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Human Papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) remains a challenging malignancy, with radiotherapy, alone or combined with immune checkpoint inhibitors, often failing to achieve durable disease control. Here, by conducting longitudinal multi-omic analyses of pre- and post-radiation biopsies from patients receiving a pre-operative hypofractionated radiation regimen, we uncover that radiation rapidly depletes a subpopulation of tumor-infiltrating lymphocytes (TIL), characterized by a proliferative, cytotoxic, and tissue-resident gene signature (T Prolif_Tox ). We provide multi-dimensional evidence for tumor antigen-specificity of T Prolif_Tox clonotypes and show that post-radiation tumors are instead repopulated by regulatory and non-specific clones. Finally, TIL depletion correlates with radiorecurrent disease after conventional radiation, emphasizing the potential impact of radiation-induced TIL loss regardless of fractionation. Thus, this study provides key insights into radiotherapy-induced alterations in the immune microenvironment that drive immunologic radioresistance and proposes restoring tumor antigen-specific T cell clonotypes as a strategy to improve radioimmunotherapy responses in HNSCC. Combining radiation therapy (RT) with immunotherapy has had limited therapeutic benefits in the treatment of head and neck cancer (HNSCC). Here, the authors present a multi-omics analysis of patient biopsies pre- and post- hypofractionated RT and uncover RT-mediated depletion of tumor-reactive CD8+ T cells as the underlying cause of immunologic radioresistance in HNSCC.

Objectives: Tracheoesophageal puncture (TEP) and prosthesis insertion is a well-established method of voice rehabilitation after laryngectomy. Maintenance of the prosthesis and tract can be challenging, and reflux to the TEP site has been proposed as a cause. The sites of TEP were evaluated for the presence of pepsin in tissue biopsy specimens and tract secretions to explore this association. Methods: Patients with TEP were interviewed for a history of symptoms related to reflux, medication use history, TEP voice quality, and incidence of TEP complications. Tissue biopsy specimens and tract secretions were obtained from TEP sites and analyzed for the presence of pepsin via sodium dodecyl sulfate–polyacrylamide gel electrophoresis Western blot analysis. Results: Twelve of 17 patients (47%) had some history of preoperative or postoperative symptoms of gastroesophageal reflux disease or laryngopharyngeal reflux. Pepsin was present within the TEP site in a total of 10 of 17 patients (58%; 7 of 17 tissue biopsy specimens and 6 of 7 secretion samples). There were no statistically significant associations between the presence of pepsin and sex, reflux history, use of acid suppressive medicine, or time since laryngectomy. Conclusions: Reflux with subsequent pepsin deposition into the TEP tract occurs in a majority of laryngectomy patients. Further studies on the effect of reflux on the health and function of the TEP tract are warranted.

Objectives: Although oropharyngeal neoplasia can often lead to dysphagia, salivary gland tumors rarely grow within the tongue base. We present the case of a 75-year-old man with adenoid cystic carcinoma of the base of the tongue causing profound dysphagia and weight loss, and provide a current literature review and update on the management of these rare tumors. Methods: We present a case report and a literature review. Results: Physical examination performed at the initial visit revealed a firm right base-of-tongue mass with no palpable lymphadenopathy. Flexible fiberoptic laryngoscopy confirmed a large submucosal mass at the right base of the tongue that obscured the right vallecula. Histopathologic analysis of the operative biopsy specimens revealed the classic features of adenoid cystic carcinoma. Treatment included radical pharyngotomy with wide local excision and primary closure, followed by postoperative radiation treatment. Conclusions: We demonstrate the clinical examination findings and histopathologic characteristics of this disease, and review the literature for clinical treatment recommendations for this rare cause of dysphagia.

ObjectiveTo implement complex, PINCER (pharmacist led information technology intervention) prescribing indicators, on a national scale with general practice data to describe the impact of the covid-19 pandemic on safe prescribing.DesignPopulation based, retrospective cohort study using federated analytics.SettingElectronic general practice health record data from 56.8 million NHS patients by use of the OpenSAFELY platform, with the approval of the National Health Service (NHS) England.ParticipantsNHS patients (aged 18-120 years) who were alive and registered at a general practice that used TPP or EMIS computer systems and were recorded as at risk of at least one potentially hazardous PINCER indicator.Main outcome measureBetween 1 September 2019 and 1 September 2021, monthly trends and between practice variation for compliance with 13 PINCER indicators, as calculated on the first of every month, were reported. Prescriptions that do not adhere to these indicators are potentially hazardous and can cause gastrointestinal bleeds; are cautioned against in specific conditions (specifically heart failure, asthma, and chronic renal failure); or require blood test monitoring. The percentage for each indicator is formed of a numerator of patients deemed to be at risk of a potentially hazardous prescribing event and the denominator is of patients for which assessment of the indicator is clinically meaningful. Higher indicator percentages represent potentially poorer performance on medication safety.ResultsThe PINCER indicators were successfully implemented across general practice data for 56.8 million patient records from 6367 practices in OpenSAFELY. Hazardous prescribing remained largely unchanged during the covid-19 pandemic, with no evidence of increases in indicators of harm as captured by the PINCER indicators. The percentage of patients at risk of potentially hazardous prescribing, as defined by each PINCER indicator, at mean quarter 1 (Q1) 2020 (representing before the pandemic) ranged from 1.11% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 36.20% (amiodarone and no thyroid function test), while Q1 2021 (representing after the pandemic) percentages ranged from 0.75% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 39.23% (amiodarone and no thyroid function test). Transient delays occurred in blood test monitoring for some medications, particularly angiotensin-converting enzyme inhibitors (where blood monitoring worsened from a mean of 5.16% in Q1 2020 to 12.14% in Q1 2021, and began to recover in June 2021). All indicators substantially recovered by September 2021. We identified 1 813 058 patients (3.1%) at risk of at least one potentially hazardous prescribing event.ConclusionNHS data from general practices can be analysed at national scale to generate insights into service delivery. Potentially hazardous prescribing was largely unaffected by the covid-19 pandemic in primary care health records in England.