Diagnostic Value of sLR11 and sIL-2R in the Cerebrospinal Fluid for Malignant Central Nervous System Lymphoma.

Objective We previously reported that patients with acute leukemia and malignant lymphoma (ML) demonstrated significantly increased serum soluble LR11 (sLR11) levels compared to normal controls. Accurately diagnosing ML of the central nervous system (CNS ML) using cytology is frequently difficult. Therefore, we evaluated the use of cerebrospinal fluid (CSF) sLR11 and soluble interleukin-2 receptor (sIL-2R) as diagnostic and treatment response markers for CNS ML. Methods We retrospectively evaluated the CSF results for CNS ML using clinical data at our institution, and then analyzed the usefulness of sLR11 and sIL-2R in CSF for both the diagnosis and as surrogate markers that reflect the therapeutic effect. Patients We enrolled patients with CNS ML who received intrathecal anticancer drugs between 2017 and 2023. We analyzed the sLR11 and sIL-2R levels in CSF and cytological malignant grades. We studied 22 patients, including 17 with central nervous system (CNS) clinical conditions and five who received prevention treatment. Results The CSF sLR11 levels were significantly and positively correlated with CSF sIL-2R levels. The CSF sLR11 and sIL-2R levels in patients with CNS ML were significantly higher than those in the prevention group. A receiver operating characteristic (ROC) curve analysis showed the cut-off value of sLR11 for CNS invasion to be 21.7 ng/mL. Moreover, the chemotherapy-responder group demonstrated significantly decreased CSF sLR11 and sIL-2R levels after treatment. Conclusion CSF sLR11 and sIL-2R of CSF were found to be useful biomarkers for the diagnostic and treatment response evaluation in patients with CNS ML.

Complications and influence of cutaneous closure technique on subdermal plexus flaps in 97 dogs (2006-2022).

OBJECTIVE: To determine the incidence and severity of complications for subdermal plexus flaps in dogs and compare the complications when using sutures or staples for cutaneous closure of subdermal plexus flaps. STUDY DESIGN: Retrospective monocentric study. SAMPLE POPULATION: Ninety-seven client-owned dogs. METHODS: Dogs that underwent wound reconstruction using subdermal plexus flaps were retrospectively identified. Type of flap, cutaneous closure technique, complications and level of complication associated with their use were recorded. Follow-up was considered adequate if it was more than 10 days postoperatively or until a complication occurred. RESULTS: Complications were seen in 52 dogs (53.6%), of which 13/18 (72.2%) of dogs had cutaneous closure with skin staples versus 39/79 (49.3%) with skin sutures. The location of the mass/wound on the head and use of an advancement flap was associated with lower incidence of complications (p < .001; p = .018 respectively). Location of the mass/wound on the proximal pelvic limb was associated with a low level of complications (p = .01) on univariable analysis only. On multivariable analysis, only an increased bodyweight was associated with an increased incidence of complications (p = .029). CONCLUSIONS: Increased weight may be associated with an increased risk of complications with subdermal plexus flaps. No risk factor was found to be associated with the severity of complications. CLINICAL SIGNIFICANCE: Overall incidence of complications for subdermal plexus flaps in dogs in this study was 53.6%. The number of dogs included in the study was not sufficient to assess if the skin closure technique affects the incidence of complications.

Successful Treatment of Primary Mediastinal Large B-cell Lymphoma with DA-EPOCH-Rituximab Therapy in a Transgender Woman.

In recent years, lesbian, gay, bisexual, and transgender (LGBT) populations have been gaining acceptance in society. However, very few cases of malignancy in the LGBT population have been reported thus far. We herein report a transgender woman receiving estrogen supplementation who developed primary mediastinal large B-cell lymphoma (PMBCL) and was treated with dose-adjusted EPOCH-rituximab (DA-EPOCH-R) therapy. The patient achieved complete remission after the sixth course of DA-EPOCH-R therapy. To help this LGBT patient continue receiving chemotherapy smoothly on admission, adjusting the hospital environment, such as the allocation of rooms, was essential.

