Aim To conduct a systematic review and meta‐analysis to understand the timing and factors associated with anti‐programmed cell death protein‐1 ( PD ‐1)/anti‐programmed cell death protein‐1 ligand ( PD ‐L1) inhibitor‐induced Type 1 diabetes. Methods We searched MEDLINE , EMBASE , SCOPUS and Cochrane databases (August 2000–2018) for studies of any design on immune checkpoint inhibitors. A total of 71 cases were reviewed from 56 publications. Comparisons were made using Fisher's exact and Student's t ‐tests. Results The mean ± sd age at Type 1 diabetes presentation was 61.7±12.2 years, 55% of cases were in men, and melanoma (53.5%) was the most frequent cancer. The median time to Type 1 diabetes onset was 49 (5–448) days with ketoacidosis in 76% of cases. The average ± sd HbA 1c concentration was 62 ± 0.3 mmol/mol (7.84±1.0%) at presentation. All cases had insulin deficiency and required permanent exogenous insulin treatment. Half of the cases had Type 1 diabetes‐associated antibodies at presentation, and those with antibodies had a more rapid onset ( P =0.005) and higher incidence of diabetic ketoacidosis ( P =0.02) compared to people without antibodies. Conclusions Many people developed Type 1 diabetes within 3 months of initial PD ‐1/ PD ‐L1 inhibitor exposure. People presenting with Type 1 diabetes‐associated antibodies had a more rapid onset and higher incidence of ketoacidosis than those without antibodies. Healthcare providers caring for people receiving these state‐of‐the‐art therapies need to be aware of this potential severe adverse event.
Background: Cannabis is widely used among patients with type 1 diabetes (T1D) in Colorado. Despite increasing use of cannabis among patients with T1D, the frequency and characteristics of unhealthy cannabis use are unknown. We investigated the differences in unhealthy cannabis use in recreational and medical cannabis users with T1D. Methods: Adult cannabis users with T1D completed an in-person questionnaire regarding their cannabis use patterns. They further divided into 2 categories; recreational and medical users. Cannabis Use Disorder Identification Test-Revised (CUDIT-R) was used to identify unhealthy cannabis use (CUDIT-R ≥ 8). Characteristics of cannabis users and unhealthy cannabis use between recreational and medical cannabis users were compared using unpaired t test. Results: Out of 117 patients, 85 patients reported recreational and 32 patients reported medical cannabis use. Based on CUDIT-R scores, 37.6% of adults with T1D had unhealthy cannabis use. Frequency of cannabis use ≥4 times a week was higher among medical users compared to recreational users (59.4% vs 28.2%, P < 0.01). There was no difference between the groups in duration of cannabis use. There was no difference in mean overall CUDIT-R score (7.14 vs 7.5, P = 0.76) between recreational and medical cannabis users. There were also no significant differences in mean CUDIT-R score between recreational and medical users within the nonhazardous use category (3.70 vs 4.4, P = 0.15) and unhealthy cannabis use category (12.84 vs 12.67, P = 0.92). Conclusions: Our study showed no difference in unhealthy cannabis use among recreational and medical cannabis users with T1D. Unhealthy cannabis use should be considered among users with T1D regardless of the reason for its use. Contexte: Le cannabis est largement utilisé chez les patients atteints de diabète de type 1 (DT1) au Colorado. Malgré l’augmentation de la consommation de cannabis chez les patients atteints de DT1, la fréquence et les caractéristiques d’une consommation de cannabis malsaine sont inconnues. Nous avons étudié les différences entre la consommation de cannabis malsaine chez les consommateurs de cannabis récréatifs et médicaux atteints de DT1. Méthodes: Les consommateurs de cannabis adultes atteints de DT1 ont rempli un questionnaire personnel sur leurs habitudes de consommation de cannabis. Ils ont été ensuite divisés en deux catégories; utilisateurs récréatifs et médicaux. Le Test d’identification des troubles liés à l’utilisation du cannabis révisé (CUDIT-R) a été utilisé pour identifier une utilisation malsaine du cannabis (CUDIT-R ≥8). Les caractéristiques des consommateurs de cannabis, ainsi que ceux d’une consommation de cannabis malsaine, entre les consommateurs de cannabis récréatifs et médicaux ont été comparées en utilisant un test t non apparié. Résultats: Sur 117 patients, 85 patients ont signalé des activités récréatives et 32 patients ont déclaré avoir utilisé du cannabis à des fins médicales. D’après les scores CUDIT-R, 37,6% des adultes atteints de DT1 avaient une consommation de cannabis malsaine. La fréquence de consommation de cannabis ≥ 4 fois par semaine était plus élevée chez les utilisateurs de médicaments que chez les utilisateurs récréatifs (59,4% contre 28,2%, p < 0,01). Il n’y avait pas de différence entre les groupes quant à la durée de consommation de cannabis. Il n’y avait pas de différence dans le score CUDIT-R global moyen (7,14 vs 7,5, p = 0,76) entre les utilisateurs de cannabis à des fins récréatives et médicales. Il n’existait pas non plus de différence significative entre le score CUDIT-R moyen entre les utilisateurs récréatifs et les utilisateurs à des fins médicales dans la catégorie d’usages non dangereux (3,70 contre 4,4, p = 0,15) et dans la catégorie d’abus de cannabis (12,84 contre 12,67, p = 0,92). Conclusions: Notre étude n’a montré aucune différence dans la consommation de cannabis malsaine chez les consommateurs de cannabis récréatifs et médicaux atteints de DT1. Une consommation de cannabis malsaine doit être envisagée chez les utilisateurs atteints de DT1, quelle que soit la raison de sa consommation.
