Induction Immunochemotherapy Yields a Higher Conversion Rate and Better Overall Survival than Chemotherapy in Initially Unresectable Esophageal Squamous Cell Carcinoma.

INTRODUCTION: This study compared the surgical conversion rate and overall survival (OS) between induction chemotherapy (iC) and induction immunochemotherapy (iIC) for patients with initially unresectable esophageal squamous cell carcinoma (iuESCC). METHODS: In this multicenter, retrospective cohort study, patients from four high-volume institutions with unresectable diseases were included. The primary endpoints were the conversion surgery rate and OS. A multivariate Cox regression analysis was used to identify the independent significant prognostic factors associated with OS. The stabilized inverse probability of treatment weighting was applied to confirm the survival comparison between the iIC and iC cohorts. RESULTS: A total of 309 patients (150 in the iIC cohort and 159 in the iC cohort) were included. A significantly higher conversion surgical rate was observed in the iIC cohort (iIC vs. iC: 127/150, 84.7% vs. 79/159, 49.7%, P < 0.001). The pathological complete response rates were 22.0% and 5.1% in the iIC and the iC cohorts, respectively (P = 0.001). A significant difference in the OS was observed between the iIC (not reached) and iC cohorts (median 95% CI 36.3 [range 27.2-45.5]). The stabilized inverse probability of treatment weighting yielded similar results. Regimen (iIC vs. iC, HR 0.215, 95% CI 0.102-0.454, P < 0.001) and operation (yes vs. no, HR 0.262, 95% CI 0.161-0.427, P < 0.001) were the significant prognostic factors for OS. CONCLUSIONS: Immunochemotherapy plus conversion surgery in the induction setting may be a better treatment option to achieve high pathological responses and improve OS in iuESCC patients.

Validation of the Reichert® Tono-Vera® Vet rebound tonometer in normal ex vivo canine eyes.

OBJECTIVE: To determine the accuracy of the Reichert® Tono-Vera® Vet rebound tonometer for canine intraocular pressure (IOP) measurement. ANIMALS STUDIED: Five normal canine ex vivo globes. PROCEDURES: The anterior chambers of five freshly enucleated normal canine eyes were cannulated and connected to a reservoir of Plasma-Lyte A and a manometer. Starting at a manometric IOP of 5 mmHg, the pressure was progressively increased to 80 mmHg by raising the reservoir. Triplicate IOP measurements were taken with the Tono-Vera® Vet from the central cornea using the dog setting and compared to the manometric pressure by linear regression analysis and Bland-Altman plots. RESULTS: There was a strong positive linear regression trend when comparing central corneal Tono-Vera® Vet IOPs to manometric pressures (r2 = .99) with solid agreement between the two methods. Compared to manometric IOPs, the Tono-Vera® Vet underestimated IOPs at higher pressures ≥70 mmHg. CONCLUSIONS: Measurement of IOPs from the central cornea with the Tono-Vera® Vet provided accurate results over a large range in normal canine globes compared to direct manometry. The mild to moderate underestimation of IOPs at high pressures was not considered clinically relevant.

Early and Persistent Dysphagia Relief Predicts Tumor Response in Esophageal Squamous Cell Carcinoma Patients Treated with Immunochemotherapy.

