Glenoid track and subcritical Hill-Sachs lesion.

Background: We have proposed the concept of glenoid track ("on-track/off-track" lesion) to evaluate the risk of engagement of the Hill-Sachs lesion with the glenoid after arthroscopic Bankart repair. This concept has been widely used and many clinical validation studies have been reported. To measure the glenoid track width, we have recommended to use 3-dimensional computed tomography (CT) images. However, the CT method has the issue of radiation exposure and involves time and effort to make 3-dimensional CT images from 2-dimensional images. For these reasons, there are several reports describing the measurement method using magnetic resonance imaging. Recently, the threshold of the critical glenoid bone loss becomes lower. A zone of bone loss below the critical size is called "subcritical bone loss", which might be related to deterioration of quality of life and bone grafting is recommended. We applied the concept of "subcritical bone loss" to the glenoid track. Patients with "on-track" lesions can be divided into 2 subgroups: those with a "peripheral-track" lesion (most medial 1/4) and those with a "central-track" lesion (the rest 3/4). More recently, similar evaluation methods to evaluate the risk of "off-track" lesions have been reported: ''distance to dislocation'' and "Hill-Sachs interval/glenoid track ratio". Also, similar concept to "peripheral-track" lesion, "near-track" lesion was reported. The concept of "peripheral-track" lesion is a concept of assessing an "on-track" lesion which is very close to the medial margin of the glenoid track (subcritical bone loss). Methods: Similar evaluation methods to evaluate the risk of "off-track" or "peripheral-track" lesions were proposed in the literature. A review was performed by searching PubMed. Journal articles published between January 2014 and January 2023 were taken into account. They were compared and their differences were explained. Results: The "near-track" lesion concept is similar to "peripheral-track" lesion. However, the cutoff value is different: Hill-Sachs occupancy ≥ 75% is the "peripheral-track" lesion, whereas "distance to dislocation" < 8 mm is the "near-track" lesion. Conclusion: We introduced update of the glenoid track concept including the evaluation method, peripheral-track lesion, and its clinical application.

Arthroscopic findings of traumatic first-time anterior shoulder instability: a comparison of adolescent versus adult patients.

Background: Recurrence rates after first-time shoulder dislocation in young patients are high, especially in their early teens. Only a few studies have arthroscopically investigated the inside of the glenohumeral joint in young patients. Such arthroscopic investigation would help in solving the cause of the greater incidence of recurrent instability in the young population, especially in their early teens. Methods: Data from 42 patients with first-time anterior shoulder dislocation were retrospectively reviewed. The participants were divided into two groups: those aged 10 to 15 years at the time of the dislocation (adolescent group) and those aged 20- 29 years (adult group). The arthroscopic findings regarding the glenohumeral joint in the adolescent group were assessed and compared to those in the adult group. The intra-articular pathology was examined in all cases and recorded with specific reference to (1) the anterior capsulolabral lesion, (2) Hill-Sachs lesion, (3) labrum-anteroinferior glenohumeral ligament complex, and (4) other concomitant lesions. Results: Anterior joint laxity was found more in the adolescent group than in the adult group (P = .046). Thirty-six (83%) shoulders had Hill-Sachs lesions: 6 shoulders (60%) in the adolescent group and 30 shoulders (97%) in the adult group, with a significant difference (P < .001). Conclusion: Pathological findings observed during arthroscopy are more common in the adult group, whereas recurrent instability is more likely in adolescent group.

Non-pharmacological treatments for anticipatory nausea and vomiting during chemotherapy: a systematic review and meta-analysis of the Clinical Practice Guidelines for Antiemesis 2023.

