The effect of glycosylated hemoglobin levels on the response to intravitreal dexamethasone implant for treating diabetic macular edema.

This study investigates the impact of glycosylated hemoglobin (HbA1c) on the efficacy of intravitreal dexamethasone (DEX) implants in patients with diabetic macular edema (DME) over a 12-month period. We retrospectively reviewed 90 DME patients treated with DEX implants, categorizing them based on baseline HbA1c levels (≤ 7% and > 7%) and 12-month changes in HbA1c ("improved", "stable", "worsened"). At the 2-month mark, the mean central subfield thickness (CST) reduction in the HbA1c ≤ 7% group was - 147.22 ± 113.79 µm compared to -130.41 ± 124.50 µm in the > 7% group (p = 0.506). Notably, 12-month outcomes between these groups showed no significant difference. The "improved" HbA1c subgroup experienced a more pronounced CST reduction at 2 months (p = 0.042), with outcomes leveling off with other groups by 12 months. Conclusively, DEX implant outcomes in DME were not influenced by either baseline HbA1c levels or their changes over time. This suggests that local alterations in the inflammation milieu may have a potentially stronger impact on DME treatment outcomes, highlighting the importance of considering local factors in DME treatment.

Dalbavancin as salvage therapy in difficult-to-treat patients for diabetes-related foot osteomyelitis.

OBJECTIVES: We aimed to describe the efficacy and safety of dalbavancin in treatment of patients with diabetes-related foot osteomyelitis with bone culture confirmation. PATIENTS AND METHODS: Between January 2019 and December 2021, all consecutive patients receiving at least one 1500 mg dose of dalbavancin for diabetes-related foot osteomyelitis were included in a retrospective study. Remission was defined as absence of relapsing infection or need for surgery at the initial or a contiguous site during 6-month follow-up from the last dose of dalbavancin. RESULTS: Thirteen patients were included. Eleven (85%) patients were surgically treated. Six (46%) patients received dalbavancin as first-line treatment and 7 (54%) as second-line treatment due to adverse events related to previous treatments. One adverse event was reported. At 6-month follow-up, 11 patients were evaluable and 9 (82%) were in remission. CONCLUSIONS: In the study, dalbavancin was well-tolerated and showed microbiological and clinical efficacy.

Smoking Cessation Pharmacotherapy Efficacy in Comorbid Medical Populations: Secondary Analysis of the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) Randomized Clinical Trial.

INTRODUCTION: This study sought to compare medication efficacy in participants with medical comorbidities who smoke in the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) trial, a double-blind, triple-dummy, placebo- and active-controlled randomized controlled trial. AIMS AND METHODS: Participants were from the U.S. cohort of the main trial and randomized (1:1:1:1) to varenicline, bupropion, nicotine replacement therapy (NRT) patch, or placebo for 12 weeks with follow-up through week 24. Medical comorbidity data were derived from the baseline medical screening questionnaire and categorized into four subgroups (cardiac, respiratory, vascular, and diabetes). Within each comorbidity, generalized linear mixed models were used to assess the association between treatment and continuous abstinence rates from weeks 9-12 to 9-24. Similar models were used to test the effect of number of comorbidities on abstinence. RESULTS: Varenicline resulted in the highest week 12 abstinence rates across all pharmacotherapies and compared to placebo in all comorbidity subgroups: Cardiac (40.0% vs. 3.6%; odds ratios [OR] = 23.3 [5.1-107.1]), respiratory (24.7% vs. 12.8%; OR = 2.2 [1.3-3.8]), vascular (29.1% vs. 10.4%; OR = 3.6 [2.3-5.7]), and diabetes (30.9% vs. 8.3%; OR = 6.5 [2.3-19.0]). This was maintained at week 24 for those with cardiac (23.3% vs. 1.8%; OR = 21.7 [2.7-178.2]), vascular (18.9% vs. 7.1%; OR = 3.1 [1.8-5.3]), and diabetes (20.6% vs. 4.2%; OR = 8.4 [2.1-33.7]) comorbidities. Treatment contrasts within some comorbidity subgroups revealed superior efficacy of varenicline over other pharmacotherapies. All pharmacotherapies increased the odds of abstinence regardless of number of comorbidities. CONCLUSIONS: Varenicline is the most efficacious option for patients with manageable cardiac, respiratory, vascular, and diabetes conditions to quit smoking, supporting recent clinical practice guidelines that recommend varenicline as first-line pharmacotherapy. Bupropion and NRT demonstrated efficacy for some comorbidity subgroups. IMPLICATIONS: This secondary analysis of the EAGLES trial demonstrated that varenicline is the most efficacious option for patients with cardiac, respiratory, vascular, and diabetes diagnoses to quit smoking. This demonstration of varenicline efficacy among individuals with comorbid medical conditions supports recent clinical practice guidelines that recommend varenicline as a first-line pharmacotherapy for smoking cessation.

