Hypoimmune islets achieve insulin independence after allogeneic transplantation in a fully immunocompetent non-human primate.

Allogeneic transplantation of pancreatic islets for patients with difficult-to-control diabetes mellitus is severely hampered by the requirement for continuous immunosuppression and its associated morbidity. We report that allogeneic transplantation of genetically engineered (B2M-/-, CIITA-/-, CD47+), primary, hypoimmune, pseudo-islets (p-islets) results in their engraftment into a fully immunocompetent, diabetic non-human primate wherein they provide stable endocrine function and enable insulin independence without inducing any detectable immune response in the absence of immunosuppression. Hypoimmune primary p-islets may provide a curative cell therapy for type 1 diabetes mellitus.

Serial assessment and long-term radiographic evaluation of the maxillary sinus after inferior maxillectomy and soft tissue free flap reconstruction in patients with oral cancer.

PURPOSE: This study evaluates serial radiographic changes in the maxillary sinus of patients with oral cancer after an inferior maxillectomy and a soft tissue free flap reconstruction. METHODS: Fifty-six patients were evaluated between Oct 2005 and Mar 2017 from an institutional database. Preoperative and surveillance imaging was reviewed at set time-points. Maxillary sinus scores were allotted based on a modification of the Lund-MacKay staging system. Patients were evaluated for change in sinus score. A univariate (UV) and multivariate (MV) analysis was performed. RESULTS: There were 53.5% T3/T4 category tumors and 68% received adjuvant treatment. Median follow-up was 24.4 months. Preoperative mean sinus score was 0.27 ± 0.44 and postoperative mean sinus score at 24 months was 1.2 ± 1.3 (p = <0.001). On UV analysis advanced T-stage at 12 months (OR 6.7, 95% CI 1.2-50.3, p = 0.01) and 24 months (OR 5.2, 95% CI 1.03-36.8, p = 0.04) was associated with significantly higher sinus score. On MV analysis, advanced T-stage continued to be associated with increased odds for higher sinus score (OR 4.9, 95% CI 1.1-26.8, p = 0.039). CONCLUSION: A mild increase in postoperative sinus score is seen in this cohort of patients. Advanced T-stage is associated with increased odds for higher sinus scores.

Hypoimmune induced pluripotent stem cells survive long term in fully immunocompetent, allogeneic rhesus macaques.

Genetic engineering of allogeneic cell therapeutics that fully prevents rejection by a recipient's immune system would abolish the requirement for immunosuppressive drugs or encapsulation and support large-scale manufacturing of off-the-shelf cell products. Previously, we generated mouse and human hypoimmune pluripotent (HIP) stem cells by depleting HLA class I and II molecules and overexpressing CD47 (B2M-/-CIITA-/-CD47+). To determine whether this strategy is successful in non-human primates, we engineered rhesus macaque HIP cells and transplanted them intramuscularly into four allogeneic rhesus macaques. The HIP cells survived unrestricted for 16 weeks in fully immunocompetent allogeneic recipients and differentiated into several lineages, whereas allogeneic wild-type cells were vigorously rejected. We also differentiated human HIP cells into endocrinologically active pancreatic islet cells and showed that they survived in immunocompetent, allogeneic diabetic humanized mice for 4 weeks and ameliorated diabetes. HIP-edited primary rhesus macaque islets survived for 40 weeks in an allogeneic rhesus macaque recipient without immunosuppression, whereas unedited islets were quickly rejected.

Single-nucleotide polymorphism at alcohol dehydrogenase 1B: A susceptible gene marker in oro-/hypopharyngeal cancers from genome-wide association study.

