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Cellular immunity plays an important role in the control of persistent virus infections such as hepatitis C virus (HCV). Antiviral CD4+ T cell responses have been shown to accompany resolution of acute disease and there is also a consistent association between HLA Class II genes, notably HLADRB1*1101 (and the closely linked HLADQB1*0301) and disease resolution. We initially mapped longitudinal CD4+ T cell responses in an individual after spontaneous resolution of acute HCV, and identified three HLA-DR11-restricted responses which vary in immunodominance over time. Functional assays and HLA Class II tetramer staining revealed one to be a response to a commonly recognized epitope, NS31248--1261, although cytokine capture assays showed these specific cells to be at a very low frequency. In this patient, and in others reported, this most frequently recognized HLA-DR11 restricted epitope is not immunodominant. We analysed whether sequence variability within and between genotypes might account for differences in recognition of HLA-DR11 restricted epitopes. We found that a limited number, including NS31248--1261, showed extreme sequence conservation. Within NS3, the ability of peptides to accept amino acid substitutions was clearly related to the structure of the protein. Overall the data provide a deeper understanding of the relationship between protein structure and variability of HLA-DR11 restricted peptides and may explain the apparent dominance of responses to NS31248--1261 across studies but not within an individual immune response. [ABSTRACT FROM AUTHOR]

SUMMARY The part played by radiology in the detection of 16 cases of tracheal stenosis following tracheostomy is reviewed. The three basic types of stenosis are described and the contribution of radiology to their management is discussed. Antero-posterior and lateral film tomography is the suggested method of investigation of such cases. [ABSTRACT FROM AUTHOR]

SUMMARY Liver abscess remains a serious and even life-threatening condition, despite advances in imaging and treatment. The diagnosis of liver abscess depends heavily on radiologic imaging, particularly ultrasound (US) and computed tomography (CT) scanning. The appearance of liver abscesses on these modalities depends mainly on the chronicity of the abscess. The US and CT features of 33 patients with liver abscesses are presented. Percutaneous drainage of pyogenic abscesses under imaging control is the treatment of choice. Eleven of 24 patients with pyogenic abscesses had percutaneous drainage with good results. [ABSTRACT FROM AUTHOR]

Background: The main aims of intestinal failure (IF) surgery are to reduce the severity of IF in patients by repairing fistulae and restoring continuity in those with short gut, and to restore body image. We report on the surgical management of IF patients at a major tertiary referral institution, in order to evaluate current management practises and outcomes. Methods: Retrospective review of outcomes between July 2005 and December 2007. Results: 60 patients (36 male; median age 47 yrs) underwent 78 operations. On presentation 42 (70%) required parenteral nutrition (PN) and 34 (57%) had stomas. IF was secondary to short gut in 19 (30%) or enterocutaneous fistulae in 42 (70%). Median number of procedures before referral was 4 (1–14). Median time from last operation to our intervention was 365 days (25–3534). Median length of stay postoperatively was 16 days, and at a median follow-up of 268 days, 54 (90%) had been discharged from surgical care. 7 (12%) required ICU care postoperatively but 30 day/inpatient mortality rates were 0%. Re-fistulation occurred in 5 patients. 23 (56%) became independent of PN. Residual small bowel length was the only significant contributing factor identified (p = 0.007). Conclusion: Surgical management of IF is safe when performed in a dedicated unit and when time is allowed for patient optimisation. [ABSTRACT FROM AUTHOR]

A response by C. Byrne, R. Philips and A. A. Uraiqat to a letter to the editor about their article "A systematic stapling defect – a potential cause of ‘anastomotic leak’ after restorative proctocolectomy" is presented.