Association of Nilotinib With Cardiovascular Diseases in Patients With Chronic Myelogenous Leukemia: A National Population-Based Cohort Study.

BACKGROUND: Tyrosine kinase inhibitor (TKI) treatment has been identified to be a risk factor for metabolic syndrome and cardiovascular diseases (CVDs) in patients diagnosed with chronic myeloid leukemia (CML). However, the specific contribution of post-TKI metabolic syndrome and the individual TKIs, including imatinib, nilotinib, and dasatinib, contribute to the development of CVDs remains unclear. METHODS: We conducted a nationwide database to investigate the incidence of post-TKI metabolic syndrome, including diabetes, hyperlipidemia, and hypertension, as well as their association with CVDs. To compare the risk of post-TKI comorbidities and CVDs among TKIs, we utilized the incidence rate ratio (IRR), and subdistribution hazard ratio (SHR) calculated from multiple Fine-Gray models. RESULTS: A total of 1211 patients without diabetes, 1235 patients without hyperlipidemia, and 1074 patients without hypertension were enrolled in the study. The incidence rate of post-TKI diabetes and hyperlipidemia was the highest in patients treated with nilotinib compared to imatinib and dasatinib (IRRs ≥ 3.15, Ps ≤ .047). After adjusting for confounders, nilotinib remained a significant risk factor for post-TKI diabetes and hyperlipidemia at an SHR of 3.83 (P < .001) and 5.15 (P < .001), respectively. Regarding the occurrence of CVDs, patients treated with nilotinib were more likely to develop CVDs than those treated with imatinib in non-hyperlipidemic group (IRR = 3.21, P = .020). Pre-existing and post-TKI hyperlipidemia were found to have a stronger association with CVDs, with SHR values of 5.81 (P = .034) and 13.21 (P = .001), respectively. CONCLUSION: The findings of this study indicate that nilotinib treatment is associated with increased risks of diabetes and hyperlipidemia, with hyperlipidemia being the most significant risk for CVDs. Therefore, we recommend that CML patients receiving nilotinib should undergo screening for diabetes and hyperlipidemia prior to initiating TKI treatment. Additionally, regular monitoring of lipid profiles during TKI therapy and implementing effective management strategies to control hyperlipidemia are crucial.

Intravitreal Triamcinolone Acetonide for Diabetic Macular Edema and Macular Edema Secondary to Retinal Vein Occlusion: A Meta-Analysis.

BACKGROUND: The comparative safety and efficacy of different doses of intravitreal triamcinolone acetonide (IVTA) for diabetic macular edema (DME) and macular edema (ME) secondary to retinal vein occlusion (RVO) is unclear. OBJECTIVES: This meta-analysis aimed to compare the safety and efficacy of different doses of IVTA in this setting. METHODS: A systematic literature search for randomized clinical trials (RCTs) was conducted on Cochrane Library, Ovid MEDLINE, and EMBASE from January 2005 to May 2022. Studies that reported on patients with DME or ME secondary to RVO that received treatment with different doses of IVTA were included. A random-effects meta-analysis was performed. Cochrane's Risk of Bias Tool 2 was used to assess the risk of bias, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines were used to assess certainty of evidence. RESULTS: Five RCTs reporting on 1,041 eyes at baseline were included in this meta-analysis. In eyes with ME secondary to RVO, high-dose (4 mg) IVTA achieved a significantly better change in best-corrected visual acuity (WMD = -4.75 ETDRS letters, 95% CI = [-7.73, -1.78], p = 0.002) and reduction in retinal thickness (WMD = -93.02 µm, 95% CI = [-153.23, -32.82], p = 0.002) at months 4-6 compared to low-dose (1-2 mg) IVTA. However, high-dose IVTA had a higher risk of intraocular pressure-related adverse events (RR = 2.99, 95% CI = [1.05, 8.50], p = 0.04) and cataract surgery (RR = 5.67, 95% CI = [3.09, 10.41], p < 0.00001) than low-dose IVTA in eyes with ME secondary to RVO. These efficacy and safety differences in high-dose and low-dose IVTA were not observed in DME eyes. CONCLUSIONS: The RCT evidence in this setting is limited. High-dose IVTA achieved greater improvements in visual acuity and reductions in retinal thickness than low-dose IVTA at months 4-6. However, high-dose IVTA had a less favorable safety profile than low-dose IVTA. The significance of these outcomes was based on patients with ME secondary to RVO, but not DME.

