CLDN18: Clinical, Pathological, and Genetic Signatures with Drug Screening in Gastric Adenocarcinoma.

INTRODUCTION: The CLDN18 gene, encoding claudin 18.1 and claudin 18.2, is a key component of tight junction strands in epithelial cells that form a paracellular barrier that is critical in Stomach Adenocarcinoma (STAD). METHODS: Our study included 1,095 patients with proven STAD, 415 from The Cancer Genome Atlas (TCGA) cohort and 680 from the Gene Expression Omnibus database. We applied various analyses, including gene set enrichment analysis, pathway analysis, and in vitro drug screening to evaluate survival, immune cells, and genes and gene sets associated with cancer progression, based on CLDN18 expression levels. Gradient boosting machine learning (70% for training, 15% for validation, and 15% for testing) was used to evaluate the impact of CLDN18 on survival and develop a survival prediction model. RESULTS: High CLDN18 expression correlated with worse survival in lymphocyte-poor STAD, accompanied by decreased helper T cells, altered metabolic genes, low necrosis-related gene expression, and increased tumor proliferation. CLDN18 expression showed associations with gene sets associated with various stomach, breast, ovarian, and esophageal cancers, while pathway analysis linked CLDN18 to immunity. Incorporating CLDN18 expression improved survival prediction in a machine learning model. Notably, nutlin-3a and niraparib effectively inhibited high CLDN18-expressing gastric cancer cells in drug screening. CONCLUSION: Our study provides a comprehensive understanding of the biological role of CLDN18-based bioinformatics and machine learning analysis in STAD, shedding light on its prognostic significance and potential therapeutic implications. To fully elucidate the molecular intricacies of CLDN18, further investigation is warranted, particularly through in vitro and in vivo studies.

Risk of thrombosis, hemorrhage and leukemic transformation in patients with myeloproliferative neoplasms: A nationwide longitudinal cohort study.

INTRODUCTION: There are few large-scale, population-based studies detailing the risks of thrombosis, hemorrhage, leukemic transformation in patients with myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). METHODS: We performed a nationwide longitudinal cohort study using the Korean National Health Insurance System (NHIS) database. MPN patients (n = 11,991) and their 1:4 age- and sex-matched controls (n = 47,964) were enrolled. The risk of thrombosis, hemorrhage, leukemic transformation was estimated using a Cox proportional hazards regression, and stratified analyses were performed for related factors. RESULTS: During a median of 7.8 years of follow-up, 30.1 % of MPN patients (3614/11,991) and 19.0 % of the matched controls (9141/47,964) developed arterial thrombosis, 11.6 % of MPN patients (1397/11,991) and 6.4 % of the matched controls (3099/47,964) developed venous thrombosis and 18.7 % of MPN patients (2251/11,991) and 12.1 % of the matched controls (5836/47,964) developed hemorrhage. 4.9 % of MPN patients (597/11,991) and 0.1 % of matched controls (50/47,964) developed leukemia. The overall risk of developing thrombosis, hemorrhage, leukemic transformation was higher in MPN patients (adjusted hazard ratio [aHR] 1.695, 95 % confidence interval [CI]: 1.629-1.765 for arterial thrombosis, aHR 1.963, 95 % CI: 1.838-2.096 for venous thrombosis, and aHR 1.714, 95 % CI: 1.630-1.802 for hemorrhage) than in the controls. Patients with MPNs had a 10-year cumulative incidence of leukemic transformation of 6.2 %. CONCLUSION: The patients with MPNs have a higher risk of thrombosis, hemorrhage, and leukemic transformation than matched controls. Strategies are warranted to reduce the risk of thrombosis, hemorrhage, and leukemic transformation in MPN patients.

Effect of a portable light emitting diode device on wound healing in a rat model.