INTRODUCTION: In the era of precision preventive medicine, susceptible genetic markers for oro-/hypopharyngeal squamous cell carcinoma (OPSCC) have been investigated for genome-wide associations. MATERIALS AND METHODS: A case-control study including 659 male head and neck squamous cell carcinoma (HNSCC) patients, including 331 oropharyngeal cancer, treated between March 1996 and December 2016 and 2400 normal controls was performed. A single-nucleotide polymorphism (SNP) array was used to determine genetic loci that increase susceptibility to OPSCC. RESULTS: We analyzed the allele frequencies of 664,994 autosomal SNPs in 659 HNSCC cases; 7 SNPs scattered in loci of chromosomes 5, 7, 9, 11, and 19 were significant in genome-wide association analysis (Pc < 1.0669 × 10-7 ). In OPSCCs (n = 331), two clustered regions in chromosomes 4 and 6 were significantly different from the controls. We successfully identified a missense alteration of the SNP region in alcohol dehydrogenase 1B (ADH1B) (https://genome.ucsc.edu; hg38); the top correlated locus was rs1229984 (p = 1 × 10-11 ). Adjusted for environmental exposure, including smoking, alcohol, and areca quid, a region in chromosome 12, related to alcohol metabolism, was found to independently increase the susceptibility to OPSCC. The ADH1B rs1229984 AA genotype had better overall survival compared to the AG and GG genotypes (p = 0.042) in OPSCC. The GG genotype in rs1229984 was significantly associated with a younger age of onset than other genotypes (p = 0.001 and <0.001, respectively) in OPSCC patients who consumed alcohol. CONCLUSION: ADH1B was an important genetic locus that significantly correlated with the development of OPSCCs and patient survival.

Human hypoimmune primary pancreatic islets avoid rejection and autoimmunity and alleviate diabetes in allogeneic humanized mice.

Transplantation of allogeneic pancreatic donor islets has successfully been performed in selected patients with difficult-to-control insulin-dependent diabetes and impaired awareness of hypoglycemia (IAH). However, the required systemic immunosuppression associated with this procedure prevents this cell replacement therapy from more widespread adoption in larger patient populations. We report the editing of primary human islet cells to the hypoimmune HLA class I- and class II-negative and CD47-overexpressing phenotype and their reaggregation into human HIP pseudoislets (p-islets). Human HIP p-islets were shown to survive, engraft, and ameliorate diabetes in immunocompetent, allogeneic, diabetic humanized mice. HIP p-islet cells were further shown to avoid autoimmune killing in autologous, diabetic humanized autoimmune mice. The survival and endocrine function of HIP p-islet cells were not impaired by contamination of unedited or partially edited cells within the p-islets. HIP p-islet cells were eliminated quickly and reliably in this model using a CD47-targeting antibody, thus providing a safety strategy in case HIP cells exert toxicity in a future clinical setting. Transplantation of human HIP p-islets for which no immunosuppression is required has the potential to lead to wider adoption of this therapy and help more diabetes patients with IAH and history of severe hypoglycemic events to achieve insulin independence.

Hypoimmune anti-CD19 chimeric antigen receptor T cells provide lasting tumor control in fully immunocompetent allogeneic humanized mice.

Manufacturing autologous chimeric antigen receptor (CAR) T cell therapeutics is complex, and many patients experience treatment delays or cannot be treated at all. Although current allogeneic CAR products have the potential to overcome manufacturing bottlenecks, they are subject to immune rejection and failure to persist in the host, and thus do not provide the same level of efficacy as their autologous counterparts. Here, we aimed to develop universal allogeneic CAR T cells that evade the immune system and produce a durable response. We generated human hypoimmune (HIP) T cells with disrupted B2M, CIITA, and TRAC genes using CRISPR-Cas9 editing. In addition, CD47 and anti-CD19 CAR were expressed using lentiviral transduction. These allogeneic HIP CD19 CAR T cells were compared to allogeneic CD19 CAR T cells that only expressed the anti-CD19 CAR (allo CAR T). In vitro assays for cancer killing and exhaustion revealed no differences between allo CAR T and HIP CAR T cells, confirming that the HIP edits did not negatively affect T cell performance. Clearance of CD19+ tumors by HIP CAR T cells in immunodeficient NSG mice was comparable to that of allo CAR T cells. In fully immunocompetent humanized mice, HIP CAR T cells significantly outperformed allo CAR T cells, showed improved persistence and expansion, and provided lasting cancer clearance. Furthermore, CD47-targeting safety strategies reliably and specifically eliminated HIP CAR T cells. These findings suggest that universal allogeneic HIP CAR T cell-based therapeutics might overcome the limitations associated with poor persistence of allogeneic CAR T cells and exert durable anti-tumor responses.

