Factors associated with successful electrolarynx use after total laryngectomy, a multi-institutional study.

Objective: To identify characteristics associated with successful electrolarynx (EL) use after total laryngectomy (TL). Methods: Records of 196 adults who underwent TL from 03/15/2012 to 03/15/2022 at the University of Washington and Puget Sound Veterans Affairs were reviewed. Characteristics included age, Charlson Comorbidity Index, social support, pre-operative radiation (RT) and chemoradiation (CRT), and 6-month post-TL swallow status. EL success was evaluated using pre-defined criteria of intelligibility, reliability, and independence with use. Poisson regressions and robust standard error estimates were used to estimate unadjusted risk ratios for each characteristic. Statistically significant characteristics were included in multivariate analysis (MVA) to estimate adjusted risk ratios. Results: Median age was 64, median Charlson Comorbidity Index was 5, 170 (87%) were male, 159 (81%) had high social support, and 159 (81%) attained post-TL full-oral diet. Pre-operatively, 110 (56%) had RT, including 55 (28%) with CRT. Ninety-three (47%) met our criteria for EL success. Characteristics significantly associated with EL success included social support (p = .037) and post-TL full-oral diet (p = .037); both approached significance on MVA. EL success varied by pre-operative treatment on univariate (p = .005) and MVA (p = .014). Compared to no prior RT or CRT, the probability of EL success was 29% higher with prior RT and 29% lower with prior CRT in MVA, although these associations did not reach significance. Conclusions: In this retrospective review, EL success correlated with high social support, post-TL full-oral diet, and pre-operative treatment history. These results warrant validation in a larger prospective study to help guide the choice of voice rehabilitation modalities or intensified speech therapy. Level of Evidence: 4.

Radiation therapy for low- and high-risk perineural invasion in head and neck cutaneous squamous cell carcinoma: Clinical outcomes and patterns of failure.

BACKGROUND: Perineural invasion (PNI) in head and neck squamous cell carcinoma (HNSCC) portends poor prognosis. Extent of treatment of nerve pathways with varying degrees of PNI and patterns of failure following elective neural radiotherapy (RT) remain unclear. METHODS: Retrospective review of HNSCC patients with high-risk (clinical/gross, large-nerve, extensive) or low-risk (microscopic/focal) PNI who underwent curative-intent treatment from 2010 to 2021. RESULTS: Forty-four patients (mean follow-up 22 months; 59% high-risk, 41% low-risk PNI) were included. Recurrence following definitive treatment occurred in 31% high-risk and 17% low-risk PNI patients. Among high-risk patients, 69% underwent surgery with post-operative RT and 46% underwent elective neural RT. Local control (83% low-risk vs. 75% high-risk), disease-free, and overall survival did not differ between groups. CONCLUSIONS: High local control rates were achieved in high-risk PNI patients treated with adjuvant or primary RT, including treatment of both involved and uninvolved, communicating cranial nerves, with few failures in electively treated regions.

Peripheral lymphocytes and lactate dehydrogenase correlate with response and survival in head and neck cancers treated with immune checkpoint inhibitors.

BACKGROUND: Little is known regarding associations between peripheral blood biomarkers (PBBMs) and survival, response, and toxicity in recurrent/metastatic head and neck squamous cell carcinomas (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs). METHODS: In this single-institution retrospective cohort study, a dataset of patients with R/M HNSCC treated with ICIs between 08/2012-03/2021 was established, including demographic and clinicopathologic characteristics. Pretreatment PBBMs were collected and evaluated for associations with grade ≥3 adverse events (G ≥ 3AE) by CTCAEv5, objective response (ORR) by RECIST 1.1, overall survival (OS), and progression-free survival (PFS). Multivariable models for each outcome were created using elastic net variable selection. RESULTS: Our study included 186 patients, with 51 (27%) demonstrating complete or partial response to immunotherapy. Multivariable models adjusted for ECOG performance status (PS), p16, and smoking demonstrated that pretreatment higher LDH and absolute neutrophils, as well as lower percent lymphocytes correlated with worse OS and PFS. Higher LDH and lower % lymphocytes also correlated with worse ORR. CONCLUSIONS: In the largest study to date examining PBBMs in ICI-treated R/M HNSCCs, our variable selection method revealed PBBMs prognostic for survival and response to immunotherapy. These biomarkers warrant further investigation in a prospective study along with validation with CPS biomarker.

Estimating deaths averted and cost per life saved by scaling up mRNA COVID-19 vaccination in low-income and lower-middle-income countries in the COVID-19 Omicron variant era: a modelling study.

