International multicenter study of ultralow graft-to-recipient weight ratio grafts in adult living donor liver transplantation.

Decreasing the graft size in living donor liver transplantation (LDLT) increases the risk of early allograft dysfunction. Graft-to-recipient weight ratio (GRWR) of 0.8 is considered the threshold. There is evidence that smaller volume grafts may also provide equally good outcomes, the cut-off of which remains unknown. In this retrospective multicenter study, 92 adult LDLTs with a final GRWR ≤0.6 performed at 12 international liver transplant centers over a 3-year period were included. Perioperative data including preoperative status, portal flow hemodynamics (PFH) and portal flow modulation, development of small for size syndrome (SFSS), morbidity, and mortality was collated and analyzed. Thirty-two (36.7%) patients developed SFSS and this was associated with increased 30-day, 90-day, and 1-year mortality. The preoperative model for end-stage liver disease and inpatient status were independent predictors for SFSS (P < .05). Pre-liver transplant renal dysfunction was an independent predictor of survival (hazard ratio 3.1; 95% confidence intervals 1.1, 8.9, P = .035). PFH or portal flow modulation were not predictive of SFSS or survival. We report the largest ever multicenter study of LDLT outcomes using ultralow GRWR grafts and for the first time validate the International Liver Transplantation Society-International Living donor liver transplantation study group-Liver Transplantation Society of India consensus definition and grading of SFSS. Preoperative recipient condition rather than GRWR and PFH were independent predictors of SFSS. Algorithms to predict SFSS and LT outcomes should incorporate recipient factors along with GRWR.

Understanding the living-related pediatric liver transplantation donor's decision process: A questionnaire-based retrospective study.

OBJECTIVES: To analyse the donor characteristics and understand the sociocultural and familial aspects of the decision to donate for living donor liver transplant. METHODS: This is a retrospective study done in the Department of Pediatric Gastroenterology and Hepatology of a liver transplant centre. We enrolled the consenting donors of pediatric liver transplantation between January 2020 and January 2022. The study was conducted through an anonymized questionnaire which was drafted in a multiple-choice format. The questionnaire had three domains having questions pertaining to demographic details, donor characteristics and sociofamilial aspects of the decision-making process. RESULTS: The study cohort consisted of 50 donors, 23 males (46%) and 27 females (54%), with the mean age being 31.8 ± 5.6 years. Parent-to-child was the most frequent relationship (n = 39, 78%). More than half of our donors had annual income <2.5 lakh/annum or <3500 USD (n = 27, 54%). Twenty-six (52%) responders had >4 members in their family; 62% were residing in urban areas and 52% of the donors were graduates. The main source of information regarding the feasibility of living donor liver transplantation was primary physicians in 46%. Financial management was the main hurdle in 72%. Majority (74%) denied any effect on their marital relationship and 6% of donors thought that the degree of information provided to them before the transplantation regarding donation was insufficient. CONCLUSION: Our study serves as an essential tool for health professionals to provide sufficient support to the donor. Clinical outcomes and cost must be part of the discussion between caregivers, health professionals and fund contributors.

Surgical closure of enlarged tracheoesophageal fistula after laryngectomy: A systematic review of techniques.

OBJECTIVES: The objectives of the study were (1) systematically review the data on surgical closure of enlarged tracheoesophageal fistula after laryngectomy and (2) to perform a comparison of reconstruction of surgical techniques. METHODS: Systematic review was performed using PRISMA methodology. Cumulative patient data were compared between patients reconstructed with vascularized tissue (sternocleidomastoid fascia and muscle, pectoralis major, deltopectoral, radial forearm) and those closed primarily (two-layer, three-layer, and tracheal transposition). RESULTS: Fourteen studies reported outcomes for the reconstruction of tracheoesophageal fistula. Primary closure was used in 98 patients, vascularized flap in 74, and occlusive device in 8. Vascularized flap resulted in successful closure of the fistula in 89 % of cases compared to primary closure in 62 % (p = 0.0003). CONCLUSION: Systematic review of the literature supports an improved surgical closure rate with vascularized flap interposed between the esophageal and tracheal lumens compared to primary closure.

Surgical site antiseptic preparations for otolaryngology - Head and neck surgery: A current review.