Discovering the Clinical and Prognostic Role of Pan-Immune-Inflammation Values on Oral Cavity Squamous Cell Carcinoma.

A newly introduced pan-immune-inflammation value (PIV) was not evaluated for its role in oral cavity squamous cell carcinoma (OSCC). In this study, the PIV was calculated with the following equation (neutrophil count × platelet count × monocyte count)/lymphocyte count from the results of the automated hematology analyzers in 853 OSCC patients from 2005 to 2017. The optimal cutoff for the preoperative PIV was 268, as determined by a receiver operating characteristic curve. Significant differences were observed for alcohol consumption, smoking, pT status, pN status, overall pathological status, extranodal extension, cell differentiation, depth of invasion, and perineural invasion between higher and lower PIV patients (all p values < 0.05). Kaplan-Meier and univariate regression analyses indicated that higher PIV was associated with worse overall survival, disease-free survival, locoregional recurrence-free survival, and distant metastasis-free survival (all p values < 0.001). Multivariate analyses adjusted by various factors further demonstrated that PIV was an independent prognostic factor for overall and distant metastasis-free survival (p = 0.027, HR: 1.281 and p = 0.031, HR: 1.274, respectively). In conclusion, a higher PIV level was associated with poor clinicopathological factors in OSCC patients and could be used to predict poor posttreatment outcomes, especially for overall and distant metastasis-free survival.

Plasma Matrix Metalloproteinase-1 as a Prognostic Biomarker in Oral Cavity Squamous Cell Carcinoma.

Purpose: Plasma matrix metalloproteinase-1 (MMP-1) is a collagenase encoded by the MMP-1 gene. However, the prognostic value of plasma MMP-1 levels in oral cavity squamous cell carcinoma (OSCC) has yet to be elucidated. The study is the first to use a cohort of OSCC patients to assess the association of plasma MMP-1 levels with clinicopathological factors/survival outcomes in OSCC patients. Patients and Methods: A total of 677 patients were retrospectively enrolled, including 276 oral potentially malignant disease (OPMD) and 401 OSCC patients from 2013 to 2021. Pretreatment plasma MMP-1 levels were measured with an enzyme-linked immunosorbent assay, and the values were compared between OPMD and OSCC patients. Furthermore, the association of plasma MMP-1 levels and clinicopathological characteristics/survival outcomes in OSCC patients was investigated. Results: Plasma MMP-1 levels were significantly higher in OSCC patients than in OPMD patients (p = 0.04). In the OSCC group, plasma MMP-1 levels were significantly higher in females, tumor depth ≥10 mm, advanced pT classification and advanced overall stage (p = 0.04, <0.001, <0.001, 0.002, respectively). Higher plasma MMP-1 levels were significantly associated with poorer overall, disease-specific, disease-free, locoregional recurrence-free and distant metastasis-free survival (p = 0.003, 0.02, 0.005, 0.01, 0.001, respectively). Multivariate analysis revealed that plasma MMP-1 levels were a significant predictor for overall, disease-free, and distant metastasis-free survival (p = 0.03, 0.02, and 0.010, respectively). Conclusion: Plasma MMP-1 levels are associated with more severe clinicopathological manifestations and can also be regarded as a significant prognostic factor for OSCC posttreatment outcomes.

Carotid arterial blowout after organ preserving chemoradiation therapy in hypopharyngeal cancer.