Antipsychotic Medication and Risk of Metabolic Disorders in People With Schizophrenia: A Longitudinal Study Using the UK Clinical Practice Research Datalink.

BACKGROUND AND HYPOTHESIS: Antipsychotics are first-line drug treatments for schizophrenia. When antipsychotic monotherapy is ineffective, combining two antipsychotic drugs is common although treatment guidelines warn of possible increases in side effects. Risks of metabolic side effects with antipsychotic polypharmacy have not been fully investigated. This study examined associations between antipsychotic polypharmacy and risk of developing diabetes, hypertension, or hyperlipidemia in adults with schizophrenia, and impact of co-prescription of first- and second-generation antipsychotics. STUDY DESIGN: A population-based prospective cohort study was conducted in the United Kingdom using linked primary care, secondary care, mental health, and social deprivation datasets. Cox proportional hazards models with stabilizing weights were used to estimate risk of metabolic disorders among adults with schizophrenia, comparing patients on antipsychotic monotherapy vs polypharmacy, adjusting for demographic and clinical characteristics, and antipsychotic dose. STUDY RESULTS: Median follow-up time across the three cohorts was approximately 14 months. 6.6% developed hypertension in the cohort assembled for this outcome, with polypharmacy conferring an increased risk compared to monotherapy, (adjusted Hazard Ratio = 3.16; P = .021). Patients exposed to exclusive first-generation antipsychotic polypharmacy had greater risk of hypertension compared to those exposed to combined first- and second-generation polypharmacy (adjusted HR 0.29, P = .039). No associations between polypharmacy and risk of diabetes or hyperlipidemia were found. CONCLUSIONS: Antipsychotic polypharmacy, particularly polypharmacy solely comprised of first-generation antipsychotics, increased the risk of hypertension. Future research employing larger samples, follow-up longer than the current median of 14 months, and more complex methodologies may further elucidate the association reported in this study.

Sirolimus-induced Hypertriglyceridemia Leads to Acute Pancreatitis and Diabetic Ketoacidosis Post Stem Cell Transplant for Sickle Cell Disease.

Sirolimus (mammalian target of rapamycin inhibitor) is a potent immunosuppressive agent, used in patients receiving hematopoietic stem cell transplant (HSCT) for Graft vs Host disease prophylaxis. Compared to calcineurin inhibitors, sirolimus has no neurotoxicity or nephrotoxicity, but sirolimus causes dose-dependent thrombocytopenia, leukopenia, delayed wound healing, hyperlipidemia, and hypertriglyceridemia. Here we report a case of acute pancreatitis and diabetic ketoacidosis in a patient with sickle cell disease post haploidentical family donor HSCT which was managed conservatively without plasmapheresis. Based on our review of the literature, this is the first reported case of developing acute pancreatitis as an adverse effect of sirolimus-induced hypertriglyceridemia leading to diabetic ketoacidosis in a recipient of HSCT.

Comparison of Class-Specific Side Effects Across Preventative Pharmacologic Therapies for Kidney Stone Disease.

INTRODUCTION: Clinical guidelines recommend monitoring for metabolic derangements while on preventive pharmacologic therapy for kidney stone disease. The study objective was to compare the frequency of side effects among patients receiving alkali citrate, thiazides, and allopurinol. METHODS: Using claims data from working-age adults with kidney stone disease (2008-2019), we identified those with a new prescription for alkali citrate, thiazide, or allopurinol within 12 months after their index stone-related diagnosis or procedure. We fit multivariable logistic regression models, adjusting for cohort characteristics like comorbid illness and medication adherence, to estimate 2-year measured frequencies of claims-based outcomes of acute kidney injury, falls/hip fracture, gastritis, abnormal liver function tests/hepatitis, hypercalcemia, hyperglycemia/diabetes, hyperkalemia, hypokalemia, hyponatremia, and hypotension. RESULTS: Our cohort consisted of 1776 (34%), 2767 (53%), and 677 (13%) patients prescribed alkali citrate, thiazides, or allopurinol, respectively. Comparing unadjusted rates of incident diagnoses, thiazides compared to alkali citrate and allopurinol were associated with the highest rates of hypercalcemia (2.3% vs 1.5% and 1.0%, respectively, P = .04), hypokalemia (6% vs 3% and 2%, respectively, P < .01), and hyperglycemia/diabetes (17% vs 11% and 16%, respectively, P < .01). No other differences with the other outcomes were significant. In adjusted analyses, compared to alkali citrate, thiazides were associated with a higher odds of hypokalemia (OR=2.01, 95% CI 1.44-2.81) and hyperglycemia/diabetes (OR=1.52, 95% CI 1.26-1.83), while allopurinol was associated with a higher odds of hyperglycemia/diabetes (OR=1.34, 95% CI 1.02-1.75). CONCLUSIONS: These data provide evidence to support clinical guidelines that recommend periodic serum testing to assess for adverse effects from preventive pharmacologic therapy.