OBJECTIVE: To review current literature and guidelines on antiseptic surgical site preparations for preventing surgical site infections with consideration of contraindications specific to head and neck surgery. DATA SOURCES: PubMed/MEDLINE, clinicaltrials.gov, accessdata.fda.gov, Manufacturer websites. REVIEW METHODS: A scoping review on the literature and clinical studies comparing the efficacy of different surgical site preparations. Studies were included if they were a randomized controlled trial (RCT) comparing at least two commonly used and available antiseptic preparations. Additionally, a compilation of warnings and contraindications from manufacturer labels and articles are included. Due to the lack of randomized controlled trials concerning antiseptic preparation use in head and neck surgery specifically, an additional search was executed for articles not limited to randomized controlled trials that compared different antiseptic preparation used in surgeries concerning the head and neck. RESULTS: Of 56,983 resulting abstracts and 3798 of them being screened, 25 RCTs were included. These RCTs included a variety of surgeries including gastrointestinal, obstetric, gynecologic, orthopedic, and vascular procedures. When searching for abstracts concerning head and neck surgeries, 9 studies were found and included. CONCLUSIONS: To reduce surgical site infections and avoid application in situations with contraindications, practicing surgeons need to be familiar with the existing literature regarding different surgical preparations and what warnings manufacturers have listed on the products. Optimal surgical site preparation for head and neck surgery is challenging as proximity to oxygen contraindicates newer alcohol-based options that are potentially flammable. We summarize evidence-based surgical site preparation for head and neck surgery.

Mechanisms of Resistance and Therapeutic Perspectives in Immunotherapy for Advanced Head and Neck Cancers.

Immunotherapy is emerging as an effective treatment for advanced head and neck cancers and interest in this treatment modality has led to rapid expansion of this research. Pembrolizumab and nivolumab, monoclonal antibodies directed against the programmed cell death-1 (PD-1) receptor, are US Food and Drug Administration (FDA)- and European Medical Agency (EMA)-approved immunotherapies for head and neck squamous cell carcinoma (HNSCC). Resistance to immunotherapy is common, with about 60% of patients with recurrent or metastatic HNSCC not responding to immunotherapy and only 20-30% of patients without disease progression in the long term. Overcoming resistance to immunotherapy is therefore essential for augmenting the effectiveness of immunotherapy in HNSCC. This review details the innate and adaptive mechanisms by which head and neck cancers can become resistant to immunotherapeutic agents, biomarkers that can be used for immunotherapy patient selection, as well as other factors of the tumor microenvironment correlated with therapeutic response and prognosis. Numerous combinations and novel immunotherapies are currently being trialed, based on better understood immune evasion mechanisms. These potential treatments hold the promise of overcoming resistance to immunotherapy in head and neck cancers.

Surgical Thromboprophylaxis in Patients With Head and Neck Cancer: An Economic Model.

Objective: To quantify postoperative venous thromboembolism (VTE) incidence in head and neck cancer (HNC) patients, and assess the economic implications of chemoprophylaxis. Study Design: Retrospective cost-effective analysis. Setting: Fifty-three health care organizations. Methods: The TriNetX Research Network was queried to identify the 1-month VTE rate in HNC patients undergoing neck dissection from 2012 to 2022. A literature search provided additional postsurgical VTE rates in HNC patients. Costs of prophylactic heparin and enoxaparin were obtained from a drug wholesaler, and VTE-associated medical costs were sourced from the literature. A break-even analysis determined the absolute risk reduction (ARR) in the VTE rate necessary for a medication to break-even on cost. Results: In TriNetX, 8193 HNC surgical patients underwent neck dissection, and an additional 1640 patients underwent neck dissection plus free flap reconstruction without chemoprophylaxis. Respective 1-month VTE rates were 1.3% (n = 103) and 2.5% (n = 41). Four additional studies of 1546 postoperative HNC patients not prescribed chemoprophylaxis reported a mean VTE rate of 3.8% (n = 59), ranging from 1.9% to 13.0%. At $8.40 per week, heparin resulted in cost savings if it decreased the VTE rate by an ARR of at least 0.05%, while enoxaparin, at $23.66 per week, needed to achieve a 0.14% ARR. Considering potential added costs from bleeding complications, heparin, and enoxaparin remained cost-effective if chemoprophylaxis did not increase bleeding complications by an absolute risk of more than 2.86% and 2.79%, respectively. Conclusion: Postoperative VTE rates varied in HNC patients. Despite this, achievable ARRs suggested the potential cost-effectiveness of routine chemoprophylaxis with heparin and enoxaparin.

