DNGR-1-mediated cross-presentation of dead cell-associated antigens.

Conventional dendritic cells type 1 (cDC1) are critical for inducing protective CD8+ T cell responses to tumour and viral antigens. In many instances, cDC1 access those antigens in the form of material internalised from dying tumour or virally-infected cells. How cDC1 extract dead cell-associated antigens and cross-present them in the form of peptides bound to MHC class I molecules to CD8+ T cells remains unclear. Here we review the biology of dendritic cell natural killer group receptor-1 (DNGR-1; also known as CLEC9A), a C-type lectin receptor highly expressed on cDC1 that plays a key role in this process. We highlight recent advances that support a function for DNGR-1 signalling in promoting inducible rupture of phagocytic or endocytic compartments containing dead cell debris, thereby making dead cell-associated antigens accessible to the endogenous MHC class I processing and presentation machinery of cDC1. We further review how DNGR-1 detects dead cells, as well as the functions of the receptor in anti-viral and anti-tumour immunity. Finally, we highlight how the study of DNGR-1 has opened new perspectives into cross-presentation, some of which may have applications in immunotherapy of cancer and vaccination against viral diseases.

Differences in presentation, treatment, and outcomes among minority head and neck cancer patient groups in Los Angeles County.

IMPORTANCE: While minorities represent around 20 % of all HNC patients, these demographics are largely understudied. Furthermore, trends in national studies may not always be fully replicated in locoregional populations, indicating a need for more nuanced study. OBJECTIVE: To better understand our patient population, we sought to understand differences in presentation, management, and outcome between Caucasians and minority groups with HNC. DESIGN: Retrospective cohort analysis of the Los Angeles County Surveillance Epidemiology and End Results (SEER) database. SETTING: Los Angeles County. PARTICIPANTS: All patients in Los Angeles County diagnosed with cancer of the head and neck from January 1, 1988 to December 31, 2018. MAIN OUTCOMES AND MEASURES: The primary outcome in our study was significant differences between racial and ethnic groups in age of diagnosis, sex, socioeconomic quintile, insurance status, stage at diagnosis, treatment modality, time to first treatment, and cancer-specific cause of death. RESULTS: Our 18,510-patient cohort was largely male (64.35 %), white (69.57 %), and were on average 62.84 years old (SD = 20.07). When stratifying patients by race and ethnicity, significant differences were found in average age at diagnosis, sex, socioeconomic quintile, insurance status, and stage at diagnosis, treatment modalities utilized, and time to first treatment (all p < 0.001). Relative to all other head and neck patients, minority groups were significantly younger, had lower proportions of male patients, were less likely to pursue surgery, were more likely to pursue chemotherapy or radiation, and endorsed longer time to first treatment (all p < 0.001). The distribution of socioeconomic quintile (all p < 0.001), insurance status (all p < 0.001), and stage at diagnosis (all p < 0.05) also significantly varied between minority and reference groups. Only African Americans exhibited significantly higher rates of cancer-specific cause of death relative to non-African Americans (p < 0.001). CONCLUSIONS AND RELEVANCE: Pervasive socioeconomic disparities between Caucasian HNC patients and those of other minority racial and ethnic groups in Los Angeles County that likely and significantly impact the diagnosis and management of HNC and its resultant outcomes. We encourage others to similarly examine their local populations to tailor the quality of care provided to patients.

Knowledge of HPV vaccination and associated HNC and treatment decision-making among minority populations.

OBJECTIVE: Understand vaccination knowledge and barriers to vaccination among minority adults. STUDY DESIGN: Cross-sectional survey. SETTING: Otolaryngology clinics at a safety net hospital and a tertiary academic center and a head and neck cancer screening event. METHODS: Survey was administered to consenting patients. Descriptive statistics and significance testing were used to characterize the data, with non-minority respondents as controls. Multivariate logistic regression was used to understand factors associated with vaccination. RESULTS: HPV vaccination among our 241 respondents (n = 41, 17.67 %) and their qualifying children (n = 52, 33.55 %) was low. Non-vaccinated minorities were significantly more likely to express interest in HPV vaccination (28.66 % vs 8.66 %, p = 0.016). Minority patients were significantly less knowledgeable about HPV causing cervical (88.64 % vs 72.45 %, p = 0.024) and head and neck (68.18 % vs 44.90 %, p = 0.005) cancer and were also less aware of HPV infection (95.45 % vs 81.12 %, p = 0.020) among non-women. Lack of knowledge about the HPV vaccine was the most cited reason why minority patients did not or were uninterested in vaccination for themselves or their children. In a multivariable logistic regression of factors associated with HPV vaccination, only increased age demonstrated a significant association with vaccination likelihood (OR = 0.91, 95 % CI = [0.88-0.95], p < 0.001). CONCLUSION: Reported HPV vaccination rates were low for both white and minority patients but did not significantly vary on univariate or multivariate analysis. However, minority respondents were significantly less knowledgeable about HPV and its manifestations; they most often cited inadequate knowledge as why did not receive or were uninterested in HPV vaccination. As such, HPV vaccination educational interventions may raise vaccination rates among minority populations.

