Circulating microRNAs modulating glycolysis as non-invasive prognostic biomarkers of HNSCC.

BACKGROUND: The identification of prognostic non-invasive biomarkers is a priority for cancer patients' care. Circulating microRNA (miRNAs) have been described in numerous human malignancies as diagnostic, prognostic, and therapeutic cancer biomarkers. The aim of our study was to analyze the expression profile of a set of miRNAs, involved in the modulation of the glycolytic pathway, as prognostic factors in human head and neck squamous cell carcinomas (HNSCC). METHODS: Serum samples of 54 patients with untreated HNSCC were obtained at the time of diagnosis. The prognostic value of circulating miR-26b, miR-124, miR-155 and miR-375 was evaluated towards disease-free survival. RESULTS: We found that there were optimal miRNAs cut-off values for lower risk of recurrence in HNSCC patients. Kaplan-Meier curves showed that higher levels of miR-26b and lower levels of miR-155 were associated with better disease-free survival rates. In the multivariate analysis, patients with serum miR-26b > 0.062 and miR-155 < 0.159 presented more than 2.9 times lower risk of poor outcome. CONCLUSION: Our results suggest that two miRNAs that modulate the glycolytic pathway, miR-26b and miR-155, are independently associated with the risk of recurrence in patients with HNSCC. The overall results in this study supports the evidence that the glucose homeostasis may be a target to improve the outcomes for patients with HNSCC. LEVEL OF EVIDENCE: Individual retrospective cohort study (2b).

Intra and interobserver agreement of narrow band imaging for the detection of head and neck tumors.

BACKGROUND: Narrow band imaging (NBI) in combination with white light endoscopy (WLE) has improved the accuracy for the diagnosis and follow-up of head and neck carcinomas by identifying changes in the vascular patterns of the mucosa. However, NBI evaluation is explorer-dependent and may be influenced by the learning curve. The aim of this study is to assess the intra and interobserver agreement of NBI and WLE at the office, under local anaesthesia, by either experienced or non-experienced observers. METHODS: Eighty-seven images of head and neck lesions were routinely collected under WLE and NBI. A group of three experienced otolaryngologists and three medical students assessed the images after a brief training. No additional patient information was provided. The same protocol was repeated after three weeks. Intra and interobserver agreement were calculated with the kappa index. RESULTS: NBI intraobserver agreement was substantial (κ = 0.62) and better than with WLE alone, which was moderate (κ = 0.57) in both groups. Interobserver agreement was moderate with WLE (κ = 0.58) and substantial with NBI (κ = 0.63). Both groups improved intraobserver and interobserver agreement with the implementation of NBI. CONCLUSIONS: Intra and interobserver agreement with NBI for the evaluation of head and neck lesions are substantial, and improve the results of WLE alone in both, professionals and trainees.

Prognostic value of CD45 transcriptional expression in head and neck cancer.

INTRODUCTION: Tumor-infiltrating lymphocytes (TILs) have a recognized antitumor activity in head and neck squamous cell carcinoma (HNSCC). CD45 is one of the most highly expressed proteins in lymphocytes. We carry out a study to assess the prognostic value of transcriptional expression of CD45 in HNSCC. MATERIAL AND METHODS: We determined the transcriptional expression of CD45 in 160 consecutive HNSCC patients and compared the TIL values according to the CD45 expression. RESULTS: Five-year disease-free survival for patients with a high transcriptional expression of CD45 (n = 107) was 62.4% and for patients with a low expression (n = 53) it was 36.2% (P = 0.003). Patients with a high expression of CD45 had a better local recurrence-free survival and disease-specific survival. The results of a multivariate analysis showed that patients with a low expression of CD45 had 2.0-fold high risk of recurrence (95% CI 1.2-3.2, P = 0.003). In oropharyngeal carcinomas, HPV-positive tumors showed a higher transcriptional CD45 expression than HPV-negative tumors. Tumors with high CD45 expression had immunohistochemical TIL scores significantly higher than those with low CD45 expression. CONCLUSION: According to our results, CD45 expression is a potential marker for tumor outcome in HNSCC patients.

Prostacyclin-synthase expression in head and neck carcinoma patients and its prognostic value in the response to radiotherapy.