Thyroid Cancer With Cutaneous Metastases.

Objectives: Thyroid carcinoma with cutaneous metastases is a rare clinical finding. Cutaneous metastases from thyroid carcinoma have been associated with a poor prognosis, but these data are limited to case reports. The exact mechanism of cutaneous metastases from thyroid carcinoma is not clear. Our study aims to report the demographic, clinical, and histologic findings of patients with cutaneous metastases from thyroid carcinoma. Methods: A review was conducted using the Medline/PubMed, Cochrane, and Scopus databases to review literature from inception to May 2023. Data extracted included patient age at diagnosis of cutaneous metastases, patient sex, thyroid carcinoma histotype, location of metastases, the time interval between diagnoses of thyroid carcinoma and cutaneous metastases, and overall survival (OS) from the time of cutaneous metastases. Results: One hundred thirty-six patients were identified and 75 were female. The most common types of thyroid carcinoma with cutaneous metastases were papillary (47.79%), followed by follicular (30.15%), and medullary (11.03%). In addition, 11 cases of anaplastic carcinoma, 2 cases of oncocytic carcinoma, and 2 cases of poorly differentiated thyroid carcinoma were reported. The average age at diagnosis of cutaneous metastases was 63.13 years, and the average time interval between the diagnoses of primary thyroid carcinoma and cutaneous metastases was 48.27 months. The most common location of metastases was the scalp (n = 48). Other common locations included the neck, chest, and face. The OS after diagnosis of metastases was only available in 34 patients with an average of 13.07 months. Of these 34 cases, 10 were medullary, 10 were papillary, 9 were anaplastic, and 5 had follicular carcinoma. Conclusions: This study represents an up-to-date review of the cases of thyroid carcinoma with cutaneous metastases. While cutaneous metastasis remains a rare finding, one needs a high index of suspicion, and their presence portends a poor prognosis.

Factors Associated With Inadequate Health Literacy: An Academic Otolaryngology Clinic Population Study.

Objective: To characterize the prevalence of inadequate health literacy among otolaryngology patients and assess the association of individual patient factors with inadequate health literacy. Study Design: Cross-sectional study. Setting: Tertiary academic medical center otolaryngology clinic. Methods: Adult patients presenting to the clinic were recruited from March to June 2022. Participants completed a validated health literacy questionnaire in the waiting room. Data on age, sex, race, insurance, county of residence, and language were extracted from the electronic medical record, linked to the survey responses, and deidentified for analysis. Logistic regression analyses assessed the association between inadequate health literacy and patient factors. Results: Of 374 participants, the mean age was 54.8 years (SD = 17.8) and most were white (79%) and native English speakers (95%). The median health literacy score was 14.5 (Q1-Q3: 12.0-15.0) and 43 participants (12%) had inadequate health literacy. Bivariate analysis showed the odds of inadequate health literacy were 2.5 times greater for those with public insurance (95% confidence interval [CI]: 1.24-5.20, P = .011), 3.5 times greater for males (95% CI: 1.75-6.92, P < .001), and significantly different among race groups (P = .003). When all factors were evaluated simultaneously with multivariable regression, only sex (P < .001) and race (P = .005) remained significant predictors of inadequate health literacy. There were no significant associations between health literacy and age or rurality. Conclusion: Inadequate health literacy was associated with sex and race, but not with age or rurality. 12% of patients had inadequate health literacy, which may perpetuate disparities in care and necessitate interventions to improve care delivery in otolaryngology.

Liver Transplantation Research from India During the Last 25 Years: 1998-2022.

