Efficacy of Anti-PD1 Blockade in Treating Recurrent or Metastatic Nasopharyngeal Cancer: A Systematic Review and Meta-analysis.

OBJECTIVES: Anti-PD1 antibody has emerged as a promising immunotherapeutic option in patients with recurrent and/or metastatic nasopharyngeal cancers (RM-NPC). We aim to summarise existing evidence on the use of anti-PD1 antibodies in the treatment of these patients and compare its effectiveness with standard-of-care palliative chemotherapy. Our secondary aim is to explore potential combination therapies with anti-PD1 antibodies. MATERIALS AND METHODS: PubMed, Embase and Cochrane databases were systematically searched for studies comparing the efficacy of various anti-PD1 antibodies in the treatment of RM-NPC (either as first or second line treatment) from inception to 2 September 2022. Meta-analyses were performed to correlate the various anti-PD1 antibodies with primary endpoints including overall response rate disease control rate (DCR), progression free survival (PFS) and overall survival (OS). RESULTS: Eighteen studies with 1,887 patients met the inclusion criteria. The use of anti-PD1 antibody monotherapy as second-line treatment of RM-NPC revealed an ORR of 23 % (95 % CI = 19 %-28 %) and DCR of 51 % (95 % CI = 42 %-60 %). The ORRs for first-line as well as a combination of first and second-line treatments were 21 % (95 % CI = 15 % - 30 %) and 22 % (95 % CI = 6 % - 56 %, I2 = 75 %) respectively. The 12-month PFS and 12-month OS was also 27 % (95 % CI = 21 %-33 %) and 63 % (95 % CI = 53 %-72 %) respectively. ORR was much higher at 73 % (95 % CI = 32 %-94 %) when anti-PD1 antibodies were combined with Gemcitabine plus Cisplatin. CONCLUSION: Anti-PD1 antibody demonstrate considerable activity in previously treated RM-NPC patients. Combining anti-PD1 antibodies with gemcitabine and cisplatin chemotherapy enhanced the efficacy of treatment.

Association of Olfactory Impairment With All-Cause Mortality: A Systematic Review and Meta-analysis.

Importance: Olfactory impairment is highly prevalent and associated with multiple comorbidities, including neurodegenerative, cardiovascular, nutritional, and immune disorders. However, epidemiologic associations between olfactory impairment and mortality are discordant. Objective: To systematically clarify the epidemiologic associations between olfactory impairment and mortality. Data Sources: The PubMed, Embase, and Cochrane Library databases were searched from inception to August 13, 2021. Study Selection: Two blinded reviewers selected observational studies published as full-length, English-language articles in peer-reviewed journals that reported the presence or severity of chronic olfactory impairment, whether objectively measured or self-reported, in association with any mortality estimate, among adults aged 18 years or older. Data Extraction and Synthesis: Two reviewers independently extracted data, evaluated study bias using the Newcastle-Ottawa Scale, and appraised the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation framework, following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and a PROSPERO-registered protocol. Maximally adjusted estimates were pooled using mixed-effects models, heterogeneity was measured using I2 statistics, sources of heterogeneity were investigated using meta-regression and subgroup meta-analyses, and publication bias was qualitatively and quantitatively assessed. Main Outcomes and Measures: Hazard ratios for all-cause mortality. Results: One retrospective cohort study and 10 prospective cohort studies (with a total of 21 601 participants) from 1088 nonduplicated records were included. Ten studies had a low risk of bias, whereas 1 study had a moderate risk; exclusion of the latter did not alter conclusions. Nine studies were included in the meta-analysis. Olfactory loss was associated with a significantly higher pooled hazard of all-cause mortality (hazard ratio, 1.52; 95% CI, 1.28-1.80; I2 = 82%). Meta-regression sufficiently explained heterogeneity, with longer mean follow-up duration weakening the pooled association, accounting for 91.3% of heterogeneity. Self-reported and objective effect sizes were similar. Associations were robust to trim-and-fill adjustment and the Egger test for publication bias. The overall quality of evidence was moderate. Conclusions and Relevance: The findings of this systematic review and meta-analysis suggest that olfactory impairment is associated with all-cause mortality and may be a marker of general health and biological aging. Further research is required to establish the underlying mechanisms and the scope for interventions.