Soluble (Pro)Renin Receptor Level in Patients with Severe Obesity Is Associated with Visceral Adiposity and Is Involved with Insulin Resistance and Renal Injury.

INTRODUCTION: High soluble (pro)renin receptor (s[P]RR) level in circulation is reported in obese patients; however, it is unclear which body composition components are responsible for it. In this study, the authors examined blood s(P)RR levels and ATP6AP2 gene expression levels in visceral and subcutaneous adipose tissue (VAT, SAT) in severely obese patients who underwent laparoscopic sleeve gastrectomy (LSG), with the aim of clarifying the relationship with body composition and metabolic factors. METHODS: Seventy five cases who underwent LSG between 2011 and 2015 and were postoperatively followed-up for 12 months at the Toho University Sakura Medical Center were included in the analysis of the cross-sectional survey at baseline, and 33 cases were included in the analysis of the longitudinal survey during the 12 months after LSG. We evaluated body composition, glycolipid parameters, liver/renal function, as well as serum s(P)RR level and ATP6AP2 mRNA expression level in VAT and SAT. RESULTS: The mean serum s(P)RR level at baseline was 26.1 ng/mL, this value was considered higher than values in healthy subjects. There was no significant difference in the expression level of ATP6AP2 mRNA between VAT and SAT. At baseline, multiple regression analysis for the association between s(P)RR and variables identified that visceral fat area, HOMA2-IR, and UACR showed the independent relationships with s(P)RR. During the 12 months after LSG, body weight, serum s(P)RR level showed a significant decrease (from 30.0 ± 7.0 to 21.9 ± 4.3). Multiple regression analysis for the association between the change in s(P)RR and variables showed that changes in visceral fat area, and alanine transaminase were independently related to the change in s(P)RR. CONCLUSION: This study showed that blood s(P)RR level was high in severely obese patients, decreased with weight loss by LSG, and was associated with visceral fat area in both pre- and postoperative changes. The results suggest that blood s(P)RR levels in obese patients may reflect the involvement of visceral adipose (P)RR in insulin resistance and renal damage mechanisms associated with obesity.

Case report: Plasmablastic neoplasm with multinucleated giant cells-Analysis of stemness of the neoplastic multinucleated giant cells.

Cancer stem cells have the capability of self-renewal and multipotency and are, therefore, associated with tumor heterogeneity, resistance to chemoradiation therapy, and metastasis. The hypothesis that multinucleated giant cells, which often emerge following chemo- and/or radiotherapy, serve as cancer stem cells has not been fully evaluated. Although a previous study demonstrated that these cells functioned as stem cells, only low levels of Yamanaka factors were expressed, contrasting with the high expression seen from their gestated first-generation mononuclear cells. Herein, we report a case of a plasmablastic neoplasm with multinucleated giant cells that were analyzed for stemness to test the above hypothesis. The patient was a male in his 80s who had a plasmablastic neoplasm that was not easily distinguishable as plasmablastic lymphoma versus plasma cell myeloma of plasmablastic type. Lymph node biopsy showed predominant mononuclear cell proliferation with admixed multinucleated giant cells. Immunohistochemistry and in situ hybridization showed that both multinucleated and mononuclear cells had the same profile: CD138(+), light chain restriction of κ>λ, cyclin D1(+), CD68(-), EBER-ISH (+). These results suggested that both cell types were neoplastic. In accordance with the previous study, the multinucleated giant cells showed low expression of Yamanaka factors, which were highly expressed in some of the mononuclear cells. Furthermore, the multinucleated giant cells showed a much lower proliferative activity (Mib1/Ki67 index) than the mononuclear cells. Based on these results, the multinucleated giant cells were compatible with cancer stem cells. This case is expected to expand the knowledge base regarding biology of cancer stem cells.

Urothelial Carcinoma With Pulmonary Tumor Thrombotic Microangiopathy After Chemotherapy for Hodgkin Lymphoma.