Laryngeal preserving concurrent chemoradiation has been advocated for hypopharyngeal cancers. The use of radiotherapy (RT) in the larynx could lead to increased rates of radionecrosis. In this study, we investigated a rare but disastrous complication, carotid blow-out syndrome (CBS), related with the persistent radionecrosis. Retrospective cohort study. This retrospective study enrolled hypopharyngeal cancer patients with biopsy-proven pharyngeal and laryngeal chondronecrosis (PLCRN), which was rated by the Chandler Grading System. From 2002 to 2018, a total of 346 hypopharygeal cancer patients received upfront radiation therapy, 13 PLCRN patients were identified in a rate of 3.8%. All PLRN patients received RT with a mean radiation dose of 70.81 ±â€…0.85 Gy. All patients had Chandler Grade IV at the time of presentation, which was a mean of 15.08 months (range: 5-109 months) from the time of cancer diagnosis to PLCRN diagnosis. In 5 of the 13 PLCRN patients developed CBS. Three of the CBS originated from superior thyroid artery, one from lingual artery and one from the carotid artery. Three (60%) of the 5 CBS patients expired due to loss of airway and hemodynamic instability. Two (40%) were rescued by emergent airway secure and emergent angiographic embolization. Persistent PLCRN could lead to disastrous vascular complications. CBSs were demonstrated to be more frequently originated from the branches of carotid artery rather than carotid artery per se. Clinical alert with early airway protection could strive for time to do interventions and prevent mortalities.

Adequacy of Disease Control by Supraomohyoid Neck Dissection in cT1/T2 Tongue Cancer.

BACKGROUND: Patients affected by oral tongue squamous cell carcinoma (OTSCC) underwent a supraomohyoid neck dissection (SOHND) or modified radical neck dissection (mRND) according to the clinical nodal status (cN0 vs. cN+). We investigate whether the type of neck dissection affects survival with the presence of extranodal extension (ENE) and multiple nodal metastases (MNM). METHODS: We conducted a retrospective study enrolling surgically treated patients affected by cT1/T2 OTSCC and MNM or ENE. The outcomes assessed were: overall survival (OS), disease-free survival (DFS), and neck-control- and metastases-free survival (NC-MFS). Survival curves were plotted by the Kaplan-Meier method and the log-rank test. Furthermore, we conducted a multivariable analysis with the Cox regression model. RESULTS: We included a total of 565 patients (36% cT1, 64% cT2). Of these, 501 patients underwent a SOHND, and 64 underwent an mRND. A total of 184 patients presented rpN+, with 28.7% of these in the SOHND group and 62.5% of these in the mRND group. We identified no significant differences in OS, DFS, and NC-MFS in the whole pN+ cohort, in the MNM, and the ENE subgroups. In the multivariable analysis, the type of ND did not affect OS and DFS. CONCLUSIONS: Treating cT1-2 N0/+ tongue cancer with SOHND is oncologically safe. ENE and MNM patients do not benefit from an mRND.

Characteristics and outcome differences in male and female oral cavity cancer patients in Taiwan.

ABSTRACT: Oral cavity squamous cell carcinoma (OSCC) is a leading cause of death in Taiwan. Most of the patients in the literature are male. The risk factors, cancer characteristics, and treatment outcomes were investigated in female patients and compared with male patients in this study.This retrospective study recruited 2046 OSCC patients between 1995 and 2019. The age, tumor subsites, and survival were reviewed and recorded. Overall survival and disease-free survival were the main outcomes.Female patients represented 6.7% of the entire study cohort. Females were diagnosed at an older age and an earlier local stage than male patients (P < .001). Female patients were less exposed to cigarettes, alcohol, and betel-quid (all P < .001). The tongue (55.1%) was the most frequent subsite in females, while the buccal cavity (38.4%) and the tongue (35.3%) were more likely (P < .001) to be associated with the male gender. Female patients in the tongue cancer subgroup presented less frequently with extra-nodal extension compared with male patients (P = .040). No significant differences in recurrence or overall deaths were observed between the genders during the follow-up period.The OSCC male to female ratio in Taiwan was 14:1. Female OSCC occurred more frequently on the tongue, and was diagnosed at an older age and at an earlier tumor stage than in male patients. No survival difference was found between female and male OSCC patients.

Developing an Algorithm for Discriminating Oral Cancerous and Normal Tissues Using Raman Spectroscopy.