BACKGROUND: In this prospective study, we aimed to investigate the role of patient-reported dysphagia relief in predicting pathological tumor responses to neoadjuvant immunochemotherapy (NAIC) in locally advanced esophageal squamous cell carcinoma (ESCC) patients. METHODS: This study was designed as a multi-center, prospective study including ESCC patients who received NAIC in the discovery and validation cohorts. The patients' responses to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-OES 18 and QLQ-C30 were collected at multiple time points. Subsequent time point-intensive esophageal cancer-specific dysphagia trajectories were depicted using growth mixture modeling (GMM) analysis. Furthermore, univariate and multivariate binary logistic regression was used to assess the independent predictors for pathological tumor responses. RESULTS: A total of 120 patients from the discovery cohort and 42 patients from the validation cohort were included in the analysis. In the discovery cohort, 19 (22.9%) of the 83 patients achieved pCR status. In the independent validation cohort, 24 patients underwent surgery, and 9 (37.5%) patients achieved pCR status. Trajectory analysis showed that, in the pCR group, the beginning of rapid declines in the slope occurred on days 3, 6, and 9. Further multivariate analysis showed that the degree of dysphagia relief (△dysphagia%) was the only significant independent predictor for pCR status (OR = 3.267, 95% CI 1.66-6.428, P < 0.001). The AUC value for △dysphagia% was 0.961 (95% CI: 0.922-0.999, P < 0.001). CONCLUSION: The current study demonstrated that a longitudinal patient-reported outcome (PRO) was an easily obtained, cost-effective, and noninvasive tool for predicting tumor responses to neoadjuvant immunochemotherapy.

Bone Metabolism Discrepancy in Type 2 Diabetes Mellitus Patients With and Without Non-Alcoholic Fatty Liver Disease.

To explore the distribution of several bone metabolic indicators in type 2 diabetes patients (T2DM) with and without non-alcoholic fatty liver disease (NAFLD) and to preliminarily evaluate the relationship of bone metabolism with NAFLD in patients with T2DM. The hospitalized patients with T2DM were divided into the group of T2DM complicated with NAFLD and the group of T2DM alone according to the results of ultrasonic diagnosis. The general information and laboratory test data such as bone metabolism indexes of these patients were collected and the differences of the indexes between the 2 groups were compared. Furthermore, the independent influencing factors of NAFLD in patients with T2DM were analyzed. A total of 186 patients were included in the study. Compared with patients with T2DM only, patients with T2DM combined with NAFLD were characterized with younger age (p < 0.001), higher BMI (p = 0.016), ALT (p = 0.001), TG (p = 0.005), HOMA-IR (p = 0.005), and lower HDL-C (p = 0.031). Significant discrepancy of age (OR 1.052, p = 0.001), ALT (OR 0.964, p = 0.047), HOMA-IR (OR 0.801, p = 0.005), and T-PINP (OR 1.022, p = 0.008) was found using multivariate logistic regression model. Significant discrepancy of T-PINP was found in T2DM patients with and without NAFLD. Further studies are needed to explore whether T-PINP could be used as a predictor of fatty liver disease, osteoporosis, and other related complications in patients with T2DM.

Gender differences in the relationships between different types of childhood trauma and resilience on depressive symptoms among Chinese adolescents.

Growing studies have paid attention to the relationships between childhood trauma, resilience and depressive symptoms. Depression is more common in girls, while gender differences in these associations have been rarely studied. Yet the study will be beneficial for prevention and intervention of depression in adolescents. The aim of this study is to examine gender differences in the effects of different types of childhood trauma and resilience on depressive symptoms. Data was collected from 6510 students (3408 males, aged 10-17 years) in Wuhan, Hubei, China from 2015 to 2016. Participants completed a self-report questionnaire assessing childhood trauma, resilience, and depressive symptoms. Multiple regression analysis was used to determine gender differences in the relationships between childhood trauma, resilience and depressive symptoms. We found that childhood trauma was positively related to depressive symptoms for both genders, but the relationship in females was stronger than in males. No significant gender difference was found in the independent effect of resilience to depressive symptoms. Resilience moderated the effects of emotional abuse, physical abuse and sexual abuse on depressive symptoms in both males and females. However, the interaction effect of resilience with emotional abuse on depressive symptoms was stronger in females compared to males. Our findings revealed gender differences in the links between childhood trauma and depressive symptoms among adolescents, and the interaction effect of resilience and childhood emotional abuse on depressive symptoms was gender-specific. These provide the basis for gender-special prevention and intervention measures for depressive symptoms in adolescents.

[Relationships among personality traits, resilience and depressive symptoms of students in Wuhan City].