Light-emitting diode (LED) lights produce a variety of wavelengths that have demonstrable efficacy in therapeutic and aesthetic fields. However, a repetitive treatment regimen is required to produce treatment outcomes, which has created a need for portable LED devices. In this study, we aimed to develop a portable therapeutic LED device and investigate its healing effect on excisional wounds in a rat model. The 35 × 35 mm-sized LED device was used on a total of 30 rats with full-thickness wounds that were divided into two groups depending on radiation intensity (11.1 and 22.2 mW/cm2 group). LED irradiation was performed every 24 h for 30 min, over 14 days, in direct contact with the wound. Percentage wound closure was measured by photographic quantification and was assessed histologically using haematoxylin and eosin (H&E) and Masson's Trichrome staining, and immunohistochemistry for Vascular endothelial growth factor (VEGF) and CD31. Percentage wound closure was significantly higher in 22.2 mW/cm2 irradiated wounds than that in the control wounds on days 7 and 10. The area of collagen deposition was remarkably larger in 22.2 mW/cm2 irradiated wounds than that in the control, with more horizontally organized fibres. CD31 immunostaining confirmed a significant increase in the number of microvessels in 22.2 mW/cm2 irradiated wounds than that in the control wounds, although there was no difference in VEGF immunostaining. Our novel portable LED device accelerates wound healing in a rat model, raising the possibility that portable LED devices can combine convenience with accessibility to play an innovative role in wound dressing.

Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea.

PURPOSE: Programmed death-1 blockade with pembrolizumab has shown promising activity in relapsed/refractory (R/R) extranodal natural killer/T-cell lymphoma (NKTCL), but studies are limited, with small patient numbers. MATERIALS AND METHODS: Thirteen institutes involved with the Consortium for Improving Survival of Lymphoma, a Korean lymphoma study group, collected the clinical data of 59 patients treated with pembrolizumab as salvage therapy between 2016 and 2022. RESULTS: The median age of the patients was 60 years (range, 22 to 87 years), and 76.3% had advanced Ann Abor stage disease. Pembrolizumab was given to 35.6%, 40.7%, and 23.7% of the patients as second-, third-, and fourth- or higher-line chemotherapy, respectively. The overall response rate was 40.7%, with 28.8% having complete response. The estimated 2-year progression-free survival (PFS) and overall survival rates for all patients were 21.5% and 28.7%, respectively; for responders, the rates were 53.0% and 60.7%, respectively. Although not statistically significant, Eastern Cooperative Oncology Group performance status ≥ 2 (hazard ratio [HR], 1.91; 95% confidence interval [95% CI], 0.93 to 3.94; p=0.078) and stage III or IV disease (HR, 2.59; 95% CI, 0.96 to 6.96; p=0.060) were associated with a trend toward shorter PFS in multivariate analysis. Grade 3 or 4 adverse events (AEs) were noted in 12 patients (20.3%); neutropenia (10.2%), fatigue (6.8%), and pneumonitis (5.1%) were most common AEs. CONCLUSION: In conclusion, while pembrolizumab had a modest effect on patients with R/R NKTCL, it may be a useful salvage therapy for patients with localized disease and good performance status.

Ultrathin Anterolateral Thigh Free Flap: An Adipocutaneous Flap with the Most Superficial Elevation Plane.