Prostacyclin (PGI2 ) plays a role in cancer progression but the mechanism is currently poorly understood. Additionally, no data are available about the prognostic value of the PGI2 pathway in head and neck squamous cell carcinoma (HNSCC) therapy. We evaluated the expression of the PGI2 pathway in HNSCC patients. PGI2 production and PGI synthase (PGIS) expression, in terms of mRNA (RT-PCR) and protein (immunoblotting), were lower in tumour samples than in non-tumoural mucosa, whereas, as expected, COX-2 expression was increased in HNSCC tumour samples. Using local control of the tumour after radiotherapy or chemoradiotherapy as a dependent variable, patients were classified into two categories of PGIS transcript levels. The high-PGIS group had a significantly lower frequency of local and distant failure than the low-PGIS group, and the 5-year cancer-specific survival was higher [90.2% (95% CI 81.0-99.4%) versus 60.5% (95% CI 44.4-76.6%)]. None of the four HNSCC cell lines analysed expressed PGIS and therefore they did not produce PGI2 . However, HNSCC-conditioned media enhanced PGI2 production in endothelial cells (ECs). The stable analogue of PGI2 , carbaprostacyclin (cPGI2 ), exerted little effect on HNSCC cell line migration, and no effect on cell cycle distribution or proliferation rate after radiation injury was observed. Nevertheless, cPGI2 promoted EP-4-dependent in vitro angiogenesis. Von Willebrand factor expression (EC marker) and capillary density were significantly higher in the group of patients with high expression of PGIS. Our results indicate that PGIS expression was associated with radiotherapy efficiency. Although we do not provide direct evidence of a relationship between tumour vascularization and radiotherapy efficiency, our results suggest that the effect of PGI2 is related to its ability to promote vascularization. These results also support the concept that co-adjuvant therapy with PGIS enhancers, such as retinoids, could have therapeutic value for HNSCC treatment.

Low blood levels of sTWEAK are related to locoregional failure in head and neck cancer.

Identifying serum pre-treatment molecular markers that can predict response to therapy is of great interest in head and neck oncology and is required to develop personalized treatments that maximize survival while minimizing morbidity. The main aim was to investigate the potential prognostic significance of tumor necrosis factor-like weak inducer of apoptosis (TWEAK), and its receptors, fibroblast growth factor-inducible 14 (Fn14) and CD163, in head and neck squamous cell carcinoma (HNSCC). The study comprised 37 consecutive patients with pathologically confirmed, untreated HNSCC. Serum and tissue samples from these patients were available for study. We determined sTWEAK and sCD163 levels in serum from 37 HNSCC patients by ELISA. TWEAK, CD163, Fn14 and TNF-α gene expression were detected by real-time RT-PCR in 111 matched tissue samples (tumoral, adjacent and distal/normal mucosa). Our results showed a significant relationship between low sTWEAK levels and poor locoregional control of the disease. Kaplan-Meier curves indicated that the locoregional recurrence-free survival rate in patients with low sTWEAK circulating levels was significantly lower than in patients with high levels, and that high CD136/TWEAK expression ratio in tumors was also related to poor prognosis. sTWEAK pre-treatment serum levels might be used as prognostic non-invasive biomarkers for locoregional control in patients with HNSCC. Future investigations are warranted to determine the potential prognostic significance of this non-invasive biomarker in the rapid discrimination according to the locoregional control achieved in patients who received a non-surgical organ preservation treatment.

Predictive capacity for local disease control of neogenin-1 (NEO1) transcriptional expression in patients with head and neck squamous cell carcinoma.

PURPOSE: To analyze the predictive capacity for local disease control of the transcriptional expression of neogenin-1 (NEO1) gene in patients with head and neck squamous cell carcinoma (HNSCC). METHODS/PATIENTS: A retrospective study was performed on tumor biopsies from 107 patients with HNSCC treated surgically. The transcriptional expression of NEO1 was determined by RT-PCR. NEO1 transcriptional expression value was categorized according to local disease control by recursive partitioning analysis. RESULTS: Lower NEO1 transcriptional expression was associated with worse local control after surgical treatment. Patients with lower NEO1 expression (n = 25, 23.4%) had a 5-year local recurrence-free survival of 61.8% (95% CI: 42.1-81.5%), while patients with higher NEO1 expression (n = 82, 76.6%) had a 5-year local recurrence-free survival of 85.6% (95% CI: 77.6-93.6%), (P = 0.003). According to the result of multivariable analysis, patients with lower NEO1 expression had a 2.7-fold increased risk of local tumor recurrence (95% CI: 1.0-7.0, P = 0.043) compared to patients with higher NEO1 expression. CONCLUSIONS: HNSCC patients with a lower transcriptional expression of NEO1 have a significantly higher risk of local recurrence after surgical treatment.