OBJECTIVE: To investigate the relationships among personality traits, resilience and depressive symptoms of primary and high school students. METHODS: Totally 6019 students aged 10-17 from 5 primary schools(grades 5-6), 3 junior middle schools(grades 7-9) and 2 senior high schools(grade 1) years were selected by cluster sampling in Wuhan, from September 2015 to January 2016. Among them, there were 2420 primary school students, 2912 junior high school students and 687 senior high school students. In addition, 3071 students were male, 2948 students were female. Participants were asked to complete self-report questionnaires, including demographic characteristic questionnaire, the center for epidemiological studies depression scale(CES-D), the connor davidson resilience scale(CD-RISC) and the NEO-five factor inventory(NEO-FFI). Multivariate Logistic regression analysis was used to analyze the influence factors of depressive symptoms in primary and high school students. RESULTS: The detection rate of depressive symptoms was 10. 5%(635/6019). Multivariate Logistic regression analysis showed that after adjusting for grade and family history of depression, neuroticism(OR=4. 53, 95% CI 3. 88-5. 28) and openness(OR=1. 33, 95% CI 1. 18-1. 50) were positively associated with depressive symptoms. But the higher level of extraversion(OR=0. 70, 95% CI 0. 62-0. 79) and conscientiousness(OR=0. 77, 95% CI 0. 67-0. 90) and resilience(OR=0. 77, 95% CI 0. 67-0. 88) were associated with lower risk of depressive symptoms in primary and high school students. CONCLUSION: Neuroticism and openness might be positively correlated with, whereas extraversion, conscientiousness and resilience might be negatively correlated with the onsets of depressive symptoms in primary and secondary school students. Thus, developing adaptive personality and improving resilience would contribute to the prevention and intervention of depression in primary and high school students.

[Childhood trauma and its correlation with resilience among primary and middle school students in Wuhan city in 2015].

OBJECTIVE: To investigate the prevalence of early trauma and resilience among adolescents in Wuhan, and explore the relationship between early trauma and resilience. METHODS: Totally 4871 students aged 10-16 years were chosen by cluster sampling in Wuhan city from September to October 2015. All subjects completed self-report questionnaires, including general information, the Childhood Trauma Questionnaire( CTQ), and the Connor Davidson Resilience Scale( CD-RISC). RESULTS: The mean score of CD-RISC of the total sample was( 64. 70 ± 18. 34). Statistical significance in different gender( t = 5. 373, P<0. 001), age( F = 49. 401, P<0. 001), single child( t = 3. 529, P<0. 001), levels of mother's education( F = 36. 129, P< 0. 001), relationship between parents( F = 89. 831, P < 0. 001), family economic status( F = 36. 547, P<0. 001). The rate of early trauma was 30. 1%. Male( χ~2= 42. 272, P < 0. 001), lower levels of mother 's education( χ~2= 44. 345, P < 0. 001), poorer relationship between parents( χ~2= 133. 045, P < 0. 001), and worse family economic status( χ~2= 31. 231, P<0. 001) were associated with increased risk of early trauma. The scores of emotional abuse, physical abuse, sexual abuse, emotional neglect and physical neglect were negatively correlated with the scores of CD-RISC( r followed by-0. 256, -0. 107, -0. 053, -0. 355 and-0. 308, P<0. 01). Regression analysis implied female, older age, emotional abuse, emotional neglect, and physical neglect( B followed by-0. 156, -0. 117, -0. 109, -0. 214 and-0. 149, P < 0. 01) of primary and middle school students assumed predictive resilience. CONCLUSION: Emotional abuse, emotional neglect, and physical neglect are negatively associated with resilience among children and adolescent. The result suggest that reducing emotional abuse, emotional neglect and physical neglect experience may contribute to child resilience.

TW37 enhances the pro-apoptosis and anti-migration ability of gefitinib in Non-Small Cell Lung Cancer.

