Nutrition of aging people with diabetes mellitus: Focus on sarcopenia.

As populations age, chronic diseases accumulate, and new health conditions emerge. One noteworthy pair that warrants further evaluation is diabetes mellitus and sarcopenia, given that the latter occurs in 28 % of the population aged over 50 who have diabetes mellitus. The management of both entails nutritional interventions, making the development of unified dietary recommendations an alluring strategy. This review aims to elucidate the current recommendations for the combined management of sarcopenia and diabetes, while featuring elements that require further research. The goal of nutritional management is to improve muscle mass and strength while regulating metabolic risk and glucose levels. To ensure muscle synthesis in the elderly, recommendations align at daily calorie intake that exceeds 30 kcal/kg, with adjustments based on comorbidities. Additionally, a protein intake of at least 1-1.2 g/kg/d is essential, emphasizing both daily and per-meal intake, and can be achieved through diet or branched-amino-acids supplements. Specific considerations for diabetes include restricted protein intake in diabetic nephropathy and exploring the potential link between branched amino acids and insulin resistance. Further recommendations that both promote metabolic health and have demonstrated at least a potential to increase muscle strength include prioritizing polyunsaturated fatty acids as a fat source and maintaining adequate levels of vitamin D. Clinicians should consult their patients on dietary optimization, but evidence is insufficient to recommend additional supplementation. Lastly, an emerging challenge of diabetes and sarcopenia is sarcopenic obesity, which requires the combination of a hypocaloric diet with increased protein intake.

Tocilizumab improves clinical outcome in patients with active corticosteroid-resistant moderate-to-severe Graves' orbitopathy: an observational study.

Background: Graves' orbitopathy (GO) is an autoimmune disorder affecting the orbital fat and muscles. A significant role of IL-6 in the pathogenesis of GO has been described and tocilizumab (TCZ), an IL-6 inhibitor targeting IL-6R has been given in some patients. The aim of our case study was to evaluate the therapeutic outcome of TCZ in non-responders to first line treatments with corticosteroids. Methods: We conducted an observational study of patients with moderate to severe GO. Twelve patients received TCZ in intravenous infusions at a dose of 8mg/kg every 28 days for 4 months and followed up for additionally 6 weeks. The primary outcome was improvement in CAS by at least 2 points, 6 weeks after the last dose of TCZ. Secondary outcomes included CAS <3 (inactive disease) 6 weeks after TCZ last dose, reduced TSI levels, proptosis reduction by > 2mm and diplopia response. Results: The primary outcome, was achieved in all patients 6 weeks after treatment course. Furthermore all patients had inactive disease 6 weeks after treatment cessation. Treatment with TCZ reduced significantly median CAS by 3 units (p=0.002), TSI levels by 11.02 IU/L (p=0.006), Hertel score on the right eye by 2.3 mm (p=0.003), Hertel score on the left eye by 1.6 mm (p=0.002), while diplopia persisted in fewer patients (25%) after treatment with TCZ (not statistically significant, p=0.250). After treatment with TCZ, there was a radiological improvement in 75% of patients, while 16.7% showed no response, and in 8.3% of patients deterioration was established. Conclusion: Tocilizumab appears to be a safe and cost effective therapeutic option for patients with active, corticosteroid-resistant, moderate to severe Graves' orbitopathy.

Presence of antiphospholipid antibodies is associated with increased implantation failure following in vitro fertilization technique and embryo transfer: A systematic review and meta-analysis.