BACKGROUND: Anticipatory chemotherapy-induced nausea and vomiting (CINV) is a conditioned response influenced by the severity and duration of previous emetic responses to chemotherapy. We aimed to evaluate the efficacy of non-pharmacologic interventions for anticipatory CINV among patients with cancer. METHODS: We conducted a systematic search in databases, including PubMed, the Cochrane Library, CINAHL, and Ichushi-Web, from January 1, 1990, to December 31, 2020. Randomized controlled trials, non-randomized designs, observational studies, or case-control studies that utilized non-pharmacological therapies were included. The primary outcomes were anticipatory CINV, with an additional investigation into adverse events and the costs of therapies. The risk-of-bias for each study was assessed using the Cochrane risk-of-bias tool, and meta-analysis was performed using Revman 5.4 software. RESULTS: Of the 107 studies identified, six met the inclusion criteria. Three types of non-pharmacological treatments were identified: systematic desensitization (n = 2), hypnotherapy (n = 2), and yoga therapy (n = 2). Among them, systematic desensitization significantly improved anticipatory CINV as compared to that in the control group (nausea: risk ratio [RR] = 0.60, 95% confidence interval [CI] = 0.49-0.72, p < 0.00001; vomiting: RR = 0.54, 95% CI = 0.32-0.91, p = 0.02). However, heterogeneity in outcome measures precluded meta-analysis for hypnotherapy and yoga. Additionally, most selected studies had a high or unclear risk of bias, and adverse events were not consistently reported. CONCLUSIONS: Our findings suggest that systematic desensitization may effectively reduce anticipatory CINV. However, further research is warranted before implementation in clinical settings.

Prevalence of impaired foot function in baseball players with and without disabled throwing shoulder/elbow: a case-control study.

Prevalence of impaired foot function among baseball players with and without a disabled throwing shoulder/elbow was investigated. The study included 138 male players. Players who had previously complained of shoulder/elbow pain during throwing motion were defined as the players with a history, and those who experienced shoulder/elbow pain during the examination were defined as having the injury. Foot function was evaluated by foot "rock paper scissors" movements and floating toes. Their prevalence was assessed and the relationships between players with and without the injuries were statistically analyzed. The prevalence of players with a history and injury was 27% and 7%, respectively. The prevalence of impaired foot function on the non-throwing side among players with injury was significantly higher than those without (60% vs. 28%, P < 0.001) and higher tendency on the throwing side than those without (60% vs. 32%). Regarding floating toes, players with a relevant history showed a significantly higher prevalence on the throwing side than those without (49% vs 28%, P < 0.001) and higher tendency on the non-throwing side than those without (49% vs 32%). Players with disabled throwing shoulder/elbow have a significantly higher prevalence of impaired foot function and floating toes than players without it.

Antibody-drug conjugates in solid tumors; new strategy for cancer therapy.

Antibody-drug conjugates (ADCs) have emerged as a novel class of anticancer treatment. ADCs are composed of three parts: a monoclonal antibody, a linker and a payload. A monoclonal antibody binds to the specific antigen present at the cancer cells, allowing selective delivery of the cytotoxic agents to the tumor site. Several ADCs are approved by the US Food and Drug Administration for the treatment of hematologic cancers and solid tumors with clinically meaningful survival benefit. However, the development of ADCs faces a lot of challenges and there is a need to get better understanding of ADCs in order to improve patient outcomes. Here, we briefly discuss the structure and mechanism of ADCs, as well as the clinical data of current approved ADCs in solid tumors.

Glenoid Track Revisited.

