Serum Albumin as an Independent Predictor of Long-Term Survival in Patients with Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma Treated with Nivolumab.

Background: Nivolumab has been shown to improve the overall survival (OS) of patients with recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, there is a need to identify factors associated with long-term survival (beyond 2 years) in these patients. This study investigated the relationship between pretreatment factors and long-term survival in patients with R/M HNSCC treated with nivolumab. Methods: Forty-nine patients with R/M HNSCC who were treated with nivolumab were retrospectively reviewed. Baseline characteristics, clinical data, and survival outcomes were evaluated. Univariate and multivariate analyses were performed to identify factors associated with long-term survival (OS ≥ 2 years). Results: The median OS in the overall cohort was 11.0 months, and the 2-year survival rate was 34.7%. Long-term survivors (OS ≥ 2 years) had significantly higher proportions of patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores of 0 or 1, serum albumin levels ≥ 3.5 g/dL, and neutrophil-to-eosinophil ratio (NER) < 32.0 compared to non-long-term survivors. On multivariate analysis, serum albumin levels ≥ 3.5 g/dL, in addition to ECOG-PS score of 0 or 1, were independent predictors of long-term survival. Conclusions: Pretreatment serum albumin levels may be useful for predicting long-term survival in R/M HNSCC patients treated with nivolumab.

A Community-Based Intervention to Enhance Subjective Well-Being in Older Adults: Study Design and Baseline Participant Profiles.

Promoting subjective well-being is a crucial challenge in aging societies. In 2022, we launched a community-based intervention trial (the Chofu-Digital-Choju Movement). This initiative centered on fostering in-person and online social connections to enhance the subjective well-being of older adults. This paper describes the study design and baseline survey. This quasi-experimental study involved community-dwelling older adults aged 65-84 years in Chofu City, Tokyo, Japan. A self-administered questionnaire was distributed to 3742 residents (1681 men and 2061 women), and a baseline survey was conducted in January 2022. We assessed subjective well-being (primary outcome); psychosocial, physical, and dietary factors; and the use of information and communication technology variables (secondary outcomes) among the participants. After the intervention involving online classes, community hubs, and community events, a 2-year follow-up survey will be conducted to evaluate the effects of the intervention, comparing the intervention group (participants) with the control group (non-participants). We received 2503 questionnaires (66.9% response rate); of these, the analysis included 2343 questionnaires (62.6% valid response rate; mean age, 74.4 (standard deviation, 5.4) years; 43.7% male). The mean subjective well-being score was 7.2 (standard deviation, 1.9). This study will contribute to the development of a prototype subjective well-being strategy for older adults.

Effects of Levothyroxine Treatment on Fertility and Pregnancy Outcomes in Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Subclinical hypothyroidism, defined by elevated thyrotropin (TSH) and normal free thyroxine levels, is associated with adverse pregnancy outcomes, including preterm birth, pre-eclampsia, and small for gestational age. Despite the uncertainty regarding the effectiveness of levothyroxine (LT4) treatment on pregnancy outcomes in subclinical hypothyroidism, LT4 is widely administered with a pre-treatment threshold TSH level of 2.5 mU/L. The aim of this study is to investigate the efficacy of periconceptional LT4 treatment for subclinical hypothyroidism, including TSH levels >2.5 mU/L, and identify the characteristics of subclinical hypothyroidism that can benefit from LT4 treatment. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials from inception to February 2023. We analyzed the pooled effects of LT4 on subclinical hypothyroidism before and during pregnancy. The main outcomes before pregnancy were live birth, pregnancy, and miscarriage. The main outcomes during pregnancy were live birth, miscarriage, and preterm birth. We conducted subgroup analyses to compare the effects of LT4 on subclinical hypothyroidism with TSH levels of 2.5-4.0 and >4.0 mU/L. Results: Of the 888 studies identified, 27 full-text articles were screened for eligibility. Five studies on pre-conception treatment with 768 participants and eight studies on treatment during early pregnancy with 2622 participants were analyzed. One of the two studies on pre-conception treatment in subclinical hypothyroidism with TSH >4.0 mU/L had high risk of bias and the other was composed of 64 participants. Pre-conception LT4 treatment had no significant effect in improving rates of live births and pregnancies, or reducing miscarriages (risk ratio [RR], 95% confidence interval): 1.41 (0.84-2.36), 1.73 (0.88-3.39), and 0.46 (0.11-2.00), respectively. LT4 treatment during pregnancy was not significantly associated with higher rates of live births (RR 1.03, 0.98-1.09) nor decreased miscarriage rates (RR 1.01, 0.66-1.53). The effect of LT4 treatment on preterm birth during pregnancy was significantly different depending on the TSH values (p = 0.04); a positive effect was shown in the subclinical hypothyroidism subgroup with TSH >4.0 mU/L (RR 0.47, 0.20-1.10), while no significant effect was observed in the subgroup with TSH 2.5-4.0 mU/L (RR 1.35, 0.79-2.31). Conclusions: Pre-conceptional LT4 treatment for subclinical hypothyroidism does not improve fertility or decrease the incidence of miscarriages. However, further well-designed studies are needed for pre-conceptional treatment, especially in TSH >4.0 mU/L. LT4 treatment during pregnancy had a positive effect on preterm birth; nevertheless, this was only applicable to subclinical hypothyroidism with TSH >4.0 mU/L.