B cell leukemia-2 (Bcl-2) plays important roles in the development of tumor and drug resistance. The growth of tumor cells can be inhibited by downregulating the abnormal expression of Bcl-2 protein. TW37, an effective inhibitor of Bcl-2 protein, has now been widely studied in many tumors. In our study, it was found that TW37 exerted a significant effect on the proliferation, apoptosis and migration of Non-Small Cell Lung Cancer cells. Bcl-2 is also a key downstream factor of many signaling pathways such as Epidermal Growth Factor Receptor (EGFR). TW37 enhanced the inhibition of tumorigenesis by gefitinib, an EGFR-Tyrosine Kinase Inhibitor drug. Moreover, TW37 can promote apoptosis ability by inhibiting the phosphorylation level of EGFR protein in H1975 cells. Overall, TW37 enhances the pro-apoptosis and anti-migration ability of gefitinib in Non-Small Cell Lung Cancer.

Updated incidence rates and risk factors of esophageal cancer in Nan'ao Island, a coastal high-risk area in southern China.

Esophageal cancer (EC) is one of the most common cancers in China. The purpose of this study was to investigate the updated incidence rates and risk factors of EC in Nan'ao Island, where the EC incidence rate was chronically the highest in southern China. To calculate the annual incidence rate, data on 338 EC cases from Nan'ao Cancer Registry system diagnosed during 2005-2011 were collected. A case-control study was conducted to explore the EC risk factors. One hundred twenty-five alive EC patients diagnosed during 2005-2011 and 250 controls were enrolled into the case-control study. A pre-test questionnaire on demography, dietary factors, drinking water treatment, and behavioral factors was applied to collect information of all participants. The average EC incidence rates during 2005-2011 were 66.09/105, 94.62/105, 36.83/105 for both genders, males and females, respectively, in Nan'ao Island. The EC incidence rate in males was 2.40- to 4.55-fold higher than that in females in the period from 2006 to 2011 (P < 0.05). Considering the onset age, males tend to be much younger than females and reached peak incidence rate at a younger age (P < 0.05). Drinking water treatment by filter (odds ratio [OR] = 0.28, 95% confidence interval [95% CI] = 0.13-0.58) and fruit consumption (OR = 0.55, 95% CI = 0.32-0.94) reduced the risk for EC. On the contrary, the pickled vegetables consumption (OR = 2.64, 95% CI = 1.46-4.76) and liquor drinking (OR = 2.32, 95% CI = 1.21-4.44) increased the risk for EC. These results may be of importance for future research on EC etiology and prevention strategies.

Serial monitoring of pancreatic lipase immunoreactivity, C-reactive protein, abdominal ultrasonography, and clinical severity in dogs with suspected pancreatitis.

BACKGROUND: Diagnosis of pancreatitis is based on clinical signs, pancreatic lipase immunoreactivity (cPLI), and abdominal ultrasonography (AUS). Diagnostic discrepancies exist between test results which might be related to differences in the timeline for resolution of these abnormalities after pancreatic injury. HYPOTHESIS/OBJECTIVES: To evaluate disease severity, ultrasonographic findings, and serum biomarkers of pancreatitis in dogs over a period of 28-days. ANIMALS: Sixteen client-owned dogs with a clinical suspicion for acute pancreatitis based on history/physical examination, an abnormal SNAP cPLI, and ultrasonographic evidence of pancreatitis. METHODS: Prospective observational study. Clinical severity (modified clinical activity index [MCAI]), cPLI, C-reactive protein (CRP), and AUS were evaluated at days 0, 2, 7, and 28. Owner assessed overall health (OH) was noted. Dogs were stratified into baseline cPLI ≥400 µg/L vs <400 µg/L groups for reporting. RESULTS: The median CRP, MCAI, and OH were 111.9 mg/L, 10, and 4/10 respectively in the cPLI ≥400 µg/L group. The median CRP, MCAI, and OH were 58.0 mg/L, 6, and 6/10 respectively in the cPLI <400 µg/L group. None of these variables were significantly different between groups. Most dogs (4/5) in the cPLI <400 µg/L group had a history of suspected pancreatitis (ie, suspect acute on chronic disease). cPLI and MCAI rapidly decreased in dogs with a baseline cPLI ≥400 µg/L, whereas sonographic evidence of pancreatitis persisted for a longer time period. CONCLUSIONS AND CLINICAL IMPORTANCE: Ultrasonographic evidence of pancreatitis in the absence of overt clinical or biochemical abnormalities might represent a resolving injury rather than active disease.

