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Malignant peritoneal mesothelioma is usually treated following recommendations developed for pleural mesothelioma, with first-line treatment with platinum-based/pemetrexed chemotherapy, but there are no approved treatments if that fails. The single-center study evaluated the combination of atezolizumab and bevacizumab as treatment for various advanced cancers. Atezolizumab is an immune checkpoint inhibitor that targets PD-L1, and bevacizumab is a VEGF inhibitor that slows the growth of new blood vessels and therefore tumor growth. The malignant peritoneal mesothelioma cohort included 20 participants, median age 60. Mean follow-up was 23.5 months. These patients had experienced disease progression at a median of 8.3 months with prior platinum-pemetrexed therapy.

The confirmed objective response rate to treatment with this combination, as measured by RECIST (Response Evaluation Criteria in Solid Tumors) was 40% (8/20 patients). Median duration of response was 12.8 months, and responses were ongoing at cutoff in 6 patients. Median progression-free survival was 17.6 months, and the 1-year progression-free survival rate was 61%. Overall survival rate at 1 year was 85%. Disease control per RECIST was 95% (19/20) at 12 weeks, and 85% (17/20) at 18 weeks. Responses occurred no matter the tumor mutational burden or PD-L1 expression status. Treatment was well-tolerated; grade 3 adverse events occurred in 10 patients, most commonly hypertension and anemia. No grade 4 or 5 events occurred.

These results address the challenges of caring for advanced forms of this orphan disease. Further studies that enroll more patients and that examine this combination as front-line treatment or as preoperative treatment are needed. (University of Texas MD Anderson Cancer Center. (2021). Drug combination shows meaningful responses for malignant peritoneal mesothelioma patients. ScienceDaily. Retrieved August 2021 from https://www.sciencedaily.com/releases/2021/07/210714110422.htm; Raghav, K., et al. (2021). Efficacy, safety and biomarker analysis of combined PD-L1 (atezolizumab) and VEGF (bevacizumab) blockade in advanced malignant peritoneal mesothelioma. Cancer Discovery: American Association for Cancer Research. Advance online publication. Retrieved August 2021 from https://cancerdiscovery.aacrjournals.org/content/candisc/early/2021/07/01/2159-8290.CD-21-0331.full.pdf)

The single-center study enrolled 159 kidney transplant recipients at the outpatient Kidney Transplantation Department of Strasbourg University Hospital in the first half of 2021. Median age was 57.6 years, 61.6% were men, and median time from transplantation was 5.3 years. More than half were receiving tacrolimus or mycophenolate mofetil and steroids as immunosuppressive maintenance therapy. All had a negative history of COVID-19 and, though they had been vaccinated, had SARS-CoV2 antispike IgG levels of less than 50 AU/mL. Of these patients, 95 (59.7%) had no antibody response at all, with titers less than 6.8 AU/mL, and 64 (40.3%) had a response below the positivity level, with titers between 6.8 and 49.9 AU/mL.

Patients received a third dose of the Moderna mRNA vaccine about 51 days after the second dose; serologic response was measured a median of 28 days later. That measure demonstrated that 78 patients (49%) did have an antibody response greater than 50 AU/mL. Those who had a weak response after the second dose were more likely than those with no response to reach this level: 81.3% vs. 27.4%, respectively. Those who were taking tacrolimus, mycophenolate mofetil, and steroids for immunosuppression were less likely to develop antibodies than those treated with other regimens: 35% vs. 63%, respectively. No serious adverse events were reported after the third dose. (Benotmane, I., et al. (2021). Antibody response after a third dose of the mRNA-1273 SARS-CoV-2 vaccine in kidney transplant recipients with minimal serologic response to 2 doses. JAMA. Retrieved August 2021 from https://jamanetwork.com/journals/jama/fullarticle/2782538;Monaco, K. (2021). Case mounts for COVID vaccine boosters in kidney transplant recipients. MedPage Today. Retrieved August 2021 from https://www.medpagetoday.com/infectiousdisease/covid19vaccine)