Survivin/BIRC5 as a novel molecular effector at the crossroads of glucose metabolism and radioresistance in head and neck squamous cell carcinoma.

BACKGROUND: Metabolic reprogramming and abnormal glucose metabolism are hallmarks of head and neck squamous cell carcinoma (HNSCC). Certain oncogenes can promote cancer-related metabolic changes, but understanding their crosstalk in HNSCC biology and treatment is essential for identifying predictive biomarkers and developing target therapies. METHODS: We assessed the value of survivin/BIRC5 as a radioresistance factor potentially modulated by glucose for predicting therapeutic sensitivity and prognosis of HNSCC in a cohort of 32 patients. Additionally, we conducted in vitro experiments to explore the role of survivin/BIRC5 in glucose metabolism concerning radiation response. RESULTS: Tumoral BIRC5 expression is associated with serum glucose and predicts locoregional disease-free survival and lower BIRC5 mRNA levels are associated with better outcomes. Upregulation of BIRC5 by radiation depends on glucose levels and provokes a pro-tumoral and radioresistant phenotype in surviving cells. CONCLUSIONS: Survivin/BIRC5 might be independently associated with the risk of recurrence in patients with HNSCC.

The Impact of the COVID-19 Pandemic on Incidence and Short-Term Survival for Common Solid Tumours in the United Kingdom: A Cohort Analysis.

Purpose: The COVID-19 pandemic profoundly affected healthcare systems and patients. There is a need to comprehend the collateral effects of the pandemic on non-communicable diseases. We examined the impact of the pandemic on short-term survival for common solid tumours, including breast, colorectal, head and neck, liver, lung, oesophageal, pancreatic, prostate, and stomach cancer in the UK. Methods: This was a population-based cohort study of electronic health records from the UK primary care Clinical Practice Research Datalink GOLD database. In sum, 12,259,744 eligible patients aged ≥18 years with ≥1 year's history identified from January 2000 to December 2022 were included. We estimated age-standardised incidence and short-term (one- and two-year) survival for several common cancers from 2000 to 2019 (in five-year strata) and compared these to 2020-2022 using the Kaplan-Meier method. Results: Incidence decreased for most cancers in 2020 and recovered to different extents in 2021-2022. Short-term survival improved for most cancers between 2000 and 2019, but then declined, albeit minimally, for those diagnosed in 2020-2022. This was most pronounced for colorectal cancer, with one-year survival falling from 78.8% (95% CI 78%-79.6%) in 2015-2019 to 77% (95% CI 75.6-78.3%) for those diagnosed in 2020-2022. Conclusion: Short-term survival for many cancers was impacted, albeit minimally, by the pandemic in the UK, with reductions in survivorship from colorectal cancer equivalent to returning to the mortality seen in the first decade of the 2000s. While data on longer-term survival are needed to fully comprehend the impact of COVID-19 on cancer care, our findings illustrate the need for an urgent and substantial commitment from the UK National Health Service to address the existing backlog in cancer screening and diagnostic procedures to improve cancer care and mortality.

The current situation of tutoring in specialised training in otorhinolaryngology-head and neck surgery in Spain. Where are we? Where do we want to go?