Treatment-related second malignancies (SMs) remain a major concern in long-term survivors of Hodgkin lymphoma (HL). In this report, the autopsy findings of a patient with HL, who was in complete remission after chemotherapy but expired of pulmonary tumor thrombotic microangiopathy (PTTM) caused by urothelial carcinoma of the renal pelvis (UCRP), were described. A 78-year-old Japanese man with a history of classical HL developed irreversible heart failure about 2.5 years after chemotherapy. The patient expired shortly after being admitted due to ineffective treatment for heart failure. However, the cause of death was not determined. The patient's autopsy findings revealed UCRP in the left kidney, as well as infiltration around the inferior vena cava and lungs, but no HL recurrence. The primary causes of mortality were respiratory and heart failure due to PTTM. Therefore, it is essential to consider the risk of SMs and search for them in patients with HL after chemotherapy.

Case Report: A Novel Lateral Approach to the C7, C8, and T1 Intervertebral Foramina for Resection of Malignant Peripheral Nerve Sheath Neoplasia, Followed by Adjunctive Radiotherapy, in Three Dogs.

This case report describes the diagnosis, management and outcome of three dogs with peripheral nerve sheath tumors (PNSTs) involving the brachial plexus, C7 (case 1), C8 (case 2), and C8 and T1 (case 3) spinal nerves and nerve roots with intrathoracic invasion. Surgical resection required thoracic limb amputation and removal of the first rib, facilitating a novel lateral approach to the spinal nerves and foramina in all cases. This was followed by hemilaminectomy and rhizotomy in cases 1 and 2. Adjunctive radiotherapy was then performed in all dogs. All three dogs regained a good quality of life in the short-term following surgery. Two were euthanased after 3 and 10 months, following detection of a pulmonary mass in one case and multiple thoracic and abdominal masses in the other. The third dog was alive and well at the time of writing (7 months post-surgery). This surgical approach facilitated good access and allowed gross neoplastic tissue to be resected. The ease of surgical access was dependent, to a degree, on the size of the patient. This surgical approach can be considered in cases of PNSTs involving the caudal cervical or cranial thoracic spinal nerves and nerve roots. Adjunctive radiotherapy should be considered as part of a multi-modal approach to these challenging tumors due to the difficulty of achieving clean margins, particularly proximally, even with optimal surgical access.

CRISPR/Cas9 Screening for Identification of Genes Required for the Growth of Ovarian Clear Cell Carcinoma Cells.

Epithelial ovarian cancer is classified into four major histological subtypes: serous, clear cell, endometrioid and mucinous. Ovarian clear cell carcinoma (OCCC) responds poorly to conventional chemotherapies and shows poor prognosis. Thus, there is a need to develop new drugs for the treatment of OCCC. In this study, we performed CRISPR/Cas9 screens against OCCC cell lines and identified candidate genes important for their proliferation. We found that quite different genes are required for the growth of ARID1A and PIK3CA mutant and wild-type OCCC cell lines, respectively. Furthermore, we found that the epigenetic regulator KDM2A and the translation regulator PAIP1 may play important roles in the growth of ARID1A and PIK3CA mutant, but not wild-type, OCCC cells. The results of our CRISPR/Cas9 screening may be useful in elucidating the molecular mechanism of OCCC tumorigenesis and in developing OCCC-targeted drugs.

PHOSPHATE exporter XPR1/SLC53A1 is required for the tumorigenicity of epithelial ovarian cancer.

Ovarian cancer is the fifth most common cause of cancer-related death in women. Ovarian clear cell carcinoma (OCCC) is a chemotherapy-resistant epithelial ovarian cancer with poor prognosis. As a basis for the development of therapeutic agents that could improve the prognosis of OCCC, we performed a screen for proteins critical for the tumorigenicity of OCCC using the CRISPR/Cas9 system. Here we show that knockdown of the phosphate exporter XPR1/SLC53A1 induces the growth arrest and apoptosis of OCCC cells in vitro. Moreover, we show that knockdown of XPR1/SLC53A1 inhibits the proliferation of OCCC cells xenografted into immunocompromised mice. These results suggest that XPR1/SLC53A1 plays a critical role in the tumorigenesis of OCCC cells. We speculate that XPR1/SLC53A1 might be a promising molecular target for the therapeutic treatment of OCCC.