Risk Factors Causing Hypothyroidism in Patients With Head and Neck Cancer After Radiotherapy Using SIB-VMAT.

BACKGROUND/AIM: We evaluated the incidence of radiation-induced hypothyroidism and its risk factors in patients with head and neck cancer who underwent radiotherapy using simultaneous integrated boost-volumetric-modulated arc therapy (SIB-VMAT). PATIENTS AND METHODS: This retrospective study included 86 patients who received definitive radiotherapy using SIB-VMAT for head and neck cancer. The incidence of ≥ grade 2 hypothyroidism was evaluated. We also evaluated the relationships between hypothyroidism development and clinical factors and thyroid dose-volume parameters. RESULTS: During a median follow-up period of 17 months (range=3-65 months), 31 patients (36.0%, 31/86) developed grade 2 hypothyroidism requiring hormone replacement therapy. No patients experienced ≥ grade 3 hypothyroidism. The cumulative incidences of hypothyroidism at 1 and 2 years after radiation therapy were 24.5% and 38.7%, respectively, with a median onset time of 10.0 months (range=3.0-35.0 months). Thyroid volume (p=0.003), volume of the thyroid spared at 60 Gy (VS60; cut-off value, 5.16 ml; p=0.009), VS70 (cut-off value, 8.0 ml; p=0.007), VS60 equivalent dose in 2 Gy fraction (EQD2; cut-off value, 7.78 ml; p=0.001), and VS70EQD2 (cut-off value, 10.59 ml; p=0.008) were significantly associated with the development of radiation-induced hypothyroidism. CONCLUSION: Radiation-induced hypothyroidism is not rare in patients with head and neck cancer undergoing radiotherapy using SIB-VMAT. Radiation dose-volume parameters detected in this study may be useful indicators to prevent this complication.

CD98 expression can be a predictive factor of resistance to radiotherapy in head and neck squamous cell carcinoma.

CD98 is a marker of cancer stem cells, and it regulates radiosensitivity in head and neck squamous cell carcinoma (HNSCC). The current study aimed to investigate whether CD98 can be used as a prognostic factor and marker of radioresistance. CD98 immunostaining was performed using biopsy specimens collected from patients diagnosed with HNSCC. The average period of postoperative monitoring was 31.6 months. The treatment options were radiation therapy with either cisplatin or cetuximab, and surgery. The participants were divided into groups of low and high fluorescence intensity. CD98 was an independent prognostic factor of radioresistance. In total, 103 patients were treated with chemoradiotherapy or bioradiotherapy. The overall survival rates of patients receiving chemoradiotherapy or bioradiotherapy were 69.2% in the low group and 36.2% in the high group. The progression-free survival rates were 60.0% and 24.6%, respectively. CD98 expression was considered an independent prognostic factor of overall survival and progression-free survival. In total, 99 patients underwent surgical treatment. The surgery group did not differ according to CD98 expression. Via CD98 immunostaining, sensitivity to radiotherapy can be determined in advance. In HNSCC, knowledge about sensitivity to radiotherapy can significantly improve prognosis.

