Impact of preoperative haemoglobin, albumin, lymphocyte, and platelet score on oral cancer prognosis.

OBJECTIVE: To evaluate the preoperative haemoglobin, albumin, lymphocyte, and platelet score as a prognostic indicator in oral squamous cell carcinoma treated by radical surgery. SUBJECTS AND METHODS: Patients (83 men, 32 women; 65.80 ± 11.47 years) who underwent radical surgery between 2012 and 2022 were included. Factors affecting overall survival and disease-free survival according to the haemoglobin, albumin, lymphocyte, and platelet score were examined. Patients were categorised into low- and high-score groups using optimal cut-off values obtained from receiver operating characteristic curve analysis. RESULTS: The low-score group had poorer overall and disease-free survival (p < 0.001 each). Multivariate analysis identified alcohol consumption (hazard ratio [HR], 3.83; 95% confidence interval [CI]: 1.56-9.41, p = 0.003); vascular invasion (HR, 3.97; 95% CI: 1.60-9.85, p = 0.003); and the haemoglobin, albumin, lymphocyte, and platelet score (HR, 0.39; 95% CI: 0.20-0.78, p = 0.007) as independent prognostic factors for overall survival and vascular (HR, 3.66; 95% CI: 1.79-7.50, p < 0.001) and lymphovascular (HR, 2.44; 95% CI: 1.36-4.41, p = 0.003) invasion as independent prognostic factors for disease-free survival. CONCLUSION: The preoperative haemoglobin, albumin, lymphocyte, and platelet score may be a significant prognostic factor for patients with oral squamous cell carcinoma undergoing radical surgery.

Polymyxin B-immobilised fibre column treatment for acute exacerbation of idiopathic pulmonary fibrosis patients with mechanical ventilation: a nationwide observational study.

BACKGROUND: The prognosis for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is poor, and there is no established treatment. Hence, we aimed to investigate the effectiveness of a polymyxin B-immobilised fibre column (PMX) for the treatment of AE-IPF. METHODS: Data were retrospectively collected from the Japanese Diagnosis Procedure Combination database from 1 July 2010 to 31 March 2018. We identified adult patients with idiopathic pulmonary fibrosis who received high-dose methylprednisolone (mPSL) therapy and mechanical ventilation upon admission. Eligible patients (n = 5616) were divided into those receiving PMX treatment combined with high-dose mPSL (PMX group, n = 199) and high-dose mPSL alone (mPSL alone group, n = 5417). To compare outcomes between the two groups, we applied a stabilised inverse probability of treatment weighting (IPTW) using propensity scores. The primary outcome was in-hospital mortality, and the secondary outcomes were 14- and 28-day mortality and length of hospital stay. RESULTS: The in-hospital mortality rates of the PMX and mPSL alone groups were 79.9% and 76.4%, respectively. The results did not significantly differ between the two groups after performing a stabilised IPTW. The odds ratio of the PMX group compared with the mPSL alone group was 1.56 (95% confidence interval 0.80-3.06; p = 0.19). The 14- and 28-day mortality and length of hospital stay (secondary outcomes) also did not significantly differ between the two groups. CONCLUSIONS: In AE-IPF patients using mechanical ventilation, the treatment outcome was not significantly better for PMX combined with high-dose mPSL than for high-dose mPSL alone.

Sick sinus syndrome diagnosed after a sinus arrest during treatment for zygomatic fracture: a case report.