SIPA1L1/SPAR1 Interacts with the Neurabin Family of Proteins and is Involved in GPCR Signaling.

Signal-induced proliferation-associated 1 (SIPA1)-like 1 (SIPA1L1; also known as SPAR1) has been proposed to regulate synaptic functions that are important in maintaining normal neuronal activities, such as regulating spine growth and synaptic scaling, as a component of the PSD-95/NMDA-R-complex. However, its physiological role remains poorly understood. Here, we performed expression analyses using super-resolution microscopy (SRM) in mouse brain and demonstrated that SIPA1L1 is mainly localized to general submembranous regions in neurons, but surprisingly, not to PSD. Our screening for physiological interactors of SIPA1L1 in mouse brain identified spinophilin and neurabin-1, regulators of G-protein-coupled receptor (GPCR) signaling, but rejected PSD-95/NMDA-R-complex components. Furthermore, Sipa1l1-/- mice showed normal spine size distribution and NMDA-R-dependent synaptic plasticity. Nevertheless, Sipa1l1-/- mice showed aberrant responses to α2-adrenergic receptor (a spinophilin target) or adenosine A1 receptor (a neurabin-1 target) agonist stimulation, and striking behavioral anomalies, such as hyperactivity, enhanced anxiety, learning impairments, social interaction deficits, and enhanced epileptic seizure susceptibility. Male mice were used for all experiments. Our findings revealed unexpected properties of SIPA1L1, suggesting a possible association of SIPA1L1 deficiency with neuropsychiatric disorders related to dysregulated GPCR signaling, such as epilepsy, attention deficit hyperactivity disorder (ADHD), autism, or fragile X syndrome (FXS).SIGNIFICANCE STATEMENT Signal-induced proliferation-associated 1 (SIPA1)-like 1 (SIPA1L1) is thought to regulate essential synaptic functions as a component of the PSD-95/NMDA-R-complex. In our screening for physiological SIPA1L1-interactors, we identified G-protein-coupled receptor (GPCR)-signaling regulators. Moreover, SIPA1L1 knock-out (KO) mice showed striking behavioral anomalies, which may be relevant to GPCR signaling. Our findings revealed an unexpected role of SIPA1L1, which may open new avenues for research on neuropsychiatric disorders that involve dysregulated GPCR signaling. Another important aspect of this paper is that we showed effective methods for checking PSD association and identifying native protein interactors that are difficult to solubilize. These results may serve as a caution for future claims about interacting proteins and PSD proteins, which could eventually save time and resources for researchers and avoid confusion in the field.

The splicing factor DHX38/PRP16 is required for ovarian clear cell carcinoma tumorigenesis, as revealed by a CRISPR-Cas9 screen.

Certain cancers, such as ovarian clear cell carcinoma (OCCC), display high levels of genetic variation between patients, making it difficult to develop effective therapies. In order to identify novel genes critical to OCCC growth, we carried out a comprehensive CRISPR-Cas9 knockout screen against cell growth using an OCCC cell line and a normal ovarian surface epithelium cell line. We identified the gene encoding DHX38/PRP16, an ATP-dependent RNA helicase involved in splicing, as critical for the growth and tumorigenesis of OCCC. DHX38/PRP16 knockdown in OCCC cells, but not normal cells, induces apoptosis and impairs OCCC tumorigenesis in a mouse model. Our results suggest that DHX38/PRP16 may play a role in OCCC tumorigenesis and could potentially be a promising therapeutic target.

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy increases carotid intima-media thickness and plaque score with von Willebrand factor activity elevation in patients with malignant lymphoma.

