Geographic variation in the association between Hashimoto's thyroiditis and Papillary thyroid carcinoma, a meta-analysis.

PURPOSE: The association between papillary thyroid cancer (PTC) and Hashimoto's thyroiditis (HT) remains a matter of debate. Several genetic and environmental factors have been found to influence this association. Because of the variation in these factors among different populations, we conducted a country- and region-based meta-analysis to examine whether the geographic area influences this association. METHODS: We searched PubMed and Web of Science databases for original articles that investigated the association between HT and PTC from February 1955 to February 28, 2023. The included studies were stratified according to their country and region of origin. Various subgroup analyses were conducted. The primary outcome was the pooled relative risk (RR) and its 95% confidence interval (CI) for each region and country. RESULTS: Forty-six studies including a total of 93,970 participants met our inclusion criteria. They originated from 16 countries distributed in five regions. Significant variation was found among countries but not among regions. Upon analysis of all 46 included studies, countries were classified based on their RR and its 95% CI. Excluding countries with pooled sample sizes <500, Sri Lanka (RR 4.23, 95% CI 2.91-6.14), Poland (RR 3.16, 95% CI 2.79-3.57) and Japan (2.68, 2.14-3.36) showed the strongest association between HT and PTC while Greece (RR 1.06, 95% CI 1.00-1.13), Spain (RR 0.70, 95% CI 0.23-2.11), and Jordan (0.62, 0.32-1.32) showed no significant association. CONCLUSION: Our findings revealed a variation in the association between HT and PTC among countries but not among regions. The country-to-country variation could be due to certain genetic and/or environmental factors subject to geographic variation that influence this association. These findings may help guide health policies aiming to mitigate the risk of PTC in the HT population by helping identify high-risk and low-risk countries.

Immune-mediated lung diseases: A narrative review.

The role of immunity in the pathogenesis of various pulmonary diseases, particularly interstitial lung diseases (ILDs), is being increasingly appreciated as mechanistic discoveries advance our knowledge in the field. Immune-mediated lung diseases demonstrate clinical and immunological heterogeneity and can be etiologically categorized into connective tissue disease (CTD)-associated, exposure-related, idiopathic, and other miscellaneous lung diseases including sarcoidosis, and post-lung transplant ILD. The immunopathogenesis of many of these diseases remains poorly defined and possibly involves either immune dysregulation, abnormal healing, chronic inflammation, or a combination of these, often in a background of genetic susceptibility. The heterogeneity and complex immunopathogenesis of ILDs complicate management, and thus a collaborative treatment team should work toward an individualized approach to address the unique needs of each patient. Current management of immune-mediated lung diseases is challenging; the choice of therapy is etiology-driven and includes corticosteroids, immunomodulatory drugs such as methotrexate, cyclophosphamide and mycophenolate mofetil, rituximab, or other measures such as discontinuation or avoidance of the inciting agent in exposure-related ILDs. Antifibrotic therapy is approved for some of the ILDs (e.g., idiopathic pulmonary fibrosis) and is being investigated for many others and has shown promising preliminary results. A dire need for advances in the management of immune-mediated lung disease persists in the absence of standardized management guidelines.

Serum IGF-1 to IGFBP-3 Molar Ratio: A Promising Diagnostic Tool for Growth Hormone Deficiency in Children.

BACKGROUND: The serum insulin-like growth factor-1 (IGF-1)/insulin-like growth factor binding protein-3 (IGFBP-3) ratio has various potential applications in growth hormone-related disorders. This study aimed to investigate the performance of the IGF-1/IGFBP-3 ratio, independently and in combination with serum IGF-1 and IGFBP-3, in the diagnosis of growth hormone deficiency (GHD) in children with short stature (SS). METHODS: A 7-year cross-sectional observational study was conducted on 235 children with SS. Participants with known disorders that may affect IGF-1 other than GHD were excluded. Participants were classified into GHD (n = 64) and non-GHD (n = 171) groups. GHD was defined as a slow growth rate (<25th percentile over 1 year) and suboptimal growth hormone (GH) response to 2 GH stimulation tests (peak GH < 6.25 ng/mL using the DiaSorin Liaison assay). The sensitivity and specificity of serum IGF-1, IGFBP-3, and IGF-1/IGFBP-3 molar ratio, independently and in various combinations, were determined. RESULTS: GHD was diagnosed in 27.2% of participants. Among all studied variables, a low serum IGF-1/IGFBP-3 ratio demonstrated the greatest sensitivity for GHD (87.5%), with a comparable specificity (83.0%). The combination of low serum IGF-1, IGFBP-3, and IGF-1/IGFBP-3 ratio demonstrated the greatest specificity for GHD (97.7%), whereas the combination of normal serum IGF-1, IGFBP-3, and IGF-1/IGFBP-3 ratio demonstrated the greatest specificity for a non-GHD cause of SS (100.0%). CONCLUSION: Our data suggest that the serum IGF-1/IGFBP-3 ratio is a useful marker for the diagnosis of GHD in children who do not have other disorders that may affect serum IGF-1 levels. Further large studies are needed to confirm the diagnostic utility of the serum IGF-1/IGFBP-3 ratio.