BACKGROUND AND OBJECTIVE: There is great heterogeneity in the methodology and evaluation in specialized health training (SHT) in otorhinolaryngology in our country. The figure of the resident tutor is the cornerstone on which the ESF system is based and the regulation and recognition of this figure varies. This article aims to take a snapshot of the current situation of the ESF in Spain and to describe the activity of tutors. MATERIALS AND METHODS: During the month of September 2023, a survey was sent in a Google Forms® format through the Spanish Society of Otolaryngology and Head and Neck Surgery. The survey consisted of 8 multiple-choice questions and 4 questions in which they were asked to rank a series of 5 weaknesses, threats, opportunities and strengths selected by the authors, in order to perform a SWOT analysis. RESULTS: A total of 103 responses were obtained, of which 81 corresponded to accredited tutors. 63% of the tutors indicated that they did not have enough time to carry out their teaching work and 48% did not carry out a regular assessment of their residents. 64% of the tutors believe that the quality of otorhinolaryngology training in Spain is good and 61% are satisfied with their job as tutors. The main weakness was the short duration of the training programme, and the pressure of care was found to be the main threat. An experienced training system was considered the main strength and the creation of a national network of tutors was seen as an opportunity for improvement. CONCLUSIONS: The creation of a common and transversal otorhinolaryngology training pathway for all accredited centres and the creation of a network of mentors and residents are necessary to address the problems of SHT. The role of the tutor must be recognised and reinforced to improve specialist training.

Relationship between transcriptional expression of pyruvate dehydrogenase and local control of disease in patients with oral cavity carcinomas.

BACKGROUND: The altered cellular metabolism is one of the hallmarks of the cancer cells, favoring the process of aerobic glycolysis, known as the Warburg effect. The pyruvate dehydrogenase (PDH) complex is one of the elements involved in this metabolic process. The present study aims to evaluate the relationship between the transcriptional expression of PDHB and the risk of local recurrence in patients with oral cavity carcinomas. METHODS: We determined the transcriptional expression of PDHB in biopsies from 41 patients with oral cavity carcinomas treated with surgery. The PDHB expression was categorized according to the local control of the disease with a recursive partitioning analysis. RESULTS: During the follow-up period 13 patients (31.7%) had a local recurrence of the tumor. Considering local disease control as the dependent variable, the recursive partitioning analysis classified the patients in two categories according to high (n=16, 39.0%) or low (n=25, 61.0%) PDHB expression. Five-year local recurrence-free survival for patients with high PDHB expression was 84.8% (95% CI: 65.2-100%), and for patients with low expression it was 54.3% (95% CI: 34.3-74.2 %) (P=0.034). The results of multivariate analysis showed that patients with a low PDHB expression had a 4.90 times higher risk of local recurrence of the tumor (95% CI: 1.02-22.68, P=0.042). CONCLUSION: There is a relationship between the metabolic characteristics of the tumor and its aggressiveness. According to our results, patients with oral cavity carcinomas with low transcriptional expression levels of PDHB have a significantly higher risk of local tumor recurrence.

Interaction between head and neck squamous cell carcinoma cells and fibroblasts in the biosynthesis of PGE2.

Prostaglandin (PG)E(2) is relevant in tumor biology, and interactions between tumor and stroma cells dramatically influence tumor progression. We tested the hypothesis that cross-talk between head and neck squamous cell carcinoma (HNSCC) cells and fibroblasts could substantially enhance PGE(2) biosynthesis. We observed an enhanced production of PGE(2) in cocultures of HNSCC cell lines and fibroblasts, which was consistent with an upregulation of COX-2 and microsomal PGE-synthase-1 (mPGES-1) in fibroblasts. In cultured endothelial cells, medium from fibroblasts treated with tumor cell-conditioned medium induced in vitro angiogenesis, and in tumor cell induced migration and proliferation, these effects were sensitive to PGs inhibition. Proteomic analysis shows that tumor cells released IL-1, and tumor cell-induced COX-2 and mPGES-1 were suppressed by the IL-1-receptor antagonist. IL-1α levels were higher than those of IL-1ß in the tumor cell-conditioning medium and in the secretion from samples obtained from 20 patients with HNSCC. Fractionation of tumor cell-conditioning media indicated that tumor cells secreted mature and unprocessed forms of IL-1. Our results support the concept that tumor-associated fibroblasts are a relevant source of PGE(2) in the tumor mass. Because mPGES-1 seems to be essential for a substantial biosynthesis of PGE(2), these findings also strengthen the concept that mPGES-1 may be \a target for therapeutic intervention in patients with HNSCC.

Prognostic capacity of the transcriptional expression of lactate dehydrogenase A in patients with head and neck squamous cell carcinoma.