OBJECTIVES: While almost 60% of the world has received at least one dose of COVID-19 vaccine, the global distribution of vaccination has not been equitable. Only 4% of the population of low-income countries (LICs) has received a full primary vaccine series, compared with over 70% of the population of high-income nations. DESIGN: We used economic and epidemiological models, parameterised with public data on global vaccination and COVID-19 deaths, to estimate the potential benefits of scaling up vaccination programmes in LICs and lower-middle-income countries (LMICs) in 2022 in the context of global spread of the Omicron variant of SARS-CoV2. SETTING: Low-income and lower-middle-income nations. MAIN OUTCOME MEASURES: Outcomes were expressed as number of avertable deaths through vaccination, costs of scale-up and cost per death averted. We conducted sensitivity analyses over a wide range of parameter estimates to account for uncertainty around key inputs. FINDINGS: Globally, universal vaccination in LIC/LMIC with three doses of an mRNA vaccine would result in an estimated 1.5 million COVID-19 deaths averted with a total estimated cost of US$61 billion and an estimated cost-per-COVID-19 death averted of US$40 800 (sensitivity analysis range: US$7400-US$81 500). Lower estimated infection fatality ratios, higher cost-per-dose and lower vaccine effectiveness or uptake lead to higher cost-per-death averted estimates in the analysis. CONCLUSIONS: Scaling up COVID-19 global vaccination would avert millions of COVID-19 deaths and represents a reasonable investment in the context of the value of a statistical life. Given the magnitude of expected mortality facing LIC/LMIC without vaccination, this effort should be an urgent priority.

Free Flap Reconstruction of the Anterior Skull Base: A Systematic Review.

Objectives Given the limitations in the available literature, the precise indications, techniques, and outcomes of anterior skull base free flap reconstruction remain uncertain. The objective of this study was to perform a systematic review of published literature and evaluate indications, methods, and complications for anterior skull base free flap reconstruction. Methods A systematic review of the literature was performed using a set of search criteria to identify patients who underwent free flap reconstruction of the anterior skull base. Articles were reviewed for inclusion based on relevance, with the primary outcome being surgical complications. Results After a comprehensive search, 406 articles were obtained and 16 articles were ultimately found to be relevant to this review-79 patients undergoing free flap reconstruction were identified. Overall complication rates were 17.7% (95% confidence interval [CI]: 16.6-33.1%) for major complications and 19.0% (95% CI: 17.8-35.5%) for minor complications. Conclusion Microvascular reconstruction of the anterior skull base is feasible with high reliability reported in the literature.

Oral Cancer: What the General Surgeon Should Know.

Oral cavity cancer represents a heterogeneous group of cancers with unique etiologic, diagnostic, and treatment considerations based on the subsite. While decreases in smoking have resulted in the development of fewer oral cavity cancers, the incidence remains high in certain geographic areas. History and physical examination, as well as tissue biopsy, are key to diagnosis. Although surgical resection is the primary treatment modality for oral cavity cancer, the optimal treatment plan for a patient is an individualized approach accounting for comorbidities, goals of care, and functional outcomes related to speech and swallowing.

A Biofabrication Strategy for a Custom-Shaped, Non-Synthetic Bone Graft Precursor with a Prevascularized Tissue Shell.

Critical-sized defects of irregular bones requiring bone grafting, such as in craniofacial reconstruction, are particularly challenging to repair. With bone-grafting procedures growing in number annually, there is a reciprocal growing interest in bone graft substitutes to meet the demand. Autogenous osteo(myo)cutaneous grafts harvested from a secondary surgical site are the gold standard for reconstruction but are associated with donor-site morbidity and are in limited supply. We developed a bone graft strategy for irregular bone-involved reconstruction that is customizable to defect geometry and patient anatomy, is free of synthetic materials, is cellularized, and has an outer pre-vascularized tissue layer to enhance engraftment and promote osteogenesis. The graft, comprised of bioprinted human-derived demineralized bone matrix blended with native matrix proteins containing human mesenchymal stromal cells and encased in a simple tissue shell containing isolated, human adipose microvessels, ossifies when implanted in rats. Ossification follows robust vascularization within and around the graft, including the formation of a vascular leash, and develops mechanical strength. These results demonstrate an early feasibility animal study of a biofabrication strategy to manufacture a 3D printed patient-matched, osteoconductive, tissue-banked, bone graft without synthetic materials for use in craniofacial reconstruction. The bone fabrication workflow is designed to be performed within the hospital near the Point of Care.