BACKGROUND: Intraoperative sinus arrest is rarely seen during zygomatic fracture treatment. The patient was diagnosed with sick sinus syndrome based on repeated postoperative sinus arrest, which could have resulted in death if diagnosed late, making this case very significant to report. CASE PRESENTATION: Sick sinus syndrome is an arrhythmia associated with reduced automaticity of the sinoatrial node or impaired sinoatrial node conduction. We report the case of a 67-year-old man diagnosed with the syndrome after a sinus arrest that occurred during a zygomatic fracture treatment. The patient had cheek pain and mouth opening disorder, dizziness after fainting and sustaining a facial injury. Preoperative examination determined that the syncope was due to drug-induced arrhythmia, and surgery was authorized after drug withdrawal. During the operation, sinus arrest was observed due to trigeminal vagal reflex, and heart rate was restarted by stopping the operation and chest compressions. After the surgery, the patient showed symptoms of dizziness and palpitations, and sinus arrest following atrial fibrillation and supraventricular tachycardia, which was diagnosed as sick sinus syndrome, and a pacemaker was implanted. Currently, 8 years have passed since the surgery, and there are no symptoms of mouth opening disorder, dizziness, or palpitations. CONCLUSIONS: In the case of maxillofacial injuries due to syncope, cardiogenic syncope is a possibility, and repeated syncope is a risk for death due to delayed diagnosis. There are no reports of maxillofacial trauma leading to a diagnosis of sick sinus syndrome. The purpose of this case report is to disseminate the importance of diagnosing the cause of syncope as well as injury treatment.

Hospital volume and outcomes following bronchoscopy in patients with interstitial lung disease: A retrospective observational study using a national inpatient database in Japan.

BACKGROUND: Interstitial lung diseases (ILDs) are a group of diffuse parenchymal lung disorders that cause inflammation and fibrosis in the interstitium of the lungs. Histopathological examination is pivotal to accurately diagnose the type of ILD, and bronchoscopy (BS) is often performed to collect lung tissue. This study aimed to determine the relationship between hospital volume and outcomes following BS in patients with ILD. METHODS: Inpatient data on patients with ILD who underwent BS between July 1, 2010 and March 31, 2021 were extracted from the Japanese Diagnosis Procedure Combination database. The annual hospital volume of BS was categorized into four (very low- [≤15 cases/year], low- [16-29 cases/year], high- [30-54 cases/year], and very high- [≥55 cases/year] volume) groups. The primary outcome was all-cause 14-day mortality after BS. Multiple imputation methods followed by multivariable logistic regression analyses fitted with generalized estimating equations were used to estimate the association between hospital volume and 14-day mortality after BS. RESULTS: A total of 89,454 patients with ILD from 1002 hospitals underwent BS. The all-cause mortality within 14 days after BS was 0.77%. An inverse trend was observed between mortality and hospital volume. Compared with the very low-hospital volume group, the very high-hospital volume group was significantly associated with a lower mortality (adjusted odds ratio = 0.63, 95% confidence interval: 0.48-0.85, p = 0.002). CONCLUSIONS: Hospital volume was inversely associated with all-cause mortality within 14 days after BS for hospitalized patients with ILD.

Phylogeny of Alisma (Alismataceae) revisited: implications for polyploid evolution and species delimitation.

Alisma L. is a genus of aquatic and wetland plants belonging to family Alismataceae. At present, it is thought to contain ten species. Variation in ploidy level is known in the genus, with diploids, tetraploids and hexaploids recorded. Previous molecular phylogenetic studies of Alisma have generated a robust backbone that reveals important aspects of the evolutionary history of this cosmopolitan genus, yet questions remain unresolved about the formation of the polyploid taxa and the taxonomy of one particularly challenging, widely distributed species complex. Here we directly sequenced, or cloned and sequenced, nuclear DNA (nrITS and phyA) and chloroplast DNA (matK, ndhF, psbA-trnH and rbcL) of multiple samples of six putative species and two varieties, and conducted molecular phylogenetic analyses. Alisma canaliculatum and its two varieties known in East Asia and A. rariflorum endemic to Japan possess closely related but heterogeneous genomes, strongly indicating that the two species were generated from two diploid progenitors, and are possibly siblings of one another. This evolutionary event may have occurred in Japan. Alisma canaliculatum var. canaliculatum is segregated into two types, each of which are geographically slightly differentiated in Japan. We reconstructed a single phylogeny based on the multi-locus data using Homologizer and then applied species delimitation analysis (STACEY). This allowed us to discern A. orientale as apparently endemic to the Southeast Asian Massif and distinct from the widespread A. plantago-aquatica. The former species was most likely formed through parapatric speciation at the southern edge of the distribution of the latter.