The risk of Hill-Sachs lesion (HSL) to cause instability depends not only on the HSL but also on the glenoid size. Clinically, the only method to assess the risk of instability considering the dynamic interaction of both, the HSL together with the glenoid bone loss, is the glenoid track concept. Since it was introduced in a cadaveric study, its clinical efficacy and validity have been reported in the literature. Sometimes, the medial margin of the footprint (lateral margin of the glenoid track) is difficult to identify when a HSL is overriding the footprint. In such cases, we propose a method to draw an imaginary line connecting two landmarks. Although 3D-CT is the most accurate and widely used method to assess on/off-track lesions, our interest gradually is shifting towards MRI, which has no radiation concern. The current MR method is still under way. There are various risk factors influencing the recurrent instability after surgery. The glenoid track concept deals with only one of these factors, i.e., instability caused by bony lesions. Therefore, the following two issues are important: 1) how to assess the glenoid track precisely and 2) how to incorporate other risk factors into consideration. The former can be achieved by obtaining the custom-made glenoid track width using not the fixed value of 83%, but more individualized value obtained by measuring the active horizontal extension angle of the opposite shoulder in the sitting position. At the same time, the gray zone (peripheral-track lesion) needs to be clearly defined. The latter can be achieved by incorporating the risk factors other than the bony lesions. One example is the glenoid track instability management score (GTIMS), a combination of the glenoid track concept and the instability severity index (ISI) score. This new scoring system is expected to increase the predictive potential of the scoring system, and accordingly to enhance clinical decision making.

Neoadjuvant nivolumab plus chemotherapy followed by resection for superior sulcus tumour with high PD-L1 expression: A case report.

The standard treatment for resectable non-small cell lung cancer (NSCLC) located in the superior sulcus is neoadjuvant chemoradiotherapy followed by highly invasive resection. Based on the results of the CheckMate 816 trial, which showed a marked improvement in the efficacy of neoadjuvant chemo-immunotherapy, we report a case of minimally invasive resection after neoadjuvant nivolumab plus chemotherapy for superior sulcus NSCLC, resulting in a pathologic complete response. The patient was a 76-year-old man with a 65-mm right superior sulcus tumour diagnosed as squamous cell carcinoma with 95% PD-L1. After two courses of neoadjuvant nivolumab plus chemotherapy, the tumour was completely resected through an 11-cm right lateral thoracotomy with second rib resection and first rib preservation. No residual tumour cells were observed in the specimen, and the patient had a pathologic complete response. This report represents a new treatment option for superior sulcus tumours.

The Tumor Immune Microenvironment Is Associated With Recurrence in Early-Stage Lung Adenocarcinoma.

Introduction: Immune checkpoint inhibitors have recently been approved for the treatment of early-stage NSCLC in the perioperative setting on the basis of phase 3 trials. However, the characteristics of such patients who are susceptible to recurrence after adjuvant chemotherapy or who are likely to benefit from postoperative immunotherapy have remained unclear. Methods: This biomarker study (WJOG12219LTR) was designed to evaluate cancer stem cell markers (CD44 and CD133), programmed death-ligand 1 (PD-L1) expression on tumor cells, CD8 expression on tumor-infiltrating lymphocytes, and tumor mutation burden in completely resected stage II to IIIA NSCLC with the use of archived DNA and tissue samples from the prospective WJOG4107 trial. Tumors were classified as inflamed or noninflamed on the basis of the PD-L1 tumor proportion score and CD8+ tumor-infiltrating lymphocyte density. The association between each potential biomarker and relapse-free survival (RFS) during adjuvant chemotherapy was assessed by Kaplan-Meier analysis. Results: A total of 117 patients were included in this study. The median RFS was not reached (95% confidence intervals [CI]: 22.4 mo-not reached; n = 39) and 23.7 months (95% CI: 14.5-43.6; n = 41) in patients with inflamed or noninflamed adenocarcinoma, respectively (log-rank p = 0.02, hazard ratio of 0.52 [95% CI: 0.29-0.93]). Analysis of the combination of tumor inflammation category and TP53 mutation status revealed that inflamed tumors without TP53 mutations were associated with the longest RFS. Conclusions: PD-L1 expression on tumor cells, CD8+ T cell infiltration, and TP53 mutation status may help identify patients with early-stage NSCLC susceptible to recurrence after adjuvant chemotherapy.

Location and Size of the Reverse Hill-Sachs Lesion in Patients with Traumatic Posterior Shoulder Instability.