BACKGROUND: Although many efforts have been made to create thinner anterolateral thigh (ALT) flaps, their thickness varies among patients, and the flap may be still too thick to match shallow defects. The authors successfully harvested an ALT flap through the most superficial elevation plane, the superficial fat layer, which was useful to match the shallow defects. METHODS: All patients who underwent ALT free flap reconstruction for upper and lower distal extremity defects were divided retrospectively into groups by ALT flap elevation plane: thin, above the deep fascia; superthin, at the superficial fascia; and ultrathin, through the superficial fat. Preoperative computed tomographic angiography and duplex ultrasonography planning were used for all patients. Anatomical characteristics of donor subcutaneous tissue and surgical details, including flap thickness, flap size, and incidence of flap necrosis were compared among the groups and between sexes. RESULTS: The average deep and superficial fascial depths were 16.7 and 10.8 mm, 12.5 and 8.2 mm, and 9.1 and 5.6 mm ( P < 0.05), and the average flap thickness was 5.8 mm, 7.9 mm, and 7.8 mm ( P = 0.29) in the ultrathin, superthin, and thin ALT groups, respectively. No significant intergroup differences existed in flap size or complications. The deep and superficial fascia were located significantly deeper in female patients (9.4 and 6.0 mm in male patients and 14.9 and 9.6 mm in female patients, respectively). CONCLUSIONS: With precise preoperative planning, the most superficially elevated, ultrathin ALT flap can achieve optimal reconstructions of thin body areas. Female patients with thicker thighs and patients with a high body mass index would benefit from this flap. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Prognostic value of FOXP3+ regulatory T cells for patients with locally advanced oropharyngeal squamous cell carcinoma.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) is the most common neoplasm originating at the base of the tongue or in the tonsils or soft palate. In this study, we investigated the prognostic value of FOXP3+ regulatory T cells in OPSCC. METHODS: Tumor tissues of patients with locally advanced OPSCC were analyzed using quantitative multiplex immunohistochemistry. Staining of CD8+ T cells, conventional CD4+FOXP3- T cells (Tconv cells), CD4+FOXP3+ regulatory T cells (Treg cells), CD20+ B cells, and CD68+ macrophages was performed, and cell density was evaluated in both the tumor and its stroma. RESULTS: Among the 71 patients included in this study, males constituted 93.0% of the cohort, and the median age was 59 years (range: 42-80 years). A total of 56 patients (78.9%) had a smoking history, and 53 (74.6%) patients were positive for human papillomavirus (HPV). The most frequent site of OPSCC was the tonsils (70.4%), followed by the base of the tongue (25.4%). The proportion of Treg cells was lower in the tumors of patients with HPV than in those of patients without HPV. Patients with OPSCC whose tumor Treg cell levels were above the median had longer relapse-free survival (RFS) periods than those with tumor Treg cell levels below the median (HR, 0.12; 95% CI, 0.03-0.46; p = 0.02). Our multivariate analysis identified high Treg levels (HR, 0.13; 95% CI, 0.02-1.00; p = 0.05) as an RFS factor that predicted a good prognosis. CONCLUSIONS: Our results demonstrated that high Treg cell density in locally advanced OPSCC tumors was correlated with longer RFS.

Prognostic model in patients with metastatic urothelial carcinoma receiving immune checkpoint inhibitors after platinum failure.

Immune checkpoint inhibitors (ICIs) have become a standard treatment for metastatic urothelial carcinoma (mUC) after platinum-based chemotherapy. However, the prognostic factors for patients with mUC receiving ICIs are not well established. We retrospectively collected clinical and laboratory data and reviewed the survival outcomes of patients with mUC who were treated with ICIs after platinum-based chemotherapy. We used univariate and multivariable Cox proportional hazard models to identify independent prognostic factors, and the concordance index (C-index) to evaluate the performance of the new prognostic model. In addition, bootstrap analysis was employed for internal validation of the prognostic model. A total of 224 patients were included in the study. With a median follow-up of 10.5 months (interquartile range, 5.1-17.4 months), median overall survival (OS) was 13.6 months (95% confidence interval [CI], 9.7-17.3 months). In multivariable analysis, independent prognostic factors predicting adverse OS were the presence of liver metastasis (LM), hypoalbuminemia, and neutrophil-lymphocyte ratio (NLR) >5. When patients were categorized into 3 risk groups, median OS was not reached (NR) (95% CI, 17.3-NR), 9.5 months (6.8-NR), and 2.9 months (2.3-4.4) for patients with a score of 0, 1, and 2+, respectively. The C-index for the new model was 0.763 (95% CI, 0.739-0.787). A novel prognostic model, including LM, hypoalbuminemia, and NLR, was developed and validated to estimate OS in patients with platinum-refractory disease on second- or subsequent-line ICI therapy. Further investigations, including prospective validation, are needed.

Intramuscular Deep Inferior Epigastric Vessels Are Insulated by Perimysial Fibroadipose Tissue Network.