A Possible Novel Effect for Dapagliflozin in the Management of Subcutaneous Insulin Resistance Syndrome: A Report of Two Cases.

Introduction: Subcutaneous insulin resistance syndrome (SIRS) is a rare condition in which patients poorly respond to subcutaneous (SC) insulin but maintain a normal response to intravenous (IV) insulin. The underlying pathophysiology remains elusive. Several treatment regimens have been tested for the management of SIRS, none of which included a sodium-glucose cotransporter-2 inhibitor (SGLT-2). Case Presentation: Two cases of type 1 diabetes initially achieved adequate glycemic control with subcutaneous insulin. Both cases later progressed into recurrent diabetic ketoacidosis that would resolve following IV insulin administration. Further investigation revealed unresponsiveness to SC, but not IV, insulin and the clinical diagnosis of SIRS was established accordingly. HbA1c values for cases 1 and 2 were 11% on 400 units/day of SC insulin, and 12% on 350 - 400 units/day of SC insulin, respectively. The patients required very high doses of intramuscular (IM) insulin. Subsequently, dapagliflozin as adjunct therapy significantly reduced the patients' IM insulin requirements beyond the anticipated dose reduction. Ultimately, case 1 achieved an HbA1c of 7 - 8% on 90 units/day of IM insulin and 10 mg/day of dapagliflozin, and case 2 achieved an HbA1c of 7 - 8% on 120 units/day of IM insulin and 10 mg/day of dapagliflozin. Conclusions: These are the first reported cases of SIRS in which dapagliflozin, an SGLT-2 inhibitor, was used. The substantial reduction in the IM insulin dose following the addition of dapagliflozin in our reported cases of SIRS suggests a possible novel mechanism for dapagliflozin beyond its glucosuric effects. In this report, we present a hypothetical basis for this possible novel mechanism.

Association between placenta accreta spectrum and third-trimester serum levels of vascular endothelial growth factor, placental growth factor, and soluble Fms-like tyrosine kinase-1: A meta-analysis.

AIM: Antenatal suspicion of placenta accreta spectrum (PAS) currently relies on ultrasonographic findings, color doppler, and MRI, which have rendered it operator and expertise-dependent. No serum markers for PAS have been integrated into clinical practice yet. The aim of this meta-analysis was to identify potential serum markers for PAS by investigating third-trimester serum levels of vascular endothelial growth factor (VEFG), placental growth factor (PIGF), and soluble Fms-like tyrosine kinase-1 (sFlt-1) among PAS-cases and controls. METHODS: PubMed, Scopus, EBSCO, Web of Science, and CNKI databases were systematically searched for relevant articles. Random-effects model was applied to calculate the overall standardized mean difference (SMD) for each marker. Subgroup analysis and meta-regression were performed to assess for potential covariates. RESULTS: Eight studies involving 366 PAS-cases and 518 controls were included. Third trimester sFlt-1 levels were significantly lower in PAS-cases when compared to controls (SMD = -7.76, 95%CI = -10.42 to -5.10). This was, to a certain extent, consistent among studies though they differed in their extent of significance. Levels of VEGF (SMD = 1.59, 95%CI = -0.07 to 3.25) and PlGF (SMD = -0.49, 95%CI = -1.66 to 0.67) were not significantly different between PAS cases and controls, in which studies demonstrated conflicting results. CONCLUSIONS: Third trimester sFlt-1 levels may be useful to predict PAS. Nonetheless, further studies are recommended to better understand conflicting results before adopting either VEGF or PlGF.