BACKGROUND: In patients with traumatic posterior shoulder instability, little is known about the precise location and size of the reverse Hill-Sachs lesion. METHODS: Forty-nine shoulders of 47 patients with traumatic posterior instability were included in this study based on the following inclusion criteria: 1) a primary or recurrent traumatic posterior shoulder dislocation, and 2) the initial event was caused by trauma. Patients were excluded if they had: 1) no history of trauma, 2) prior shoulder surgery, 3) no CT examination, or 4) seizure cases. Three-dimensional images of the humerus reconstructed from CT images were reviewed using an image analysis software. The location and size of the reverse Hill-Sachs lesion were measured and described on a clock face on the humeral head. RESULTS: The reverse Hill-Sachs lesion was observed in 25 of 49 shoulders (51%). The reverse Hill-Sachs lesions were located between 1:37 and 2:48. The depth of the reverse Hill-Sachs lesion (mean ± SD) was 5.8 ± 2.2 mm. The extent of the reverse Hill-Sachs lesion was 35° ± 12°. The average orientation of the reverse Hill-Sachs lesion, represented by an angle measured from the 12 o'clock position, was 64° ± 12° and pointing towards 2:09 on a clock face. Length and width of reverse Hill-Sachs lesions were 9.7 ± 4.7 mm, 11.1 ± 3.6 mm, respectively. CONCLUSION: The reverse Hill-Sachs lesion was a semicircular compression fracture located on the anteromedial aspect of the humeral head. Compared with shoulders with anterior shoulder instability, the humeral defect was smaller and located more inferiorly in shoulders with posterior instability.

A novel NFKB1 variant in a Japanese pedigree with common variable immunodeficiency.

Recently, heterozygous loss-of-function NFKB1 variants were identified as the primary cause of common variable immunodeficiency (CVID) in the European population. However, pathogenic NFKB1 variants have never been reported in the Japanese population. We present a 29-year-old Japanese woman with CVID. A novel variant, c.136 C > T, p.(Gln46*), was identified in NFKB1. Her mother and daughter carried the same variant, demonstrating the first Japanese pedigree with an NFKB1 pathogenic variant.

Association of immune-related adverse events with durvalumab efficacy after chemoradiotherapy in patients with unresectable Stage III non-small cell lung cancer.

BACKGROUND: Immune-related adverse events (irAEs) have been found to predict PD-L1 inhibitor efficacy in metastatic NSCLC. However, the relation of irAEs to clinical outcome for nonmetastatic NSCLC has remained unknown. METHODS: In this multicenter prospective study of Stage III NSCLC treated with PACIFIC regimen, the relation of irAEs to PFS was evaluated by 8-week landmark analysis to minimise lead-time bias as well as by multivariable analysis adjusted for baseline factors. irAEs were categorised as mild or nonmild according to whether they were treated with systemic steroid. RESULTS: Median PFS was 16.0 months, not reached, and 9.7 months for patients without (85 cases) or with mild (21 cases) or nonmild (21 cases) irAEs, respectively. Multivariable analysis indicated that nonmild irAEs were associated with poor PFS, with HRs of 3.86 (95% CI, 1.31-11.38) compared with no irAEs and 11.58 (95% CI, 2.11-63.63) compared with mild irAEs. This pattern was consistent after irAE grade, the number of durvalumab doses and immune profiles (PD-L1 score, CD8+ tumour-infiltrating lymphocyte density, and tumour mutation burden) were taken into consideration. CONCLUSIONS: The development of mild irAEs might predict a better survival outcome, whereas immunosuppressive steroid-treated irAEs were associated with a worse outcome, regardless of baseline clinical and immune profiles.

Mannitol versus furosemide in patients with thoracic malignancies who received cisplatin-based chemotherapy using short hydration: A randomized phase II trial.