Relationship of preoperative oral hypofunction with prognostic nutritional index in gastric cancer: A case-control retrospective study.

Preoperative nutritional status is an important prognostic factor in gastric cancer patients. This study will evaluate whether preoperative oral dysfunction is associated with prognostic nutrition index (PNI). This case-control study analyzed 95 patients who underwent oral function management. We assessed the following parameters: body mass index, stage of gastric cancer, C-reactive protein, total lymphocyte count, albumin, and prognostic nutritional index. The patients were divided into groups with prognostic nutritional indexes <45 and >45. Logistic regression analysis was used to assess the association between the measurements of oral function and the prognostic nutritional index. Univariate analysis of factors associated with decreased oral function and prognostic nutritional index showed significant differences between the two groups in C-reactive protein, neutrophils, and tongue pressure (p<0.01). However, oral hygiene, oral dryness, occlusal force, tongue-lip motor function, masticatory function, and swallowing function were not significantly different. Multivariate analysis showed that C-reactive protein (odds ratio: 0.12, 95% confidence interval: 0.30-0.45, p<0.01) and tongue pressure (odds ratio: 3.62, 95% confidence interval: 1.04-12.60, p<0.05) were independent risk factors for oral hypofunction. Oral function decreased in perioperative patients with gastric cancer, and decreased tongue pressure is associated with a decreased prognostic nutritional index.

Skeletal muscle atrophy and short-term mortality in patients with acute exacerbation of idiopathic pulmonary fibrosis: an observational cohort study.

BACKGROUND: Skeletal muscle atrophy, a common complication of idiopathic pulmonary fibrosis (IPF), and its presence upon diagnosis can indicate a poor prognosis. Patients with IPF frequently experience acute exacerbations (AE), which is associated with a high mortality rate. However, the association between skeletal muscle atrophy and short-term mortality remains unknown. METHODS: We performed a retrospective, multicenter cohort study of patients admitted for AE-IPF in Japan. The cross-sectional areas of the erector spinae muscle (ESMCSA) and the pectoralis muscle (PMCSA) were analyzed via single-slice computed tomography (CT). The primary outcome was 90-day mortality. Survival probability was estimated using the Kaplan-Meier method, and the log-rank test was used between the low and high groups of ESMCSA and PMCSA. We used multivariable Cox proportional-hazards models to evaluate the association between ESMCSA and PMCSA and prognosis. RESULTS: Of the 212 patients included, 94 (44%) died during the observation period. The low ESMCSA group (<25.6 cm2) had a significantly worse prognosis than that of the high ESMCSA group (≥25.6 cm2) (hazard ratio (HR) [95% confidence interval (CI)]: 1.52 [1.00-2.33], P = 0.049). Multivariable analyses showed that all-cause mortality was associated with low ESMCSA (model 1, adjusted HR [95% CI]: 1.59 [0.98-2.60]; model 2, 1.55 [0.95-2.56], and model 3, 1.67 [1.00-2.78], respectively). The adjusted HR of low PMCSA (<20.4 cm2) vs. high PMCSA (≥20.4 cm2) was 1.39 (95% CI: 0.88-2.20). CONCLUSIONS: Low ESMCSA on CT images is associated with a high 90-day mortality rate in patients with AE-IPF.

Correlation of suprascapular notch morphology with suprascapular nerve palsy: a 3D-computed tomography study.