An increased risk for atherosclerosis has been noted in cancer survivors; however, studies that focus on the risk of atherosclerosis in patients treated with chemotherapy are scarce. Therefore, we evaluated 32 patients who received rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy for B-cell malignant lymphoma by analysing the changes in atherosclerosis. Just before each treatment course, plasma levels of von Willebrand Factor (vWF) activity were evaluated, and carotid ultrasonography was performed at baseline and after the final treatment. Throughout the follow-up period, plasma vWF levels showed significantly transient increased by approximately 20%-40%. Both mean carotid intima-media thickness (IMT) and plaque score (PS) significantly increased during the 36.6 ± 26.0 weeks of observation (mean IMT: 0.724 ± 0.118 to 0.767 ± 0.129 mm; PS: 4.31 ± 3.53 to 4.87 ± 3.88, P < 0.001). Our study suggests that R-CHOP therapy promotes atherosclerosis.

Effect of Conventional Medical Therapy or Laparoscopic Sleeve Gastrectomy on Urinary Albumin in Japanese Subjects with Severe Obesity: An Observational Study.

INTRODUCTION: In patients with severe obesity, albuminuria can be improved by both conventional medical therapy and bariatric surgery. The purpose of this study was to compare the impact of weight loss achieved through conventional medical therapy or laparoscopic sleeve gastrectomy (LSG) on albuminuria in Japanese subjects with severe obesity and identify the factors involved. METHODS: We retrospectively evaluated the clinical characteristics including the urinary albumin/creatinine ratio (UACR) of 340 consecutive subjects with a body mass index ≥35 who received LSG (n = 242) or medical therapy (n = 98) between 2010 and 2018 and were followed for at least 12 months. RESULTS: The baseline of the UACR was not different between the 2 groups. At the 12-month follow-up, total weight loss (TWL) and decreases in glycosylated hemoglobin (HbA1c) and loge UACR were greater in the LSG group than in the medical therapy group (body weight; -35.7 kg vs. -8.0 kg, p < 0.001, HbA1c; -1.4% vs. -0.7%, p < 0.001, loge UACR; -0.3 vs. 0.9, p < 0.001). The rate of complete remission of diabetes was significantly higher in the LSG group than in the medical therapy group. At 12 and 36 months (n = 111 in the medical therapy group, n = 56 in the LSG group at 36 months), loge UACR increased in the medical therapy group, while it remained unchanged or decreased in the LSG group. In subjects with microalbuminuria and macroalbuminuria, changes in the loge UACR correlated with percent total body weight loss (%TWL) in both groups at 12 months. Percent TWL contributed independently to the change in the loge UACR, irrespective of whether LSG was performed. In receiver-operating characteristic analysis, a weight loss of 7.8% predicted a decrease in the UACR (∆UACR <0 at 12 months). CONCLUSION: Our analysis suggests that albuminuria may increase over time if only medical therapy is continued. To improve albuminuria, weight loss may be more important than whether LSG is performed.

Determinants of type 2 diabetes remission after bariatric surgery in obese Japanese patients: a retrospective cohort study.

OBJECTIVE: Bariatric surgery (BS) improves glycemic control in type 2 diabetes; however, some patients show insufficient improvement. Understanding the pathophysiology of type 2 diabetes in obese patients can facilitate appropriate treatment for type 2 diabetes after BS. The homeostatic model assessment (HOMA) 2 enables the calculation of the values from C-peptide data and evaluation of insulin users. We aimed to evaluate the pathophysiology of type 2 diabetes using pre- and postoperative parameters and HOMA2 in obese patients who underwent BS. METHODS: We retrospectively reviewed data from 45 obese patients with type 2 diabetes who underwent BS. They were followed-up for 12 months. The relationship between the HOMA2 score and complete remission (CR) of type 2 diabetes after BS was analyzed. Patients with and without CR were assigned to the CR and non-CR groups, respectively. Multiple regression analysis was used to identify factors associated with improvement in type 2 diabetes after BS. RESULTS: BS significantly improved body weight and glucose metabolism. The preoperative glycosylated hemoglobin A1c level and insulin secretion (HOMA2-%B) significantly differed between the CR and non-CR groups. Postoperative weight reduction and improved insulin sensitivity correlated significantly with CR; multiple regression showed that the preoperative HOMA 2-%B independently predicted CR of type 2 diabetes after BS. CONCLUSION: Preoperative insulin secretion, improvement in insulin sensitivity, and weight reduction after BS are related to CR of type 2 diabetes after BS. The results better reveal the pathophysiology of and treatment for type 2 diabetes in obese patients who undergo BS.