BACKGROUND: Mannitol is exclusively recommended in the National Comprehensive Cancer Network guidelines for diuresis in cisplatin (CDDP)-based chemotherapy. The utility of furosemide, a widely used and convenient diuretic, thus requires clarification. METHODS: This is a prospective, single-centered, open-label, noninferiority phase II study. Patients with thoracic malignancies who planned to receive CDDP-based chemotherapy were randomly assigned to receive either mannitol (arm A) or furosemide (arm B). The primary end point was set as the proportion of patients who experienced any grade of "creatinine (Cr) increased" based on the upper limit of the normal range (ULN) during the first cycle as assessed by Common Terminology Criteria for Adverse Events Version 4.0. Secondary end points were Cr increased based on the baseline value during the first cycle, Cr increased after the completion of CDDP, and the proportion of patients with phlebitis. RESULTS: Between April 2018 and March 2022, 115 patients were enrolled and 106 were analyzed. Any grade of Cr increased based on the ULN during the first cycle was 17.3% (arm A) and 24.1% (arm B), respectively (p = 0.34). Therefore, the primary end point was not met. After completion of chemotherapy, any grade of Cr increased was observed in 23.1% (arm A) and 31.5% (arm B), respectively. However, the actual serum Cr level and Cr clearance during the courses were not different between the arms. Phlebitis occurred more frequently in arm A (28.8%) than arm B (16.7%). CONCLUSIONS: Mannitol should remain the standard diuresis in CDDP-based chemotherapy assessed by conventional CTCAE grading, but furosemide can be room for consideration when assessed by actual serum Cr level and Cr clearance.

Statistical shape models that predict native glenoid width based on glenoid height are inaccurate in their current form: A cross-sectional study.

BACKGROUND: The extent of measurement errors of statistical shape models that predict native glenoid width based on glenoid height to subsequently determine the amount of anterior glenoid bone loss is unclear. Therefore, the aim of this study was to (1) create a statistical shape model based on glenoid height and width measured on 3D-CT and determine the accuracy through measurement errors and (2) determine measurement errors of existing 3D-CT statistical shape models. MATERIALS AND METHODS: A retrospective cross-sectional study included all consecutive patients that underwent CT-imaging before undergoing primary surgical treatment of traumatic anterior shoulder dislocation between 2007 and 2022 at the Tohoku University Hospital and affiliated hospitals. Patients were included when instability was unilateral and CT scans of both the injured and contralateral uninjured shoulder were available. 3D segmentations were created and glenoid height and width of the injured and contralateral uninjured side (gold standard) were measured. Accuracy was determined through measurement errors, which were defined as a percentage error deviation from native glenoid width (contralateral uninjured glenoid), calculated as measurement error = ((estimated glenoid width with a statistical shape model - native glenoid width) / native glenoid width) x 100%. A linear regression analysis was performed to create a statistical shape model based on glenoid height according to the formula native glenoid width = a * glenoid height + b. RESULTS: The diagnosis and procedure codes identified 105 patients, of which 69 (66%) were eligible for inclusion. Glenoid height demonstrated a very strong correlation (r= 0.80) with native glenoid width. The linear regression formula based on this cohort was native glenoid width = 0.75 * glenoid height - 0.61 and demonstrated an absolute average measurement error of 5 ± 4%. The formulas by Giles et al, Chen et al and Rayes et al demonstrated absolute average measurement errors of 10 ± 7%, 6 ± 5% and 9 ± 6%, respectively CONCLUSION: Statistical shape models that estimate native glenoid width based on glenoid height demonstrate unacceptable measurement errors, despite a high correlation. Therefore, great caution is advised when using these models to determine glenoid bone loss percentage. To minimize errors caused by morphological differences, preference goes to methods that use the contralateral side as reference.

Laparoscopic polyglycolic acid spacer placement for locally recurrent rectal cancer.