PURPOSE: A systematic review and meta-analysis was conducted comparing the presence of anti-phospholipid (anti-PL) antibodies between women of reproductive age, without diagnosis of antiphospholipid syndrome, who experienced at least two implantation failures following in vitro fertilization and embryo transfer (IVF-ET), and either women who had a successful implantation after IVF-ET or women with at least one successful spontaneous pregnancy or unselected healthy fertile women with no history of IVF-ET. METHODS: Systematic search of the literature and meta-analysis of the relevant studies studying presence of antiphospholipid antibodies in women experiencing at least two implantation failures in IVF-ET as compared to either women who had a successful implantation after IVF-ET or/and women with at least one successful spontaneous pregnancy or unselected healthy fertile women with no history of IVF-ET. Six hundred ninety-four published reports were retrieved; 17 of them fulfilled the inclusion criteria set. RESULTS: Presence of either any type of anti-phospholipid or anticardiolipin antibodies or lupus-anticoagulant in women experiencing at least two implantation failures in IVF-ET was associated with increased implantation failure compared to women who had a successful implantation after IVF-ET (relative risk, RR: 3.06, 5.06 and 5.81, respectively). Presence of either anticardiolipin or lupus-anticoagulant or anti-beta2 glycoprotein-I or anti-phosphatidylserine antibodies in women experiencing at least two implantation failures in IVF-EΤ was associated with increased implantation failure compared to unselected healthy fertile women with no history of IVF-ET (RR:13.92, 6.37, 15.04 and 164.58, respectively). CONCLUSION: The prevalence of antiphospholipid antibodies, particularly that of anti-beta2 glycoprotein-I and anti-phosphatidylserine antibodies, in women experiencing at least two implantation failures in IVF-ET without diagnosis of antiphospholipid syndrome is significantly greater than either in women who had a successful implantation after IVF-ET or women with at least one successful spontaneous pregnancy or unselected healthy fertile women with no history of IVF-ET. TRIAL REGISTRATION NUMBER: PROSPERO ID: CRD42018081458.

Hashimoto Thyroiditis, Anti-Parietal Cell Antibodies: Associations With Autoimmune Diseases and Malignancies.

Background: Hashimoto thyroiditis (HT) is an autoimmune disease which may result in extensive damage of the thyroid gland. Chronic atrophic gastritis (CAG), is the most frequent HT-associated disorder, with anti-parietal cell autoantibodies (APCA) being a screening test for autoimmune CAG. The aim of this study was to investigate, in a cohort of HT patients: a) the prevalence of APCA in an attempt to define their clinical phenotype and b) any possible associations of APCA with other autoimmune diseases and malignancies. Methods: This is a single-center, case-control study, conducted at a University Hospital. The study included patients with HT diagnosed between November 2017 and November 2020. Excluded were patients <18 years old, with sonographic features of HT but negative thyroid peroxidase (TPOAbs) or thyroglobulin autoantibodies (TgAbs), Graves' disease, Down or Turner's syndrome. Results: A total of 840 patients with HT were included in the study, from whom 180 (21.4%) had positive APCA. A total of 79 patients (9.4%) had one or more organ-specific autoimmune diseases and 61 (7.3%) had a systemic autoimmune disease. Autoimmune diseases were more frequent in female than in male patients (17.9% versus 10.9%, p = 0.05). APCA-positive patients were older than APCA-negative (54.1 ± 13.5 versus 49.0 ± 14.6, p <0.001) and had more often positive TPOAbs (93.3% versus 83.9%, p=0.001). Gastric neoplasms were documented only in APCA-positive patients (p <0.001). A higher frequency of organ-specific autoimmune diseases was observed in the APCA-positive group (14.4% versus 8%, p = 0.024). In the subgroup of patients with additional autoimmune diseases (n = 140), younger age and positive APCA were independently associated with the presence of organ-specific autoimmunity (OR 0.954, 95% CI 0.927-0.982 and OR 3.100, 95% CI 1.256-7.652, respectively). Papillary thyroid cancer (PTC) occurred in 3.5% of patients (26/29 women). Positive family history for thyroid autoimmunity and negative TPOAbs were the only independent risk factors for PTC among women (OR 3.228, 95% CI 1.173-8.887 and 0.315, 95% 0.113-0.881, respectively). Conclusion: This study reveals for the first time an association of APCA with organ-specific autoimmunity in HT patients. APCA together with patient age were independently associated with the presence of organ-specific autoimmunity. Finally, this study showed an association between APCA and gastric neoplasms in these patients.

Bisphenol A correlates with fewer retrieved oocytes in women with tubal factor infertility.