Patients in the study had moderately to severely active ulcerative colitis with a confirmed diagnosis of at least 4 months, and treatment failure or intolerance to oral or IV glucocorticoids, azathioprine, mercaptopurine, infliximab, or adalimumab. The pooled OCTAVE 1 and 2 studies randomized 234 patients to placebo and 905 to tofacitinib. The patients self-administered the IBDQ questionnaire at baseline, week 4, and week 8, with higher scores indicating better health-related quality of life. Significant improvements were observed in all 32 IBDQ items from baseline, grouped into four domains—bowel symptoms, systemic symptoms, emotional function, and social function. The largest differences reported in the bowel symptom domains were in loose bowel movements (1.1-point improvements at weeks 4 and 6) and rectal bleeding (1.1-point improvement at week 8). The largest differences reported in the systemic symptoms domain were reported in improvements in sleep (0.8-point improvement at week 4 and 0.9-point improvement at week 8). The largest improvements reported in the emotional function domain were seen in “fear of not finding a restroom” (0.6-point improvement at week 4 and 0.8-point improvement at week 8) and in embarrassment and anger (both improved by 0.6 points at week 4). The largest improvements reported in the social function domain were seen in avoidance of attendance at events (0.8-point improvement at week 4 and 1-point improvement at week 8) and in “difficulty doing leisure/sports” (1.0-point improvement at week 8).

Larger effect sizes (above 0.65 points) were seen, therefore, in two bowel symptoms (loose bowel movements and rectal bleeding), and small or medium effect sizes in all other components of the IBDQ except for “problems with maintaining weight” and “lack of understanding from others.” The effect sizes were mostly unchanged between week 4 and week 8 for many items, indicating that most of the treatment effect was observed early as the patient’s inflammatory burden and symptoms improved. (Dubinsky, M. C., et al. (2020). Tofacitinib in patients with ulcerative colitis: Inflammatory Bowel Disease Questionnaire items in phase 3 randomized controlled induction studies. Inflammatory Bowel Dis; 27(7): 983–993. Retrieved August 2021 from https://academic.oup.com/ibdjournal/article/27/7/983/5892619)

Patients with greater adherence to antidepressants appeared to experience fewer complications and a lower risk of mortality when compared to those with suboptimal use of their antidepressant medications. Overall, 9,670 patients developed macrovascular diabetes complications, 6,837 patients developed microvascular diabetes complications, and 3,820 patients died. Compared with poor use, regular use of oral antidepressants was associated with an 8% decreased risk for macrovascular complications (adjusted hazard ratio [HR], 0.92) and a 14% decreased risk for all-cause mortality (adjusted HR, 0.86). It was not associated with changes in risk of microvascular complications.

On further analysis, regular use of SSRIs was associated with a 17% decreased risk for macrovascular complications (adjusted HR, 0.83) and a 25% reduced risk for all-cause mortality (adjusted HR, 0.75). Regular use of tetracyclic or tricyclic antidepressants was associated with a 22% decreased risk for all-cause mortality (adjusted HR, 0.78). Regular use of benzodiazepines, on the other hand, showed no association with diabetic outcomes.

Patients with diabetes are at higher risk for depression, and depression worsens diabetes complications related to stress, body weight changes, and lack of exercise. This makes these patients more likely to develop diabetes complications, including heart and kidney disease, stroke, and eye and foot problems. Controlling comorbid depression is therefore important in these patients. Clinicians should encourage antidepressant treatment adherence among patients with diabetes and depression. (The Endocrine Society. (2021). Antidepressants may improve outcomes in people with diabetes and depression. ScienceDaily. Retrieved August 2021 from https://www.sciencedaily.com/releases/2021/07/210714131927.htm; Wu, C-S., et al. (2021). Associations between Antidepressant Use and Advanced Diabetes Outcomes in Patients with Depression and Diabetes Mellitus. J Clin Epidemiol Metab, Article dgab443. Retrieved August 2021 from https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgab443/6321009?redirectedFrom=fulltext)