Circulating Tumor DNA in the Immediate Postoperative Setting.

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as an accurate real-time biomarker of disease status across many solid tumor types. Most studies evaluating the utility of ctDNA have focused on time points weeks to months after surgery, which, for many cancer types, is significantly later than decision-making time points for adjuvant treatment. In this systematic review, we summarize the state of the literature on the feasibility of using ctDNA as a biomarker in the immediate postoperative period. METHODS: We performed a systematic review evaluating the early kinetics, defined here as 3 days of ctDNA in patients who underwent curative-intent surgery. RESULTS: Among the 2057 studies identified, eight cohort studies met the criteria for evaluation. Across six different cancer types, all studies showed an increased risk of cancer recurrence in patients with detectable ctDNA in the immediate postoperative period. CONCLUSION: While ctDNA clearance kinetics appear to vary based on tumor type, across all studies detectable ctDNA after surgery was predictive of recurrence, suggesting early postoperative time points could be feasibly used for determining minimal residual disease. However, larger studies need to be performed to better understand the precise kinetics of ctDNA clearance across different cancer types as well as to determine optimal postoperative time points.

Human Papillomavirus-Associated Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis.

Objective: Human papillomavirus (HPV) is known to affect head and neck sites beyond the oropharynx, including the nasopharynx. Unlike HPV-associated oropharyngeal squamous cell carcinoma (HPV+OPSCC), HPV-associated nasopharyngeal carcinoma (HPV+NPC) is not well characterized and the true prevalence in non-endemic regions is poorly described. Here, we sought to obtain a global point prevalence of HPV in NPC, stratified by geographic region. Data Sources: EMBASE, OVID Medline, and Web of Science were systematically searched for available evidence on September 21, 2022 for articles published between January 1, 1990 and September 21, 2022. Review Methods: We reviewed the literature for all studies examining NPC and HPV status in adult patients that provided a quantitative HPV prevalence. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Main outcome and measures included HPV+NPC prevalence estimates stratified by geographic region, along with other clinical and demographic features. Results: Of the 1567 citations retrieved, 46 studies encompassing 6314 NPC patients were eligible for statistical analysis. The global prevalence of HPV+NPC was 0.18 (95% CI 0.14-0.23). When stratified by geographic region, prevalence was highest in North America (0.25, 95% CI 0.17-0.36), which is a non-endemic region for NPC and also has highest prevalence for HPV+OPSCC. Asia, an endemic area, had the lowest HPV prevalence estimate (0.13, 95% CI 0.08-0.22). HPV 16 (44%) and 18 (33%) were the predominant genotypes in HPV+NPC, dissimilar to HPV+OPSCC. Conclusion: This systematic review and meta-analysis provides a global point prevalence of HPV+NPC stratified by geographic region and suggests that HPV is a significant etiological factor of NPC in North America.

Comparing the Diagnostic Performance of Quantitative PCR, Digital Droplet PCR, and Next-Generation Sequencing Liquid Biopsies for Human Papillomavirus-Associated Cancers.

Human papillomavirus (HPV)-associated cancers, including oropharyngeal squamous cell carcinoma (HPV + OPSCC), cervical cancer, and squamous cell carcinoma of the anus (HPV + SCCA), release circulating tumor HPV DNA (ctHPVDNA) into the blood. The diagnostic performance of ctHPVDNA detection depends on the approaches used and the individual assay metrics. A comparison of these approaches has not been systematically performed to inform expected performance, which in turn affects clinical interpretation. A meta-analysis was performed using Ovid MEDLINE, Embase, and Web of Science Core Collection databases to assess the diagnostic accuracy of ctHPVDNA detection across cancer anatomic sites, detection platforms, and blood components. The population included patients with HPV + OPSCC, HPV-associated cervical cancer, and HPV + SCCA with pretreatment samples analyzed by quantitative PCR (qPCR), digital droplet PCR (ddPCR), or next-generation sequencing (NGS). Thirty-six studies involving 2986 patients met the inclusion criteria. The sensitivity, specificity, and quality of each study were assessed and pooled for each analysis. The sensitivity of ctHPVDNA detection was greatest with NGS, followed by ddPCR and then qPCR when pooling all studies, whereas specificity was similar (sensitivity: ddPCR > qPCR, P < 0.001; NGS > ddPCR, P = 0.014). ctHPVDNA from OPSCC was more easily detected compared with cervical cancer and SCCA, overall (P = 0.044). In conclusion, detection platform, anatomic site of the cancer, and blood component used affects ctHPVDNA detection and must be considered when interpreting results. Plasma NGS-based testing may be the most sensitive approach for ctHPVDNA overall.