Neuropathic Pain in Aged People: An Unresolved Issue Open to Novel Drug Approaches, Focusing on Painful Diabetic Neuropathy.

A majority of older patients suffer from neuropathic pain (NP) that significantly alters their daily activities and imposes a significant burden on health care. Multiple comorbidities and the risk of polypharmacy in the elderly make it challenging to determine the appropriate drug, dosage, and maintenance of therapy. Age-dependent processes play a contributing role in neuropathy given that diabetic neuropathy (DN) is the most common form of neuropathy. This narrative review is mainly focused on the drug treatment approach for neuropathy-associated pain in aged people including both drugs and dietary supplements, considering the latter as add-on mechanism-based treatments to increase the effectiveness of usual treatments by implementing their activity or activating other analgesic pathways. On one hand, the limited clinical studies assessing the effectiveness and the adverse effects of existing pain management options in this age segment of the population (> 65), on the other hand, the expanding global demographics of the elderly contribute to building up an unresolved pain management problem that needs the attention of healthcare providers, researchers, and health authorities as well as the expansion of the current therapeutic options.

Amelioration of nutritional properties of bakery fat using omega-3 fatty acid-rich edible oils: a review.

Bakery products have gained prominence in modern diets due to their convenience and accessibility, often serving as staple meals across diverse regions. However, the fats used in these products are rich in saturated fatty acids and often comprise trans fatty acids, which are considered as a major biomarker for non-communicable diseases like cardiovascular disorders, obesity and diabetes. Additionally, these fats lack the essential omega-3 fatty acids, which are widely known for their therapeutic benefits. They play a major role in lowering the risk of cardiovascular diseases, cancer and diabetes. Thus, there is need for incorporating these essential fatty acids into bakery fats. Nevertheless, fortifying food products with polyunsaturated fatty acids (PUFAs) poses several challenges due to their high susceptibility to oxidation. This oxidative deterioration leads to not only the formation of undesirable flavors, but also a loss of nutritional value in the final products. This review focuses on the development of healthier trans-fat-free bakery fat enriched with omega-3 fatty acids and its effect on the physicochemical, functional, sensory and nutritional properties of bakery fats and products. Further, the role of various technologies like physical blending, enzymatic interesterification and encapsulation to improve the stability of PUFA-rich bakery fat is discussed, where microencapsulation emerged as a novel and effective technology to enhance the stability and shelf life. By preventing deteriorative changes, microencapsulation ensures that the nutritional, physicochemical and sensory properties of food products remain intact. Novel modification methods like interesterification and microencapsulation used for developing PUFA-rich bakery fats have a potential to address the health risks occurring due to consumption of bakery fat having higher amount of saturated and trans fatty acids. © 2023 Society of Chemical Industry.

Safety and antitumor activity of metformin plus lanreotide in patients with advanced gastro-intestinal or lung neuroendocrine tumors: the phase Ib trial MetNET2.

In retrospective studies, metformin use has been associated with better clinical outcomes in diabetic patients with advanced, well-differentiated neuroendocrine tumors (WDNETs). However, prospective evidence of metformin safety and activity is lacking. Here, we conducted the first-in-human phase Ib MetNET2 trial to investigate the safety and antitumor activity of metformin in combination with the somatostatin analog lanreotide autogel (ATG) in both diabetic and non-diabetic patients with advanced WDNETs of the gastrointestinal (GI) or thoracic tract. Enrolled patients received lanreotide ATG 120 mg plus oral metformin, up to a maximum dosage of 2550 mg/day. We enrolled 20 patients, of whom 18 (90%) and 2 (10%) had WDNETs of the GI and thoracic tract, respectively. Fourteen patients (70%) were non-diabetic. With a 5% incidence of SAEs, the study met its primary objective of demonstrating treatment safety. With a median follow-up of 39 months (95% CI 28-NE), median PFS was 24 months (95% CI 16-NE), with 12-month and 24-month PFS probability of 75% (95% CI 58-97) and 49% (95% CI 31-77), respectively. We found no statistically significant PFS differences between diabetic and non-diabetic patients. Among exploratory analyses, the presence of tumor genomic alterations in DNA damage pathways was associated with trend towards worse PFS, whereas a precocious reduction of HOMA-IR index and plasma cholesterol concentration showed a trend towards an association with better PFS. In conclusion, metformin plus lanreotide ATG is a safe and well tolerated combination treatment that is associated with promising antitumor activity in both non-diabetic and diabetic patients with WDNETs, and that warrants further investigation in larger clinical trials.