LAT1 is associated with poor prognosis and radioresistance in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) has been identified as the sixth most common disease in the world, and its prognosis remains poor. The basic treatment of HNSCC includes a combination of chemoradiation and surgery. With the advent of immune checkpoint inhibitors, the prognosis has improved; however, the efficacy of checkpoint inhibitors is limited. L-type amino acid transporter 1 (LAT1), an amino acid transporter, is highly expressed in a cancer-specific manner. However, to the best of our knowledge, LAT1 expression in HNSCC has not been determined. Therefore, the present study aimed to examine the role of LAT1 expression in HNSCC. A total of three HNSCC cell lines (Sa3, HSC2 and HSC4) were used to investigate the characteristics of LAT1-positive cells, including their ability to form spheroids, and their invasion and migration. The present study also examined LAT1 by immunostaining of biopsy specimens from 174 patients diagnosed, treated and followed-up at Akita University (Akita, Japan) between January 2010 and December 2019, and overall survival, progression-free survival and multivariate analyses were performed. The results demonstrated that LAT1-positive cells in HNSCC were an independent prognostic factor for overall survival and progression-free survival, and were resistant to chemoradiation. Therefore, JPH203, a LAT1 inhibitor, may be effective in treating chemoradiotherapy-resistant HNSCC and may improve the prognosis of patients with HNSCC.

Tocolytic Therapy Inhibiting Preterm Birth in High-Risk Populations: A Systematic Review and Meta-Analysis.

This systematic review aimed to identify the benefits and possible harms of tocolytic therapy for preterm labour management in the context of pregnant women with extremely preterm birth, multiple gestations, or growth-restricted foetuses. A comprehensive search using MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, CINAHL, and the WHO Global Index Medicus databases was conducted from 10 to 15 July 2021. We included randomized controlled trials and non-randomized studies that assessed the effects of tocolysis compared with placebo or no treatment. We found 744 reports and, finally, nine studies (three randomized controlled trials and six cohort studies) pertaining to women with <28 weeks of gestation were included. No eligible studies were identified among women with a multiple pregnancy or a growth-restricted foetus. A meta-analysis of the trial data showed that there were no clear differences in perinatal death nor for a delay in birth. Non-randomized evidence showed that tocolysis delayed birth by 7 days, though there was no clear difference for preterm birth. In summary, it remains unclear whether tocolytic therapy for inhibiting preterm labour is beneficial for these subgroups of women and their newborns. Further well-designed randomized controlled trials and observational studies are needed to address the lack of evidence regarding tocolytic agents in these populations.

Optimal threshold of a control parameter for tomotherapy respiratory tracking: A phantom study.

BACKGROUND: Radixact Synchrony® , a real-time motion tracking and compensating modality, is used for helical tomotherapy. Control parameters are used for the accurate application of irradiation. Radixact Synchrony® uses the potential difference, which is an index of the accuracy of the prediction model of target motion and is represented by a statistical prediction of the 3D distance error. Although there are several reports on Radixact Synchrony® , few have reported the appropriate settings of the potential difference threshold. PURPOSE: This study aims to determine the optimal threshold of the potential difference of Radixact Synchrony® during respiratory tumor-motion-tracking irradiation. METHODS: The relationship among the dosimetric accuracy, motion tracking accuracy, and control parameter was evaluated using a moving platform, a phantom with a basic respiratory model (the fourth power of a sinusoidal wave), and several irregular respiratory model waveforms. The dosimetric accuracy was evaluated by gamma analysis (3%, 1 mm, 10% dose threshold). The tracking accuracy was measured by the distance error of the difference between the tracked and driven positions of the phantom. The largest potential difference for 95% of treatment time was evaluated, and its correlation with the gamma-pass ratio and distance error was investigated. The optimal threshold of the potential difference was determined by receiver operating characteristic (ROC) analysis. RESULTS: A linear correlation was identified between the potential difference and the gamma-pass ratio (R = -0.704). A linear correlation was also identified between the potential difference and distance error (R = 0.827). However, as the potential difference increased, it tended to underestimate the distance error. The ROC analysis revealed that the appropriate cutoff value of the potential difference was 3.05 mm. CONCLUSION: The irradiation accuracy with motion tracking by Radixact Synchrony® could be predicted from the potential difference, and the threshold of the potential difference should be set to ∼3 mm.

Evaluation of the direction and extent of ice formation during cryoballoon ablation: an experimental study.