Ocular effects of Rho kinase (ROCK) inhibition: a systematic review.

Topical therapies targeting Rho-associated protein kinase (ROCK) signalling, including netarsudil (Rhopressa®) and ripasudil (Glanatec®), have become widely adopted as part of standard clinical practice to lower intraocular pressure (IOP) in patients with ocular hypertension or glaucoma. Given the pleiotropic roles of ROCK signalling, ROCK inhibition has the potential to cause unintended ocular side effects beyond IOP lowering in other substructures of the eye, both beneficial and deleterious. Additional experience and observation of patients treated with this class of medications have uncovered both new side effects not reported in the initial clinical trials, as well as potential benefits that have inspired off-label uses and that have been the topic of numerous clinical studies, case series, case reports, and translational studies. Here, we performed a comprehensive systematic review and identified 170 studies describing ocular effects of ROCK inhibition. In addition to describing well-established ocular effects associated with inhibition of ROCK signalling, such as conjunctival hyperaemia, corneal verticillata, and reticular corneal epithelial oedema, we also highlight other effects, such as corneal haemorrhages, changes in corneal contour, anterior subcapsular opacities, contact dermatitis, punctal stenosis, and eyelid wound dehiscence, which have been described in case series and case reports. Finally, we evaluated studies describing potential novel applications of ROCK inhibition for treating disorders affecting the cornea, the retina, and the optic nerve, finding strong evidence in support of a beneficial effect of ROCK inhibitors on corneal oedema due to corneal endothelial cell dysfunction. The other potential applications require further research.

Spontaneous recovery from amblyopia following fellow eye vision loss: a systematic review and narrative synthesis.

BACKGROUND: The effectiveness of traditional amblyopia therapies is largely restricted to childhood. However, spontaneous recovery in adulthood is possible following vision loss in the fellow eye due to enucleation, injury, or disease. The twofold purpose of this study was (1) to define the incidence of recovery and (2) to elucidate the clinical features associated with greater amblyopic eye gains. METHODS: A systematic review of three databases yielded 24 reports containing 110 cases of patients ≥18 years old with unilateral amblyopia and vision-limiting fellow eye pathology. RESULTS: Our analysis revealed that 25 of 42 of adult patients (59.5%) gained ≥2 logMAR lines in the amblyopic eye after fellow eye vision loss. The degree of improvement is clinically meaningful (median, 2.6 logMAR lines). Recovery occurs within 12 months of initial loss of fellow eye vision. Regression analysis demonstrated that younger age, worse baseline visual acuity in the amblyopic eye, and worse vision in the fellow eye independently conferred greater gains in amblyopic eye visual acuity. Recovery occurs across amblyopia types and fellow eye pathologies, although disease entities affecting fellow eye retinal ganglion cells demonstrate shorter latencies to recovery. CONCLUSIONS: Amblyopia recovery after fellow eye injury demonstrates that the adult brain harbors the neuroplastic capacity for clinically meaningful recovery, which could potentially be harnessed by novel approaches to treat adults with amblyopia.

Intraoperative Ultrasound for the Management of Oral Tongue Cancer: a Systematic Review and Meta-Analysis.

Objective: To evaluate for correlation between intraoperative ultrasound (IOUS)-measured tumor thickness (TT) (uTT) and histopathological TT (hTT), and to compare IOUS-assisted resection with conventional resection in patients with oral tongue cancers. Data Sources: Ovid MEDLINE (1946-2023), Embase.com (1947-2023), and Web of Science (All Databases 1900-2023). Review Methods: Inclusion criteria were the use of IOUS for the management of oral tongue cancer. Studies that did not report quantitative data were excluded. Additionally, studies that were not contributory to meta-analysis, or a narrative analysis of pooled results were excluded. Selection was carried out by 2 reviewers. A total of 2417 studies were initially identified, with 12 ultimately being included in this review, and 7 included in the meta-analysis. Data were extracted by 2 investigators and were pooled using a random-effects model. Results: Our meta-analysis reveals a pooled correlation coefficient of 0.92 (95% confidence interval: 0.80-0.96) for studies comparing uTT to hTT. Studies comparing IOUS-assisted resection to conventional resection found IOUS-assisted resection yielded wider nearest margins in all studies reporting this outcome. Conclusion: IOUS reliably measures TT, similarly to that of histopathology measurement. IOUS-assisted resection, which allows the surgeon to view the deep extent of tumor invasion, may increase closest radial margin distance compared to conventional resection. IOUS-assisted resection may represent a more reliable approach to achieving clear margins than conventional resection.