Background and aims: Liver transplant surgery has been performed in India for the last 25 years. We aimed to analyse the trends, characteristics, and key elements in the field of liver transplantation research from India. Methods: On April 23, 2023, we conducted a search of the Scopus database for the literature on liver transplantation research, using a well-defined search strategy. MS Excel and VOS viewer software programs were used to examine the articles for organisation, author, journal, keywords, and high-cited literature. Results: This analysis examined a total of 556 papers, which constituted only a 1.55% share of the global output. These papers involved 442 organizations, 1575 authors, and 147 journals. External funding was received in 4.13% and 23.56% were involved in international collaboration. Three Delhi-NCR organizations, namely the Medanta-The Medicity (n = 63), Institute of Liver & Biliary Sciences (n = 60), and Indraprastha Apollo Hospital (n = 48) led in publication productivity. M. Rela (n = 90) and A.S. Soin (n = 63) were the leading authors in publication productivity, while S. Sudhindran and P. Bhangui were the most impactful authors. Liver Transplantation (n = 96) and Journal of Clinical & Experimental Hepatology (n = 65) published the maximum number of these papers, whereas, Annals of Surgery and Journal of Hepatology led in the citation impact per paper. The most significant keywords were "Liver Transplantation" (n = 484), and "Living Donor" (n = 254). Only 1.80% (n = 10) of the papers were highly cited papers that received 50 to 142 citations and they together registered 69.9 citations per paper. Conclusion: Although the number of publications on liver transplantation from India started growing recently, it forms only 1.55% of the global report. There is an unmet need to increase government-supported research and multicenter collaborative studies at national and international levels for high-quality patient care.

The Influence of Vasopressors on Free Flap Outcomes in Head and Neck Cancer Patients.

OBJECTIVE: To compare free flap outcomes between those who received and did not receive vasopressors (VPs) at the time of free flap reconstruction. STUDY DESIGN: This retrospective cohort study includes patients from January 2013 to January 2023. SETTING: This multicenter cohort study utilized data from the TriNetX Research Network which includes 80 health care organizations. METHODS: Head and neck cancer patients older than 18 years who underwent free flap reconstruction were separated into those who received or did not receive VPs on the day of surgery. The primary outcomes were flap failure defined by need for secondary free flap procedures, blood vessel repair, and other flap revision procedures. RESULTS: After propensity score matching, 7446 patients were analyzed. The VP group included 3723 patients (mean age [SD], 62.9 [11.4] years; 2511 males [67.4%]). The non-VP group included 3723 patients (mean age [SD], 63.0 [11.2] years; 2479 males [66.6%]). Free flap outcomes were not statistically different between groups (secondary free flap: 166 [4.5%] VP vs 155 [4.2%] non-VP, P = .04; vessel repair: 314 [8.4%] vs 319 [8.6%], P = .06; other flap revision procedures: 416 [11.2%] vs 449 [12.1%], P = .02). Bony flaps were found to have decreased rates of vessel repair in the VP group (47 [6.1%] vs 69 [9.0%], P = .003]. For secondary outcomes, pneumonia (173 [4.6%] vs 231 [6.2%], P = .0002), urinary tract infection (34 [1.0%] vs 59 [1.6%], P = .0007), and deep vein thrombosis (93 [2.5%] vs 122 [3.3%], P = .004) were significantly different. CONCLUSION: VP use is not significantly associated with free flap complications. These results imply that VP use on the same day as surgery may be safe if clinically necessary.

Current and Emerging Diagnostic, Prognostic, and Predictive Biomarkers in Head and Neck Cancer.

Head and neck cancers (HNC) are a biologically diverse set of cancers that are responsible for over 660,000 new diagnoses each year. Current therapies for HNC require a comprehensive, multimodal approach encompassing resection, radiation therapy, and systemic therapy. With an increased understanding of the mechanisms behind HNC, there has been growing interest in more accurate prognostic indicators of disease, effective post-treatment surveillance, and individualized treatments. This chapter will highlight the commonly used and studied biomarkers in head and neck squamous cell carcinoma.

Preoperative Serum Albumin as Predictor of Outcomes After Thyroidectomy.