PURPOSE: Serum and urinary bisphenol A (BPA) concentrations have been associated negatively with the number of retrieved oocytes after in vitro fertilization (IVF). The impact of BPA upon women with polycystic ovary syndrome (PCOS) and women with tubal factor infertility (TFI), following IVF, was investigated. To this purpose, associations among serum and urinary and follicular fluid (FF) BPA concentrations and the number of retrieved and fertilized oocytes and comparisons between pregnancy rates were evaluated. METHODS: This was a cross-sectional study conducted at a university-affiliated assisted conception unit between January and November 2019, including 93 women of reproductive age (PCOS: 45; TFI: 48) following IVF. Unconjugated FF and serum BPA concentrations and total urinary BPA concentration were measured using a novel gas chromatography-mass spectrometry method. The number of retrieved and fertilized oocytes and pregnancy rate were documented and evaluated. RESULTS: The number of oocytes retrieved from PCOS women was greater than that of 21 TFI women, independently of BMI. Lower FF BPA concentrations were found in all PCOS women and in overweight/obese PCOS compared to TFI women (0.50, 0.38, and 1.13 ng/mL, respectively). In TFI women, FF BPA concentrations correlated negatively with the number of retrieved oocytes. Serum and FF and urinary BPA concentrations did not significantly affect the number of fertilized oocytes and pregnancy rate in both groups. CONCLUSION: FF BPA concentrations were lower in all PCOS women and in overweight/obese PCOS than in TFI women. In TFI women, FF BPA concentrations correlated negatively with retrieved oocytes. Confirmation of these findings might lead to moderation of use of BPA-containing products by women undergoing IVF.

Staged correction of varus knee and lateral thrust in an achondroplastic (ACH) juvenile patient who underwent limb lengthening with IM nails: tips for proper timing and prioritisation of procedures.

We present the case of a fifteen-year-old achondroplastic (ACH) woman who requested to have her femurs lengthened by intramedullary nails. She had undergone bilateral tibial lengthening at the age of eleven and presented with a varus deformity of the right lower limb, lateral thrust of the right knee and valgus deformity of the left lower limb. We performed deformity analyses based on mechanical axis measurements, and we came with a staged surgical plan. In ACH adolescences, correction of bony deformity needs to encounter continuous fibula growth dynamics. Lateral knee thrust was corrected by gradual distal translation of the fibula head via an Ilizarov frame and the amount of translation we decided clinically. Tibial lengthening and valgus osteotomy of the distal femur accentuate lateral collateral ligament (LCL) complex laxity. In patients with ACH, tibial lengthening and valgus osteotomy of the distal femur-if needed-should precede LCL complex tightening, and femoral lengthening should follow.

p53 protein expression in synchronously occurring dedifferentiating stages of thyroid cancer in a patient with neurofibromas: A case report.

Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) have been hypothesized to arise from well-differentiated thyroid carcinoma (WDTC) due to frequently reported synchronous and metachronous occurrence. Loss of normal p53 function has been implicated in this dedifferentiation process. The current case report presents a 60-year-old male with multiple neurofibromas who underwent total thyroidectomy due to multiple palpable thyroid nodules. Histopathological examination revealed three foci of predominantly papillary, but also follicular carcinoma growth pattern, and two lesions with histological features of insular and trabecular variant, with the larger one showing foci of anaplastic transition. Nuclear p53 protein accumulation, corresponding to mutant abnormally stabilized p53, was higher in more aggressive variants compared with WDTC. The somatic molecular events and downstream pathways of this dedifferentiation course have not been unraveled yet. The present case report demonstrated the simultaneous presence of three divergent histological subtypes in a single thyroid gland, with progressive enhancement of nuclear p53 protein expression, associated with mutant p53 protein, in the more aggressive variants. This is a rare case of progressive enhancement of mutant nuclear p53 protein expression in multifocal thyroid tumor areas consisting of WDTC, PDTC and ATC histological types, highlighting the possibility that WDTC can progress to PDTC and then ATC through an intricate procedure, involving loss of normal p53 function.

Thyroid cancer surgery during the coronavirus disease 2019 pandemic: perioperative management and oncological and anatomical considerations.