The effects of psychosocial determinants on post-operative complications of head and neck free flap patients.

PURPOSE: Not much is known about how pre-operative psychosocial factors affect head and neck free flap outcomes. Hence, the objective of the study is to determine if a patient's pre-operative self-perception and quality of life affect post-operative complications and hospital length of stay after free flap surgery. MATERIALS AND METHODS: This was a prospective cohort study. Patients who underwent a free flap surgery at an academic tertiary care center between January 2021 and March 2022 were asked to fill out the Rosenberg Self Esteem Scale and the Short Form 36 Health Questionnaire before surgery. A chart review of their medical records was then performed. Analysis of the data was performed using Spearman Correlation, Fisher exact test, Mann-Whitney and Multivariate Logistic Regression on STATA 15. RESULTS: Sixty-one patients (73.8 % male; mean [SD; range] age: 60.9 [14.0, 23.1-86.8]) who underwent free flap surgery agreed to participate in the study. Most of the participants were not Caucasian (59 %). The most common indication for surgery was malignancy (93 %). The post-operative complication rate was 34.4 % and included 3 hematoma (4.9 %), 3 free flap failure (4.9 %), 9 wound dehiscence (14.8 %), 10 salivary fistulas (16.4 %), and 3 aspiration pneumonia or chyle leak (4.9 %). There were no mortalities. The mean role limitations due to physical health subscore [SD; range], social functioning subscore, pain subscore, and general health subscore of the SF-36 were 61.9 [39.2, 0-100], 70.7 [27.5, 0-100], 62.1 [25.7, 0-100], and 67.8 [20.3, 20-100], respectively. On univariate analysis, decreased physical limitations, better social functioning, less pain and better general health were associated with fewer overall post-operative complications, but was not correlated with length of stay. This held true for social functioning and general health even in multivariate analysis accounting for age and smoking history. The mean Rosenberg Self Esteem Scale score was 24.3 [4.1, 13-30]. CONCLUSIONS: In this study, patients with more limited social function and worse general health had more overall post-operative complications. It is important to continue to explore how pre-operative quality of life and other psychosocial factors can affect surgical outcomes.

Procalcitonin and High APACHE (Acute Physiological and Chronic Health Evaluation) Level Are Associated with the Course of Acute Kidney Injury in Patients with SARS-CoV-2.

Background: Acute kidney injury (AKI) is associated with poor outcomes in patients infected with SARS-CoV-2. Sepsis, direct injury to kidney cells by the virus, and severe systemic inflammation are mechanisms implicated in its development. We investigated the association between inflammatory markers (C-reactive protein, procalcitonin, D-dimer, lactate dehydrogenase, and ferritin) in patients infected with SARS-CoV-2 and the development of AKI. Methods: A prospective cohort study performed at the Civil Hospital (Dr. Juan I. Menchaca) Guadalajara, Mexico, included patients aged >18 years with a diagnosis of SARS-CoV-2 pneumonia confirmed by RT-PCR and who did or did not present with AKI (KDIGO) while hospitalized. Biomarkers of inflammation were recorded, and kidney function was estimated using the CKD-EPI formula. Results: 291 patients were included (68% males; average age, 57 years). The incidence of AKI was 40.5% (118 patients); 21% developed stage 1 AKI, 6% developed stage 2 AKI, and 14% developed stage 3 AKI. The development of AKI was associated with higher phosphate (p = 0.002) (RR 1.39, CI 95% 1.13-1.72), high procalcitonin levels at hospital admission (p = 0.005) (RR 2.09, CI 95% 1.26-3.50), and high APACHE scores (p = 0.011) (RR 2.0, CI 95% 1.17-3.40). The survival analysis free of AKI according to procalcitonin levels and APACHE scores demonstrated a lower survival in patients with procalcitonin >0.5 ng/ml (p = 0.001) and APACHE >15 points (p = 0.004). Conclusions: Phosphate, high procalcitonin levels, and APACHE levels >15 were predictors of AKI development in patients hospitalized with COVID-19.

