The efficacy and toxicity of immune checkpoint inhibitors in a real-world older patient population

ImportanceImmunotherapy has emerged as an effective treatment option for the management of advanced cancers. The effects of these immune checkpoint inhibitors in the older patient population has not been adequately assessed.ObjectiveTo understand the impact of aging on CTLA-4 and PDL-1 inhibitors efficacy and immune-related adverse events (irAE) in the context of real-world management of advanced solid cancers.Design, Setting, and ParticipantsThis retrospective study involved all non-study patients with histologically-confirmed metastatic or inoperable solid cancers receiving immunotherapy at Kingston Health Sciences Centre. We defined ‘older patient’ as age ≥ 75. All statistical analyses were conducted under SPSS IBM for Windows version 24.0.Main Outcomes and MeasuresStudy outcomes included immunotherapy treatment response, survival, as well as number, type, and severity of irAEs.ResultsOur study (N = 78) had 29 (37%) patients age <65, 26 (33%) patients age 65–74, and 23 (30%) patients age ≥75. Melanoma, non-small cell lung cancer, and renal cell carcinoma accounted for 70%, 22%, and 8% of the study population, respectively. Distributions of ipilimumab (32%), nivolumab (33%), and pembrolizumab (35%) were similar in the study. The response rates were 28%, 27%, and 39% in the age <65, age 64–74, age ≥75 groups, respectively (P = 0.585). Kaplan-Meier curve showed a median survival of 28 months (12.28–43.9, 95% CI) and 17 months (0–36.9, 95% CI) in the age <65 and age 64–74 groups, respectively; the estimated survival probability did not reach 50% in the age ≥75 group (P = 0.319). There were no statistically significant differences found in terms of irAEs, multiple irAEs, severity of grade 3 or higher, types of irAEs, and irAEs resolution status when comparing between different age groups.Conclusion and RelevanceOur results suggest that patients age ≥75 are able to gain as much benefit from immunotherapy as younger patients, without excess toxicity. Our findings suggest that single agent immunotherapy is generally well-tolerated across different age groups with no significant difference in the type, frequency or severity of irAEs. Future studies evaluating aging and combination immunotherapy are warranted.     

Circumstances of substance use by street youth in Egypt support the case for intervening to prevent adverse childhood experiences

Background: Egyptian street youth use substances including tobacco, illicit drugs, and pharmaceutical drugs. To understand the circumstances, including adverse childhood experiences, that place adolescents at risk for engaging in substance use, we conducted in-depth interviews among a sample of Egyptian street children. Methods: From youth residing at or attending Caritas, a non-profit organization, which provides shelter and education to street youth, seven girls and twelve boys, aged 12–18 years, participated in open-ended, in-depth interviews. Results: Eight out of the 19 participants reported family history (early exposure) to substance use; and seven of them were initiated by either a family member (sibling), friend or coworker. Most of the participants reported a history of conflict with or abuse (verbal or physical) by their parents or siblings, or stressful situations at home; they used substance(s) to alleviate their stress. Few attended school, and some were forced to work and help their family. Conclusions: Among Egyptian youth, adverse childhood experiences, such as poverty, child abuse, and family substance use, challenge somewhat susceptible youths and lead them to the path of substance use and addiction. Prevention intervention should be multifaceted, culturally adaptable, and primarily targeting the social environment during childhood.     

Successful Use of Surgically Placed Impella 5.0 and Central Extracorporeal Membrane Oxygenation Circuit in a Patient with Postcardiotomy Shock

The Impella 5.0, a percutaneously inserted left ventricular assist device, has been used to support patients who have severe heart failure or who are undergoing high-risk percutaneous coronary intervention. We report our surgical placement of the Impella 5.0, through a graft sewn to the aorta, to unload the left ventricle of a 59-year-old man who was undergoing venoarterial extracorporeal membrane oxygenation for postcardiotomy shock. The patient underwent successful placement of a long-term left ventricular assist device before his discharge from the hospital. The versatility of the Impella 5.0 is exemplified in this patient who was successfully bridged to long-term support.     

Complications in Intermediate Uveitis: Prevalence,Time of Onset,and Effects on Vision in Short-Term and Long-Term Follow-Up

Purpose: To study the prevalence and time of onset of ocular complications in intermediate uveitis (IU) and to assess their effects on visual outcome in short-term and long-term follow-up.

Methods: A retrospective cohort study of patients with IU who had a minimal follow-up of one year.

Results: 96 patients (174 eyes, 70% females) were included with a mean age at presentation of 30 years. Children constituted 38% of all patients. Mean follow- up was 64.9 months. Pars planitis was the most common form followed by sarcoidosis and multiple sclerosis. Cystoid macular edema (CME), cataract, epiretinal membrane and posterior synechiae were the most prevalent complications. Posterior synechiae, band keratopathy, cataract and papillitis at presentation were associated with worse presenting visual acuity (VA). Of the late-onset complications, glaucoma/ocular hypertension (OHT) was the most significantly associated with worse long-term VA. Most sight-threatening complications (namely CME and glaucoma) were diagnosed at presentation while late complications predominantly affected the posterior segment and included among others peripheral retinal elevations, vasoproliferative tumors, and vitreous hemorrhage. Median LogMAR VA improved at short-term and long-term follow-up, from 0.2 to 0.1 (p<0.001). Subgroup analysis revealed significant VA improvement for eyes with all the different complications except for eyes with glaucoma/OHT.

Conclusion: IU is a chronic low-grade uveitis that may be associated with protean early and late complications of the anterior or posterior segments or both. Optimal treatment regimens are imperative for the strict control of inflammation and proper management of complications thus allowing a favorable long-term prognosis.     

Potential roles of chromium on inflammatory biomarkers in diabetes: A Systematic

Diabetes, as a low‐grade chronic inflammatory disease, causes disruption in proper function of immune and metabolic system. Chromium is an important element required for normal lipid and glucose metabolism. Chromium deficiency is correlated with elevation in cardiometabolic risk, which results from increased inflammation. This systematic review was conducted to discover the potential roles of chromium on inflammatory biomarkers. Eligible studies were all in vitro, animal and human studies published in English‐language journals from inception until October 2018. PubMed, Scopus, Embase, ProQuest and Google Scholar databases were searched to fined interventional studies from the effects of chromium on inflammatory biomarkers such as tumour necrosis factor a (TNF‐a), C‐reactive protein (CRP), interleukins, monocyte chemoattractant protein–1 (MCP‐1), intercellular adhesion molecule‐1 (ICAM‐1) and adipocytokines in hyperglycaemia and diabetes. Out of 647 articles found in the search, only 14 articles were eligible for analysis, three in vitro studies, eight animal studies and three human studies. Twelve of the 14 studies included in this review, chromium significantly decreased inflammatory factors. The findings of this review indicate, based on in vitro and in vivo studies, that chromium might have potential anti‐inflammatory properties, but some of the studies did not show anti‐inflammatory effects for chromium (two studies). There are only three studies in humans with controversial results. Therefore, more consistent randomized double‐blind controlled trials are needed to reach relevant clinical recommendations, as well as to determine the precise mechanism, of chromium on inflammation in diabetes.     

Specific rubella virus IgG and IgM in umbilical cord sera in Saudi Arabia.

The sensitive ELISA assay was used to measure the specific rubella virus IgG & IgM, and also the total IgM in the umbilical cord sera taken from 182 Saudi mothers during delivery in the Maternity Department at Al Ali General Hospital, Riyadh, Saudi Arabia. Nearly 84.6% (154 out of 182) Saudi women tested were found to be immune to rubella virus.