Retraction: Bipolar Affective Disorder: A Case of Antidepressant-Induced Hypomania.

[This retracts the article DOI: 10.7759/cureus.12399.].

Case of Esophageal Perforation and Repair with a Supraclavicular Artery Island Fascial Flap 15 Years After Anterior Spine Surgery.

BACKGROUND: Esophageal perforation represents a rare but potentially life-threatening complication of an anterior cervical diskectomy and fusion (ACDF). Delayed presentations of esophageal perforation more than 10 years following surgery are exceedingly rare and difficult to diagnose. Here, we discuss the case of an 80-year-old man who presented to the emergency department with progressive dysphagia 15 years after his ACDF. CASE DESCRIPTION: While prior outpatient workup was suggestive of a diverticulum, there was no evidence of esophageal perforation. Progressive symptoms and repeat imaging on admission were suggestive of retropharyngeal phlegmon. Operative esophagoscopy revealed that the spinal hardware had eroded through the posterior wall of the esophagus, creating a traction diverticulum. The hardware was removed, and the esophageal perforation was closed primarily and buttressed with vascularized tissue from a supraclavicular artery island fascial flap. CONCLUSIONS: This case emphasizes the importance of considering an esophageal perforation in patients who present with dysphagia at any interval following an ACDF, even in the extremely delayed setting. Furthermore, this is the first report, to the best of our knowledge, using a supraclavicular artery island fascial flap to reconstruct an esophageal perforation following an ACDF, and we introduce a novel strategy for managing these complicated injuries.

Brucellosis: An Elusive Backyard Agent.

Brucellosis is a form of zoonotic infection caused by various Brucella organisms. It most commonly presents as a case of pyrexia of unknown origin, alongside symptoms such as night sweats, malaise, arthralgias, and myalgias. This report describes the case of a man who presented with pyrexia of unknown origin for one month; he was diagnosed to be a case of brucellosis after enteric fever was ruled out. Investigations were ordered as it was a differential diagnosis with high clinical suspicion due to the presenting complaint and potential exposure of tainted consumable products. The systemic disease was determined to be brucellosis following blood results demonstrating positive antibody titers, and the suspicion of exposure due to widespread inadequacies in sterilization of food products.

Elective neck dissection during salvage laryngectomy: A systematic review and meta-analysis.

OBJECTIVES: The primary objective was to determine the rate of occult cervical nodal metastasis in patients undergoing elective neck dissection (END) during salvage laryngectomy. The secondary objective was to compare survival and postoperative complication rates between patients undergoing END versus observation. METHODS: A medical librarian performed a comprehensive search for END outcomes in laryngeal cancer patients undergoing salvage laryngectomy after primary chemoradiation therapy. Seventeen retrospective studies and 1 prospective study met inclusion criteria, with a total of 1,141 patients (799 END, 350 observed). RESULTS: The rate of nodal positivity was 11% among patients who underwent END during their salvage laryngectomy. Three studies and 155 patients were included in a 5-year overall survival (OS) analysis with no significant difference in OS (95% confidence interval [CI]: 0.82-2.22). After inclusion of six studies and 494 patients (249 END, 245 observed), the risk of fistula formation was not statistically different (95% CI: 0.61-2.56). Due to significant heterogeneity between studies and inadequate data, most patients could not be included in the meta-analysis of outcomes. CONCLUSION: Salvage laryngectomy patients undergoing END have an occult nodal positivity rate of 11%. Meta-analysis showed no statistically significant differences in 5-year OS between patients undergoing END versus observation. Laryngoscope, 130:899-906, 2020.

Bipolar Affective Disorder: A Case of Antidepressant-Induced Hypomania.

Bipolar affective disorder (BAD) is found among 1-3% of the world's population and leads to a significant burden due to its chronicity. This report describes a case of antidepressant-induced BAD, presenting in the hypomanic phase. Diagnostic criteria in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) were used for the diagnosis, after having performed investigations and excluding organic causes. The patient presented with typical features of altered mood, pressured speech, hyperactivity, and irritability. He was diagnosed according to the criteria available and managed promptly.

Erythema Nodosum: A Consequence of Tuberculosis.

Erythema nodosum is a form of panniculitis that presents as red lumps most commonly on the shins. It commonly presents due to tuberculosis, streptococcal infections, sarcoidosis, or can be drug related. This report describes the case of a young woman who presented with erythema nodosum and reactive arthritis; this was determined to be a sequelae of tuberculosis. Investigations were ordered as there was a high level of clinical suspicion for an underlying systemic cause for the presenting complaints. The systemic condition was determined to be tuberculosis due to the endemic environment and a positive tuberculin skin test.