The coronavirus disease 2019 (COVID-19) pandemic has changed many aspects of our everyday lives and medical practice, including oncology treatment; thyroid cancer surgery is not an exception. The reported number of fine-needle aspirations performed during the first semester of 2020 was significantly reduced. Poorly differentiated, medullary and anaplastic thyroid tumors are considered important indications for immediate surgical intervention. By contrast, most well-differentiated carcinomas present slow growth, and thus surgery can be deferred for a short period of time during which patients are under active surveillance. Thyroid surgeries have decreased during the COVID-19 pandemic. Furthermore, prior to any intervention, negative COVID-19 status - with the use of a nasopharyngeal swab and reverse transcription PCR assay as the gold standard and chest CT scan as a complementary modality in some cases - must be confirmed to achieve a COVID-free pathway. Thorough preoperative assessment regarding both oncological and anatomical aspects should be performed to identify optimal timing for safe management.

Occurrence and Antigenic Specificity of Perinuclear Anti-Neutrophil Cytoplasmic Antibodies (P-ANCA) in Systemic Autoimmune Diseases.

Perinuclear anti-neutrophilic cytoplasmic antibodies (P-ANCA) recognize heterogeneous antigens, including myeloperoxidase (MPO), lactoferrin, elastase, cathepsin-G and bactericidal/permeability-increasing protein. Although P-ANCA have diagnostic utility in vasculitides, they may also be found in patients with various other systemic autoimmune rheumatic diseases (SARDs). Nevertheless, the clinical significance and the targets recognized by P-ANCA in such patients remain unclear. For this purpose, herein we investigated the occurrence of ANCA-related antigenic specificities in 82 P-ANCA-positive sera by multiplex ELISA, as well as their association with other autoantibodies. The P-ANCA-positive sera corresponded to patients with vasculitides (n = 24), systemic lupus erythematosus (n = 28), antiphospholipid syndrome (n = 5), Sjögren's syndrome (n = 7), rheumatoid arthritis (n = 3), systemic scleroderma (n = 1), sarcoidosis (n = 1) and Hashimoto's thyroiditis (n = 13). In most P-ANCA-positive patients studied (51/82, 62.3%), these autoantibodies occurred in high titers (>1:160). The analysis of P-ANCA-positive sera revealed reactivity to MPO in only 50% of patients with vasculitides, whereas it was infrequent in the other disease groups studied. Reactivity to other P-ANCA-related autoantigens was also rarely detected. Our findings support that high P-ANCA titers occur in SARD. The P-ANCA-positive staining pattern is associated with MPO specificity in vasculitides, while in other autoimmune diseases, it mostly involves unknown autoantigens.

Single-session high-intensity focused ultrasound (HIFU) ablation for benign thyroid nodules: a systematic review.

BACKGROUND: Thyroid nodules are common; the majority of them are benign and asymptomatic. Thyroidectomy might be an option; however, the frequency of post-operative complications mandates the development of alternative approaches, such as high-intensity focused ultrasound ablation (HIFU). HIFU induces thermal destruction without penetrating the skin. The present systematic review aims to synthesize all available data, evaluating studies with single-session HIFU therapy and investigating its efficacy. MATERIALS AND METHODS: This systematic review was conducted in accordance with the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and MetaAnalyses). Eligible articles were identified by a search of Medline bibliographic database (PubMed) and Cochrane Library. Out of 39 results, 11 articles were considered to meet the inclusion criteria. RESULTS: All eligible studies included patients with solid or predominantly solid benign thyroid nodules. All patients were treated with the same HIFU device. The success rate of the method was defined in the majority, with the volume reduction rate (VRR) over 50% from baseline. The mean or median VRR ranged from 48.7 to 70.41%, depending on the last follow-up date. No major complications were observed. CONCLUSION: Single-session HIFU is safe and effective for the treatment of benign thyroid nodules.

Recurrent myelitis and asymptomatic hypophysitis in IgG4-related disease: case-based review.