Objective: To identify practices in microvascular techniques in routine and challenging scenarios., Study Design: Cross-sectional study., Methods: A national survey addressing practices related to microvascular free flap reconstruction was distributed to AHNS members between October and November 2021., Results: The respondents encompassed 95 microvascular surgeons. Median years of practice was 6 (interquartile range, 2-13) and median flaps per year was 35 (22-50). Common practices in arterial anastomosis included limited cleaning of artery (84.2%), use of a double approximating clamp (64.2%), and use of interrupted suture (88.4%). Common practices in venous anastomosis included limited cleaning (89.5%), downsizing the coupler (53.7%), and coupling to two independent venous systems (47.4%). In arterial anastomosis, respondents felt that kinking (50.5%) and tension (24.2%) were the riskiest challenges. Kinking was handled by loose sutures or native tissue/dissolvable biomaterial to orient pedicle. Excess tension was handled by additional dissection. With regards to associated practices, most surgeons perform anastomosis after partial inset (52.6%), give aspirin immediately postoperatively (66.3%), reserve transfusion for hemodynamic instability (69.5%), and utilize intraoperative pressors when needed (72.6%). More senior surgeons reported placing more suture to address leaks (p = 0.004) and perform end to side anastomosis on larger vein in case of venous mismatch (p = 0.012). In cases of tension, higher volume surgeons perform more extensive dissection (p = 0.035) and end to side coupling (p = 0.029)., Conclusions: This survey of AHNS members indicates patterns of microvascular techniques in routine and challenging scenarios. There exists a variation in approaches amongst surgeons based on volume and practice length., Level of Evidence: 5 Laryngoscope, 134:1265-1277, 2024., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Esophageal defects can result from primary pathologies such as malignancy or stricture, or secondary ones such as perforation due to trauma or iatrogenic injury. Techniques, management, and outcomes of reconstruction in this setting are poorly understood. Herein, we aim to highlight surgical outcomes in patients undergoing local and free flap reconstruction of esophageal defects in the setting of an intact larynx., Methods: Retrospective review of patients who underwent esophageal reconstruction with an intact larynx between 2009 and 2022 at our institution was performed., Results: Ten patients met inclusion criteria. Esophageal reconstruction was performed for extruded spinal hardware (n = 8), and esophageal stricture (n = 2). Four patients underwent reconstruction with free tissue transfer, and six with local pedicled flaps. There were no cases of flap failure, esophageal fistula, hematoma, or wound dehiscence. One patient had post-operative bleeding requiring return to the operating room. Three patients had a postoperative wound infection, two of whom required washout. There were no unplanned 30-day readmissions. At three months after operation, all patients who were not tube feed-dependent prior to surgery returned to oral intake. Of the four patients who were tube feed-dependent preoperatively, three were tolerating oral intake at nine months postoperatively. Nine patients (90%) had stable flexible laryngoscopy exams pre- and postoperatively with no voice changes., Conclusions: Reconstruction of esophageal defects in the setting of an intact larynx can be challenging. In this series, surgical intervention with free tissue transfer and local pedicled flaps was effective in returning patients to oral intake with low long-term morbidity., Level of Evidence: 4 Laryngoscope, 134:1227-1233, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Orbital defects have a profound impact on orbital function and symmetry of the face and are difficult to reconstruct given the complexity of this area. The paramedian forehead flap (PMFF) has not been well studied in reconstruction of orbital defects., Methods: Retrospective review of patients who underwent reconstruction of periorbital defects with PMFF between 2016 and 2021. Variables were ocular adnexal asymmetry, functional outcomes, and orbital complications., Results: Eighteen patients met inclusion criteria. Mean defect size was 11.1 ± 7.5 cm. The most common subsite involved was medial canthus in 88.9% of patients. There was no statistically significant difference between mean medial canthus to midline ratio and mean medial brow to midline ratio when compared to the assumed normal of 1. The medial canthus to pupil ratio and medial canthus to lateral canthus ratio had a statistically significant mean difference from 1.0 (p = 0.003 for both). In 22.2% of patients, the orbit was functional with impairment; the remaining had no impairment. Surgical sequelae occurred in 12/18 (66.7%) of patients, most commonly epiphora in 9/18 (50%) of patients, and ectropion in 5/18 (27.7%)., Conclusion: The PMFF is feasible for medial periorbital reconstruction with acceptable functional and symmetrical outcomes and low morbidity., Level of Evidence: 4 Laryngoscope, 133:2584-2589, 2023., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Patients with recurrent oropharyngeal cancer can achieve survival benefits from surgical salvage, and often require simultaneous free-flap reconstruction. Resection and