 21.4% 214 21 (21.4% men range 2268 22 68 22-6 years. . years) 003 0 03 0.0 0.010.08 001008 0.01 0.08 01 08 (0.01-0.08) 36 3. 1.25.2 1252 1.2 5.2 2 5 (1.2-5.2) 002 02 mIUL mIU L 0.013.35 001335 3.35 35 (0.01-3.3 mIU/L) 23 2. ngdL ng dL 1.07.0 1070 1.0 7.0 7 (1.0-7. ng/dL) 56 5. pmolL pmol 2.615.2 26152 2.6 15.2 15 (2.6-15. pmol/L) mmh mm h 17.087 17087 17.0 87 17 (17.0-8 mm/h) mgdL mg 3.0188 30188 3.0 188 (3.0-18 mg/dL. mg/dL) fundamental values changes 20 (TSH (fT4 (fT3 (ESR 75.6 (75.6 21.4 (21.4 226 22- 00 0. 010 0.010.0 00100 001 008 (0.01-0.08 25 1.25. 125 12 1. 52 (1.2-5.2 013 0.013.3 00133 335 3.3 (0.01-3. 07 1.07. 107 70 7. (1.0-7 615 2.615. 2615 26 152 15. (2.6-15 087 17.08 1708 170 17. 8 (17.0- 0188 3.018 3018 30 18 (3.0-1 (fT 75. (75. 21. (21. 0.010. 0010 (0.01-0.0 1.25 (1.2-5. 0.013. 0013 33 (0.01-3 1.07 (1.0- 61 2.615 261 (2.6-1 (17.0 018 3.01 301 (3.0- (75 (21 0.010 (0.01-0. (1.2-5 0.013 (0.01- (1.0 2.61 (2.6- (17. (3.0 (7 (2 (0.01-0 (1.2- (0.01 (1. (2.6 (17 (3. ( (1.2 (0.0 (1 (2. (3 (0. (0