Objective: Albumin is considered to be a surrogate marker for inflammation and nutritional status. Levels usually decrease after surgery but little is known about the predictive value of preoperative albumin levels in patients undergoing thyroidectomy. This study aimed to investigate the 30-day incidence of postoperative outcomes in thyroidectomy patients with and without preoperative hypoalbuminemia. Study Design: Retrospective cohort study. Setting: TriNetX Database. Methods: TriNetX, a federated deidentified database, was retrospectively queried to identify patients who underwent thyroidectomy. Postoperative outcomes within 30 days of thyroidectomy, based on International Classification of Disease, 10th Revision and Current Procedural Terminology codes, in patients with preoperative hypoalbuminemia (≤3.4 g/dL) (cohort 1) were analyzed and compared to patients without hypoalbuminemia (cohort 2). Results: After propensity score matching, 2398 patients were identified in each cohort. Hypoalbuminemia patients were more likely to have postoperative pneumonia (odds ratio, OR: 3.472, 95% confidence interval, CI [2.016-5.978]), acute renal failure (OR: 3.872, 95% CI [2.412-6.217]), venous thromboembolism (OR: 1.766, 95% CI [1.016-2.819]), and surgical site infection (OR: 2.353, 95% CI [1.282-4.32]). Rates of recurrent laryngeal nerve injury were comparable between cohorts. Conclusion: Patients undergoing thyroidectomy with preoperative hypoalbuminemia have a higher prevalence of postoperative complications compared to patients without preoperative hypoalbuminemia. While not routinely assessed, preoperative evaluation of serum albumin levels may help guide expectations and optimal management of thyroidectomy patients.

Evaluation of Hypocalcemia Following Total Laryngectomy With and Without Thyroidectomy.

OBJECTIVE: Hypoparathyroidism and associated hypocalcemia are well-established complications following laryngectomy. This study further characterizes the rates of hypocalcemia in patients undergoing total laryngectomy (TL) with and without thyroidectomy and hemithyroidectomy. STUDY DESIGN: Retrospective cohort study. SETTING: TriNetX. METHODS: We queried TriNetX, a deidentified patient database, to identify patients who underwent TL with and without thyroidectomy and hemithyroidectomy. Rates of hypocalcemia, low parathyroid hormone (PTH), calcium, and calcitriol supplementation were compared between groups with multivariable repeated measures logistic regression. RESULTS: We identified 870 patients in the TL without thyroidectomy cohort, 158 patients in the hemithyroidectomy cohort, and 123 in the total thyroidectomy cohort. Rates of hypocalcemia differed between patients receiving total thyroidectomy versus TL alone for 0 to 1 month (odds ratio [OR]: 2.88 [1.95-4.26]) 1 to 6 months (OR: 5.08 [2.29-11.3]), and 6 to 12 months (OR: 2.63 [1.003-6.88]) postoperatively, with adjustment for age at laryngectomy, race, ethnicity, and gender. Results were similar among those who received calcium supplementation. The rate of low PTH levels differed in these groups for 0 to 1 month (OR: 5.13 [3.10-8.51]), 1 to 6 months (OR: 3.47 [1.46-8.22]), and 6 to 12 months (OR: 3.63 [1.40-9.38]) following surgery. Rates of postoperative calcium supplementation were increased for patients receiving total thyroidectomy versus TL for 1 to 6 months (OR: 2.44 [1.62-3.68]), and 6 to 12 months following surgery (OR: 1.79 [1.18-2.72]). CONCLUSION: Patients undergoing TL with total thyroidectomy have a higher risk of postoperative hypocalcemia compared to patients receiving TL alone. Risk of parathyroid injury in these patients may warrant further emphasis on PTH measurement after surgery and a multidisciplinary approach to management.

Near-Infrared Induced miR-34a Delivery from Nanoparticles in Esophageal Cancer Treatment.

Current nucleic acid delivery methods have not achieved efficient, non-toxic delivery of miRNAs with tumor-specific selectivity. In this study, a new delivery system based on light-inducible gold-silver-gold, core-shell-shell (CSS) nanoparticles is presented. This system delivers small nucleic acid therapeutics with precise spatiotemporal control, demonstrating the potential for achieving tumor-specific selectivity and efficient delivery of miRNA mimics. The light-inducible particles leverage the photothermal heating of metal nanoparticles due to the local surface plasmonic resonance for controlled chemical cleavage and release of the miRNA mimic payload. The CSS morphology and composition result in a plasmonic resonance within the near-infrared (NIR) region of the light spectrum. Through this method, exogenous miR-34a-5p mimics are effectively delivered to human squamous cell carcinoma TE10 cells, leading to apoptosis induction without adverse effects on untransformed keratinocytes in vitro. The CSS nanoparticle delivery system is tested in vivo in Foxn1nu athymic nude mice with bilateral human esophageal TE10 cancer cells xenografts. These experiments reveal that this CSS nanoparticle conjugates, when systemically administered, followed by 850 nm light emitting diode irradiation at the tumor site, 6 h post-injection, produce a significant and sustained reduction in tumor volume, exceeding 87% in less than 72 h.