BACKGROUND: To analyze the relationship between the transcriptional expression of lactate dehydrogenase A (LDHA) and the disease control in patients with a head and squamous cell carcinoma (HNSCC). METHODS: We determined the transcriptional expression of LDHA in 110 HNSCC patients treated with surgery. RESULTS: Five-year disease-free survival for patients with a high transcriptional expression of LDHA (n = 51) was 39.2% (95% confidence interval [CI]: 25.3%-53.1%), and for patients with a low expression (n = 59), it was 63.6% (95% CI: 51.1%-76.1%) (p = 0.004). According to the results of a multivariate analysis, patients with a high transcriptional expression of LDHA had a 3.4-fold increased risk of tumor recurrence. Patients with a high transcriptional expression of LDHA tended to show a higher intensity of immunohistochemical expression of LDHA at the tumor cells (p = 0.086). CONCLUSION: In HNSCC patients treated with surgery, a high transcriptional expression of LDHA was associated with a significant decrease in disease-free survival.

Semaphorin-3F/Neuropilin-2 Transcriptional Expression as a Predictive Biomarker of Occult Lymph Node Metastases in HNSCC.

The expression of the semaphorin-3F (SEMA3F) and neuropilin-2 (NRP2) is involved in the regulation of lymphangiogenesis. The present study analyzes the relationship between the transcriptional expression of the SEMA3F-NRP2 genes and the presence of occult lymph node metastases in patients with cN0 head and neck squamous cell carcinomas. We analyzed the transcriptional expression of SEMA3F and NRP2 in a cohort of 53 patients with cN0 squamous cell carcinoma treated with an elective neck dissection. Occult lymph node metastases were found in 37.7% of the patients. Patients with occult lymph node metastases (cN0/pN+) had significantly lower SEMA3F expression values than patients without lymph node involvement (cN0/pN0). Considering the expression of the SEMA3F-NRP2 genes, patients were classified into two groups according to the risk of occult nodal metastasis: Group 1 (n = 34), high SEMA3F/low NRP2 expression, with a low risk of occult nodal involvement (14.7% cN0/pN+); Group 2 (n = 19), low SEMA3F or high SEMA3F/high NRP2 expression, with a high risk of occult nodal involvement (78.9% cN0/pN+). Multivariate analysis showed that patients in Group 2 had a 26.2 higher risk of lymph node involvement than patients in Group 1. There was a significant relationship between the transcriptional expression values of the SEMA3F-NRP2 genes and the risk of occult nodal metastases.

Predictive capacity of IL-8 expression in head and neck squamous carcinoma patients treated with radiotherapy or chemoradiotherapy.

OBJECTIVE: To analyse the relationship between the transcriptional expression of interleukin-8 (IL-8) and response to treatment with radiotherapy or chemo-radiotherapy in patients with squamous cell carcinoma of the head and neck (SCCHN). MATERIAL AND METHODS: Retrospective study from tumour biopsies obtained before a treatment with radiotherapy or chemo-radiotherapy in 87 patients with SCCHN. We had a sample of healthy mucosa in 35 cases. We determined the transcriptional expression of IL-8 with RT-PCR. The transcriptional expression of IL-8 was categorized according to the local control of the disease with a recursive partitioning analysis. RESULTS: The transcriptional expression of IL-8 in tumour tissue was about 50 times higher than that in the samples of healthy mucosa. Patients with a high transcriptional expression of IL-8 (n = 56) had a 5-year local recurrence-free survival of 65.6%, and for patients with low expression (n = 31) it was 90.2% (P = 0.017). According to the results of a multivariate analysis, patients with high expression of IL-8 had a 4.1 higher risk of local recurrence of the tumour. CONCLUSIONS: SCCHN have a significant increase in transcriptional expression of IL-8 in relation to non-tumour tissue. Tumours with high IL-8 expression have an increased risk of local recurrence after treatment with radiotherapy or chemo-radiotherapy.

The aspartate aminotransaminase/alanine aminotransaminase (De Ritis) ratio predicts sensitivity to radiotherapy in head and neck carcinoma patients.