reconstruction can impact function, leading to tube dependence., Primary Objective: describe rates of tracheostomy and gastrostomy tube dependence after oropharyngeal resection and free flap after prior radiation., Secondary Objective: evaluate patient, tumor, and treatment factors associated with tube dependence., Study Design: Retrospective, multi-institutional cohort study. Patients treated from 2003 to 2020. Average follow-up 21.4 months., Setting: Five tertiary care centers., Methods: Consecutive cohort of patients undergoing resection and simultaneous free-flap reconstruction for oropharyngeal squamous cell carcinoma after head and neck radiation., Primary Outcomes: gastrostomy tube dependence and tracheostomy or tracheostoma 1 year after surgery. Univariable and multivariable logistic regression were performed to identify factors associated with dependence., Results: 89 patients underwent oropharyngectomy and free-flap reconstruction; 18 (20%) underwent total laryngectomy as part of tumor extirpation. After surgery, 51 patients (57%) lived 12 months. Among patients alive at 12 months, 22 (43%) were at least partially-dependent on gastrostomy tube, and 15 (29%) had either tracheostomy or tracheostoma. On multivariable analysis, extensive glossectomy (OR 16.6, 95% CI 1.83-389, p = 0.026) and total laryngectomy (OR 11.2, 95% CI 1.71-105, p = 0.018) were associated with long-term gastrostomy tube. No factors were associated with long-term tracheostomy on multivariable analysis., Conclusion: Even among long-term survivors after salvage resection and free-flap reconstruction, rates of tube dependence are significant. This multi-institutional review is the largest such study to the date and may help inform shared decision-making., Level of Evidence: 4 Laryngoscope, 133:2141-2147, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: To analyze CD8+ and FoxP3+ T-cell cellular density (CD) and intercellular distances (ID) in head and neck squamous cell carcinoma (HNSCC) samples from a neoadjuvant trial of durvalumab +/- metformin., Methods: Paired pre- and post-treatment primary HNSCC tumor samples were stained for CD8+ and FoxP3+. Digital image analysis was used to determine estimated mean CD8+ and FoxP3+ CDs and CD8+-FoxP3+ IDs in the leading tumor edge (LTE) and tumor adjacent stroma (TAS) stratified by treatment arm, human papillomavirus (HPV) status, and pathologic treatment response. A subset of samples was characterized for T-cell related signatures using digital spatial genomic profiling., Results: Post-treatment analysis revealed a significant decrease in FoxP3+ CD and an increase in CD8+ CDs in the TAS between patients receiving durvalumab and metformin versus durvlaumab alone. Both treatment arms demonstrated significant post-treatment increases in ID. Although HPV+ and HPV- had similar immune cell CDs in the tumor microenvironment, HPV+ pre-treatment samples had 1.60 times greater ID compared with HPV- samples, trending toward significance (p = 0.05). At baseline, pathologic responders demonstrated a 1.16-fold greater CD8+ CDs in the LTE (p = 0.045) and 2.28-fold greater ID (p = 0.001) than non-responders. Digital spatial profiling revealed upregulation of FoxP3+ and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) in the TAS (p = 0.006, p = 0.026) in samples from pathologic responders., Conclusions: Analysis of CD8+ and FoxP3+ detected population differences according to HPV status, pathologic response, and treatment. Greater CD8+-FoxP3+ ID was associated with pathologic response. CD8+ and FoxP3+ T-cell distributions may be predictive of response to immune checkpoint inhibition., Clinicaltrials: gov (Identifier NCT03618654)., Level of Evidence: 3 Laryngoscope, 133:1875-1884, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Determine which variables impact postoperative discharge destination following head and neck microvascular free flap reconstruction., Study Design: Retrospective review of prospectively collected databases., Methods: Consecutive patients undergoing head and neck microvascular free flap reconstruction between January 2010 and December 2019 (n = 1972) were included. Preoperative, operative and postoperative variables were correlated with discharge destination (home, skilled nursing facility [SNF], rehabilitation facility, death)., Results: The mean age of patients discharged home was lower (60 SD ± 13, n = 1450) compared to those discharged to an SNF (68 SD ± 14, n = 168) or a rehabilitation facility (71 SD ± 14, n = 200; p < 0.0001). Operative duration greater than 10 h correlated with a higher percentage of patients being discharged to a rehabilitation or SNF (25% vs. 15%; p < 0.001). Patients were less likely to be discharged home if they had a known history of cardiac disease (71% vs. 82%; p < 0.0001). Patients were less likely to be discharged home if they experienced alcohol withdrawal (67% vs. 80%; p = 0.006), thromboembolism (59% vs. 80%; p = 0.001), a pulmonary complication (46% vs. 81%; p < 0.0001), a cardiac complication (46% vs. 80%; p < 0.0001), or a cerebral vascular event (25% vs. 80%; p < 0.0001). There was no correlation between discharge destination and occurrence of postoperative wound infection, salivary fistula, partial tissue necrosis or free flap failure. Thirty-day readmission rates were similar when stratified by discharge destination., Conclusion: There was no correlation with the anatomic