Deficiency of the sedoheptulose kinase (Shpk) does not alter the ability of hematopoietic stem cells to rescue cystinosis in the mouse model.

Cystinosis is an autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene encoding the lysosomal cystine transporter, cystinosin, and leading to multi-organ degeneration including kidney failure. A clinical trial for cystinosis is ongoing to test the safety and efficacy of transplantation of autologous hematopoietic stem and progenitor cells (HSPCs) ex vivo gene-modified to introduce functional CTNS cDNA. Preclinical studies in Ctns-/- mice previously showed that a single HSPC transplantation led to significant tissue cystine decrease and long-term tissue preservation. The main mechanism of action involves the differentiation of the transplanted HSPCs into macrophages within tissues and transfer of cystinosin-bearing lysosomes to the diseased cells via tunneling nanotubes. However, a major concern was that the most common cystinosis-causing mutation in humans is a 57-kb deletion that eliminates not only CTNS but also the adjacent sedopheptulose kinase SHPK/CARKL gene encoding a metabolic enzyme that influences macrophage polarization. Here, we investigated if absence of Shpk could negatively impact the efficiency of transplanted HSPCs to differentiate into macrophages within tissues and then to prevent cystinosis rescue. We generated Shpk knockout mouse models and detected a phenotype consisting of perturbations in the pentose phosphate pathway (PPP), the metabolic shunt regulated by SHPK. Shpk-/- mice also recapitulated the urinary excretion of sedoheptulose and erythritol found in cystinosis patients homozygous for the 57-kb deletion. Transplantation of Shpk-/--HSPCs into Ctns-/- mice resulted in significant reduction in tissue cystine load and restoration of Ctns expression, as well as improved kidney architecture comparable to WT-HSPC recipients. Altogether, these data demonstrate that absence of SHPK does not alter the ability of HSPCs to rescue cystinosis, and then patients homozygous for the 57-kb deletion should benefit from ex vivo gene therapy and can be enrolled in the ongoing clinical trial. However, because of the limits inherent to animal models, outcomes of this patient population will be carefully compared to the other enrolled subjects.

Low prevalence of asthma in Mexican children and adults with a positive rtRT-PCR test for SARS-CoV-2: a cross-sectional study during the 2020 pandemic.

BACKGROUND: It has recently been argued that asthma does not increase the risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. If so, the prevalence of asthma in subjects diagnosed with COVID-19 should be lower than in the general population. OBJECTIVE: To determine the prevalence of asthma in Mexican children and adults with SARS-CoV-2 infection. METHODS: A public database of the Epidemiological Surveillance System for Viral Respiratory Disease in Mexico was analyzed. Those who underwent the real-time reverse transcriptase-polymerase chain reaction-SARS-CoV-2 (rtRT-PCR-SARS-CoV-2) test from February 27 to June 21, 2020, were included. In addition to the prevalence of asthma, some factors associated with it were investigated. RESULTS: Data from 417,366 subjects were analyzed. Asthma prevalence in children, adults, and global were 3.7%, 3.3%, and 3.3%, respectively. Although the asthma prevalence was lower in SARS-CoV-2 positive over negative patients, significant differences were only found in adults (2.8% vs. 3.7% respectively; odds ratio (OR) = 0.74; 95% confidence interval (CI): 0.71-0.77); but not in children (3.5% vs. 3.8%, respectively; OR = 0.91; 95%CI: 0.76-1.10). Multivariate analysis showed in younger than 18 years that girls and immunosuppression were factors associated with a decrease in the odds to develop asthma. In adults, asthma was positively associated with females, obesity, smoking, immunosuppression, chronic obstructive pulmonary disease, arterial hypertension, and cardiovascular disease. CONCLUSION: The prevalence of asthma in child and adult were lower than those previously reported. Our study seems to support the hypothesis that asthma patients have a lower risk of SARS-CoV-2 infection. Further studies are required to demonstrate the consistency of our findings.

Subcutaneous rapid-acting insulin analogues for diabetic ketoacidosis.