Margin distance in oral tongue cancer surgery: A systematic review of survival and recurrence outcomes.

The status of resection margins is a proxy for the completeness of resection in oral tongue cancer surgery and is therefore a useful predictor for post-operative prognosis. Historically, a margin distance of 5 mm or greater has been deemed a negative margin and is believed to yield a benefit in terms of control and survival. To summarize the literature more completely on this topic, we conducted a systematic review that examines radial margin distance and its relationship to disease control and survival in oral tongue cancer. Our review includes 34 studies which reported survival and/or recurrence outcomes for oral tongue cancer patients based on margin status. Most studies reported outcomes for the 5 mm margin, while the minority utilized other margin cutoffs. For the 5 mm cutoff, outcomes were generally favorable regarding survival and recurrence outcomes. Nonetheless, studies using 4 mm, 3.3 mm, and 10 mm cutoffs also found favorable survival and recurrence outcomes; however, these are a minority of the included studies.

circulating tumor DNA in the immediate post-operative setting.

Background: Circulating tumor DNA (ctDNA) has emerged as an accurate real-time biomarker of disease status across most solid tumor types. Most studies evaluating the utility of ctDNA have focused on time points weeks to months after surgery, which for many cancer types, is significantly later than decision-making time points for adjuvant treatment. In this systematic review, we summarize the state of the literature on the feasibility of using ctDNA as a biomarker in the immediate postoperative period. Methods: We performed a systematic review evaluating the early kinetics, defined here as three days, of ctDNA in patients who underwent curative-intent surgery across several cancer types. Results: Among the 2057 studies identified, we evaluated eight cohort studies with ctDNA levels measured within the first three days after surgery. Across six different cancer types, all studies showed an increased risk of cancer recurrence in patients with a positive early postoperative ctDNA level. Discussion: While ctDNA clearance kinetics appear to vary based on tumor type, across all studies- detectable ctDNA after surgery was predictive of recurrence, suggesting early postoperative timepoints could be feasibly used for determining minimal residual disease. However, larger studies need to be performed to better understand the precise kinetics of ctDNA clearance across different cancer types as well as to determine optimal postoperative time points. Synopsis: This systematic review analyzed the use of ctDNA as a biomarker for minimal residual disease detection in the early postoperative setting and found that ctDNA detection within three days after surgery is associated with an increased risk of recurrence.

Association Between Early-Onset Osteoporosis With Hearing Loss and Benign Paroxysmal Positional Vertigo (BPPV): A Systematic Review and Meta-Analysis.

OBJECTIVE: Osteoporosis is a chronic systemic disease characterized by low bone mass, progressive microarchitectural deterioration and increased bone fragility. Hearing loss and benign paroxysmal positional vertigo (BPPV) have been found in patients diagnosed with osteoporosis over 65 years, however, there is lack of information about these conditions in young patients. Herein, we conducted a systematic review and meta-analysis to provide evidence of the association between osteoporosis and audio-vestibular findings in young subjects. METHODS: Systematic review and meta-analysis were performed according to PRISMA guidelines. Searches were conducted in PubMed, Embase, and Web of Science Core Collection. Mean age, proportion of patients with low mineral density, hearing loss, and BPPV were calculated for the systematic review and meta-analysis. Odds Ratio (OR) with their corresponding 95% confidence intervals (CI) were calculated. RESULTS: A total of 26 articles were reviewed. Only 10 studies met inclusion criteria for the meta-analysis. Six were assessed pursuing the association between osteoporosis and hearing loss. Pooled evidence suggested in patients with osteoporosis, an increased risk for developing hearing loss (OR = 1.52, 95% CI 1.06-2.19; P = .02) compared to controls. Another 6 studies reported the association between osteoporosis and BPPV. A significant increased risk for BPPV was found in individuals with osteoporosis (OR = 1.58, 95% CI 1.02-2.4; P = .04). There was no publication bias. CONCLUSION: Subjects younger than 65 years with osteoporosis have an increase odds for hearing loss and BPPV compared to controls. These conditions could be associated with early inner or middle ear bone morphologic changes.

Functional considerations between flap and non-flap reconstruction in oral tongue cancer: A systematic review.