Nationwide analysis of unplanned 30-day readmissions after transsphenoidal pituitary surgery.

BACKGROUND: Transsphenoidal pituitary surgery has evolved into a safe procedure with shorter hospitalizations, yet unplanned readmissions remain a quality measure for which there is a paucity of data. We sought to examine rates, timing, etiologic factors, and costs surrounding readmission after transsphenoidal pituitary surgery. METHODS: The Nationwide Readmissions Database (NRD) was queried for patients who underwent transsphenoidal pituitary between January 2013 and November 2013. Patient, procedure, admission, and hospital-level characteristics were compared for patients with and without unplanned 30-day readmission. Multivariate logistic regression was used to identify readmission predictors. A total of 8546 patients were included in this retrospective study. RESULTS: A total of 8546 patients with a median age of 54 years and female predominance were identified, with 742 patients experiencing at least 1 unplanned readmission within 30 days of index admission. Hypertension, hypothyroidism, diabetes, and obesity were common comorbidities among readmitted patients. Readmission was most frequently because of nervous system complications, followed by neurohypophyseal or electrolyte disorders, cerebrospinal fluid leak, hemorrhage, and meningitis. Median length and cost of stay of index admission was greater in the readmission group (p < 0.001). Fluid and electrolyte disorders as well as neurologic disease (most commonly epilepsy or convulsions) present on initial admission were predictive of length of initial stay and readmission (p < 0.001). Median readmission cost was $7723 and was expected to occur within 7 days. CONCLUSION: Approximately 8.7% of patients undergoing transsphenoidal pituitary surgery experience an unplanned readmission within 30 days of discharge. Risk factors identified should be considered to reduce preventable readmissions and identify medically complex patients.

Treatment outcomes of patients with primary squamous cell carcinoma of the retromolar trigone.

OBJECTIVES/HYPOTHESIS: Squamous cell carcinoma of the retromolar trigone (RMT SCC) is a relatively uncommon primary site for oral cavity malignancy. However, given its proximity to the mandible and buccal mucosa, RMT SCC typically exhibits early invasion and generally presents at an advanced stage. Large-sample studies are needed to assess the epidemiology and clinical outcomes of this tumor. Our aim was to describe the determinants of survival in patients with RMT SCC. STUDY DESIGN: Retrospective cohort study. METHODS: Retrospective, population-based cohort study of patients in the Surveillance, Epidemiology, and End Results tumor registry who were diagnosed with RMT SCC from 1973 to 2012. Primary endpoints were overall survival (OS) and disease-specific survival (DSS). RESULTS: A total of 4,022 cases of RMT SCC were identified. The mean age at diagnosis was 65 years. Thirty-nine percent of cases presented with stage IV disease. The median OS by stages I to IV were 73.7, 52.4, 27.5, and 23.4 months, respectively (P < .05). Overall, 34.3% of patients underwent surgery, 23.5% received radiation therapy, and 34.1% had both surgical and radiation therapy. On multivariate analysis, advanced age, greater tumor size, and advanced stage were associated with worse OS and DSS (P < .05), surgery predicted improved OS and DSS (P < .05), and radiation therapy predicted improved OS only (P < .05). CONCLUSIONS: RMT SCC is an aggressive malignancy that portends a poor prognosis, though early-stage tumors (stages I and II) have significantly improved survival. Any surgical intervention independently predicted higher survival outcomes. There may be a role of dual modality approaches, particularly for larger tumors. LEVEL OF EVIDENCE: 4 Laryngoscope, 128:2740-2744, 2018.

The microRNA-200/Zeb1 axis regulates ECM-dependent ß1-integrin/FAK signaling, cancer cell invasion and metastasis through CRKL.

Tumor cell metastasis is a complex process that has been mechanistically linked to the epithelial-mesenchymal transition (EMT). The double-negative feedback loop between the microRNA-200 family and the Zeb1 transcriptional repressor is a master EMT regulator, but there is incomplete understanding of how miR-200 suppresses invasion. Our recent efforts have focused on the tumor cell-matrix interactions essential to tumor cell activation. Herein we utilized both our Kras/p53 mutant mouse model and human lung cancer cell lines to demonstrate that upon miR-200 loss integrin ß1-collagen I interactions drive 3D in vitro migration/invasion and in vivo metastases. Zeb1-dependent EMT enhances tumor cell responsiveness to the ECM composition and activates FAK/Src pathway signaling by de-repression of the direct miR-200 target, CRKL. We demonstrate that CRKL serves as an adaptor molecule to facilitate focal adhesion formation, mediates outside-in signaling through Itgß1 to drive cell invasion, and inside-out signaling that maintains tumor cell-matrix contacts required for cell invasion. Importantly, CRKL levels in pan-cancer TCGA analyses were predictive of survival and CRKL knockdown suppressed experimental metastases in vivo without affecting primary tumor growth. Our findings highlight the critical ECM-tumor cell interactions regulated by miR-200/Zeb1-dependent EMT that activate intracellular signaling pathways responsible for tumor cell invasion and metastasis.