BACKGROUND: Diabetic ketoacidosis (DKA) is an acute, life-threatening complication of uncontrolled diabetes that mainly occurs in individuals with autoimmune type 1 diabetes, but it is not uncommon in some people with type 2 diabetes. The treatment of DKA is traditionally accomplished by the administration of intravenous infusion of regular insulin that is initiated in the emergency department and continued in an intensive care unit or a high-dependency unit environment. It is unclear whether people with DKA should be treated with other treatment modalities such as subcutaneous rapid-acting insulin analogues. OBJECTIVES: To assess the effects of subcutaneous rapid-acting insulin analogues for the treatment of diabetic ketoacidosis. SEARCH METHODS: We identified eligible trials by searching MEDLINE, PubMed, EMBASE, LILACS, CINAHL, and the Cochrane Library. We searched the trials registers WHO ICTRP Search Portal and ClinicalTrials.gov. The date of last search for all databases was 27 October 2015. We also examined reference lists of included randomised controlled trials (RCTs) and systematic reviews, and contacted trial authors. SELECTION CRITERIA: We included trials if they were RCTs comparing subcutaneous rapid-acting insulin analogues versus standard intravenous infusion in participants with DKA of any age or sex with type 1 or type 2 diabetes, and in pregnant women. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data, assessed studies for risk of bias, and evaluated overall study quality utilising the GRADE instrument. We assessed the statistical heterogeneity of included studies by visually inspecting forest plots and quantifying the diversity using the I² statistic. We synthesised data using random-effects model meta-analysis or descriptive analysis, as appropriate. MAIN RESULTS: Five trials randomised 201 participants (110 participants to subcutaneous rapid-acting insulin analogues and 91 to intravenous regular insulin). The criteria for DKA were consistent with the American Diabetes Association criteria for mild or moderate DKA. The underlying cause of DKA was mostly poor compliance with diabetes therapy. Most trials did not report on type of diabetes. Younger diabetic participants and children were underrepresented in our included trials (one trial only). Four trials evaluated the effects of the rapid-acting insulin analogue lispro, and one the effects of the rapid-acting insulin analogue aspart. The mean follow-up period as measured by mean hospital stay ranged between two and seven days. Overall, risk of bias of the evaluated trials was unclear in many domains and high for performance bias for the outcome measure time to resolution of DKA.No deaths were reported in the included trials (186 participants; 3 trials; moderate- (insulin lispro) to low-quality evidence (insulin aspart)). There was very low-quality evidence to evaluate the effects of subcutaneous insulin lispro versus intravenous regular insulin on the time to resolution of DKA: mean difference (MD) 0.2 h (95% CI -1.7 to 2.1); P = 0.81; 90 participants; 2 trials. In one trial involving children with DKA, the time to reach a glucose level of 250 mg/dL was similar between insulin lispro and intravenous regular insulin. There was very low-quality evidence to evaluate the effects of subcutaneous insulin aspart versus intravenous regular insulin on the time to resolution of DKA: MD -1 h (95% CI -3.2 to 1.2); P = 0.36; 30 participants; 1 trial. There was low-quality evidence to evaluate the effects of subcutaneous rapid-acting insulin analogues versus intravenous regular insulin on hypoglycaemic episodes: 6 of 80 insulin lispro-treated participants compared with 9 of 76 regular insulin-treated participants reported hypoglycaemic events; risk ratio (RR) 0.59 (95% CI 0.23 to 1.52); P = 0.28; 156 participants; 4 trials. For insulin aspart compared with regular insulin, RR for hypoglycaemic episodes was 1.00 (95% CI 0.07 to 14.55); P = 1.0; 30 participants; 1 trial; low-quality evidence. Socioeconomic effects as measured by length of mean hospital stay for insulin lispro compared with regular insulin showed a MD of -0.4 days (95% CI -1 to 0.2); P = 0.22; 90 participants; 2 trials; low-quality evidence and for insulin aspart compared with regular insulin 1.1 days (95% CI -3.3 to 1.1); P = 0.32; low-quality evidence. Data on morbidity were limited, but no specific events were reported for the comparison of insulin lispro with regular insulin. No trial reported on adverse events other than hypoglycaemic episodes, and no trial investigated patient satisfaction. AUTHORS' CONCLUSIONS: Our review, which provided mainly data on adults, suggests on the basis of mostly low- to very low-quality evidence that there are neither advantages nor disadvantages when comparing the effects of subcutaneous rapid-acting insulin analogues versus intravenous regular insulin for treating mild or moderate DKA.

[Systematic review with meta-analysis: Subcutaneous insulin glargine coadministration for diabetic ketoacidosis]. / Revisión sistemática con metaanálisis. Coadministración de insulina glargina en el manejo de la cetoacidosis diabética (CAD).