The aim of this study was to investigate the clinical potential of Raman spectroscopy (RS) in detecting oral squamous cell carcinoma (OSCC) in tumor and healthy tissues in surgical resection specimens during surgery. Raman experiments were performed on cryopreserved specimens from patients with OSCC. Univariate and multivariate analysis was performed based on the fingerprint region (700-1800 cm-1) of the Raman spectra. One hundred thirty-one ex-vivo Raman experiments were performed on 131 surgical resection specimens obtained from 67 patients. The principal component analysis (PCA) and partial least square (PLS) methods with linear discriminant analysis (LDA) were applied on an independent validation dataset. Both models were able to differentiate between the tissue types, but PLS-LDA showed 100% accuracy, sensitivity, and specificity. In this study, Raman measurements of fresh resection tissue specimens demonstrated that OSCC had significantly higher nucleic acid, protein, and several amino acid contents than adjacent healthy tissues. The specific spectral information obtained in this study can be used to develop an in vivo Raman spectroscopic method for the tumor-free resection boundary during surgery.

Parotid Space, a Different Space from Other Deep Neck Infection Spaces.

Deep neck infections (DNIs) such as parotid abscesses are medical emergencies with a seemingly different etiology and treatment course from other DNIs. We sought to confirm this in the present retrospective population-based cohort study. Between August 2016 and January 2020, 412 patients with DNIs seen at a tertiary medical center were enrolled in this study. Infections of the parotid space were compared with those of other deep neck spaces, according to patient characteristics. All patients were divided into parotid space (PS; n = 91, 22.08%) and non-parotid space (NPS; n = 321, 77.92%) subgroups. We further divided the patients into single parotid space (PS-single; n = 50, 12.13%), single non-parotid space (NPS-single; n = 149, 36.16%), multiple parotid space (PS-multiple; n = 41, 9.95%), and multiple non-parotid space (NPS-multiple; n = 172, 41.76%) DNI subgroups. In the PS-single and PS-multiple subgroups, a longer duration of symptoms (p = 0.001), lower white blood cell count (p = 0.001), lower C-reactive protein level (p = 0.010), higher rate of ultrasonography-guided drainage (p < 0.001), and lower rates of surgical incision and drainage (p < 0.001) were observed compared with the NPS-single and NPS-multiple subgroups. The PS group had a higher positive Klebsiella pneumoniae culture rate (p < 0.001), and lower positive Streptococcus constellatus (p = 0.002), and Streptococcus anginosus (p = 0.025) culture rates than the NPS group. In a multivariate analysis, K. pneumoniae was independently associated with parotoid space involvement in comparisons of the PS and NPS groups, PS-single and NPS-single subgroups, and PS-multiple and NPS-multiple subgroups. The clinical presentation of a parotid space infection differs from that of other deep neck space infections.

Factors Affecting the Necessity of Tracheostomy in Patients with Deep Neck Infection.

Deep neck infection (DNI) is a serious disease that can lead to airway obstruction, and some patients require a tracheostomy to protect the airway instead of intubation. However, no previous study has explored risk factors associated with the need for a tracheostomy in patients with DNI. This article investigates the risk factors for the need for tracheostomy in patients with DNI. Between September 2016 and February 2020, 403 subjects with DNI were enrolled. Clinical findings and critical deep neck spaces associated with a need for tracheostomy in patients with DNI were assessed. In univariate and multivariate analysis, older age (≥65 years old) (OR = 2.450, 95% CI: 1.163-5.161, p = 0.018), multiple spaces involved (≥3 spaces) (OR = 4.490, 95% CI: 2.153-9.360, p = 0.001), and the presence of mediastinitis (OR = 14.800, 95% CI: 5.097-42.972, p < 0.001) were independent risk factors associated with tracheostomy in patients with DNI. Among the 44 patients with DNI that required tracheostomy, ≥50% of patients had involvement of the parapharyngeal or retropharyngeal space (72.72% and 50.00%, respectively). Streptococcus constellatus (25.00%) was the most common pathogen in patients with DNI who required tracheostomy. In conclusion, requiring a tracheostomy was associated with a severe clinical presentation of DNI. Older age (≥65 years old), multiple spaces (≥3 spaces), and presence of mediastinitis were significant risk factors associated with tracheostomy in patients with DNI. The parapharyngeal and retropharyngeal spaces were the most commonly involved, and Streptococcus constellatus was the most common pathogen in the patients with DNI that required tracheostomy.

Polygenic Panels Predicting the Susceptibility of Multiple Upper Aerodigestive Tract Cancer in Oral Cancer Patients.