BACKGROUND: The aim of this study is to evaluate the relationship between the aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) ratio and local disease control in patients with head and neck squamous cell carcinomas (HNSCC) treated with radiotherapy/chemoradiotherapy. METHODS: We calculated the pre-treatment AST/ALT ratio in 670 patients with HNSCC treated with radiotherapy (n = 309, 46.1%) or chemoradiotherapy (n = 361, 53.9%). RESULTS: Five-year local recurrence-free survival for patients with a low AST/ALT ratio value (n = 529, 79.0%) was 75.0% (95% CI: 71.1-78.9), and for patients with a high value (n = 141, 21.0%) it was 53.4% (CI 95: 44.4-62.4) (p = 0.0001). In a multivariable analysis, patients with a high ratio had nearly twice the risk of having a local tumor recurrence (HR 1.97, 95% CI 1.42-2.75, p = 0.0001). CONCLUSION: The AST/ALT ratio was independently associated with the risk of local recurrence in patients with HNSCC treated with radiotherapy or chemoradiotherapy.

Transoral laser microsurgery in locally advanced laryngeal cancer: Prognostic impact of anterior versus posterior compartments.

BACKGROUND: To evaluate the importance of larynx compartments in the prognosis of T3-T4a laryngeal cancer treated with transoral laser microsurgery. METHODS: Two hundred and two consecutive pT3-T4a larynx carcinomas. Pre-epiglottic space involvement, anterior and posterior paraglottic space (PGS) involvement, vocal cord, and arytenoid mobility were determined. Local control with laser (LC), overall survival (OS), disease-specific survival (DSS), and laryngectomy-free survival (LFS) were evaluated. RESULTS: The lowest LC was found in tumors with fixed arytenoid. In the multivariate analysis, positive margins (hazard ratio [HR] = 0.289 [0.085-0.979]) and anterior (HR = 0.278 [0.128-0.605]) and posterior (HR = 0.269 [0.115-0.630]) PGS invasion were independent factors of a reduced LC. Anterior (HR = 3.613 [1.537-8.495]) and posterior (HR = 5.195 [2.167-12.455]) PGS involvement were independent factors of total laryngectomy. Five-year OS, DSS, and LFS rates were 63.9%, 77.5%, and 77.5%, respectively. Patients with posterior PGS presented a reduced 5-year LFS. CONCLUSIONS: Tumor classification according to laryngeal compartmentalization depicts strong correlation with LC and LFS.

Succinate Pathway in Head and Neck Squamous Cell Carcinoma: Potential as a Diagnostic and Prognostic Marker.

Head and neck squamous cell carcinoma (HNSCC) is characterized by high rates of mortality and treatment-related morbidity, underscoring the urgent need for innovative and safe treatment strategies and diagnosis practices. Mitochondrial dysfunction is a hallmark of cancer and can lead to the accumulation of tricarboxylic acid cycle intermediates, such as succinate, which function as oncometabolites. In addition to its role in cancer development through epigenetic events, succinate is an extracellular signal transducer that modulates immune response, angiogenesis and cell invasion by activating its cognate receptor SUCNR1. Here, we explored the potential value of the circulating succinate and related genes in HNSCC diagnosis and prognosis. We determined the succinate levels in the serum of 66 pathologically confirmed, untreated patients with HNSCC and 20 healthy controls. We also surveyed the expression of the genes related to succinate metabolism and signaling in tumoral and nontumoral adjacent tissue and in normal mucosa from 50 patients. Finally, we performed immunohistochemical analysis of SUCNR1 in mucosal samples. The results showed that the circulating levels of succinate were higher in patients with HNSCC than in the healthy controls. Additionally, the expression of SUCNR1, HIF-1α, succinate dehydrogenase (SDH) A, and SDHB was higher in the tumor tissue than in the matched normal mucosa. Consistent with this, immunohistochemical analysis revealed an increase in SUCNR1 protein expression in tumoral and nontumoral adjacent tissue. High SUCNR1 and SDHA expression levels were associated with poor locoregional control, and the locoregional recurrence-free survival rate was significantly lower in patients with high SUCNR1 and SDHA expression than in their peers with lower levels (77.1% [95% CI: 48.9-100.0] vs. 16.7% [95% CI: 0.0-44.4], p = 0.018). Thus, the circulating succinate levels are elevated in HNSCC and high SUCNR1/SDHA expression predicts poor locoregional disease-free survival, identifying this oncometabolite as a potentially valuable noninvasive biomarker for HNSCC diagnosis and prognosis.