High presepsin concentrations in bile and its marked elevation in biliary tract diseases: A retrospective analysis.

BACKGROUND: Presepsin is a diagnostic and prognostic biomarker of both bacterial infection and sepsis; however, elevated presepsin levels have also been observed without sepsis. We conducted several analyses to evaluate the clinical laboratory parameters affecting presepsin levels. METHOD: We analyzed the association between sequential organ failure assessment (SOFA) scores and plasma presepsin levels and then analyzed clinical laboratory parameters in 567 patients with univariate and multivariate regression analysis and analysis of covariance (ANCOVA). We also determined presepsin in the bile of 11 patients and examined the presepsin immunostaining in liver. RESULTS: Spearman's rank correlation analysis with loge change revealed that presepsin levels were closely associated with loge-transformed SOFA score (ρ = 0.541), alkaline phosphatase (ALP); (ρ = 0.454) and gamma-glutamyl transferase; (ρ = 0.505). Multivariate regression analysis revealed that loge-transformed SOFA score (ß-coefficient = 0.316), ALP level (ß-coefficient = 0.380), and creatinine level (ß-coefficient = 0.290) independently and significantly affected loge presepsin levels. ANCOVA revealed that presepsin levels were significantly higher in patients with hepatobiliary disease. Patients who presented with dilatation of the bile ducts and elevated ALP levels or total bilirubin levels exhibited high presepsin levels in the bile. Presepsin production in liver Kupffer cells was also confirmed by immunostaining. CONCLUSION: Presepsin levels is correlated with the elevation of biliary enzymes in patients without renal dysfunction or sepsis. Additionally, presepsin exists with high concentrations in the bile and is positive in Kupffer cells.

Employing multiple-attribute utility technology to evaluate publicity activities for cancer information and counseling programs in Japan.

BACKGROUND: Cancer Information and Support Centers (CISCs), which are set up at designated cancer care hospitals (DCCHs) according to the national cancer control programs in Japan, are expected to provide cancer patients and their families with information and counseling, but their public recognition remains low. Therefore, it is necessary to evaluate the publicity activities of CISCs. METHODS: In this study, we evaluated two types of activities for publicizing CISCs conducted inside and outside one of the DCCHs ('Inside Activity' and 'Outside Activity', respectively) by multi-attribute utility technology (MAUT). Seven types of stakeholders, including physicians (n = 5), nurses (n = 4), CISC cancer counselors (n = 5), executives (n = 5), office department staff (n = 5), and licensed social insurance consultants in the hospital (n = 5), as well as patients and citizens (n = 19) were involved in the evaluation. RESULTS: Eight goals of the program for publicizing CISCs were determined. The utility score for each goal was separately calculated for Inside Activity and Outside Activity, and those of the eight goals were summed up to obtain an overall utility score for each activity. Finally, no substantial difference in overall utility score was found between the activity types (Inside Activity = 82.00 vs. Outside Activity = 81.18). CONCLUSIONS: It is implied that omitting or reducing either activity should be avoided in streamlining publicity activities at the CISCs. Despite the limited external validity of the finding, the methodology presented in this study is widely applicable to evaluate other multifaceted programs under an increasingly tight budget in the oncology setting. As the MAUT approach enables us to obtain numerical data for priority settings, it will contribute to rationalized healthcare management, especially in the oncology setting in which objective evaluations of the national cancer-related control programs are lacking and a broad range of stakeholders is involved.

Azacitidine decreases reactive oxygen species production in peripheral white blood cells: A case report.