BACKGROUND: The difficulty of elevating a deep inferior epigastric perforator (DIEP) flap largely depends on the intramuscular course of the vessel and the perforator. Previous studies, however, have lacked histologic descriptions of the vessels and surrounding structures. The present study analyzed the histologic aspects of the deep inferior epigastric vessels and perforators, focusing on their perivascular relationships with muscle fibers. METHODS: The abdomen of a cadaver was histologically evaluated to identify intramuscular deep inferior epigastric vessels. Tissue samples were stained with hematoxylin and eosin and with Masson trichrome stain to visualize fibrous components. Twenty-one DIEPs from 12 patients were also evaluated to determine the histologic aspects of the perivascular structure. In the cross-section of each perforator and adjacent tissue, the perforator-to-muscle distance and trichrome-stained area were measured, and the correlation of the perforator size with the perforator-to-muscle distance and the percent collagenous portion of the distance were determined. RESULTS: Histologic analysis showed that the deep inferior epigastric vessels and perforators were encased by perimysial connective tissue and were not in direct contact with the muscle fibers. The smaller perimysia branched out from the larger perimysia, forming an interconnecting network structure. Correlation analysis showed that larger vessels had more collagenous portions in the perimysial structures (Spearman's ρ = 0.537, p = 0.012). CONCLUSION: The deep inferior epigastric vessels and perforators reside in a perimysial fibroadipose tissue network. This may provide surgeons with a microscopic perspective during DIEP dissections. Having an idea of the perforator anatomy in microscopic level can help us to perform safer perforator dissections.

The Use of Color Duplex Ultrasound for Local Perforator Flaps in the Extremity.

BACKGROUND: The local flaps, especially perforator and keystone flaps, are used as first-line treatment option in reconstruction of small tomoderate-sized defect of the extremity. However, the high complication rate associated with these flaps may hinder this usage. METHODS: This article reviews the technical and clinical aspect of using color duplex ultrasound )CDU) in the preoperative, intraoperative, and postoperative period for propeller and keystone flaps. RESULTS: CDU allows the surgeon to understand the anatomical aspect of the perforator such as the location, point of penetration on the deep fascia, subcutaneous pathway )axiality) and physiological aspect such as velocity and flow volume. Understanding and utilizing this information will allow accurate preoperative design, intraoperative decision making, and postoperative monitoring, leading to better outcome. CONCLUSION: Carefully designed local perforator flaps based on anatomy and physiology using CDU will be a powerful armamentarium for reconstruction of the lower extremity.

Treatment of Pediatric Sternotomy Wound Complications: A Minimally Invasive Approach.

BACKGROUND: Pediatric sternal wound complications (SWCs) include sterile wound dehiscence (SWD) and superficial/deep sternal wound infections (SSWI/DSWI), and are generally managed by repetitive debridement and surgical wound approximation. Here, we report a novel nonsurgical management strategy of pediatric sternotomy wound complications, using serial noninvasive wound approximation technique combined with single-use negative pressure wound therapy (PICO) device. METHODS: Nine children with SWCs were managed by serial approximation with adhesive skin tapes and serial PICO device application. Thorough surgical debridement or surgical approximations were not performed. RESULTS: Three patients were clinically diagnosed as SWD, two patients as SSWI, and four patients as DSWI. None of the wounds demonstrated apparent mediastinitis or bone destructions. PICO device was applied at 16.1 days (range: 6-26 days) postoperatively, together with serial wound approximation by skin tapes. The average duration of PICO use was 16.9 days (range: 11-29 days) and the wound approximation was achieved in all patients. None of the patients underwent aggressive surgical debridement or invasive surgical approximation by sutures. CONCLUSION: We report our successful management of selected pediatric SWCs, using serial noninvasive wound approximation technique combined with PICO device.

Outcome Assessment According to the Thickness and Direction of the Acellular Dermal Matrix after Implant-Based Breast Reconstruction.