Background: The morphology of the suprascapular (SS) notch is a very important factor in treatment of suprascapular nerve (SSN) palsy. Several studies have reported SS notch morphology in cadavers or using a three-dimensional computed tomography (3D-CT); however, none has reported the distribution of SS notch morphology according to the age group. In addition, the correlation between SS notch morphology and SSN palsy remains unclear. The purposes of this study were to investigate the morphological distribution of the SS notch by age group in a large population and to assess the relationship between SS notch morphology and SSN palsy. Methods: We studied the 3D-CT images of 1063 shoulders in 1009 patients (mean age, 60.8 years; age range, 14-96 years). There were 53 shoulders with SSN palsy and 1010 shoulders without SSN palsy. Morphology of the SS notch was classified by Rengachary's classification (types I-VI). Shoulders with types I-IV were classified into the nonossified superior transverse scapular ligament (STSL) group (group N) and those with types V and VI into the ossified STSL group (group O). Results: The Rengachary's classifications of the 1063 shoulders were as follows: type I: n = 113, 10.6%; type II: n = 313, 29.4%; type III: n = 383, 36.0%; type IV: n = 109, 10.3%; type V: n = 107, 10.0%; and type VI: n = 38, 3.6%. Mean age was significantly older in the ossified STSL group, and the age was <40 years for only two shoulders in this group. The Rengachary's classifications of the SSN palsy cases were as follows: type I: 7.5%, II: 24.5%, III: 34.0%, IV: 15.1%, V: 13.2%, and VI: 5.7%. There was no statistical difference in age and sex, Rengachary type, or ossification between SSN palsy and non-SSN palsy cases. Conclusions: Ossification of the STSL was significantly more common in older patients, which suggests age-related change. In addition, no relation was identified between narrow notch or ossification of the STSL with the onset of SSN palsy.

Validity of diagnoses of respiratory diseases recorded in a Japanese administrative database.

BACKGROUND: Validating the information recorded in administrative databases is essential. However, no study has comprehensively validated the accuracy of Japanese Diagnosis Procedure Combination (DPC) data on various respiratory diseases. Therefore, this study aimed to evaluate the validity of diagnoses of respiratory diseases in the DPC database. METHODS: We conducted chart reviews of 400 patients hospitalized in the departments of respiratory medicine in two acute-care hospitals in Tokyo, between April 1, 2019 and March 31, 2021, and used them as reference standards. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DPC data on 25 respiratory diseases were determined. RESULTS: Sensitivity ranged from 22.2% (aspiration pneumonia) to 100% (chronic eosinophilic pneumonia and malignant pleural mesothelioma) and was <50% for eight diseases, while specificity was >90% for all diseases. PPV ranged from 40.0% (aspiration pneumonia) to 100% (coronavirus disease 2019, bronchiectasis, chronic eosinophilic pneumonia, pulmonary hypertension, squamous cell carcinoma, small cell carcinoma, lung cancer of other histological types, and malignant pleural mesothelioma) and was >80% for 16 diseases. Except for chronic obstructive pulmonary disease (82.9%) and interstitial pneumonia (other than idiopathic pulmonary fibrosis) (85.4%), NPV was >90% for all diseases. These validity indices were similar in both hospitals. CONCLUSIONS: The validity of diagnoses of respiratory diseases in the DPC database was high in general, thereby providing an important basis for future studies.

Electromyographic activities of glenohumeral joint muscles during shoulder forward flexion with isometric horizontal abduction loading.