IgG4-related disease (IgG4-RD) is a disorder with various clinical manifestations. Central nervous system (CNS) involvement is well recognized, with hypertrophic pachymeningitis and hypophysitis being the most common manifestations. Spinal cord involvement is an extremely rare manifestation. We present the first case of an IgG4-RD patient with spinal cord parenchymal disease and concurrent hypophysitis. We review also the current literature about CNS parenchymal involvement in the context of IgG4-RD. A young female presented with clinical symptoms of myelitis. Cervical spinal cord magnetic resonance imaging (MRI) displayed features of longitudinally extensive transverse myelitis (LETM). Brain MRI showed a small number of high-intensity lesions in the deep white matter and enlargement of hypophysis with homogeneous gadolinium enhancement (asymptomatic hypophysitis). Diagnostic workup revealed elevated IgG4 serum levels (146 mg/dL). Our patient fulfilled the organ-specific diagnostic criteria of IgG4-hypophysitis. Treatment with intravenous glucocorticoids led to rapid clinical response, and to the substantial resolution of imaging findings. Azathioprine was used as a maintenance treatment. One relapse occurred 2 years after the initial diagnosis and patient was re-treated with glucocorticoids. Three years after relapse, patient is in remission with azathioprine. We present the first case of myelitis with radiological features of LETM associated with increased IgG4 serum levels and the simultaneous presence of asymptomatic IgG4-related hypophysitis.

Histone Deacetylase Inhibitors and Anaplastic Thyroid Carcinoma.

BACKGROUND/AIM: Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies, remaining generally incurable. Histone deacetylase (HDAC) seems to play a role in regulating transcription of genes involved in ATC, making HDAC inhibitors (HDACI) promising anticancer drugs for ATC. The purpose of this review was to evaluate the role of HDACIs in ATC treatment and describe the latest trends of current research on this field. MATERIALS AND METHODS: This literature review was performed using the MEDLINE database. The keywords/phrases were; thyroid cancer, anaplastic, HDAC, histone, deacetylase*, HDACI. RESULTS: Compounds, such as SuberoylAnilide Hydroxamic Acid, valproic acid, sodium butyrate, butyrate, phenylbutyrate, trichostatin A, AB1-13, panobinostat or LBH589, belinostat, MS-275, depsipeptide, CUDC101, CUDC907, N-Hydroxy-7-(2-naphthylthio)-Hepanomide (HNHA), and PXD101 have shown promising antitumor effects against ATC. CONCLUSION: HDACIs represent a promising therapy for ATC management, both as monotherapy and in combination with other anticancer drugs.

Long-term sequelae of the less than total thyroidectomy procedures for benign thyroid nodular disease.

INTRODUCTION: Nodular goiter is the most common disorder of the thyroid gland. Less than total thyroidectomy procedures are considered the gold standard in the surgical management of nodular thyroid disease despite its propensity for recurrence. The aim of the study was to assess long-term sequelae of the less than total thyroidectomy procedures. MATERIAL AND METHODS: In this single-center retrospective study, records of 154 patients that underwent less than total thyroidectomy, for nodular disease and/or hyperthyroidism between 1998 and 2013, were reviewed. Patients with malignant findings in the histology report and a follow-up of less than 5 years were excluded. RESULTS: The mean age of the recorded patients was 65.1 ± 12.91 years of which 132 were females. Subtotal thyroidectomy was performed in 45.5% of the study population, 22.1% underwent partial thyroidectomy, while the remaining 32.5% underwent lobectomy. Long-term thyroxine supplementation was administered in 138 patients (89.6%). Recurrence of clinically important nodules (>1 cm) was observed in 68.2% of patients but only 11% of the population underwent completion thyroidectomy. In the univariate analysis, the duration of follow-up (p = 0.00005, C.I.: 0.903-0.965) as well as the type of operation (p = 0.035, C.I.: 1.031-2.348) appeared to have a significant correlation with nodular recurrence. The multivariate analysis identified the duration of follow-up (p = 0.0005, C.I.: 0.908-0.973) as the only significant predictive factor of nodular recurrence. CONCLUSION: This is the first study with such a long duration of post-operative follow-up. The high rate of nodular recurrence in less than total thyroidectomy procedures along with the lifelong need for thyroxine supplementation suggest that a more conservative surgical approach is needed. When surgery is recommended, we suggest total thyroidectomy as the treatment of choice to avoid the recurrence of disease, the high cost associated with frequent follow-ups by means of sonography as well as thyroxine replacement therapy.