Head and neck cancer was closely related with habitual use of cigarette and alcohol. Those cancer patients are susceptible to develop multiple primary tumors (MPTs). In this study, we utilized the single nucleotide polymorphisms (SNPs) array (Affymetrix Axion Genome-Wide TWB 2.0 Array Plate) to investigate patients' risks of developing multiple primary cancers. We recruited 712 male head and neck cancer patients between Mar 1996 and Feb 2017. Two hundred and eighty-six patients (40.2%) had MPTs and 426 (59.8%) had single cancer. Four hundred and twelve normal controls were also recruited. A list of seventeen factors was extracted and ten factors were demonstrated to increase the risks of multiple primary cancers (alcohol drinking, rs118169127, rs149089400, rs76367287, rs61401220, rs141057871, rs7129229, older age, rs3760265, rs9554264; all were p value < 0.05). Polygenic scoring model was built and the area under curve to predict the risk developing MPTs is 0.906. Alcohol drinking, among the seventeen factors, was the most important risk factor to develop MPT in upper aerodigestive tract (OR: 7.071, 95% C.I.: 2.134-23.434). For those with high score in polygenic model, routine screening of upper digestive tract including laryngoscope and esophagoscope is suggested to detect new primaries early.

Endoscopic-Assisted Oropharyngectomy for Early Oropharyngeal Cancer in Trismus Patients.

Objective: Management of the early-stage oropharyngeal carcinoma in trismus patients underlying with multiple head and neck cancer history is a clinical challenge because minimal invasive surgery such as transoral robotic surgery or transoral laser microsurgery is contraindicated, while open surgery or concurrent chemoradiation (CCRT) wound cause long-term adverse effect. Therefore, we developed a novel endoscopic surgical approach for these patients. Methods: Four patients were enrolled for endoscopic-assisted oropharyngectomy. The oropharyngeal tumor was resected with an adequate margin via a one-surgeon bimanual approach with the aid of a high-resolution videoendoscopic system, scope holder, and designed surgical instruments. The postoperative surgical margin status, trismus status, perioperative complication, average hospital stay, and follow-up period were recorded. Results: The endoscopic-assisted oropharyngectomy was successfully applied in all 4 patients with en bloc tumor excision and adequate free margin status. The mean hospital stay was 6.5 days, and all patients could tolerate oral diet within 2 weeks. There was no perioperative complication noted. No tumor recurrence was identified in patients followed up 2 years after surgery. Conclusion: Endoscopic-assisted oropharyngectomy for patients with trismus and multiple head and neck cancer history is a safe, minimal invasive, and effective treatment choice other than open surgery or CCRT. It provides a safe option for patients with limited mouth opening.

Familial Aggregation of Head and Neck Cancer in Taiwan.

OBJECTIVES: Head and neck cancer (HNC) incidence has been increasing worldwide. We investigated the familial aggregation of developing HNC if a first-degree relative (FDR) is affected in a large database. METHODS: This retrospective study utilized Taiwan National Health Insurance Database to assemble a cohort of all registered beneficiaries from 1997 to 2013 and identified diagnosed HNC patients with affected FDRs. RESULTS: Of the 55,916 individuals diagnosed with HNC, 566 (1.01%) had affected FDRs. There were 525 (0.56%) males and 41 (0.05%) females. Age of onset of HNC was found to be earlier for those with an affected FDR at the fourth decade of life compared to the general population. The adjusted relative risks (RRs) of an individual with an affected FDR to develop HNC is 2.04 (95% confidence interval [CI], 1.85-2.26): 2.07 (95% CI, 1.88-2.29) if the affected relative was male, and 1.74 (95% CI, 1.31-2.30) if the affected relative was female. The greatest risk to develop HNC is if the affected individual is a twin with adjusted RR 33.04 (95% CI, 12.89-84.69). This is followed by an affected sibling at RR (95% CI) 3.46 (1.68-7.13), offspring at RR 2.28 (95% CI, 1.94-2.69), and parent at RR 1.66 (95% CI, 1.48-1.87). CONCLUSION: Familial tendency of HNC proves the probable contribution of genetic factors to develop cancer. In areca quid endemic region, there is a high likelihood that both environmental and genetic factors work in synergy to develop HNC. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:806-812, 2021.