BACKGROUND: The distal hemisphere of a balloon is generally cooled during cryoapplication. However, a wide ablation area can be acquired after cryoballoon ablation. This study aimed to evaluate the extent of ice formation on two types of balloon surfaces through experimental and simulation studies. METHODS: A standard cryoballoon (SCB; Arctic Front Advance Pro, Medtronic) and novel cryoballoon (NCB; POLARx, Boston Scientific) were frozen for 240 s in 36 °C normal saline solution to observe ice formation on the balloon surface. Pieces of porcine tissue were placed between the upper and lower sides of the balloon, and the balloon was frozen in the horizontal direction for 240 s in 20 attempts (10 for SCB and NCB each). The measured areas of ice formation were evaluated and compared between the upper and lower sides of each balloon. RESULTS: Ice formation was greater on the lower side of the balloon than on the upper side. A larger area of ice formation in the tissue slab was observed on the lower side than on the upper side in both balloons, and the ice formation extended to the proximal hemisphere on the lower side of the balloon. The ice formation area in the NCB was significantly larger than that in SCB. CONCLUSIONS: Ice formation was significantly greater on the lower side of the cryoballoon than on the upper side and extended to the proximal hemisphere of the balloon, which might facilitate the acquisition of a wide ablation area on the left atrial posterior wall after cryoballoon ablation. Different ice formation after cryoballoon ablation Greater ice formation on the lower side of cryoballoon and an extensive ice formation in the proximal hemisphere, especially in novel cryoballoon.

[Construction of a System That Links Treatment RIS Terminals and Smartphones to Facilitate Radiation Therapy Operations].

Confirmation of patient information is required to ensure the safety of radiation therapy. The purpose of this study was to construct a system that facilitates radiation therapy operations by linking a radiation therapy information system to a smartphone. By linking a smartphone to a radiation therapy operation support system, without using a PC terminal, we were able to input information about the patient's position and fixation into images taken with a smartphone. In addition, patient information could be directly linked into the radiation therapy information system. In addition, patient information could be verified in the irradiation room by synchronizing the smartphone with the radiation therapy support system. The questionnaire was highly evaluated in terms of radio reception, usability, visibility and barcode reading. In this study, by linking a smartphone to a radiotherapy information system, it was possible to construct a system that facilitates radiotherapy operations by checking and registering patient information at hand.

The Current Concept of Paternal Bonding: A Systematic Scoping Review.

Bonding is crucial to perinatal mental health. Despite an extensive body of literature on maternal bonding, few studies have focused on paternal bonding. This scoping review aimed to clarify the current state of the concept of paternal-infant/fetus bonding. The eligibility criteria were drawn from the population concept and context elements to answer the following questions: "what is paternal bonding?" and "what are the constructs of the concept of paternal bonding?" The review comprised 39 studies. Paternal bonding was associated with both positive and negative paternal behavior and thought and may be determined based on fathers' beliefs and rearing history. Most studies showed that father-child interaction is one of the factors promoting paternal bonding. However, fathers generally felt more distant from their babies post-delivery than mothers. Only a few studies originally defined paternal bonding; most relied on the definitions of maternal bonding. We found different descriptions lacking consensus. Few studies examined the differences between paternal and maternal bonding. No consensus exists on the concept, constructs, and assessment of paternal bonding. The causal relationship between paternal bonding and other variables is unexplored. Future studies should explore fathers' perspectives and experiences, focusing on the unknown aspects of paternal bonding identified in this review.

GPNMB-Positive Cells in Head and Neck Squamous Cell Carcinoma-Their Roles in Cancer Stemness, Therapy Resistance, and Metastasis.