BACKGROUND: The standard treatment of diabetic ketoacidosis involves intravenous infusion of regular insulin until recovery of the episode: this is associated with high costs. Coadministration of insulin glargine from the onset of management may prove beneficial, potentially avoiding rebound hyperglycemia, and hopefully improving the time to resolution of the disease. METHODS: We searched MEDLINE, EMBASE, and CENTRAL for randomized controlled trials comparing coadministration of insulin glargine versus standard treatment in patients with diabetic ketoacidosis. To be eligible, studies must assess the efficacy of insulin glargine and report clinically important outcomes. Two reviewers extracted data, assessed risk of bias and summarized strength of evidence using the GRADE approach. RESULTS: Four studies (135 participants during hospital follow-up) were included in this review. Low-quality evidence from three trials suggested that subcutaneously administered insulin glargine, in addition to the standard treatment, significantly reduces the time to resolution of diabetic ketoacidosis (MD -4.19 hours; 95% CI: -7.81 to 0.57; p = 0.02). There was neutral difference between the two groups regarding length of hospital stay and hypoglycemic episodes. CONCLUSIONS: subcutaneously administered insulin glargine, in addition to standard treatment, significantly reduces the time to resolution of diabetic ketoacidosis, with neutral effects on hypoglycemic episodes.

Heparin versus placebo for non-ST elevation acute coronary syndromes.

BACKGROUND: Non-ST elevation acute coronary syndromes (NSTEACS) represent a spectrum of disease including unstable angina and non-ST segment myocardial infarction (NSTEMI). Despite treatment with aspirin, beta-blockers and nitroglycerin, unstable angina/NSTEMI is still associated with significant morbidity and mortality. Although evidence suggests that low molecular weight heparin (LMWH) is more efficacious compared to unfractionated heparin (UFH), there is limited data to support the role of heparins as a drug class in the treatment of NSTEACS. This is an update of a review last published in 2008. OBJECTIVES: To determine the effect of heparins (UFH and LMWH) compared with placebo for the treatment of patients with non-ST elevation acute coronary syndromes (unstable angina or NSTEMI). SEARCH METHODS: For this update the Cochrane Heart Group Trials Search Co-ordinator searched the Cochrane Central Register of Controlled Trials on The Cochrane Library (2013, Issue 12), MEDLINE (OVID, 1946 to January week 1 2014), EMBASE (OVID, 1947 to 2014 week 02), CINAHL (1937 to 15 January 2014) and LILACS (1982 to 15 January 2014). We applied no language restrictions. SELECTION CRITERIA: Randomized controlled trials of parenteral UFH or LMWH versus placebo in people with non-ST elevation acute coronary syndromes (unstable angina or NSTEMI). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed quality of studies and independently extracted data. MAIN RESULTS: There were no new included studies for this update. Eight studies (3118 participants) were included in this review. We found no evidence for difference in overall mortality between the groups treated with heparin and placebo (risk ratio (RR) = 0.84, 95% confidence interval (CI) 0.36 to 1.98). Heparins compared with placebo, reduced the occurrence of myocardial infarction in patients with unstable angina and NSTEMI (RR = 0.40, 95% CI 0.25 to 0.63, number needed to benefit (NNTB) = 33). There was a trend towards more major bleeds in the heparin studies compared to control studies (RR = 2.05, 95% CI 0.91 to 4.60). From a limited data set, there appeared to be no difference between patients treated with heparins compared to control in the occurrence of thrombocytopenia (RR = 0.20, 95% CI 0.01 to 4.24). Assessment of overall risk of bias in these studies was limited as most of the studies did not give sufficient detail to allow assessment of potential risk of bias. AUTHORS' CONCLUSIONS: Compared with placebo, patients treated with heparins had a similar risk of mortality, revascularization, recurrent angina, and thrombocytopenia. However, those treated with heparins had a decreased risk of myocardial infarction and a higher incidence of minor bleeding. Overall, the evidence assessed in this review was classified as low quality according to the GRADE approach. The results presented in this review must therefore be interpreted with caution.

Cost-Effectiveness Analysis of PET-CT Surveillance After Treatment of Human Papillomavirus-Positive Oropharyngeal Cancer.