BACKGROUND: Isometric horizontal abduction loading has been applied to improve imbalanced scapular muscle activities during shoulder exercises; however, the effect on glenohumeral joint muscle activity remains unclear. The purpose of this study was to investigate the changes in electromyographic activity of shoulder muscles during forward flexion with isometric horizontal abduction loading in healthy participants. METHODS: Thirteen healthy men were recruited for this study. Participants performed shoulder forward flexion with isometric horizontal abduction loading using an elastic band (Flex-band condition) and forward flexion without shoulder loading (Normal-flex condition). Muscle activities were evaluated while maintaining shoulder flexion at 60°, 90°, 120°, and 150° (static task) and during active shoulder flexion from 0° to maximum elevation (dynamic task). Surface electrodes were placed on the deltoid, pectoralis major, infraspinatus, and teres minor muscles to measure the activities of the shoulder muscles during each task. The muscle activities during the static task were compared using a 2-way analysis of variance with repeated measures of the 2 factors, loading condition and flexion position, and a paired t test was used for comparisons between the 2 conditions during the dynamic task (significance level set at P < .05). RESULTS: For the static task, the Flex-band condition significantly increased the deltoid middle and posterior activities by 2-15 times and the infraspinatus and teres minor activities by 2-3 times compared with the Normal-flex condition at all positions. In contrast, the Flex-band condition significantly decreased (by about half) the activities of the deltoid anterior (at 120° and 150°) and pectoralis major (at all positions) compared with the Normal-flex condition. For the dynamic task, the Flex-band condition significantly increased the deltoid middle, deltoid posterior, infraspinatus, and teres minor activities by 2-7 times and decreased the deltoid anterior activity by approximately two-thirds. CONCLUSIONS: Applying isometric horizontal abduction loading during shoulder forward flexion may be useful in improving the imbalanced muscle activities of the glenohumeral joint, such as excessive activity of the deltoid anterior and pectoralis major and dysfunction of the deltoid middle, deltoid posterior, and shoulder external rotator muscles. Shoulder forward flexion with horizontal abduction loading could be available for exercise in patients who have massive rotator cuff tears or who have undergone rotator cuff repair and shoulder arthroplasty.

Adult T-cell leukemia/lymphoma complicated by Pneumocystis pneumonia in a non-endemic area.

Adult T-cell leukemia/lymphoma (ATLL) is a human T-cell leukemia virus type 1-inducing unevenly-distributed T-cell malignancy, which is often complicated by opportunistic infections. Here, we discuss the case of a 75-year-old woman presenting with Pneumocystis pneumonia (PCP) who was subsequently diagnosed with ATLL in Tokyo, a non-endemic area of ATLL. In addition to the elevated soluble interleukin-2 receptor and the detection of flower cells in the screening blood test, the high-resolution computed tomography findings, atypical of PCP, were clues to the diagnosis of ATLL. ATLL should be considered as an underlying disease when patients present with PCP, even in non-endemic areas.

Prognostic impact of preoperative Geriatric Nutritional Risk Index in oral squamous cell carcinoma.

OBJECTIVES: To investigate the prognostic impact of preoperative Geriatric Nutritional Risk Index (GNRI) values in older adults undergoing radical surgery for oral squamous cell carcinoma (OSCC). SUBJECTS AND METHODS: This retrospective study included 61 patients ≥65 years old with OSCC (43 men, 18 women; age: 72.1 ± 5.4 years) who underwent radical surgery between 2013 and 2020. Factors influencing overall survival (OS) and disease-free survival (DFS) were examined. RESULTS: Receiver operating characteristic curve analysis indicated that the optimal GNRI value for classifying patients into low-GNRI (<93.7; OS: n = 19 [31.1%], DFS: n = 42 [68.9%]) and high-GNRI groups (≥93.7; OS, n = 19 [31.1%]; DFS, n = 42 [68.9%]) was 93.7. OS and DFS rates were significantly lower in the low-GNRI group than in the high-GNRI group. Univariate analysis indicated that alcohol use, preoperative serum C-reactive protein level, lymphatic invasion, postoperative treatment, and GNRI were significantly correlated with OS, while lymphatic invasion, postoperative treatment, and GNRI were significantly correlated with DFS. In multivariate analysis, only GNRI was significantly correlated with OS. DFS and postoperative treatment were independent predictors of DFS. CONCLUSIONS: Preoperative GNRI may be a significant prognostic factor in older adults with OSCC. GNRI assessment and nutritional intervention may improve prognosis in patients at high nutritional risk.