Treatment-Related Pneumonitis of EGFR Tyrosine Kinase Inhibitors Plus Thoracic Radiation Therapy in Patients With Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Thoracic radiation therapy (RT) for non-small cell lung cancers may overcome resistance to tyrosine kinase inhibitors (TKIs). However, the risk of severe treatment-related pneumonitis (TRP) is a major concern, and the results of the combined treatment remain controversial. Therefore, we aimed to systematically review existing publications and provide a meta-analysis of TRP from a combined therapy of thoracic RT and TKIs. A systematic literature review was performed using the PubMed-MEDLINE and Embase databases to identify eligible publications. The number of severe TRP cases of grade 3 or higher was extracted and then analyzed by fixed or randomized model meta-analysis. Heterogeneity tests were performed using the I² and τ² statistics. Subgroup analyses were conducted on the types of RT and the sequence of the combined treatment. Our literature search identified 37 eligible studies with 1143 patients. Severe TRP occurred in 3.8% (95% CI, 1.8%-6.5%) of patients overall, and fatal pneumonitis occurred rarely in 0.1% (95% CI, 0.0%-0.3%). In the subgroup analysis, the severe TRP proportion was 2.3% (95% CI, 1.0%-4.1%) for patients under definitive (chemo)RT (19 studies, n = 702) versus 2.9% (95% CI, 1.3%-5.1%) for patients who received local stereotactic body RT or palliative RT (15 studies, n = 361). The severe TRP rate was 4.9% (95% CI, 2.4%-8.1%) for concurrent TKI and RT (26 studies, n = 765), which was significantly higher than TRP of 0.4% (95% CI, 0.0%-3.1%) for sequential therapy (6 studies, n = 200). Our meta-analysis showed that combined thoracic RT and epidermal growth factor receptor-TKI therapy has an acceptable risk of severe TRP and rare mortality in patients with non-small cell lung cancers. Concurrent treatment is less tolerable and should be administered with caution. Further investigations using osimertinib are required as the data on its effects are limited.

Serum calcium concentrations are inversely correlated with pancreatic lipase concentrations in dogs.

OBJECTIVE: (1) Determine if a relationship exists between ionized calcium (iCa) and pancreatic lipase (cPLI) concentration in dogs, and (2) assess for correlation between resolving hypercalcemia and cPLI concentrations in dogs after treatment for primary hyperparathyroidism (PHPT). SAMPLES: Phase I, 44 residual serum samples (collected April 2023) from client-owned dogs with a clinical indication for cPLI quantification. Phase II, 24 residual serum samples (collected August 2022 through February 2023) from client-owned dogs with PHPT pre- and postcorrection of hypercalcemia. METHODS: Serum cPLI and iCa concentrations were measured via the Spec cPL assay and a spectrophotometric method respectively. Spearman's rank correlation coefficients were used to investigate if there was a correlation between serum calcium and cPLI concentrations. A paired t-test was used to investigate the effect of the resolution of hypercalcemia on serum cPLI concentrations. RESULTS: Phase I, serum cPLI concentrations were negatively correlated with serum iCa concentrations (r = -.429, 95% CI [-.64, -.14], P = .005) in dogs with a clinical indication for cPLI quantification. Phase II, median serum cPLI concentrations were higher before (median: 228.5 µg/L, IQR: 351.3 µg/L) than after (median: 141.0 µg/L, interquartile ranges (IQR): 279.5 µg/L) management of hypercalcemia (PHPT model). However, the decrease in cPLI concentration was not statistically significant (P = .70). CLINICAL RELEVANCE: Calcium depletion may result in an inverse relationship between serum cPLI and iCa concentrations in dogs with a clinical indication for cPLI quantification. Hypercalcemia may be associated with an above reference interval cPLI concentration in some dogs.