Objective: Despite the use of surgical and chemoradiation therapies, head and neck squamous cell carcinoma (HNSCC) still has a poor prognosis. Immune checkpoint inhibitors have been shown to prolong life expectancy but have limited efficacy. Glycoprotein nonmetastatic melanoma protein B (GPNMB) has received significant attention in breast cancer treatment, in which it has been associated with cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT); however, the function of GPNMB in HNSCC is completely unknown. This study aimed to clarify the characteristics of GPNMB-positive cells in vitro and their association with the prognosis by immunostaining clinical specimens. Methods: We examined the sphere formation, invasion, and migration ability of GPNMB-positive cells in four HNSCC cell lines in vitro. We also immunostained biopsy specimens with GPNMB from 174 patients with HNSCC diagnosed, treated, and followed-up in our institution to evaluate overall survival and progression-free survival. Results: GPNMB-positive cells showed enhanced sphere formation, invasion, and migration, suggesting that they could have CSC characteristics and the ability to induce EMT, as reported for breast cancer. Clinical specimens showed that overall survival was 39.4% and 57.8% (p = 0.045) and that progression-free survival was 27.6% and 51.6% (p = 0.013) for the high-expression and the low-expression groups, respectively, indicating poor prognosis for the high GPNMB group. The high GPNMB group was also more resistant to chemoradiation and bioradiotherapy. GPNMB was more highly expressed in metastatic lymph nodes than in the primary tumor. Conclusion: GPNMB-positive cells might have CSC characteristics and induce EMT. Detailed functional analyses of GPNMB in HNSCC and the establishment of therapies targeting GPNMB will lead to improved prognoses.

Protective Effect of Polaprezinc and Hyperbaric Oxygen Therapy on Radiation-induced Small Intestinal Damage in Mice.

BACKGROUND/AIM: To investigate the effect of polaprezinc (antioxidant) administration and hyperbaric oxygen therapy on radiation-induced intestinal injury. MATERIALS AND METHODS: Forty-five C57BL/6J mice underwent total body radiation of 2 Gy. Polaprezinc was given in 12 mice, hyperbaric oxygen in 12 mice, and both in 12 mice. The other 9 mice did not undergo any treatment. Mice were sacrificed 2, 4, and 6 h after radiation, and 9 specimens (3 each from the duodenum, jejunum, and ileum) were harvested. Apoptotic intestinal crypt cells were histologically evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. RESULTS: Apoptotic cell number per 1,000 crypt cells was 31.0±6.7 at 2 h, 28.4±5.2 at 4 h, and 32.9±5.1 at 6 h in the mice group treated by radiation alone. Both polaprezinc administration and hyperbaric oxygen therapy significantly suppressed apoptosis. Although the effect of polaprezinc administration on suppressing apoptosis became less over time (4.9±5.7 and 19.4±13.2 at 2 and 6 h, respectively), that of hyperbaric oxygen therapy was stable regardless of time (23.6±4.8 and 25.8±4.1 at 2 and 6 h). Administration of both polaprezinc and hyperbaric oxygen showed a significant synergetic or additive effect on suppressing apoptosis at 6 h (11.4±10.5, p<0.0035 vs. polaprezinc, p<0.0001 vs. hyperbaric oxygen). CONCLUSION: Both polaprezinc administration and hyperbaric oxygen therapy are effective in relieving radiation-induced small intestinal damage, and a synergistic or additive effect is expected when using both.

Cardiopulmonary exercise responses in patients with non-ischemic heart failure and a mildly reduced ejection fraction.

Background: The cardiopulmonary response to exercise in patients with heart failure exhibiting a mildly reduced ejection fraction (41% ≤ EF ≤ 49%) remains unclear. Materials & methods: A total of 193 consecutive patients with heart failure (excluding those with coronary artery disease) who underwent cardiopulmonary exercise (CPX) tests were examined. CPX variables were compared among patients with reduced, mildly reduced, and preserved EF. Results: The CPX test responses of patients with mildly reduced EF were similar to those of patients with reduced or preserved EF; however, increases in systolic blood pressure during exercise differed significantly (32 ± 26, 50 ± 24, and 41 ± 31 mmHg, respectively; p = 0.016). Grip strength and an increase in systolic blood pressure during exercise were independently associated with peak oxygen uptake in patients with mildly reduced EF (ß = 0.41, 0.35, respectively; p < 0.05). Conclusion: Measurements of grip strength and blood pressure during exercise are useful predictors of prognoses in patients with non-ischemic and mildly reduced EF.

Cardiopulmonary exercise (CPX) test is widely used to evaluate the function related to heart in heart failure patients. The heart failure patients are divided into three groups: with reduced wall motion (HFrEF), with mildly reduced wall motion (HFmrEF) and with preserved wall motion (HFpEF). We compared the cardiopulmonary reaction to exercise among the three groups. The CPX test responses of patients with HFmrEF were similar to those of patients with HFrEF or HFpEF. However, increases in systolic blood pressure during exercise differed (32 ± 26, 50 ± 24, and 41 ± 31 mmHg, respectively; p = 0.016). Grip strength and an increase in systolic blood pressure during exercise were independently associated with peak oxygen uptake, which is an important predictor of rate of death in patients with HFmrEF. Measurements of grip strength and blood pressure during exercise are useful predictors of progress in patients with enough blood supply to the heart and HFmrEF.