Nivolumab-induced diabetes mellitus-a case report with literature review of the treatment options.

Background: Immune checkpoint inhibitor (ICI) treatment has become important for treating various cancer types, including metastatic renal cell carcinoma. However, ICI treatment can lead to endocrine immune-related adverse events (irAEs) by overstimulating the patient's immune system. Here, we report a rare case of a new onset of diabetes mellitus (DM), caused by nivolumab, and we discuss the feasible treatment options with a focus on TNF antagonism. Case presentation: A 50-year-old man was diagnosed with metastatic renal cell carcinoma. Due to systemic progression, a combined immunotherapy with ipilimumab and nivolumab was initiated, according to the current study protocol (SAKK 07/17). The administration of ipilimumab was stopped after 10 months, due to partial response as seen in the computer tomography (CT), and nivolumab was continued as monotherapy. Fourteen months after the start of the treatment, the patient was admitted to the emergency department with lethargy, vomiting, blurred vision, polydipsia, and polyuria. The diagnosis of DM with diabetic ketoacidosis was established, although autoantibodies to ß-cells were not detectable. Intravenous fluids and insulin infusion treatment were immediately initiated with switching to a subcutaneous administration after 1 day. In addition, the patient received an infusion of the TNF inhibitor infliximab 4 days and 2 weeks after the initial diagnosis of DM. However, the C-peptide values remained low, indicating a sustained insulin deficiency, and the patient remained on basal bolus insulin treatment. Two months later, nivolumab treatment was restarted without destabilization of the diabetic situation. Conclusions: In contrast to the treatment of other irAEs, the administration of corticosteroids is not recommended in ICI-induced DM. The options for further treatment are mainly based on the low numbers of case series and case reports. In our case, the administration of infliximab-in an attempt to salvage the function of ß-cells-was not successful, and this is in contrast to some previous reports. This apparent discrepancy may be explained by the absence of insulin resistance in our case. There is so far no evidence for immunosuppressive treatment in this situation. Prompt recognition and immediate start of insulin treatment are most important in its management.

Use of sugar in coffee and tea and long-term risk of mortality in older adult Danish men: 32 years of follow-up from a prospective cohort study.

BACKGROUND: Tea and coffee are the most consumed beverages worldwide and very often sweetened with sugar. However, the association between the use of sugar in tea or coffee and adverse events is currently unclear. OBJECTIVES: To investigate the association between the addition of sugar to coffee or tea, and the risk of all-cause mortality, cardiovascular mortality, cancer mortality and incident diabetes mellitus. METHODS: Participants from the prospective Copenhagen Male Study, included from 1985 to 1986, without cardiovascular disease, cancer or diabetes mellitus at inclusion, who reported regular coffee or tea consumption were included. Self-reported number of cups of coffee and tea and use of sugar were derived from the study questionnaires. Quantity of sugar use was not reported. Primary outcome was all-cause mortality and secondary endpoints were cardiovascular mortality, cancer mortality and incident diabetes mellitus, all assessed through the Danish national registries. The association between adding sugar and all-cause mortality was analyzed by Cox regression analysis. Age, smoking status, daily alcohol intake, systolic blood pressure, body mass index, number of cups of coffee and/or tea consumed per day and socioeconomic status were included as covariates. Vital status of patients up and until 22.03.2017 was assessed. Sugar could be added to either coffee, tea or both. RESULTS: In total, 2923 men (mean age at inclusion: 63±5 years) were included, of which 1007 (34.5%) added sugar. In 32 years of follow-up, 2581 participants (88.3%) died, 1677 in the non-sugar group (87.5%) versus 904 in the sugar group (89.9%). Hazard ratio of the sugar group compared to the non-sugar group was 1.06 (95% CI 0.98;1.16) for all-cause mortality. An interaction term between number of cups of coffee and/or tea per day and adding sugar was 0.99 (0.96;1.01). A subgroup analysis of coffee-only drinkers showed a hazard ratio of 1.11 (0.99;1.26). The interaction term was 0.98 (0.94;1.02). Hazard ratios for the sugar group compared to the non-sugar group were 1.11 (95% CI 0.97;1.26) for cardiovascular disease mortality, 1.01 (95% CI 0.87;1.17) for cancer mortality and 1.04 (95% CI 0.79;1.36) for incident diabetes mellitus. CONCLUSION: In the present population of Danish men, use of sugar in tea and/or coffee was not significantly associated with increased risk of mortality or incident diabetes.