Efficacy and safety of immunochemotherapy, immunotherapy, chemotherapy, and targeted therapy as first-line treatment for advanced and metastatic esophageal cancer: a systematic review and network meta-analysis.

Background: The treatment of esophageal cancer has entered a new phase with the development of immunotherapy. The current investigation purpose is to investigate and contrast the efficacy and safety of immunotherapy, immunochemotherapy, chemotherapy, and targeted therapy as first-line treatment for individuals suffering from advanced and metastatic esophageal cancer. Methods: Within the framework of this systematic review and network meta-analysis, clinical trials published or reported in English up until 01 May, 2022, were retrieved from Embase, PubMed, Cochrane Central Register of Controlled Trials, the ClinicalTrials.gov databases, ESMO, and ASCO. The analysis incorporated randomized controlled trials (RCTs) from phase 2 to 3 that evaluated a minimum of two first-line therapeutic regimens for metastatic esophageal cancer were included in the analysis. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary clinical outcomes included the incidence of objective response rate (ORR), and adverse events (AEs) of any grade and ≥3 grade. Relative summary data were extracted from included studies by GZ, HS, WS, and TD. For clear statistical analysis, chemotherapy was divided into two categories of fluorouracil-based chemotherapy (FbCT) and fluorouracil-free chemotherapy (FfCT). Bayesian frequentist approach was employed to conduct the network meta-analysis. The indirect intercomparison between regimens was presented with league tables (HRs and 95% CI for OS and PFS, ORs and 95% CI for ORR and AEs). A greater surface value under the cumulative ranking (SUCRA) indicates a higher potential ranking for the corresponding treatment. A further calculation of relative results about esophageal squamous cell cancer was performed in the subgroup analysis. The current protocol for the systematic review has been properly registered on PROSPERO (registration number: CRD42021241145). Findings: The final analysis comprised 17 trials that involved 9128 patients and 19 distinct treatment regimens. Within the scope of investigated immunotherapy (IO) combinations, toripalimab + FfCT (tori + FfCT) demonstrated the best OS advantages (tori + FfCT vs. FbCT, HR 0.57, 95% CI 0.38-0.85; tori + FfCT vs. FfCT, HR 0.58, 95% CI 0.43-0.78). In terms of PFS, camrelizumab + FfCT (cam + FfCT) demonstrated the best PFS advantages (FbCT vs. cam + FfCT, HR 1.79, 95% CI 1.22-2.63; FfCT vs. cam + FfCT, HR 1.79, 95% CI 1.47-2.17). Nivolumab + FbCT (nivo + FbCT vs. FfCT, OR 3.29, 95% CI 1.43-7.56) showed the best objective responses. Compared to the conventional chemotherapy regimen, the toxicity was observed to be the slightest for the tori + FfCT (FbCT vs. tori + FfCT, OR 3.07, 95% CI 1.22-7.7) and sintilimab + FfCT (FbCT vs. sin + FfCT, OR 2.93, 95% CI 1.16-7.37). The results in this study were evaluated as having a low heterogeneity since the I2 value was ≤25% in all analyses. Interpretation: Compared to foreign IO combinations, sin + FfCT, tori + FfCT, cam + FfCT, and tisle + FbCT are superior first-line treatment options for patients with advanced and metastatic esophageal cancer. Although foreign IO combinations, such as pembro + FbCT and nivo + FbCT obtained better objective response rates than other IO combinations, the addition of chemotherapy to IO worsens the safety profiles. Our findings could provide complementary evidence for current guideline recommendations. Funding: This work was supported by a grant from the Science and Technology Program of Guangzhou, China (202206010103); and Natural Science Foundation of Guangdong Province (2022A1515012469).

Unpleasant symptoms of immunotherapy for people with lung cancer: A mixed-method study.