Association of XRCC2 rs2040639 with the survival of patients with oral squamous cell carcinoma undergoing concurrent chemoradiotherapy.

OBJECTIVE: To investigate the association between the variants of DNA double-strand break repair genes and the clinical outcomes of patients with oral squamous cell carcinoma (OSCC) undergoing concurrent chemoradiotherapy. METHODS: Five variants of DNA double-strand break repair genes in samples from 319 patients with OSCC were genotyped using the Sequenom iPLEX MassARRAY system. Kaplan-Meier curves and Cox proportional hazards analysis were used to identify the factors associated with patient survival. RESULTS: The XRCC2 rs2040639 (G3063A) polymorphism in the codominant model was associated with decreased recurrence risk (hazard ratio [HR] = 0.55, 95% confidence interval [CI] = 0.31-0.98; p = 0.042). A marginally significant interaction was observed between XRCC2 rs2040639 and PRKDC rs7003908 in patients carrying the AA and AA genotypes; these patients showed reduced recurrence risk (HR = 0.36, 95% CI = 0.17-0.79; p = 0.010). CONCLUSION: The A-allele of XRCC2 rs2040639 is a favorable prognostic factor for disease-free survival. Patients with these genotypes may benefit from concurrent chemoradiotherapy. Additional confirmation from studies with larger samples or other ethnic populations is warranted.

Predictive value of genetic variants XRCC1 rs1799782, APEX1 rs1760944, and MUTYH rs3219489 for adjuvant concurrent chemoradiotherapy outcomes in oral squamous cell carcinoma patients.

Genetic variations in DNA base excision repair (BER) genes may affect tumor sensitivity to chemotherapy and radiotherapy. Thus, we investigated the effects of single-nucleotide polymorphisms (SNPs) in key BER pathway genes on clinical outcomes in male patients who received concurrent chemoradiotherapy (CCRT). Seven SNPs from XRCC1, OGG1, APEX1, and MUTYH were genotyped using the Sequenom iPLEX MassARRAY system in samples from 319 men with advanced oral squamous cell carcinoma. The disease-free survival (DFS) rates of the MUTYH rs3219489 genotypes and those of the other genotypes differed significantly (log-rank test p = 0.027). Multivariate Cox proportional hazard analysis showed that the MUTYH rs3219489 GG genotype was associated with poor DFS (recessive model: hazard ratio [HR] = 2.01, 95% confidence interval [CI] = 1.31-3.10; p = 0.002). The CT + TT genotypes of XRCC1 rs1799782 (dominant model: HR = 0.65, 95% CI = 0.43-0.99; p = 0.044) and GG genotype of APEX1 rs1760944 (recessive model: HR = 1.64, 95% CI = 1.00-2.70; p = 0.050) were associated with overall survival (OS). Carrying the two risk genotypes, CC and GG of XRCC1 rs1799782 and APEX1 rs1760944, respectively, (HR = 2.95, 95% CI = 1.47-5.88; p = 0.002) increased mortality risk. Our findings showed that carrying the two risk genotypes of XRCC1 rs1799782 and APEX1 rs1760944 was associated with poor OS, while the GG genotype of MUTYH rs3219489 was associated with poor DFS. Patients carrying the risk genotypes may not benefit from CCRT; therefore, they will need alternative treatments.

Validation of Korean version of scrub nurses’ intra-operative non-technical skills evaluation system / 의료커뮤니케이션

Background@#: This is a methodological study for validation of the Korean version of scrub practitioners’ list of intra-operative nontechnical skills system, K-SPLINTS.Method : Data were collected from multidisciplinary expert panel (n=6) and a group of scrub nurses (n=40) with minimum two years of operative theatre experience in two university hospitals in Seoul. Contents validity was calculated from expert panel and reliability, completeness, observability and usability were analyzed from scrub nurses group.Result : K-SPLINTS is deemed to be adequate for assessing and training scrub nurses’ intraoperative behaviours. @*Conclusion@#: K-SPLINTS could be useful to inspire scrub nurses non-technical skills in the operating theatre.