This systematic review aims to provide insight into the ideal reconstructive approach of the oral tongue in oral tongue cancer (OTC) by investigating the relationship between functional outcomes and the extent of tongue resection. A structured search was performed in Ovid MEDLINE, EMBASE, and Web of Science. Studies comparing patient-reported and objective measurements of the oral tongue function between flap vs. non-flap reconstruction were included. Functional outcomes of interest were speech production, deglutition efficiency, tongue mobility, overall quality of life, and postoperative complications. A total of nine studies were retrieved and critically appraised. Patients with 20 % or less of oral tongue resected had superior swallowing efficiency and speech intelligibility with a non-flap reconstruction while patients with a tongue defect of 40-50 % self-reported or demonstrated better swallowing function with a flap repair. The data in intermediate tongue defects (20-40 % tongue resected) was inconclusive, with several studies reporting comparable functional outcomes between approaches. A longitudinal multi-institutional prospective study that rigidly controls the extent of tongue resected and subsites involved is needed to determine the percentage of tongue resected at which a flap reconstruction yields a superior functional result in OTC.

Recovery from Amblyopia in Adulthood: A Meta-Analysis.

Purpose: The effectiveness of traditional amblyopia therapies is largely restricted to childhood. However, recovery in adulthood is possible following removal or vision-limiting disease of the fellow eye. Study of this phenomenon is currently limited to isolated case reports and a few case series, with reported incidence ranging from 19-77% 1-5 . We set out to accomplish two distinct goals: (1) define the incidence of clinically meaningful recovery and (2) elucidate the clinical features associated with greater amblyopic eye gains. Methods: A systematic review of 3 literature databases yielded 23 reports containing 109 cases of patients ≥18 years old with unilateral amblyopia and vision-limiting fellow eye pathology. Results: Study 1 revealed 25/42 (59.5%) of adult patients gained ≥2 logMAR lines in the amblyopia eye after FE vision loss. The overall degree of improvement is clinically meaningful (median 2.6 logMAR lines). Study 2 showed that for cases with amblyopic eye visual acuity improvement, recovery occurs within 12 months of initial loss of fellow eye vision. Regression analysis revealed that younger age, worse baseline acuity in the amblyopic eye, and worse vision in the fellow eye independently conferred greater gains in amblyopic eye visual acuity. Recovery occurs across amblyopia types and fellow eye pathologies, although disease entities affecting fellow eye retinal ganglion cells demonstrate shorter latencies to recovery. Conclusions: Amblyopia recovery after fellow eye injury demonstrates that the adult brain harbors the neuroplastic capacity for clinically meaningful recovery, which could potentially be harnessed by novel approaches to treat adults with amblyopia.

Comparison of patient-reported upper extremity disability following free flaps in head and neck reconstruction: A systematic review and meta-analysis.

BACKGROUND: Comparisons of patient-reported donor site morbidity based on the Disabilities in Arm, Shoulder, and Hand (DASH) instrument across upper trunk free flaps in head and neck surgery, including radial forearm (RFFF), osteocutaneous radial forearm (OCRFF), scapular tip (STFF), and serratus anterior (SAFF) free flaps, may help inform donor tissue selection. METHODS: In this meta-analysis, 12 studies were included and the primary outcome was average DASH score. RESULTS: The pooled DASH scores were 12.14 (95% CI: 7.40-16.88) for RFFF (5 studies), 17.99 (11.87-24.12) for OCRFF (2 studies), 12.19 (8.74-15.64) for STFF (3 studies), and 16.49 (5.92-27.05) for SAFF (2 studies) and were not significantly different. CONCLUSIONS: Results suggest that patients generally function well, with minimal to mild donor site morbidity, when assessed at an average of 20 months after flap harvest. These results are based on few effects from primarily retrospective studies of fair quality, and further research is needed.

A Contemporary Review of Molecular Therapeutic Targets for Adenoid Cystic Carcinoma.

ACC is a rare malignant tumor of the salivary glands. In this contemporary review, we explore advances in identification of targetable alterations and clinical trials testing these druggable targets. A search of relevant articles and abstracts from national meetings and three databases, including PubMed, Medline, and Web of Science, was performed. Following keyword search analysis and double peer review of abstracts to ensure appropriate fit, a total of 55 manuscripts were included in this review detailing advances in molecular targets for ACC. The most researched pathway associated with ACC is the MYB-NFIB translocation, found to lead to dysregulation of critical cellular pathways and thought to be a fundamental driver in a subset of ACC disease pathogenesis. Other notable molecular targets that have been studied include the cKIT receptor, the EGFR pathway, and NOTCH1, all with limited efficacy in clinical trials. The ongoing investigation of molecular abnormalities underpinning ACC that may be responsible for carcinogenesis is critical to identifying and developing novel targeted therapies.

Reflecting on the COVID-19 Surgical Literature Surge: A Scoping Review of Pandemic Otolaryngology Publications.