Carbon ion radiotherapy (CIRT) has received attention for the treatment of locally recurrent rectal cancer. When the surrounding primary organs are close to the irradiation site, a spacer is required to ensure safe irradiation. This work describes a novel technique using a bioabsorbable polyglycolic acid spacer placed laparoscopically and presents a technical report with five case studies. The short-term surgical outcomes were as follows: mean operating time 235 min with blood loss of 38 mL. CIRT was planned, and the patients underwent irradiation within 2 months of surgery. No pelvic infections occurred, and all procedures were performed safely. Herein, were present a technical report with reference to a video of the surgical procedure.

Efficacy of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in Metastatic Non-Small Cell Lung Cancer Patients with Poor Performance Status and Epidermal Growth Factor Receptor Mutations: Findings from the Japanese Lung Cancer Registry Database.

BACKGROUND: In advanced non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations, those with impaired performance status (PS) treated with EGFR-tyrosine kinase inhibitors (TKIs) have demonstrated comparable activities to good-PS patients. Due to the limited sample size and inclusion of older adult patients with good PS, these findings may not accurately depict the efficacy of EGFR-TKI in poor-PS patients. We investigated the benefit of EGFR-TKIs in this population and identified relevant prognostic factors. PATIENTS AND METHODS: This nationwide prospective registry study included 9872 patients with local or advanced NSCLC. Outcomes were compared between poor- and good-PS patients treated with EGFR-mutated lung cancer therapies. RESULTS: Of 9872 NSCLC patients, 1965 (19.9%) had EGFR mutations, with 1846 (93.9%) presenting common EGFR mutations. Poor PS (PS score ≥ 3) was noted in 171 patients (8.7%) and identified as an independent prognostic factor; those with poor PS had a significantly lower 1-year survival rate. The median overall survival (OS) for EGFR-TKI-treated good-PS patients was 31.5 (95% confidence interval, 29.6-33.4) months. Among poor-PS patients with EGFR mutations, 135 (78.9%) of whom were treated with EGFR-TKI had an OS of 15.5 (12.7-18.3) months, while those receiving only supportive care had an OS of 2.5 (1.4-3.6) months (P < .001). Hypoalbuminemia (< 3.5 g/dL), liver metastasis, and uncommon EGFR mutations were associated with poor prognosis. CONCLUSION: Poor PS at diagnosis was rare and associated with limited EGFR-TKI efficacy and a dismal prognosis. Liver metastasis and hypoalbuminemia may reduce EGFR-TKI efficacy in these patients.

A Multi-Institutional, Randomized, Phase III Trial Comparing Anatomical Segmentectomy and Lobectomy for Clinical Stage IA3 Pure-Solid Non-Small-Cell Lung Cancer: West Japan Oncology Group Study WJOG16923L (STEP UP Trial).

INTRODUCTION: Although the standard treatment for patients with resectable early-stage non-small-cell lung cancer (NSCLC) is pulmonary lobectomy, recent clinical trials have demonstrated the efficacy of anatomical segmentectomy for small-sized early-stage NSCLC measuring ≤2 cm. Segmentectomy is gaining attention as an alternative procedure to lobectomy for early-stage NSCLC. PATIENTS AND METHODS: In January 2024, we have initiated a randomized phase III trial in Japan to confirm the noninferiority of anatomical segmentectomy to lobectomy in patients with peripheral clinical stage IA3 pure-solid NSCLC (tumor measuring >2 cm and ≤3 cm; consolidation-to-tumor ratio = 1.0). We plan to enroll 520 patients from 61 institutions over a period of 5 years. The primary endpoint is overall survival, and the secondary endpoints include relapse-free survival, postoperative respiratory function, proportion of patients with respiratory failure and cerebrovascular disease, cumulative incidence of death from other diseases, cumulative incidence of local recurrence, proportion of patients who undergo segmentectomy, number of resected segments, operative time, blood loss, and adverse events. This trial has been registered in the UMIN Clinical Trials Registry under the code UMIN000052064. CONCLUSIONS: This trial will help establish a novel treatment strategy for patients with peripheral clinical stage IA3 pure-solid NSCLC.