Trainee participation does not adversely affect the safety of thyroid surgery: Systematic review and meta-analysis.

Surgical traineeship is essential but must be safe for patients. In thyroid surgery, surgeon volume correlates with improved clinical/economic outcomes. However, it is presently unclear how far does trainee participation affect post-thyroidectomy complication rates in real-world and randomized data. We systematically searched four databases for associations of trainee participation with any post-thyroidectomy outcome. We conducted univariate meta-analyses, sensitivity analyses, and assessed publication bias qualitatively and quantitatively. We included 1 randomized and 15 observational studies from 3755 records, comprising 34 774 thyroid surgical patients. Trainee participation was associated with 12 min longer operative time, but not higher complication rates (hypoparathyroidism, recurrent laryngeal nerve palsy, hematoma, blood loss, return to operating room, hospitalization duration, readmission, and mortality). Sensitivity, publication bias, and multivariate analyses did not change our findings. Real-world and limited randomized data suggest that trainee participation in thyroid surgery is safe, given adequate consultant supervision and appropriate case selection.

Associations of Hearing Loss and Dual Sensory Loss With Mortality: A Systematic Review, Meta-analysis, and Meta-regression of 26 Observational Studies With 1 213 756 Participants.

IMPORTANCE: Hearing loss (HL) and dual sensory loss (DSL) are prevalent, disabling, and associated with numerous age-related health conditions, including dementia and frailty. To date, no evidence-based summary of their mortality risk is available. OBJECTIVE: To clarify the epidemiological associations between HL/DSL and mortality. DATA SOURCES: PubMed, Embase, and Cochrane Library, from inception until June 18, 2021. STUDY SELECTION: Two blinded reviewers selected observational or interventional studies, published as full-length English articles in peer-reviewed journals, that reported the presence or severity of HL or DSL (ie, comorbid HL and vision loss), whether objectively measured or self-reported, in association with any mortality estimate, among adults 18 years and older. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted data and evaluated study bias using the Newcastle-Ottawa Scale, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)/Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and a PROSPERO-registered protocol. The analysis pooled maximally adjusted estimates using mixed-effects models, measured heterogeneity using I2, investigated sources of heterogeneity using meta-regression and subgroup meta-analyses, examined and adjusted for publication bias, performed influence and cumulative meta-analyses, and assessed evidence quality using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) for all-cause, cardiovascular, or other mortality estimates. RESULTS: This review included 14 retrospective and 12 prospective observational studies (1 213 756 participants) from 3220 records. Risk of bias was low to moderate; exclusion of 3 high-risk studies did not alter conclusions. Hearing loss was associated with excess all-cause mortality (HR, 1.13; 95% CI, 1.07-1.19; I2 = 77%; n = 21; 95% prediction interval [PI], 0.93-1.37) and cardiovascular mortality (HR, 1.28; 95% CI, 1.10-1.50; I2 = 60%; n = 6; 95% PI, 0.84-1.96), while DSL was associated with larger excess risks (all-cause: HR, 1.40; 95% CI, 1.30-1.51; I2 = 34%; n = 10; 95% PI, 1.18-1.66; cardiovascular: HR, 1.86; 95% CI, 1.31-2.65; I2 = 0%; n = 2), after adjustment for demographics and comorbidities. Prespecified meta-regression sufficiently explained heterogeneity, with longer follow-up duration weakening the pooled association, leaving low (29%) residual heterogeneity. Meta-regression among audiometric studies showed a dose-response association (doubling of HR per 30-dB increase in HL). Self-reported and audiometric effect sizes were similar, with lower heterogeneity in the latter. Associations were robust to trim-and-fill adjustment for publication bias and single-study influence and cumulative meta-analyses. Associations with accident/injury, cancer, and stroke mortality were inconclusive, with only 1 to 3 studies. Overall evidence quality was moderate. CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, HL and DSL were associated with excess all-cause and cardiovascular mortality. Physicians caring for patients with HL should consider its relevance to general health and longevity.