Timing of elective tracheotomy and duration of mechanical ventilation among patients admitted to intensive care with severe COVID-19: A multicenter prospective cohort study.

BACKGROUND: Optimal timing for tracheotomy for critically ill COVID-19 patients requiring invasive mechanical ventilation (IMV) is not established. METHODS: Multicenter prospective cohort including all COVID-19 patients admitted to intensive care units (ICUs) in 36 hospitals who required tracheotomy during first pandemic wave. With a target emulation trial framework, we studied the causal effects of early (7-10 days) versus late (>10 days) tracheotomy (LT) on time from tracheotomy to weaning, postoperative mortality, and tracheotomy complications. RESULTS: Of 696 patients, 20.4% received early tracheotomy (ET). ET was associated with faster weaning (hazard ratio [HR] [95% confidence interval, CI]: 1.25 [1.00-1.56]) without differences in mortality (HR [95% CI]: 0.85 [0.60-1.21]) or complications (adjusted rate ratio [95% CI]: 0.56 [0.23-1.33]). CONCLUSIONS: ET had a similar or lower post-tracheotomy weaning time than LT, potentially shortening IMV and ICU stays, without changing complication or mortality rates in COVID-19 patients.

Use of dialysis, tracheostomy, and extracorporeal membrane oxygenation among 842,928 patients hospitalized with COVID-19 in the United States.

OBJECTIVE: To estimate the proportion of patients hospitalized with COVID-19 who undergo dialysis, tracheostomy, and extracorporeal membrane oxygenation (ECMO). DESIGN: A network cohort study. SETTING: Seven databases from the United States containing routinely-collected patient data: HealthVerity, Premier, IQVIA Hospital CDM, IQVIA Open Claims, Optum EHR, Optum SES, and VA-OMOP. PATIENTS: Patients hospitalized with a clinical diagnosis or a positive test result for COVID-19. INTERVENTIONS: Dialysis, tracheostomy, and ECMO. MEASUREMENTS AND MAIN RESULTS: 842,928 patients hospitalized with COVID-19 were included (22,887 from HealthVerity, 77,853 from IQVIA Hospital CDM, 533,997 from IQVIA Open Claims, 36,717 from Optum EHR, 4,336 from OPTUM SES, 156,187 from Premier, and 10,951 from VA-OMOP). Across the six databases, 35,192 (4.17% [95% CI: 4.13% to 4.22%]) patients received dialysis, 6,950 (0.82% [0.81% to 0.84%]) had a tracheostomy, and 1,568 (0.19% [95% CI: 0.18% to 0.20%]) patients underwent ECMO over the 30 days following hospitalization. Use of ECMO was more common among patients who were younger, male, and with fewer comorbidities. Tracheostomy was broadly used for a similar proportion of patients regardless of age, sex, or comorbidity. While dialysis was generally used for a similar proportion among younger and older patients, it was more frequent among male patients and among those with chronic kidney disease. CONCLUSION: Use of dialysis among those hospitalized with COVID-19 is high at around 4%. Although less than one percent of patients undergo tracheostomy and ECMO, the absolute numbers of patients who have undergone these interventions is substantial.

Transoral reconstruction of oropharyngeal tumors. The Hospital Clínic algorithm.

Transoral approaches to the oropharynx have evolved rapidly in the past years. The development of technical instruments such as specific oropharyngeal retractors, 2D and 3D endoscopic systems, robotic platforms, and a combination of energies, has facilitated transoral resection and bleeding control. This new scenario has raised the need for new reconstructive alternatives after resection to achieve adequate oncologic and functional outcomes. The purpose of this work is to provide a guiding algorithm to plan the transoral resection and reconstruction of oropharyngeal tumors, based on the known anatomical landmarks that determine functionality after surgery. The Hospital Clínic transoral resection and reconstruction classification of the oropharynx (HC-TRR oropharynx) is based on the size and location of the defect after the surgery and considers the scenario of salvage surgery after radiotherapy failure. The reconstructive algorithm is adapted to the concept of a reconstructive ladder and represents a non-dogmatic and flexible vision that may facilitate clinical decision making.