International cooperation to improve access to and sustain effectiveness of antimicrobials.

Securing access to effective antimicrobials is one of the greatest challenges today. Until now, efforts to address this issue have been isolated and uncoordinated, with little focus on sustainable and international solutions. Global collective action is necessary to improve access to life-saving antimicrobials, conserving them, and ensuring continued innovation. Access, conservation, and innovation are beneficial when achieved independently, but much more effective and sustainable if implemented in concert within and across countries. WHO alone will not be able to drive these actions. It will require a multisector response (including the health, agriculture, and veterinary sectors), global coordination, and financing mechanisms with sufficient mandates, authority, resources, and power. Fortunately, securing access to effective antimicrobials has finally gained a place on the global political agenda, and we call on policy makers to develop, endorse, and finance new global institutional arrangements that can ensure robust implementation and bold collective action.

Strategies for achieving global collective action on antimicrobial resistance.

Global governance and market failures mean that it is not possible to ensure access to antimicrobial medicines of sustainable effectiveness. Many people work to overcome these failures, but their institutions and initiatives are insufficiently coordinated, led and financed. Options for promoting global collective action on antimicrobial access and effectiveness include building institutions, crafting incentives and mobilizing interests. No single option is sufficient to tackle all the challenges associated with antimicrobial resistance. Promising institutional options include monitored milestones and an inter-agency task force. A global pooled fund could be used to craft incentives and a special representative nominated as an interest mobilizer. There are three policy components to the problem of antimicrobials--ensuring access, conservation and innovation. To address all three components, the right mix of options needs to be matched with an effective forum and may need to be supported by an international legal framework.

Les dysfonctionnements de la gouvernance et du marché à l'échelle mondiale se traduisent par une impossibilité de garantir l'accès à des médicaments antimicrobiens durablement efficaces. De nombreuses personnes s'emploient à pallier ces dysfonctionnements, mais leurs institutions et leurs initiatives manquent de coordination, de direction et de moyens financiers. La création d'institutions, l'élaboration de mesures d'incitation et la mobilisation des parties intéressées font partie des options possibles pour promouvoir une action collective mondiale sur l'accès aux antimicrobiens et sur leur efficacité. Aucune option isolée ne suffira à venir à bout de tous les problèmes associés à la résistance aux antimicrobiens. Parmi les options institutionnelles prometteuses, il convient de mentionner le suivi des étapes importantes et une équipe spéciale interorganisations. Des fonds mis en commun à l'échelle mondiale pourraient être utilisés pour élaborer des mesures d'incitation et un représentant spécial pourrait être chargé de mobiliser les parties intéressées. Le problème des antimicrobiens comporte trois aspects stratégiques: garantir l'accès, la conservation et l'innovation. Pour agir à l'égard de ces trois aspects, il est nécessaire d'associer les options, harmonieusement combinées, à une structure efficace et, peut-être, de les inscrire dans un cadre juridique international.

Los fracasos de gobernanza mundial y de los mercados significan que no es posible garantizar el acceso a medicamentos antimicrobianos de efectividad sostenible. Muchas personas trabajan para solucionar estos problemas, pero sus instituciones e iniciativas no están lo suficientemente coordinadas, guiadas y financiadas. Las opciones para promocionar una acción colectiva global en cuanto al acceso a los antimicrobianos y la efectividad incluyen la creación de instituciones, la elaboración de incentivos y la movilización de intereses. Ninguna opción por sí sola es suficiente para afrontar todos los desafíos asociados con la resistencia a los antimicrobianos. Las opciones institucionales prometedoras incluyen hitos supervisados y un grupo de acción interinstitucional. Se podría utilizar un fondo combinado global para elaborar incentivos y nominar un representante especial como un movilizador de intereses. El problema de los antimicrobianos tiene tres componentes de las políticas: asegurar el acceso, la conservación y la innovación. Para abordar los tres componentes se necesita que la mezcla correcta de opciones se una a un foro efectivo, y podría necesitar el apoyo de un marco legal internacional.