BACKGROUND: Immunotherapy has changed the outlook for lung cancer treatment. A closer look at the accompanying symptoms from the patient's perspective is necessary to improve their tolerance to the treatment, which is also the basis for standardized symptom management. OBJECTIVE: To describe the symptomatic experiences of patients receiving immunotherapy for lung cancer and explore whether symptoms reported during immunotherapy were associated with survival outcomes. DESIGN: Exploratory sequential mixed-method study. SETTINGS: Patients were continuously recruited from the oncology day ward of Guangdong Provincial People's Hospital between October 2019 and January 2020. PARTICIPANTS: 59 patients with advanced lung cancer and receiving immunotherapy (median [IQR] age was 64 [58-69]; 72.9 % pathological stage was IV) were included in the study. METHODS: A sequential qualitative interview on symptom experiences was conducted from the perspective of lung cancer patients in immunotherapy. Summative content analysis was used to develop a standardized symptom reporting checklist. Survival outcome follow-ups of each patient were conducted 2 years after the interview. RESULTS: 47 symptoms were extracted from the 124 interviews of 59 patients, the common symptoms including musculoskeletal pain (52.5 %), itchy skin (45.8 %), fatigue (45.8 %), cough (44.1 %), shortness of breath (32.2 %), lack of appetite (32.2 %), and rashes (32.2 %). The timing, severity, and interference of symptoms were different among patients. The symptoms of shortness of breath, fatigue and chest pain were more common in chemo-immunotherapy, while dry mouth and blurred vision were more frequent with immunotherapy. The symptoms of musculoskeletal pain, shortness of breath, lack of appetite, drowsiness and taste change were more common for those who died two years after the interviews; for those who survived, the symptoms of rash and chill were more common. CONCLUSIONS: We generated a symptom list related to lung cancer immunotherapy from the patients, provided a closer look at symptoms from the patient's perspective, and suggested differences in the presence of symptoms between the group of treatment and survival outcome. This enables clinicians and nurses to better understand and empathize with the patient's experience, so as to truly practice the essence of patient-centered care, and provide a basis for the development of standardized symptom measurement tools in the future. TWEETABLE ABSTRACT: At least 47 unpleasant symptoms were present in immunotherapy from the perspective of lung cancer patients.

Ocular pulse amplitude (OPA) in canine ADAMTS10-open-angle glaucoma (ADAMTS10-OAG).

Introduction: The role of ocular rigidity and biomechanics remains incompletely understood in glaucoma, including assessing an individual's sensitivity to intraocular pressure (IOP). In this regard, the clinical assessment of ocular biomechanics represents an important need. The purpose of this study was to determine a possible relationship between the G661R missense mutation in the ADAMTS10 gene and the ocular pulse amplitude (OPA), the difference between diastolic and systolic intraocular pressure (IOP), in a well-established canine model of open-angle glaucoma (OAG). Methods: Animals studied included 39 ADAMTS10-mutant dogs with different stages of OAG and 14 unaffected control male and female dogs between 6 months and 12 years (median: 3.2 years). Dogs were sedated intravenously with butorphanol tartrate and midazolam HCl, and their IOPs were measured with the Icare® Tonovet rebound tonometer. The Reichert Model 30™ Pneumotonometer was used to measure OPA. Central corneal thickness (CCT) was measured via Accutome® PachPen, and A-scan biometry was assessed with DGH Technology Scanmate. All outcome measures of left and right eyes were averaged for each dog. Data analysis was conducted with ANOVA, ANCOVA, and regression models. Results: ADAMTS10-OAG-affected dogs displayed a greater IOP of 23.0 ± 7.0 mmHg (mean ± SD) compared to 15.3 ± 3.6 mmHg in normal dogs (p < 0.0001). Mutant dogs had a significantly lower OPA of 4.1 ± 2.0 mmHg compared to 6.5 ± 2.8 mmHg of normal dogs (p < 0.01). There was no significant age effect, but OPA was correlated with IOP in ADAMTS10-mutant dogs. Conclusion: The lower OPA in ADAMTS10-mutant dogs corresponds to the previously documented weaker and biochemically distinct posterior sclera, but a direct relationship remains to be confirmed. The OPA may be a valuable clinical tool to assess ocular stiffness and an individual's susceptibility to IOP elevation.