site, free flap donor selection, or free flap survival and discharge destination. Patient age, operative duration and occurrence of a medical complication postoperatively did correlate with discharge destination., Level of Evidence: 4 Laryngoscope, 133:95-104, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: We aim to 1) evaluate trends in adjuvant treatment of human papilloma virus (HPV)-related oropharyngeal cancer; 2) assess change in complications and functional outcomes over time; and 3) assess change in overall and disease-free survival (DFS) over time., Study Design: Retrospective analysis., Methods: Charts of patients who underwent transoral robotic surgery for HPV-related oropharyngeal cancer between 2011 and 2019 were reviewed. Trend analysis was used to compare rate of adjuvant treatment over time. The Kaplan-Meier method was conducted to analyze overall survival (OS) and DFS., Results: Three hundred and forty-two patients met inclusion criteria. One hundred and sixty-three (47.7%) patients underwent adjuvant radiation, and 90 (26.3%) patients underwent adjuvant chemoradiation. Rate of extranodular extension decreased significantly from 38.9% to 24.0% (P = .004). Rate of adjuvant therapy decreased significantly from 90.9% to 62.5% between 2011 and 2019 (P = .001). In patients who received adjuvant treatment, rate of adjuvant chemoradiation therapy decreased significantly from 40.0% to 20.0% (P < .0005). There was a decrease in rate of 1-year gastrostomy tube dependence in patients treated in 2015 to 2019 versus 2011 to 2014 (2.2% vs. 7.1%, P = .025). In 2011 to 2014, 2-year OS and DFS were 96% and 89%, respectively; in 2015 to 2019, 2-year OS and DFS were 96% and 94%, respectively. There was no difference in OS or DFS between the two time periods., Conclusions: The rate of adjuvant therapy, particularly chemotherapy, has decreased over time. One-year gastrostomy tube dependence rate has decreased significantly from 2011 to 2014 to 2015 to 2019. There was no change in OS and DFS over this time period., Level of Evidence: 3 Laryngoscope, 132:806-812, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To describe multidimensional quality of life (QOL) outcomes in patients with sinonasal malignancies (SNM). To elucidate factors predicting worse QOL in this population., Study Design: Retrospective chart review at tertiary institution., Methods: A retrospective chart review on patients treated for SNM from 2006 to 2019 at a tertiary medical center was conducted. QOL outcomes were measured using the Hospital Anxiety and Depression Scale (HADS) and the Functional Assessment Cancer Therapy - Nasopharynx (FACT-NP) score. A stepwise multiple linear regression analysis was conducted to assess factors predicting worse QOL., Results: Eighty-one patients met inclusion criteria. Twelve (14.8%) patients had a subscale score >11 for anxiety (HADS-A) or depression (HADS-D) indicating significant anxiety or depression, at a median of 24 (8-68.5) months post treatment. The median FACT-NP total score was 136 (110-152). On multivariable analysis, advanced T classification, single status, and worse social support survey score were significant predictors of worse HADS score. Worse social support survey score was a significant predictor of worse total FACT-NP score., Conclusion: After adjusting for confounders, at a median of 24 months after completion of definitive therapy for SNM, advanced T classification and single relationship status were found to be significant predictors of anxiety and depression (based on HADS). A worse social support survey score was associated with worse anxiety, depression, and QOL (based on HADS and FACT-NP). Identifying these factors early may help to guide treatment and psychiatric referral to at-risk individuals after the treatment of SNM., Level of Evidence: 3 Laryngoscope, 131:E2212-E2221, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To assess the feasibility of jet ventilation in obese patients and to compare complications of jet ventilation in obese and nonobese patients., Study Design: Retrospective review of medical records., Methods: We reviewed 46 patient charts (70 procedures) with the diagnosis of tracheal or subglottic stenosis who underwent endoscopic surgery with jet ventilation between March 2014 and January 2017. Adequacy of jet ventilation was assessed by chest rise, avoidance of endotracheal intubation, and length of case and ventilation. Records were reviewed for demographic details, anesthesia records, and complications., Results: In 29/70 (41.4%) of cases, patients were obese; in 9/29 (31.0%) of these cases, patients were morbidly obese. Jet ventilation was successful in 28/29 (97%) of obese cases. In 1/29 (3.4%) of cases, the patient required alternative airway management. There were no significant differences between obese and nonobese patients in chest rise, need for endotracheal intubation, and length of surgery or ventilation (P > .05). There were 2/29 (6.9%) cases of intra- and postoperative complications including laryngospasm (1/29, 3.4%) and tachycardia (1/29, 3.4%). Rate of complications did not differ between obese and nonobese patients (P = .178)., Conclusions: Jet ventilation in obese patients can be done successfully, and complications are similar between obese patients and nonobese patients., Level of Evidence: 4. Laryngoscope, 1887-1892, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)