BACKGROUND: In myelodysplastic syndrome (MDS), oxidative stress is closely related to iron overload and DNA damage. A recent study suggested the possibility that increased oxidative stress causes not only iron overload but also disease progression of MDS with DNA damage. We present a case of MDS with decreased reactive oxygen species (ROS) production in peripheral white blood cells (WBCs) and decreased diacron-reactive oxygen metabolites (d-ROMs) in serum after azacitidine therapy. CASE SUMMARY: A 74-year-old man presented to the hematological department with the chief complaint of anemia. His vital signs were within normal limits at admission with a heart rate of 80 bpm and blood pressure of 135/60 mmHg. Laboratory tests indicated pancytopenia, a WBC count of 2190 cells/µL, a hemoglobin level of 6.2 g/dL and a platelet count of 7.4 × 104/µL. The patient was diagnosed with MDS with fibrosis after a bone marrow examination. This case showed decreased ROS production in WBCs, d-ROMs in serum and Wilms' tumor 1 after azacitidine therapy, after which his hematopoiesis recovered. CONCLUSION: Azacitidine therapy can improve hematopoiesis and decrease ROS and d-ROM production.

Importance of doctor-initiated management of the balance between work and treatment for lung cancer patients: Results of a nationwide survey by the Japan Lung Cancer Society.

BACKGROUNDS: Since the recent development of molecular targeted drugs and immune checkpoint inhibitors has improved lung cancer treatment options and outcomes, supporting patients in balancing work and pharmacotherapy have become even more important in the field of lung cancer treatment. This study sought to identify the current status and roles of doctors in balancing work and treatment for lung cancer patients. METHODS: Patients and doctors were recruited to complete a web-based questionnaire survey by the Japan Lung Cancer Society. RESULTS: About 287 lung cancer patients and 381 doctors were included in the analysis. About 42.9% of patients responded that "there was no discussion" about their working conditions or work before the initiation of pharmacotherapy, while 22.6% responded that "there was an inquiry from a doctor/health care provider and a discussion that included the doctor was held." About 45.3% of patients took leave or resigned from work at the time of diagnosis. The most common reasons for patients to resign before or during pharmacotherapy were "poor physical condition due to side effects of treatment or illness" and "concern about causing problems in the workplace." To assist in balancing work and pharmacotherapy, patients desired "increased opportunities to consult about work" (36.9%) and "provision of treatment options with few adverse events" (28.9%). CONCLUSION: This study highlights the importance of doctor-initiated management of the balance between work and treatment for lung cancer patients. An important first step is for doctors themselves to take an interest in their patients' professions and initiate discussions of work-related topics with their patients.

New Horizons of Arterial Stiffness Developed Using Cardio-Ankle Vascular Index (CAVI).

Arterial stiffness is recognized mainly as an indicator of arteriosclerosis and a predictor of cardiovascular events. Cardio-ankle vascular index (CAVI), which reflects arterial stiffness from the origin of the aorta to the ankle, was developed in 2004. An important feature of this index is the independency from blood pressure at the time of measurement. A large volume of clinical evidence obtained using CAVI has been reported. CAVI is high in patients with various atherosclerotic diseases including coronary artery disease and chronic kidney disease. Most coronary risk factors increase CAVI and their improvement reduces CAVI. Many prospective studies have investigated the association between CAVI and future cardiovascular disease (CVD), and proposed CAVI of 9 as the optimal cut-off value for predicting CVD. Research also shows that CAVI reflects afterload and left ventricular diastolic dysfunction in patients with heart failure. Furthermore, relatively acute changes in CAVI are observed under various pathophysiological conditions including mental stress, septic shock and congestive heart failure, and in pharmacological studies. CAVI seems to reflect not only structural stiffness but also functional stiffness involved in acute vascular functions. In 2016, Spronck and colleagues proposed a variant index CAVI0, and claimed that CAVI0 was truly independent of blood pressure while CAVI was not. This argument was settled, and the independence of CAVI from blood pressure was reaffirmed. In this review, we summarize the recently accumulated evidence of CAVI, focusing on the proposed cut-off values for CVD events, and suggest the development of new horizons of vascular function index using CAVI.