OBJECTIVE: To determine the cost-effectiveness of surveillance imaging with PET/CT scan among patients with human papillomavirus-positive oropharyngeal squamous cell carcinoma. STUDY DESIGN: Cost-effectiveness analysis. SETTING: Oncologic care centers in the United States with head and neck oncologic surgeons and physicians. METHODS: We compared the cost-effectiveness of 2 posttreatment surveillance strategies: clinical surveillance with the addition of PET/CT scan versus clinical surveillance alone in human papillomavirus-positive oropharyngeal squamous cell carcinoma patients. We constructed a Markov decision model which was analyzed from a third-party payer's perspective using 1-year Markov cycles and a 30-year time horizon. Values for transition probabilities, costs, health care utilities, and their studied ranges were derived from the literature. RESULTS: The incremental cost-effectiveness ratio for PET/CT with clinical surveillance versus clinical surveillance alone was $89,850 per quality-adjusted life year gained. Flexible fiberoptic scope exams during clinical surveillance would have to be over 51% sensitive or PET/CT scan cost would have to exceed $1678 for clinical surveillance alone to be more cost-effective. The willingness-to-pay threshold at which imaging surveillance was equally cost-effective to clinical surveillance was approximately $80,000/QALY. CONCLUSION: Despite lower recurrence rates of human papillomavirus-positive oropharyngeal cancer, a single PET/CT scan within 6 months after primary treatment remains a cost-effective tool for routine surveillance when its cost does not exceed $1678. The cost-effectiveness of this strategy is also dependent on the clinical surveillance sensitivity (flexible fiberoptic pharyngoscopy), and willingness-to-pay thresholds which vary by country.

Assessing Laryngectomy Patient Education on YouTube: Investigating Quality and Reliability.

Objective: This study aimed to characterize the quality of laryngectomy-related patient education on YouTube and understand factors impacting video content quality. Study Design: Cross-sectional cohort analysis. Setting: Laryngectomy-related videos on YouTube. Methods: YouTube was anonymously queried for various laryngectomy procedure search terms. Video quality was evaluated using the validated DISCERN instrument which assesses treatment-related information quality. Descriptive statistics were used to characterize our cohort. Univariate and multivariable linear regression were used to assess factors associated with increased DISCERN score. Significance was set at P < .05. Results: Our 78-video cohort exhibited moderate levels of engagement, averaging 13,028.40 views (SD = 24,246.93), 69.79 likes (SD = 163.75), and 5.27 comments (SD = 18.81). Videos were most frequently uploaded to accounts belonging to physicians (43.59%) or health care groups (41.03%) and showcased operations (52.56%) or physician-led education (20.51%). Otolaryngologists were featured in most videos (85.90%), and most videos originated outside the United States (67.95%). Laryngectomy videos demonstrated poor reliability (mean = 2.35, SD = 0.77), quality of treatment information (mean = 1.92, SD = 0.86), and overall video quality (mean = 1.97, SD = 1.12). In multivariable linear regression, operative videos were associated with lower video quality relative to nonoperative videos (ß = -1.63, 95% confidence interval [CI] = [-2.03 to -1.24], P < .001); the opposite was true for videos from accounts with higher subscriber counts (ß = 0.02, 95% CI = [0.01-0.03], P = .005). Conclusion: The quality and quantity of YouTube's laryngectomy educational content is limited. There is an acute need to increase the quantity and quality of online laryngectomy-related content to better support patients and caregivers as they cope with their diagnosis, prepare for, and recover from surgery.

Prospective Outcomes After Serial Platelet-Rich Plasma (PRP) Injection in Vocal Fold Scar and Sulcus.

OBJECTIVE: Vocal fold scar and sulcus pose significant treatment challenges with no current optimal treatment. Platelet-rich plasma (PRP), an autologous concentration of growth factors, holds promise for regenerating the superficial lamina propria. This study aims to evaluate the potential benefits of serial PRP injections on mucosal wave restoration and vocal function. METHODS: In a prospective clinical trial across two institutions, patients with vocal fold scar underwent four serial PRP injections, one month apart. Blinded independent laryngologists and expert listeners used pretreatment and one-month post-fourth injection videostroboscopy and CAPE-V assessments to evaluate mucosal wave and voice quality changes, respectively. Additionally, patient reported outcome measures (PROMs) were evaluated. RESULTS: In the study, 15 patients received 55 PRP injections without adverse effects. Eight patients (53.3%) had mild, three patients (20%) had moderate, and four patients (26.7%) had severe scar. There was an average reduction of 8.7 points in post-treatment VHI-10 scores (p = 0.007). The raters observed an improvement in post-treatment voice in 73.4% of cases, and CAPE-V scores showed a reduction of 18.8 points on average (p = 0.036). The videostroboscopic VALI ratings showed an improvement in mucosal wave rating from 2.0 to 4.0. On average, the raters perceived the post-PRP exams to be better in 56.7% of cases. CONCLUSIONS: PRP has been validated as a safe autologous option for treatment of vocal fold scar. While results for mucosal wave and voice quality varied, there was a consistent improvement in PROMs. LEVEL OF EVIDENCE: Level 3: Prospective cohort study, with blinded analysis Laryngoscope, 2024.