Background Advanced hepatocellular carcinoma (HCC) generally has a dismal prognosis. Bone metastases from HCC are infrequent, with a poorer prognosis. However, the survival influencing factors are not yet well understood. Aim The aim of the present study was to assess the clinical features and tumor characteristics of HCC patients with bone metastasis. Methods A cohort of 170,576 adult patients with HCC was studied using the National Cancer Database (NCDB) spanning from 2010 to 2019, and within this group, 5285 patients (3.1%) were diagnosed with bone metastasis. We performed the Kaplan–Meier method to calculate the median overall survival (OS). We included demographics (age at diagnosis, gender, race, insurance status), comorbidity score, and treatment characteristics. Results Of a total of 5285 HCC patients with bone metastasis, 86.2% were male and 61.2% were non-Hispanic white. Most patients (55.1%) were below 65, and 89% had a total Charlson-Deyo comorbidity score of under 3. Among patients with known tumor grade, 24.8% had well-differentiated tumors, and 36.1% had poorly differentiated tumors. Chemotherapy was administrated to 39.5% of patients. In univariate analysis, patients with well-differentiated tumors had better OS compared to poorly differentiated tumors (5.4 months vs 3.0 months, p = 0.001). Patients who received single or multiagent chemotherapy were significantly associated with improved OS compared to patients who did not receive chemotherapy (7.0 and 8.5 months vs 1.94 months, respectively). We also found mortality difference between age, comorbidity scores, facility types and race groups. Conclusion In this cohort analysis of NCDB data, we found better OS in treatment receipt, lower tumor grade, younger age, non-Hispanic Black and Hispanic race, treatment at academic facility and lower comorbidity score in HCC patients with bone metastasis. The study results may have a consequential impact on the treatment decisions for HCC patients with bone metastasis.
Immune checkpoint inhibitors (ICI) that target programmed cell death protein-1 (PD-1) and its ligand (PD-L1) are beneficial cancer immunotherapies but infrequently cause type 1 diabetes (T1D), which can present with life-threatening diabetic ketoacidosis (DKA). We conducted a systematic review and meta-analysis to understand the timing and factors associated with ICI-induced T1D. We searched MEDLINE, EMBASE, SCOPUS and Cochrane databases (August 2000-2018) for studies of any design on ICI and identified 71 cases in 55 publications. Comparisons were made using Fisher’s exact and Student t-tests. Mean age at T1D presentation was 61.7±12.2 years, 55% were male, and melanoma (53.5%) was the most frequent cancer. Mean duration to T1D onset was only 83.5±88.5 days with DKA in 76% of cases. Average HbA1c was 7.84±1.0% at presentation. All cases had insulin deficiency and required permanent insulin treatment. The majority of patients developed T1D within just 3-months of initial ICI exposure (Figure). Half of the cases reported T1D associated antibodies at diabetes presentation, and those with antibodies had a more rapid onset (p=0.005) and higher incidence of DKA (p=0.02) compared to patients without antibodies. This study provides a framework for prospective clinical studies to screen patients receiving these state-of-the-art therapies for risk factors associated with T1D onset to prevent life-threatening DKA. Disclosure H.K. Akturk: Advisory Panel; Self; Sanofi. Research Support; Self; Eli Lilly and Company, MannKind Corporation, REMD Biotherapeutics. Speaker's Bureau; Self; MannKind Corporation. D. Kahramangil: None. A. sarwal: None. M. Murad: None. A. Michels: Stock/Shareholder; Self; IM Therapeutics. Funding National Institutes of Health (DK108868, DK110845, DK032083)
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