Effect of dexamethasone administration for postoperative nausea and vomiting prophylaxis on glucose levels in adults with diabetes undergoing elective surgery: a systematic review with meta-analysis.

OBJECTIVE: The objective of this review was to evaluate the effect of intravenous dexamethasone given intraoperatively for postoperative nausea and vomiting prophylaxis on maximal blood glucose level within the initial 24 hours following elective surgery for patients with diabetes. INTRODUCTION: Postoperative nausea and vomiting is a prevalent adverse effect of anesthesia that leads to morbidity, increased health care costs, and unanticipated hospital admissions. Dexamethasone is an effective prophylactic agent that confers secondary analgesic and anti-inflammatory benefits. However, its use in patients with diabetes remains controversial due to the potential for increased postoperative blood glucose levels. INCLUSION CRITERIA: This review considered studies with participants 18 years of age or older with type 1 or 2 diabetes undergoing an elective surgical procedure. Eligible studies reported postoperative blood glucose levels in adults with diabetes after receiving a single 4-10 mg prophylactic dose of intravenous dexamethasone intraoperatively for postoperative nausea and vomiting. The primary outcome was maximum blood glucose level in the first 24 hours after surgery. All study designs were eligible for inclusion. Studies were excluded if they lacked a control group with diabetes or if they did not report maximum blood glucose values in both groups. METHODS: A search of MEDLINE, CINAHL Complete, Embase, Web of Science, TRIP database, and the Cochrane Database of Systematic Reviews was completed in October 2021. Gray literature resources were also searched. No date or language restrictions were applied. Methodological quality was assessed using JBI appraisal tools for randomized controlled trials, cohort studies, and case-control studies. A meta-analysis of maximal postoperative blood glucose level within 24 hours of surgery was performed, as well as subgroup analyses by dexamethasone dose, insulin treatment, and study design type. RESULTS: Eleven studies (4 randomized controlled trials, 6 cohort studies, and 1 case-control study) were included in this review, with 1 study excluded from meta-analysis and results reported narratively. The total sample size of studies included in meta-analysis was 2567. The administration of dexamethasone significantly increased maximal blood glucose levels in the 24 hours immediately following surgery compared with control groups with diabetes, as demonstrated by randomized controlled trials (mean difference [MD] 39.56 mg/dL; 95% CI 16.18 to 62.94; P < 0.001; I2 = 87%) and observational studies (MD 26.31 mg/dL; 95% CI 7.10 to 45.52; P = 0.007; I2 = 92%). This increase in blood glucose was significant for all doses of dexamethasone: 4 mg (MD 40.81 mg/dL; 95% CI 2.42 to 79.19; P = 0.001; I2 = 91%), 8 mg (randomized controlled trials only; MD 39.45 mg/dL; 95% CI 15.32 to 63.58; P = 0.001; I2 = 86%), and mixed 4-10 mg dose (MD 30.82 mg/dL; 95% CI 6.75 to 54.88; P < 0.012; I2 = 93%). Postoperative hyperglycemia persisted in studies using insulin treatment as well as those not using insulin protocols. The overall certainty of the findings ranged from very low for outcomes that included cohort studies to moderate when outcomes from randomized controlled trials were analyzed separately. However, the quantitative findings of the experimental and observational studies were clinically similar. Risk of bias presented minimal concerns in all included studies. CONCLUSIONS: Dexamethasone leads to transient postoperative hyperglycemia in patients with diabetes undergoing elective surgery when given as a single 4-10 mg intravenous dose for postoperative nausea and vomiting prophylaxis. The clinical relevance of hyperglycemia is debatable given its small magnitude and transient nature. Without more tightly controlled data, methodological consistency, and baseline blood glucose values, it is impossible to test causal links between hyperglycemia and pre-existing patient factors (eg, hemoglobin A1C levels) or postoperative complications. REVIEW REGISTRATION: PROSPERO CRD42020185607.

Prevalence and risk factors of peri-implant diseases at patient-level: A cross-sectional study in Syria.