Low-Dose Thymoglobulin versus Basiliximab Induction Therapy in Low-Risk Living Related Kidney Transplant Recipients: Three-Year Follow-Up Study.

BACKGROUND: The optimal dose of rabbit anti-thymocyte globulin (r-ATG) in renal transplantation is still under debate. We previously reported that a low-dose r-ATG induction of 3 mg/kg can be used safely and effectively in low-risk kidney transplants with good results in the first year after transplantation compared to basiliximab induction. AIMS: The purpose of this study is to evaluate the long-term impact of this trial of low-dose r-ATG versus basiliximab on post-transplant outcomes (patient and graft survival, biopsy-proven acute rejection incidence [BPAR], infectious complications, and side effects). METHODS: Observational study (three-year follow-up) of a 12-month single-center, open-label RCT in de novo kidney allograft recipients assigned to receive either thymoglobulin or basiliximab before transplantation. RESULTS: Patients in the basiliximab group (BG) underwent more kidney transplant biopsies than patients in the low-dose r-ATG group (TG) (50 vs. 31.8%, p = 0.07). Although the 12-month cumulative incidence of BPAR was lower in BG, by the end of the three-year follow-up period this incidence was higher (22%) than in the low-dose TG (15%) (p = ns). Steroids were withdrawn more frequently in the TG group and sirolimus was most frequently indicated. Graft function and graft survival were higher in the low-dose TG than in the BG at three-year follow-up but not statistically significant. Patient survival was similar between groups (>90%). CONCLUSIONS: These three-year follow-up data confirm the efficacy and favorable safety aspects of the low-dose r-ATG (3 mg/kg) in low-risk kidney transplantation.

Head and Neck Cancer Online Support Groups: Disparities in Participation and Impact on Patients.

Objective: To characterize the users of the head and neck cancer (HNC) online support group (OSG) and describe the perceived benefits of membership. Study Design: Cross-sectional. Setting: Online. Methods: An administered survey with questions asking about demographics, cancer history, treatment choices, and feelings about OSGs was posted on the 5 largest HNC OSGs on Facebook. Results: A total of 97 participants completed the survey. Mean age was 57.8 years old (standard deviation = 10.7 years). Most participants were female (50.5%) and Caucasian (92.8%). This cohort was well educated with 65.5% holding at least a college degree. Annual income was high with 41.8% reporting annual income of $100,000 or greater. The most common treatment modality was radiation (88.7%). The most common surgery was neck dissection (46.4%). Most participants preferred OSGs (70.8%) over other support group types. OSGs were heavily utilized with our cohort reporting using the OSG at least several times a week (80.0%). The top reasons for joining the OSG were sharing one's experience of HNC (76.3%) and gaining support from others with HNC (85.6%). OSGs were ranked as the #3 source of medical information for HNC behind otolaryngologists and oncologists. Membership in a HNC OSG had a minimal impact on decision-making. Conclusion: HNC OSGs appear to provide a beneficial community for HNC patients. Otolaryngologists should consider incorporating HNC OSG as a possible supplemental resource for their HNC patients.

An Exploratory Analysis of the Chronic Rhinosinusitis Online Support Community.

Objective: To characterize the users of the largest chronic rhinosinusitis (CRS) online support communities (OSCs), describe the perceived benefits of OSCs for their users, and understand how patient medical decision making is affected by membership in OSCs. Study Design: Cross-sectional online survey. Setting: Online. Methods: A cross-sectional online survey was adapted from the existing literature on patient support groups and modified for CRS patients. The survey was posted on multiple Facebook/Reddit groups aimed at providing support toward patients with CRS. Survey data was collected over 3 months and analyzed thereafter. Results: There were 127 total participants. The majority were female (65.35%), white (76.98%), and the median age was 38 years. Just under half of patients had nasal polyps (48.67%) and 54.54% had undergone surgery. Many participants (69.42%) reported engaging in the OSC at least multiple times per month. The most common reason for joining an OSC was to learn tips on how to manage CRS (89.7%) and the most achieved goal from membership was hearing from others undergoing a similar experience (79.5%). Involvement in an OSC impacted knowledge of CRS in 87.41% of participants. Most users (81.1%) would recommend membership in an OSC and 54.33% reported the OSC influenced their medical decision-making. Conclusion: A majority of patients with CRS who frequently engage in an OSC for CRS have a positive experience. OSCs are a resource that CRS patients utilize to manage their disease.