Cytomorphometric and flow cytometric analyses using liquid-based cytology materials in subtypes of lung adenocarcinoma.

BACKGROUND: The histological classifications of invasive lung adenocarcinoma subtypes are considered to predict patient prognosis after surgical treatment. The objectives of this study were to evaluate cytomorphological characteristics and proliferative activities among the histological predominant patterns by performing cytomorphometric and flow cytometric analyses using liquid-based cytology materials. METHODS: Cytological samples fixed by liquid-based cytology preservatives from 53 surgically-resected lung adenocarcinoma specimens were obtained between August 2018 and November 2019. The Papanicolaou-stained and paired Ki-67-stained slides were analyzed for calculating nuclear morphology (nuclear area, nuclear perimeter and nuclear circularity) and Ki-67 labeling index using software. The cell proliferation index (CPIx) was calculated and cellular information including cell cycle stage of tumor cells was obtained by flow cytometry. RESULTS: The 53 cases included papillary (n = 29), acinar (n = 8), lepidic (n = 5), and solid (n = 4) subtypes, and invasive mucinous adenocarcinoma (n = 7) were also included. In the lepidic pattern, nuclear area (79.6 ± 28.8 µm2 ) and perimeter (34.1 ± 6.1 µm) were relatively larger and longer than those of the other predominant patterns. The Ki-67 labeling index of the solid pattern (27.9 ± 12.5%) was highest compared with those of other predominant patterns. There were statistically significant differences in the lepidic versus solid patterns and the papillary versus solid patterns (p = .013 and p = .039, respectively). The calculated mean CPIx of the lepidic and the acinar patterns were approximately two-fold higher than those of the other predominant patterns. CONCLUSION: By revealing the differences of cytomorphological characteristics, these methodologies might be used for diagnosing cytopathological materials using digital cytopathology.

COVID-19 Vaccination in Patients with Cancer.

Patients with cancer are concerned about the effects of the COVID-19 vaccination. We conducted an online survey on the COVID-19 vaccination status and side effects among patients with cancer in Japan between 8 and 14 August 2021. We included 1182 female patients with cancer aged 20-70 years and registered on an online patient website. Of the patients, 944 had breast cancer, 216 had gynecological cancer, 798 were undergoing drug/radiation therapy, and 370 were in follow-up. At the time of the survey, 885 patients had already received at least one dose. Of these, 580 had also received their second dose. The incidence rate of side effects was equivalent to previous reports. In patients with breast cancer, problems such as the onset or worsening of lymphedema or axillary lymphadenopathy metastasis requiring differential diagnosis were encountered following vaccination. A total of 768 patients were concerned about the vaccine at some point, and 726 consulted with their attending physicians about the timing or side effects of the vaccination. Of the 110 patients undergoing chemotherapy or radiation therapy, 75 adjusted the timing of the vaccination based on their therapy. The cross-analysis revealed that 81% of those who consulted their physician had received at least one dose of the COVID-19 vaccination compared with 65% of those who had not consulted their physician. Consulting with a physician about the COVID-19 vaccination was found to alleviate the concerns of patients with cancer and encourage them to get vaccinated.