OBJECTIVES: This research aims to assess the prevalence of peri-implant diseases and to analyze variables of the probable risk at the patient level associated with the occurrence of peri-implant diseases in Syrian patients. MATERIALS AND METHODS: A cross-sectional study has been carried out on 142 patients with 380 dental implants placed between 2015 and 2021. Patients were invited by phone to return to Damascus University's Periodontology Department for clinical and radiological examination. A descriptive statistical analysis was implemented for the prevalence of peri-implant diseases at the level of the patients. Also, the peri-implant diseases' factors of risk were determined by the multivariate analytical model. RESULTS: The prevalence rate of peri-implant mucositis and peri-implantitis in patients was 58.5% and 25.4%, respectively. Peri-implant disease is associated with multivariate risk indices, gender female (peri-implant mucositis [OR = 0.269; 95% CI: 0.131-0.552] and peri-implantitis [OR = 0.561; 95% CI: 0.561-0.216]), diabetes (peri-implant mucositis [OR = 3.4; 95% CI: 1.73-12.73]), periodontitis (peri-implant mucositis [OR = 2.409; 95% CI: 1.760-2.613], peri-implantitis [OR = 10.445; 95% CI: 4.097-26.629]). CONCLUSIONS: Peri-implant diseases are common in the Syrian community. Several patient-level variables (gender female, diabetes, and periodontitis) are associated with peri-implant disease.

Machine learning-based prediction of risk factors for abnormal glycemic control in diabetic cancer patients receiving nutrition support: a case-control study.

PURPOSE: To date, risk factors affecting abnormal glycemic control have not been investigated. This study aimed to analyze risk factors for hypoglycemia or hyperglycemia in diabetic cancer patients receiving nutritional support by using machine learning methods. METHODS: This retrospective two-center study was performed using medical records. Odds ratios and adjusted odds ratios were estimated from univariate and multivariate analyses, respectively. Machine learning algorithms, including five-fold cross-validated multivariate logistic regression, elastic net, and random forest, were developed to predict risk factors for hypoglycemia and hyperglycemia. RESULTS: Data from 127 patients were analyzed. The use of sulfonylurea (SU) and blood urea nitrogen (BUN) level > 20 mg/dL increased hypoglycemia by 6.3-fold (95% CI 1.30-30.47) and 5.0-fold (95% CI 1.06-23.46), respectively. In contrast, patients who received an actual energy intake/total energy expenditure (TEE) ≥ 120% and used dipeptidyl peptidase-4 (DPP-4) inhibitors had a higher risk of hyperglycemia by 19.3- (95% CI 1.46-254.78) and 3.3-fold (95% CI 1.23-8.61), respectively. An initial blood glucose level ≥ 182.5 mg/dL also increased the risk of hyperglycemia by 15.3-fold. AUROC values for all machine learning methods indicated acceptable and excellent performance for hypoglycemia and hyperglycemia. CONCLUSION: The use of SU and BUN level > 20 mg/dL increased the risk of hypoglycemia, whereas an initial blood glucose level ≥ 182.5 mg/dL, a supplied actual energy intake/ TEE ≥ 120%, and the use of DPP-4 inhibitors increased the risk of hyperglycemia.

Real-world adherence to toxicity management guidelines for immune checkpoint inhibitor-induced diabetes mellitus.

Objective: Immune checkpoint inhibitors(ICIs) have improved survival and are increasingly used for cancer. However, ICIs use may be limited by immune-related adverse events (irAEs), such as ICI-induced diabetes mellitus(ICI-DM). The objective of the present study was to characterize ICI-DM patients and real-world adherence to guidelines. Research design and methods: The present study was a retrospective review of electronic records of ICI-DM patients at the First Affiliated Hospital of Nanjing Medical University between July 2018 and October 2022. Results: 34.8% (8/23)patients monitored blood glucose in every treatment cycle. The proportion of patients with severe diabetic ketoacidosis(DKA) was lower in the tight glycemic monitoring group than the non-tight glycemic monitoring group (16.7% vs. 55.6%, p = 0.049). 78.3%(18/23) patients with hyperglycemia visited a non-endocrinologist first, but 95.7% of patients were then referred to an endocrinologist. Twenty patients were tested for distinguishing the etiology of hyperglycemia and 20% patients with positive glutamic acid decarboxylase antibody(GADA), 55% with C-peptide <3.33pmol/L. High screening rates for other ICI-induced endocrinopathies were observed and half of the patients with ICI-DM developed other endocrine gland irAEs, with the most common being thyroiditis. Moreover, five patients developed non-endocrine serious adverse events(SAEs). Twelve (52.2%) patients were withdrawn from ICI due to ICI-DM. The time to progression of tumor in ICI-DM patients in the continue and interruption group was longer than in the withdrawal group (333.5 ± 82.5 days vs. 183.1 ± 62.4 days, p = 0.161). Only 17.4% of ICI-DM patients were completely managed according to guidelines. Thus, the present study proposed a screening, diagnosis, and management algorithm for ICI-DM in real-world practice. Conclusion: The present study reported the largest number of ICI-DM cases described in a single institute, providing insight into real-world ICI-DM management guideline adherence and highlighting the clinical challenges in ICI-DM management.

Same-Day Bilateral Intravitreal Dexamethasone Implants for the Treatment of Diabetic Macular Edema.