Correlation between geriatric nutritional risk index and oral condition in gastric cancer patients.

OBJECTIVES: Nutritional status is a useful prognostic factor in gastric cancer patients. Since oral hypofunction may cause undernutrition, we cross-sectionally investigated whether the Geriatric Nutritional Risk Index (GNRI) is affected by the number of remaining teeth, occlusal support status and denture use. MATERIALS AND METHODS: The participants were 114 patients diagnosed with gastric cancer between April 2017 and March 2020. The stage of gastric cancer, body mass index, albumin level, total lymphocyte count, C-reactive protein level and GNRI were evaluated. The number of remaining teeth was also evaluated, and the occlusion state was determined based on the Eichner classification. The patients were divided into three main groups representing different occlusal states based on the Eichner index and were also categorised based on denture use. RESULTS: The mean age ± standard deviation of the patients was 75.2 ± 5.5 years. The Eichner classification had a significant positive correlation with GNRI. Low GNRI was associated with a poor occlusal state in group C, while a higher GNRI was associated with a stable occlusal state in group A. However, the denture-related groups showed no significant differences in GNRI. CONCLUSION: The GNRI was associated with the occlusal support level but not with denture use.

Improvements in asymmetry in knee flexion motion during landing are associated with the postoperative period and quadriceps strength after anterior cruciate ligament reconstruction.

This study investigated the relationship between quadriceps strength and knee kinematics during a drop vertical jump (DVJ) at 6, 9 and 12 months after anterior cruciate ligament reconstruction (ACLR) in 9 male and 22 female athletes (16.6 ± 2.1 years old). Isokinetic quadriceps strength was measured by a dynamometer (Biodex System 3). Knee flexion excursion was assessed using two-dimensional analysis. Knee flexion excursion at 6 months was significantly smaller in the involved limb than in the uninvolved limb independent of quadriceps strength (56.7° ± 9.3°, 63.4° ± 11.4°, P < 0.001). At 9 months, only the low quadriceps strength group demonstrated a similar interlimb difference (57.2°± 12.3°, 63.3° ± 10.5°, P < 0.001). At 12 months, there was no significant interlimb difference in knee flexion excursion regardless of quadriceps strength. These findings indicate that restoration in symmetrical knee flexion excursion during a DVJ requires rehabilitation as well as quadriceps strength.

Ex vivo chemosensitivity assay using primary ovarian cancer organoids for predicting clinical response and screening effective drugs.

Selecting the best treatment for individual patients with cancer has attracted attention for improving clinical outcomes. Recent progress in organoid culture may lead to the development of personalized medicine. Unlike molecular-targeting drugs, there are no predictive methods for patient response to standard chemotherapies for ovarian cancer. We prepared organoids using the cancer tissue-originated spheroid (CTOS) method from 61 patients with ovarian cancer with 100% success rate. Chemosensitivity assays for paclitaxel and carboplatin were performed with 84% success rate using the primary organoids from 50 patients who received the chemotherapy. A wide range of sensitivities was observed among organoids for both drugs. All four clinically resistant organoids were resistant to both drugs in 18 cases in which clinical response information was available. Five out of 18 cases (28%) were double-resistant, the response rate of which was compatible with the clinical remission rate. Carboplatin was significantly more sensitive in serous than in clear cell subtypes (P = 0.025). We generated two lines of organoids, screened 1135 drugs, and found several drugs with better combinatory effects with carboplatin than with paclitaxel. Some drugs, including afatinib, have shown an additive effect with carboplatin. The organoid sensitivity assay did not predict the clinical outcomes, both progression free and overall survival.

Efficacy and safety of desmopressin orally disintegrating tablets 25 and 50 µg in male patients with nocturia: A Japanese real-world multicenter clinical study.