Hyperstabilization of T cell microvilli contacts by chimeric antigen receptors.

T cells typically recognize their ligands using a defined cell biology-the scanning of their membrane microvilli (MV) to palpate their environment-while that same membrane scaffolds T cell receptors (TCRs) that can signal upon ligand binding. Chimeric antigen receptors (CARs) present both a therapeutic promise and a tractable means to study the interplay between receptor affinity, MV dynamics and T cell function. CARs are often built using single-chain variable fragments (scFvs) with far greater affinity than that of natural TCRs. We used high-resolution lattice lightsheet (LLS) and total internal reflection fluorescence (TIRF) imaging to visualize MV scanning in the context of variations in CAR design. This demonstrated that conventional CARs hyper-stabilized microvillar contacts relative to TCRs. Reducing receptor affinity, antigen density, and/or multiplicity of receptor binding sites normalized microvillar dynamics and synapse resolution, and effector functions improved with reduced affinity and/or antigen density, highlighting the importance of understanding the underlying cell biology when designing receptors for optimal antigen engagement.

Cochlear implantation in Waardenburg syndrome: Systematic review and meta-analysis.

OBJECTIVE: Waardenburg syndrome (WS) is a genetic condition associated with moderate to profound sensorineural hearing loss. The aim of this review is to characterize cochlear implant (CI) outcomes in patients with a confirmed clinical diagnosis of WS. DATA SOURCES: MEDLINE, Ovid EMBASE, and Cochrane Library. REVIEW METHODS: All reports describing defined sets of patients with WS who underwent CI and subsequent evaluation of clinical outcomes were included. To harmonize outcome data between studies that used different measures, a binary variable Favored CI was developed to capture success of procedures (1 = favored, 0 = unfavored) based on original authors' description, commentary, discussion, and conclusions. Expert reviewers independently reviewed and selected articles, extracted data and scored Favored CI values. Synthetic and analytic meta-analyses were implemented using standard analytic techniques. RESULTS: Twenty articles meeting inclusion criteria provided data on 192 WS patients and 210 CIs. The mean age at CI was 3.8 years (95% confidence interval [95%CI]; 3.1-4.5 years), and the mean duration of follow up was 5.2 years (95% CI; 3.4-7.0 years). Surgical complications were rare (11/210 implants, 5.2%) where gusher was the most common complication. CIs yielded favorable hearing outcomes in 90% (95% CI; 84-94%) of cases, and appear successful for those with temporal bone anomalies (p = 0.04). CONCLUSIONS: Quantitative synthesis of the study data demonstrates that in the majority of patients with WS, CI yield favorable hearing outcomes and low rates of surgical complications. CI has shown to provide clinical benefits in patients with WS.

Opioid Sparing Multimodal Analgesia for Transoral Robotic Surgery: Improved Analgesia and Narcotic Use Reduction.

Objective: To compare postoperative pain scores and opioid consumption in patients after transoral robotic surgery (TORS). Study Design: Single institution retrospective cohort study. Setting: TORS was performed at a single academic tertiary care center. Methods: This study compared traditional opioid-based and opioid-sparing multimodal analgesia (MMA) regimens in patients with oropharyngeal and supraglottic malignancy after TORS. Data were obtained from the electronic health records from August 2016 to December 2021. The average postoperative pain scores and total opioid consumption in morphine milligram equivalents were calculated for postoperative days (PODs) 0 to 3. The secondary objectives were to quantify and characterize opioid prescriptions upon hospital discharge. Results: A total of 114 patients were identified for this study, 58 patients in the non-MMA cohort and 56 in the MMA cohort. Postoperative pain levels in the MMA cohort were statistically lower on POD 0 (p = 0.001), POD 1 (p = 0.001), and POD 3 (p = 0.004). Postoperative opioid consumption decreased significantly in the MMA cohort from 37.7 to 10.8 mg on POD 0 (p = 0.002), 65.9 to 19.9 mg on POD 1 (p < 0.001), 36.0 to 19.3 mg on POD 2 (p = 0.02), and 45.4 to 13.8 mg on POD 3 (p = 0.02). The number of patients discharged from the hospital with a prescription for narcotics was significantly lower in the MMA cohort (71.4%) compared with the non-MMA cohort (98.3%) (p < 0.001). Conclusion: Implementation of our MMA pain protocol reduced pain levels and narcotic consumption in the immediate postoperative period.