Efficacy and safety of basal insulins in people with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized clinical trials.

Aim: The comparative effectiveness of basal insulins has been examined in several studies. However, current treatment algorithms provide a list of options with no clear differentiation between different basal insulins as the optimal choice for initiation. Methods: A comprehensive search of MEDLINE, Embase, Cochrane Library, ISI, and Scopus, and a reference list of retrieved studies and reviews were performed up to November 2023. We identified phase III randomized controlled trials (RCTs) comparing the efficacy and safety of basal insulin regimens. The primary outcomes evaluated were HbA1c reduction, weight change, and hypoglycemic events. The revised Cochrane ROB-2 tool was used to assess the methodological quality of the included studies. A random-effects frequentist network meta-analysis was used to estimate the pooled weighted mean difference (WMD) and odds ratio (OR) with 95% confidence intervals considering the critical assumptions in the networks. The certainty of the evidence and confidence in the rankings was assessed using the GRADE minimally contextualized approach. Results: Of 20,817 retrieved studies, 44 RCTs (23,699 participants) were eligible for inclusion in our network meta-analysis. We found no significant difference among various basal insulins (including Neutral Protamine Hagedorn (NPH), ILPS, insulin glargine, detemir, and degludec) in reducing HbA1c. Insulin glargine, 300 U/mL (IGlar-300) was significantly associated with less weight gain (mean difference ranged from 2.9 kg to 4.1 kg) compared to other basal insulins, namely thrice-weekly insulin degludec (IDeg-3TW), insulin degludec, 100 U/mL (IDeg-100), insulin degludec, 200 U/mL (IDeg-200), NPH, and insulin detemir (IDet), but with low to very low certainty regarding most comparisons. IDeg-100, IDeg-200, IDet, and IGlar-300 were associated with significantly lower odds of overall, nocturnal, and severe hypoglycemic events than NPH and insulin lispro protamine (ILPS) (moderate to high certainty evidence). NPH was associated with the highest odds of overall and nocturnal hypoglycemia compared to others. Network meta-analysis models were robust, and findings were consistent in sensitivity analyses. Conclusion: The efficacy of various basal insulin regimens is comparable. However, they have different safety profiles. IGlar-300 may be the best choice when weight gain is a concern. In contrast, IDeg-100, IDeg-200, IDet, and IGlar-300 may be preferred when hypoglycemia is the primary concern.

Statins and thyroid eye disease (TED): a systematic review.

PURPOSE: Thyroid eye disease (TED) is the foremost extrathyroidal manifestation of Graves' disease (GD). Currently, available treatments do not entirely prevent the long-term consequences of TED and have distinct disadvantages. Therefore, this systematic review explored available evidence regarding the efficacy of statins in preventing and treating TED. METHODS: Relevant studies investigating statin usage in patients with GD or TED were identified by searching Medline (Pubmed and Ovid), Scopus, Web of Science, ProQuest, and Cochrane Library databases (from the database inception to September 2023). The review was done according to the PRISMA statement. Web searching was done independently by two investigators. Two researchers independently extracted the data, and any disagreement was adjudicated by consensus. Based on the study design, the studies' quality appraisal was done using the Newcastle-Ottawa Scale (NOS) and Version 2 of the Cochrane risk-of-bias tool (RoB2). RESULTS: The literature search identified 145 publications, of which four met the inclusion criteria (Three retrospective cohort studies and one randomized clinical trial) and were reviewed in full text. The two retrospective cohort studies demonstrated the beneficial effects of statins on TED in newly diagnosed GD Stein et al. showed that statins, regardless of the type, prevent or delay TED (HR: 0.74 (0.65-0.84)), especially in men or treatment duration of more than one year. Nilsson et al. fascinatingly revealed that at least 60 days of statin usage in the preceding year could decrease the risk of TED development by around 40%. One RCT showed a higher treatment response for active moderate-to-severe TED in patients with hypercholesterolemia who took atorvastatin 20 mg in addition to ivGC for 24 weeks without any increase in serious side effects. The retrospective study revealed that the need for reconstructive surgery was reduced in patients with severe TED who received statin therapy. CONCLUSION: Statin therapy could be a potential adjunctive modality for preventing and treating TED. TRIAL REGISTRATION: PROSPERO registration number: CRD42022315522.

MiR-20b Tissue Expression Level Displays the Diagnostic Value in Papillary Thyroid Carcinoma.