INTRODUCTION: The aim of this study was to evaluate the outcomes and complications associated with the use of same-day bilateral intravitreal dexamethasone (DEX) implants for the treatment of diabetic macular edema (DME). METHODS: This retrospective analysis of an open-label, multicenter, consecutive case series included 130 eyes of 65 patients with bilateral DME who were treated with intravitreal DEX implants. The patients were divided into two groups: a control group (comprising 40 eyes treated with an alternating unilateral regimen) and a study group (comprising 90 eyes treated with concomitant bilateral DEX implants). All patients were followed up monthly after implantation. The changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to sixth month after implantation, and ocular adverse effects such as intraocular pressure, cataract, and tolerability of bilateral implantation were reviewed. The primary endpoint was to assess the safety of the same-day bilateral treatment protocol. The secondary endpoints focused on evaluating the functional and anatomical changes associated with bilateral simultaneous or alternating implantations. RESULTS: At 6 months after implantation, mean BCVA increased and CRT decreased in both groups. Moreover, no serious ocular adverse effects were observed. In addition, no differences were observed between the two groups in the number of patients who required extra follow-up visits or the number of extra visits made in addition to the treatment schedule. CONCLUSIONS: Same-day bilateral intravitreal DEX implants are associated with a low complication rate and are well tolerated by patients. This safe practice may optimize efficiency and reduce the burden on both the health-care system and patients, when used to treat bilateral DME.

Dexamethasone intravitreal implant in diabetic macular oedema refractory to anti-vascular endothelial growth factors: the AUSSIEDEX study.

AIM: To evaluate effectiveness of dexamethasone intravitreal implant 0.7 mg (DEX) monotherapy in the AUSSIEDEX study non-responder subgroup, defined by diabetic macular oedema (DME) refractory to anti-vascular endothelial growth factor (anti-VEGF) agents. METHODS: This prospective, open-label, observational, real-world study included pseudophakic and phakic (scheduled for cataract surgery) eyes that did not achieve a ≥5-letter best corrected visual acuity (BCVA) gain and/or clinically significant central subfield retinal thickness (CRT) improvement after 3-6 anti-VEGF injections for DME (N=143 eyes), regardless of baseline BCVA and CRT. After an initial DEX injection (baseline visit), reinjection was permitted at ≥16-week intervals. PRIMARY ENDPOINTS: changes in mean BCVA and CRT from baseline to week 52. Safety assessments included adverse events. RESULTS: Of 143 eyes, 53 (37.1%) and 89 (62.2%) switched to DEX after 3-6 (early) and >6 (late) anti-VEGF injections, respectively; 1 (0.7%) had missing information. With 2.3 injections (mean) over 52 weeks, the change in mean BCVA from a baseline of 57.8 letters was not significant at week 52. Mean CRT improved significantly from a baseline of 417.8 µm at week 52 (mean change -60.9 µm; p<0.001). Outcomes were similar in eyes switched to DEX early and late. No unexpected adverse events were reported; no filtration surgeries were required. CONCLUSION: To date, AUSSIEDEX is the largest prospective, real-world study of DEX monotherapy for treatment-naïve or anti-VEGF-refractory DME. Following early or late switch from anti-VEGF agents, DEX significantly improved anatomic outcomes at 52 weeks without new safety concerns, supporting use in anti-VEGF-refractory DME. TRIAL REGISTRATION NUMBER: NCT02731911.

Macular Thickness Fluctuations in Eyes With Diabetic Macular Edema Treated With Intravitreal Steroid.

BACKGROUND AND OBJECTIVE: Macular thickness fluctuations (MTF) over time may be more predictive of visual outcomes than absolute macular thickness in patients with diabetic macular edema (DME) treated with anti-vascular endothelial growth factor (anti-VEGF). It is unclear whether this association exists in DME patients treated with intravitreal steroids or whether steroids confer reduced MTF versus anti-VEGF treatments. PATIENTS AND METHODS: MTF was compared before and after initiation of steroids in DME patients treated with intravitreal steroids. A mixed-effects linear regression model was used to determine the association between MTF and best-corrected visual acuity (BCVA). RESULTS: Mean 12-month MTF significantly decreased after steroid initiation (61.1 µm versus 53.5 µm, P = 0.04, n = 105 eyes). Mean BCVA after 12 months was not significantly different from baseline. No significant association between post-steroid MTF and 12-month BCVA was found. CONCLUSION: Steroid treatment decreases MTF while BCVA remains stable in DME patients previously treated with anti-VEGF. [Ophthalmic Surg Lasers Imaging Retina 2023;54:454-460.].