OBJECTIVES: To clarify Japanese real-world clinical data on the use of desmopressin 25 and 50 µg orally disintegrating tablets (ODT) for male patients with nocturia and evaluate the predictive factors to improve nighttime frequency. METHODS: We retrospectively accumulated real-world clinical data from 27 institutions in Japan. Male patients with two or more episodes of nocturia who received desmopressin ODT for nocturnal polyuria (NP) from 2019 through 2021 were included. The primary endpoint was the change of nighttime frequency until 3 months after desmopressin administration. The secondary endpoints were to clarify the persistence rate, adverse events, and predictive factors of decreasing nighttime frequency. RESULTS: A total of 118 patients were eligible to participate in this study. The persistence rate of desmopressin on the Kaplan-Meier curve at week 12 was 51.3. The reason for discontinuation was mainly the occurrence of adverse events in 67 patients (56.8%), particularly hyponatremia in 7 patients (5.9%). Nighttime frequencies at baseline, - 1 month and 1 - 3 months after desmopressin administration were 4.1 ± 1.3, 2.9 ± 1.4 (P < .01), and 2.6 ± 1.3 (P < .01), respectively. The mean nighttime urine volume voided at baseline was significantly larger in patients whose nighttime frequency decreased by two or more times than in those with a decrease of less than two times. CONCLUSIONS: Desmopressin 25 and 50 µg ODT treatments are feasible for male patients with NP in Japanese real-world clinical practice. Patients with higher voided volumes, particularly in the nighttime, may have great benefit from desmopressin.

Liquid biopsy for detecting epidermal growth factor receptor mutation among patients with non-small cell lung cancer treated with afatinib: a multicenter prospective study.

BACKGROUND: This study aimed to determine the effectiveness of liquid biopsy in detecting epidermal growth factor receptor (EGFR) mutations at diagnosis, disease progression, and intermediate stages. METHODS: This prospective, multicenter, observational study included 30 patients with non-small cell lung cancer treated with afatinib, harboring a major EGFR mutation confirmed by tumor tissue biopsy. We collected blood samples for liquid biopsy at diagnosis, intermediate stage, and progressive disease. Tissue and liquid biopsies were examined using Cobas ® EGFR Mutation Test v2. RESULTS: Liquid biopsy detected EGFR mutations in 63.6% of the patients at diagnosis. The presence of metastasis in the extrathoracic, brain, and adrenal glands correlated positively with the detection of EGFR mutations. Patients with positive EGFR mutations at diagnosis had significantly shorter overall and progression-free survival than patients with negative EGFR mutations. Four of the 18 patients (22.2%) who reached progressive disease had positive EGFR T790M mutations. Three of 10 patients (30.0%) with progressive disease were positive and negative for T790M using tumor re-biopsy and liquid biopsy, respectively. The results of EGFR mutation by tissue re-biopsy were the same as those of liquid biopsy in the three patients who were positive for significant EGFR mutations but negative for the T790M mutation using liquid biopsy at progressing disease. Only two patients were positive for major EGFR mutations at intermediate levels. CONCLUSIONS: Liquid biopsy can be a prognostic factor in EGFR-tyrosine kinase inhibitor treatments at diagnosis. Tumor re-biopsy can be omitted in patients with positive EGFR mutations by liquid biopsy at PD.

Association between tumor response to systemic therapy and patient-reported disease symptoms.