Background: Detection of cancer in patients with thyroid nodules requires sensitive and specific diagnostic modalities that are accurate and inexpensive. This study aimed to identify a potential microRNA(miRNA) panel to detect papillary thyroid carcinoma (PTC). Methods: Following a comprehensive literature review as well as miRNA target predictor databases, Real-time PCR was used to quantify the expression of candidate miRNAs in 59 tissue specimens from 30 patients with PTC and 29 patients with benign nodules. A receiver operating characteristic (ROC) curve analysis was used to assess the accuracy of miRNA expression levels compared to the pathology report as the gold standard. Based on prediction results, four miRNAs, including miR-9, miR-20b, miR-221, and miR-222, were selected to evaluate their expression level in Iranian thyroid samples. Results: A significant difference between the tissue expression level of miR-20b, miR-9, miR-222, and miR-221 was detected in the PTC group compared with non-PTC (P < 0.05). The area under the curves for the included miRs were 1, 0.98, 0.99, 0.98, and 1, respectively. Conclusion: Our results confirmed deregulations of miR-20b as well as miR-222, miR-221, and miR-9 in PTC and, therefore, could be used as a helpful miRNA panel to differentiate PTC from benign nodules, which results in the more efficient clinical management of PTC patients.

Methadone-induced hypoglycemia: A case report.

Hypoglycemia is rare in patients without diabetes mellitus. Methadone is a synthetic µ-opioid receptor agonist used for cancer or non-cancer pain and the treatment of opioid dependence. Here, we report a case of a 31-year-old man who presented with recurrent hypoglycemic events that resolved on discontinuation of methadone. Thus, if hypoglycemia occurs while a patient takes methadone, the amount should be reduced or replaced with another opioid before a full investigation for inappropriate hyperinsulinism is initiated.

Efficacy and safety of peptide receptor radionuclide therapy in advanced radioiodine-refractory differentiated thyroid cancer and metastatic medullary thyroid cancer: a systematic review.

BACKGROUND: It has been shown that a subgroup of patients with differentiated thyroid cancer (DTC) and medullary thyroid carcinoma (MTC) would progress to advanced stages of thyroid cancer. Therefore, the present study was done to systematically review available evidence in order to investigate efficacy and safety of peptide receptor radionuclide therapy (PRRT) in the patients with advanced radioiodine refractory differentiated thyroid cancer (RR-DTC) and metastatic MTC. METHODS: For this purpose, relevant studies investigated safety and efficacy of PRRT in the patients with advanced RR-DTC and metastatic MTC were identified by searching Medline (Pubmed, Ovid, and Ebsco), Scopus, Embase, Web of Science, and Cochrane Library databases (from database inception to March 24, 2021). The review was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Searching was done independently by two investigators. Two researchers independently extracted the data and any disagreement was adjudicated by consensus. Quality of the studies was assessed using the tool of case reports/series in systematic reviews. RESULTS: Among 2284 related papers, 41 papers met the inclusion criteria. A total of 157 patients with RR-DTC were treated with PPRT. Biochemical and objective responses (partial and complete) were observed in 25.3 and 10.5% of patients, respectively. Among 220 patients with metastatic MTC, biochemical and objective responses were observed in 37.2 and 10.6% of the patients, respectively. Forty-six deaths were reported in 95 patients with advanced RR-DTC. In addition, 63 deaths were observed in 144 patients with metastatic MTC. Major side effects were reported in 124 patients treated with 90Y -based agent. In the patients treated with 177Lu-DOTA-TATE and 111In-Octreotide, mild and transient hematologic or renal complications were reported. CONCLUSION: Findings of the study revealed that in the absence of the established treatment for the patients with RR-DTC and metastatic MTC, PRRT could be effective with few adverse events. TRIAL REGISTRATION: PROSPERO registration number: CRD42019125245 .

Elevated CXCL-8 expression in bronchoalveolar lavage correlates with disease severity in patients with acute respiratory distress syndrome resulting from tuberculosis.

BACKGROUND: Tuberculosis (TB) is a rare but known cause of acute respiratory distress syndrome (ARDS). The role of inflammatory cytokines in the progression of ARDS in TB patients is unknown. OBJECTIVES: In this study we investigated the possible link between the levels of inflammatory cytokines in bronchoalveolar lavage (BAL) in patients with TB or ARDS alone or in patients with TB-induced ARDS (ARDS + TB). METHODS: 90 patients were studied: 30 with TB alone, 30 with ARDS alone and 30 with ARDS + TB. BAL was collected by fiberoptic bronchoscopy and the concentrations of interleukin(IL)-6, CXCL8, TNF-α and IL-1ß and the amounts of total protein were measured by ELISA and bicinchoninic acid assay (BCA) methods respectively. The correlation between disease severity measured by Murray scores, SOFA and APACHE II analysis and BAL mediators and cells was also determined. RESULTS: CXCL8 levels in BAL were significantly higher in the ARDS + TB group compared to TB and ARDS alone groups. Disease severity in the ARDS + TB group as determined by Murray score correlated with BAL CXCL8 and neutrophils but not with IL-6, IL-1ß and TNF-α concentrations. In addition, CXCL8 levels and neutrophils were increased in non-miliary TB versus miliary TB. This difference in CXCL8 was lost in the presence of ARDS. CONCLUSIONS: BAL CXCL8 levels were significantly higher in patients with ARDS induced by TB and could suggest an important role of CXCL8 in the pathogenesis of this form of ARDS. This further suggests that CXCL8 inhibitors or blockers may be useful to control the onset and/or development of these combined diseases.