Machine learning analysis of pathological images to predict 1-year progression-free survival of immunotherapy in patients with small-cell lung cancer.

BACKGROUND: In small-cell lung cancer (SCLC), the tumor immune microenvironment (TIME) could be a promising biomarker for immunotherapy, but objectively evaluating TIME remains challenging. Hence, we aimed to develop a predictive biomarker of immunotherapy efficacy through a machine learning analysis of the TIME. METHODS: We conducted a biomarker analysis in a prospective study of patients with extensive-stage SCLC who received chemoimmunotherapy as the first-line treatment. We trained a model to predict 1-year progression-free survival (PFS) using pathological images (H&E, programmed cell death-ligand 1 (PD-L1), and double immunohistochemical assay (cluster of differentiation 8 (CD8) and forkhead box P3 (FoxP3)) and patient information. The primary outcome was the mean area under the curve (AUC) of machine learning models in predicting the 1-year PFS. RESULTS: We analyzed 100,544 patches of pathological images from 78 patients. The mean AUC values of patient information, pathological image, and combined models were 0.789 (range 0.571-0.982), 0.782 (range 0.750-0.911), and 0.868 (range 0.786-0.929), respectively. The PFS was longer in the high efficacy group than in the low efficacy group in all three models (patient information model, HR 0.468, 95% CI 0.287 to 0.762; pathological image model, HR 0.334, 95% CI 0.117 to 0.628; combined model, HR 0.353, 95% CI 0.195 to 0.637). The machine learning analysis of the TIME had better accuracy than the human count evaluations (AUC of human count, CD8-positive lymphocyte: 0.681, FoxP3-positive lymphocytes: 0.626, PD-L1 score: 0.567). CONCLUSIONS: The spatial analysis of the TIME using machine learning predicted the immunotherapy efficacy in patients with SCLC, thus supporting its role as an immunotherapy biomarker.

Prospective observational study to explore genes and proteins predicting efficacy and safety of brigatinib for ALK-gene rearranged non-small-cell lung cancer: study protocol for ABRAID study (WJOG11919L).

Background: ALK-tyrosine kinase inhibitors (ALK-TKIs) are effective for treating non-small-cell lung cancer with ALK gene rearrangement; however, resistance is inevitable. Brigatinib is a unique ALK-TKI that is effective against many resistance mutations. However, data on factors associated with its efficacy and resistance mechanisms are limited. Objectives: This study will evaluate the efficacy and safety of brigatinib in the real world and explore factors related to its efficacy, safety, and resistance mechanisms. Design: Prospective observational study. Ethics: This study is approved by the Ethics Committee of Wakayama Medical University. Written informed consent will be obtained from all patients before study-related procedures. Methods and analysis: This study comprises three cohorts. Cohorts A, B, and 0 will enroll patients receiving alectinib as the first ALK-TKI, receiving alectinib as the first ALK-TKI and subsequently cytotoxic agents and/or lorlatinib after alectinib, and without a history of ALK-TKI, respectively. Overall, 100, 30, and 50 patients will be enrolled in Cohorts A, B, and 0, respectively. Circulating tumor DNA before starting brigatinib and at disease progression will be analyzed in all cohorts using a hypersensitive next-generation sequencing (NGS) PGDx Elio plasma resolve panel. Serum protein levels will be analyzed using the Milliplex xMAP assay system with a Luminex 200 (Luminex, Austin, USA). The enrollment period is 31 months and the patients will be observed for 2 years after enrollment. Archived tissues will be collected for NGS analysis, gene expression analysis, and immunohistochemistry staining 1 year after completion of registration. Quality of life and safety evaluation using electronic patient-reported outcomes will be investigated. Discussion: This study will elucidate predictors of ALK-TKI efficacy and resistance mechanisms and evaluate the efficacy and safety of brigatinib in a real-world setting. The results will provide crucial information for establishing treatment strategies, discovering novel biomarkers, and developing new therapeutic agents. Trial registration: UMIN000042439.