BACKGROUND: The association of treatment-induced tumor shrinkage with symptom palliation for patients with lung cancer remains unknown. We investigated this correlation using the Edmonton Symptom Assessment System-Revised. METHODS: Using the in-hospital cancer registry, we identified patients receiving chemotherapy and/or immunotherapy for newly diagnosed advanced or metastatic lung cancer. Tumor response and post-treatment Edmonton Symptom Assessment System-Revised were obtained after 2-3 treatment cycles. Patients were divided into groups with or without >30% unidirectional tumor shrinkage (objective response [OR] or non-OR [N-OR] groups, respectively). They were further classified as good-objective response (>50% unidirectional tumor shrinkage), moderate-objective response (30-50% shrinkage), progressive disease (>20% tumor growth or new lesion) or stable disease (SD; N-objective response and non-progressive disease). The primary endpoint was change in the total Edmonton Symptom Assessment System-Revised score from baseline. The Mann-Whitney U test was used for analysis. RESULTS: In total, 113 patients were enrolled. The total Edmonton Symptom Assessment System-Revised score was significantly more improved in the OR group versus the N-OR group (median: 5 vs. 2, respectively; P = 0.013). This association was more prominent in patients with small-cell lung cancer and large-cell neuroendocrine tumor than those with other histology. Sensitivity analyses showed that the total Edmonton Symptom Assessment System-Revised score was more improved in the OR group versus the SD group (median: 5 vs. 3, respectively; P = 0.029) and in the 'good-OR' group versus the 'moderate-OR and SD' group (median: 7.5 vs. 2, respectively; P = 0.003), suggesting that greater tumor shrinkage led to more symptom amelioration. CONCLUSIONS: Tumor shrinkage was associated with Edmonton Symptom Assessment System-Revised score improvement in patients with lung cancer receiving systemic therapy.

Rate of Torque Development in the Quadriceps after Anterior Cruciate Ligament Reconstruction with Hamstring Tendon Autografts in Young Female Athletes.

This study aims to compare the limb symmetry index (LSI) of the rate of torque development (RTD) of the quadriceps with that of the peak torque after anterior cruciate ligament reconstruction (ACLR) using semitendinosus and gracilis tendon (STG) autografts and to investigate the associations of the LSI of torque parameters with patient-reported knee function. The participants included 23 female athletes after ACLR with STG grafts. Isometric quadriceps tests were performed using an isokinetic dynamometer. The peak torque, RTD100 (0 to 100 ms) and RTD200 (100 to 200 ms) were determined using torque-time curves. Comparisons of the LSI of torque parameters was performed by ANOVA. Univariate regression analysis was used to examine the relationship between the LSI of torque parameters and the patient-reported knee function. The LSIs of the peak torque and RTD200 were significantly lower than that of the RTD100 (p = 0.049, p = 0.039, respectively). Regression analysis showed that the LSI of the peak torque was associated with the patient-reported knee function (R2 = 0.40, p = 0.001). It would be useful to evaluate the peak torque in young female athletes under the age of 18 and at 8-10 months after ACLR with STG grafts.

Polarity switching of ovarian cancer cell clusters via SRC family kinase is involved in the peritoneal dissemination.

Peritoneal dissemination is a predominant pattern of metastasis in patients with advanced ovarian cancer. Despite recent progress in the management strategy, peritoneal dissemination remains a determinant of poor ovarian cancer prognosis. Using various histological types of patient-derived ovarian cancer organoids, the roles of the apicobasal polarity of ovarian cancer cell clusters in peritoneal dissemination were studied. First, it was found that both ovarian cancer tissues and ovarian organoids showed apicobasal polarity, where zonula occludens-1 (ZO-1) and integrin beta 4 (ITGB4) served as markers for apical and basal sides, respectively. The organoids in suspension culture, as a model of cancer cell cluster floating in ascites, showed apical-out/basal-in polarity status, while once embedded in extracellular matrix (ECM), the organoids switched their polarity to apical-in/basal-out. This polarity switch was accompanied by the SRC kinase family (SFK) phosphorylation and was inhibited by SFK inhibitors. SFK inhibitors abrogated the adherence of the organoids onto the ECM-coated plastic surface. When the organoids were seeded on a mesothelial cell layer, they cleared and invaded mesothelial cells. In vivo, dasatinib, an SFK inhibitor, suppressed peritoneal dissemination of ovarian cancer organoids in immunodeficient mice. These results suggest SFK-mediated polarity switching is involved in peritoneal metastasis. Polarity switching would be a potential therapeutic target for suppressing peritoneal dissemination in ovarian cancer.