OBJECTIVE: To assess the high-volume 2020 COVID-19-related surgical literature, with special attention to otolaryngology articles in regard to content, level of evidence, citations, and public attention. STUDY DESIGN: A scoping literature review was performed with PubMed and Web of Science, including articles pertaining to COVID-19 and surgical specialties (March 20-May 19, 2020) or otolaryngologic subspecialties (March 20-December 31, 2020). SETTING: Scoping literature review. METHODS: Otolaryngology-specific COVID-19-related articles were reviewed for publication date, county of origin, subspecialty, content, level of evidence, and Altmetric Attention Score (a weighted approximation of online attention received). Data were analyzed with Pearson correlation coefficients, analysis of variance, independent t tests, and univariable and logistic regressions. RESULTS: This review included 773 early COVID-19 surgical articles and 907 otolaryngology-specific COVID-19-related articles from 2020. Otolaryngology was the most represented surgical specialty within the early COVID-19-related surgical literature (30.4%). The otolaryngology-specific COVID-19 surgical literature responsively reflects the unique concerns within each otolaryngologic subspecialty. Although this literature was largely based on expert opinion (64.5%), articles with stronger levels of evidence received significantly more citations (on Web of Science and Google Scholar, P < .001 for both) and public attention (according to Altmetric Attention Scores, P < .001). CONCLUSION: Despite concerns of a surge in underrefereed publications during the COVID-19 pandemic, our review of the surgical literature offers some degree of reassurance. Specifically, the COVID-19 otolaryngology literature responsively reflects the unique concerns and needs of the field, and more scholarly citations and greater online attention have been given to articles offering stronger levels of scientific evidence.

A systematic review of federated learning applications for biomedical data.

OBJECTIVES: Federated learning (FL) allows multiple institutions to collaboratively develop a machine learning algorithm without sharing their data. Organizations instead share model parameters only, allowing them to benefit from a model built with a larger dataset while maintaining the privacy of their own data. We conducted a systematic review to evaluate the current state of FL in healthcare and discuss the limitations and promise of this technology. METHODS: We conducted a literature search using PRISMA guidelines. At least two reviewers assessed each study for eligibility and extracted a predetermined set of data. The quality of each study was determined using the TRIPOD guideline and PROBAST tool. RESULTS: 13 studies were included in the full systematic review. Most were in the field of oncology (6 of 13; 46.1%), followed by radiology (5 of 13; 38.5%). The majority evaluated imaging results, performed a binary classification prediction task via offline learning (n = 12; 92.3%), and used a centralized topology, aggregation server workflow (n = 10; 76.9%). Most studies were compliant with the major reporting requirements of the TRIPOD guidelines. In all, 6 of 13 (46.2%) of studies were judged at high risk of bias using the PROBAST tool and only 5 studies used publicly available data. CONCLUSION: Federated learning is a growing field in machine learning with many promising uses in healthcare. Few studies have been published to date. Our evaluation found that investigators can do more to address the risk of bias and increase transparency by adding steps for data homogeneity or sharing required metadata and code.

Strategies to Increase Racial and Ethnic Diversity in the Surgical Workforce: A State of the Art Review.

OBJECTIVE: To evaluate strategies to increase racial and ethnic diversity in the surgical workforce among trainees and faculty across surgical specialties. DATA SOURCES: Embase, OVID/Medline, and Web of Science Core Collection. REVIEW METHODS: A review of US-based, peer-reviewed articles examining the effect of targeted strategies on racial and ethnic diversity in the surgical workforce was conducted from 2000 to 2020 with the PRISMA checklist and STROBE tool. Studies without an outlined strategy and associated outcomes were excluded. Eleven studies met inclusion criteria and were completed in general surgery, orthopaedic surgery, and otolaryngology-head and neck surgery. CONCLUSIONS: Efforts to increase exposure to surgery through internship programs and required clerkships with efforts to improve mentorship were common (6 of 11 [54.5%] and 3 of 11 [27.3%] studies, respectively). Three (27.3%) studies aimed to diversify the recruitment and selection process for the residency match and faculty hiring, and 2 (18.2%) aimed to increase representation among trainees, faculty, and leadership through holistic review processes paired with departmental commitment. Outcome metrics included surgical residency applications for individuals underrepresented in medicine, interview and match rates, faculty hiring, measures of a successful academic surgical career, and leadership representation. All strategies were successful in increasing diversity in the surgical workforce. IMPLICATIONS FOR PRACTICE: A convincing yet limited body of literature exists to describe strategies and outcomes that address racial and ethnic diversity in the surgical workforce. While future inquiry is needed to move this field of interest forward, the evidence presented provides a framework for surgical residency programs/departments to develop approaches to increase racial and ethnic diversity.