A Phase II Study of High-Flow Nasal Cannula for Relieving Dyspnea in Advanced Cancer Patients.

CONTEXT: The efficacy and tolerability of high-flow nasal cannula (HFNC) for relieving dyspnea in advanced cancer patients with limited prognosis requires elucidation. OBJECTIVES: The primary aim of this trial was to assess the efficacy and tolerability of HFNC regarding dyspnea including severe as well as moderate for longer durations in patients under palliative care. METHODS: In this prospective study, hospitalized patients with advanced cancer who had dyspnea at rest (numeric rating scale, NRS≥3) and hypoxemia were enrolled. They were treated with HFNC for five days in the respiratory unit. Primary endpoint was mean change of modified Borg scale at 24 hours. Key secondary endpoints consisted of mean changes in modified Borg scale during the study period and feasibility (Trial Identifier, UMIN000035738). RESULTS: Between February 2019 and February 2022, 25 patients were enrolled and 21 were analyzed. Twenty patients used inspired oxygen and the mean fraction of inspired oxygen (FiO2) was 0.34 (range, 0.21-1.0). At baseline, mean NRS (dyspnea) was 5.9 (range, 3-10). Median survival time was 19 days (range, 3-657). The mean change of modified Borg scale was 1.4 (80% confidence interval [CI]: 0.8-1.9) at 24 hours, 12 patients (57%) showed 1.0 points improvement of modified Borg scale. Within two hours, 15 patients showed 1.0 points improvement of modified Borg scale and such early responders were likely to maintain dyspnea improvement for 24 hours. Nineteen patients could continue HFNC for 24 hours and 11 patients completed five days of HFNC. CONCLUSION: To our knowledge, this trial is the first prospective study to assess the five-day efficacy and tolerability of HFNC for dyspnea in patients under palliative care. Although this did not reach the prespecified endpoint, about half of the patients showed 1.0 point improvement, a minimally clinically important difference (MCID) in the chronic lung disease. HFNC can be a palliative treatment option in advanced cancer patients with dyspnea.

When and how much does the muscle strength recover after arthroscopic superior capsular reconstruction?

BACKGROUND: Recently, arthroscopic superior capsular reconstruction (SCR) has been performed for irreparable large to massive rotator cuff tears and excellent clinical results have been reported. Although the muscle strength is reported to recover, it has not yet been clarified when and how much it recovers. The purpose of this study was to determine the recovery pattern of muscle strength after SCR. METHODS: We retrospectively reviewed 35 patients (mean age, 65 years) who met the following inclusion criteria: (1) patients with large to massive irreparable tears of the rotator cuff including the supraspinatus and infraspinatus tendons; (2) those with severe muscle atrophy and fatty change; (3) those who underwent assessment of muscle quality and strength by magnetic resonance imaging and dynamometry at 6 months, 1 year, and 2 years; (4) those with a minimum follow-up period of 2 years; and (5) those without severe osteoarthritis. The isometric muscle strength of scaption (ie, scapular-plane elevation), internal rotation, and external rotation in adduction was measured twice for each motion by a dynamometer. RESULTS: Relative to the muscle strength on the uninvolved side, the involved side showed 61% ± 21% in scaption, 63% ± 20% in external rotation, and 103% ± 29% in internal rotation at 2 years after surgery. Whereas no significant differences were observed between the 1-year and 2-year follow-up assessments, a significant difference in muscle strength of scaption was found between 6 months and 1 year (P = .0174). Graft retear was seen in 5 cases (14%). There was a trend that the muscle strength of scaption and external rotation in the no-retear group was greater than that in the retear group despite no significant difference (P = .0717 and P = .0824, respectively). CONCLUSION: The recovery of the muscle strength after SCR was observed until 1 year after surgery, and the muscle strength of scaption and external rotation returned to 60% of that on the uninvolved side at 2 years.