Tumor Infiltrating Lymphocytes are Prognostic Factors and Can Be Markers of Sensitivity to Chemoradiotherapy in Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are assessed by the ratio of the area of lymphocytes infiltrating the stroma. TILs are important in breast cancer and malignant melanoma and are being established as a marker of prognosis and sensitivity to chemotherapy. This has resulted in various therapies being developed in fields such as breast cancer. However, the evaluation of TILs in head and neck squamous cell carcinoma (HNSCC) is not progressing, and the prognosis is still poor. Thus, investigating whether or not the evaluation of TILs is also effective in HNSCC and prognoses can be predicted with just biopsy samples alone is required. METHODS: This study included 153 patients who were diagnosed with HNSCC between January 2010 and December 2019, underwent treatment, and could be followed up thereafter at our institution. RESULTS: TILs, overall survival (OS), and progression-free survival (PFS) were evaluated in all patients, the chemoradiotherapy arm, and the surgery arm. The cut-off value for TILs was 50%. In all patients, OS was 69.8% and 40.2% (P = 0.01) and PFS was 58.4% and 31.6% (P = 0.003) in the high and low TIL groups, respectively. Multivariate analyses revealed that TILs independently predicted prognosis. In the chemoradiotherapy arm, OS was 70.8% and 31.6% (P = 0.012) and PFS was 63.4% and 20.3% (P = 0.001) in the high and low TIL groups, respectively. No significant differences were noted in the surgery arm. CONCLUSIONS: In HNSCC, TILs can be used as a prognosis predictor and chemoradiotherapy biomarker. Assessments can be performed just with hematoxylin-eosin staining and is very simple. This will greatly contribute to report personalized therapy progress. Further evaluations and, thus, prospective clinical multicenter trials are needed to use TILs in clinical practice for HNSCC.

Immune gene activation by NPR and TGA transcriptional regulators in the model monocot Brachypodium distachyon.

The nonexpressor of pathogenesis-related (NPR) gene family is well known to play a crucial role in transactivation of TGA transcription factors for salicylic acid (SA)-responsive genes, including pathogenesis-related protein 1 (PR1), during plants' immune response after pathogen attack in the model dicot Arabidopsis thaliana. However, little is known about NPR gene functions in monocots. We therefore explored the functions of NPRs in SA signaling in the model monocot Brachypodium distachyon. BdNPR1 and BdNPR2/3 share structural similarities with A. thaliana AtNPR1/2 and AtNPR3/4 subfamilies, respectively. The transcript level of BdNPR2 but not BdNPR1/3 appeared to be positively regulated in leaves in response to methyl salicylate. Reporter assays in protoplasts showed that BdNPR2 positively regulated BdTGA1-mediated activation of PR1. This transactivation occurred in an SA-dependent manner through SA binding at Arg468 of BdNPR2. In contrast, BdNPR1 functioned as a suppressor of BdNPR2/BdTGA1-mediated transcription of PR1. Collectively, our findings reveal that the TGA-promoted transcription of SA-inducible PR1 is orchestrated by the activator BdNPR2 and the repressor BdNPR1, which function competitively in B. distachyon.

Usefulness of the Snare Technique During Leadless Pacemaker Implantation for a Patient with a Severely Dilated Right Atrium.

We report here the case of a 92-year-old woman with atrial fibrillation bradycardia in which leadless pacemaker implantation was performed with a difficult delivery of the catheter sheath due to an extremely large right atrium. Using a snare technique with correction of the direction of the force on the catheter toward the right ventricle (RV) can result in successful delivery of the pacemaker catheter and stable placement of the pacemaker system in the RV septum. This specific snare technique has the potential to facilitate leadless pacemaker implantation safely in a severely dilated chamber of the heart, making this technique effective to use in clinical practice.

A survey of oral health status, subjective oral symptoms and oral health behaviors among first-year dental students at a Japanese university.

PURPOSE: The rapid deterioration of oral health in young adults is an alarming problem in Japan. The aim of the present study is to investigate the oral health status, subjective oral symptoms and oral health behaviors of dental students. METHODS: Participants were 108 first-year students attending dental school in 2018-2019. Oral examinations were performed to assess dental caries indices, oral hygiene status, gingival bleeding on probing (BOP) and pocket depth. A self-administered questionnaire was used to assess subjective oral symptoms and oral health behaviors. RESULTS: The prevalence of decayed teeth (DT) and gingivitis (BOP ≥ 10%) were 43.5% and 50.0%, respectively. Having DT and gingivitis were significantly associated with poorer oral hygiene. No association was observed between DT and subjective symptoms. Having gingivitis was significantly associated with xerostomia, mouth-breathing and less use of interdental cleaning tools. Multiple logistic regression analysis for gingivitis yielded an odds ratio of 1.41 (95% confidence interval: 1.19-1.67) for plaque score, and 2.75 (1.27-5.98) for xerostomia. CONCLUSION: Since a relatively high ratio of students had DT and gingivitis without clear subjective symptoms, they require regular dental visits for early treatment and oral hygiene maintenance from the start of their time at university.