PURPOSE: The acellular dermal matrix plays an important role in reinforcing thin mastectomy skin and repositioning the implant in prosthetic breast reconstruction. As the concept of prepectoral plane has become widespread, the role of the acellular dermal matrix has become increasingly important. However, evidences and standards for appropriate thickness and direction during placement remain insufficient. This study is aimed at testing the assumption that differences in the acellular dermal matrix thickness and orientation during placement may affect surgical outcomes including the incidence of postoperative complications. METHODS: This was a retrospective single-centered analysis of 43 patients (50 breasts) who underwent implant-based reconstruction with MegaDerm® (L&C Bio, Seoul, Korea) and 23 patients (23 breasts) who underwent implant-based reconstruction with DermACELL® (LifeNet Health, Virginia Beach, VA, USA), two types of human-derived acellular dermal matrix. All surgeries were performed by a single surgeon. Demographic variables, surgery-related factors, and complications were compared between a thick matrix group (1.5-2.3 mm) and a thin matrix group (1.0-1.5 mm). The same processes were performed in the nonreverse and reverse matrix insertion groups. RESULTS: Baseline demographics and surgery-related data were summarized according to matrix thickness and direction. There were no significant intergroup differences in the demographic variables such as history of smoking, radiation, or chemotherapy. The mean drain volume was significantly higher in the thick matrix group than that in the thin matrix group (p = 0.0445). However, there were no significant differences in overall complication rates by matrix thickness (p = 0.3139). Additionally, there were no significant differences in complications between the nonreverse and reverse matrix insertion groups (p = 0.538). CONCLUSION: Our findings suggest that patients with a thick acellular dermal matrix need a prolonged period for engraftment. However, the thickness did not directly affect the surgical outcomes between the thick and thin matrix groups. Likewise, the orientation in which the acellular dermal matrix was inserted did not affect the surgical outcomes including postoperative complications.

Outcomes of bortezomib combination chemotherapies in autologous stem cell transplantation-ineligible patients with AL amyloidosis.

BACKGROUND: Treatment protocols for light chain (AL) amyloidosis have been derived from myeloma treatment. Bortezomib is a key drug used for the treatment of myeloma and AL amyloidosis. We retrospectively investigated the efficacy and toxicity of bortezomib- based chemotherapy in patients with newly diagnosed AL amyloidosis. METHODS: We reviewed the outcomes of newly diagnosed autologous stem cell transplantation (auto-SCT)-ineligible AL amyloidosis patients who received bortezomib-based chemotherapy at a referral center between 2011 and 2017. RESULTS: Of 63 patients who received bortezomib-based chemotherapy, 32 were male, and the median age was 66 years (range, 42‒82 yr). The hematologic overall response rate (ORR) was 65.1%, and the chemotherapy regimen with the best hematologic response was VMP (75.7%, 28/37). Sixty patients had significant organ (heart or kidney) involvement; 28.3% of patients (N=17) had major organ responses after chemotherapy. With a median follow- up of 34 months, there was no significant difference in progression-free survival (P=0.49) or overall survival (P =0.67) according to regimen. Most hematologic and non-hematologic problems were manageable. CONCLUSION: Various chemotherapy combinations based on bortezomib are currently employed in the clinical setting, but no difference was found in terms of efficacy or toxicity.

Clinical significance of C-Reactive Protein to Lymphocyte Count Ratio as a prognostic factor for Survival in Non-small Cell Lung Cancer Patients undergoing Curative Surgical Resection.

Purpose: We assessed the clinical feasibility of C-reactive protein to lymphocyte ratio (CLR) as a determinant of survival in patients with non-small cell lung cancer (NSCLC) undergoing curative surgical resection. Methods: A retrospective study was conducted on patients with stage I and II NSCLC undergoing curative resection. Demographic and clinical variables, including CLR, were collected and analyzed. The Cox proportional hazards model was used to calculate hazard ratios for overall survival (OS) and cancer-specific survival (CSS). The Mann-Whitney U test was used to compare differences between two independent groups. Results: The median age of the patients was 69.0 years, and male patients comprised 63.9% of all patients. A total of 164 (75.9%) patients were categorized as having stage I disease and 52 (24.1%) as having stage II disease. Using the multivariate Cox model, age (hazard ratio [HR] 1.08, p<0.001), lymphatic invasion (HR 3.12, p=0.004), stage (HR 5.10, p<0.001), and CLR (HR 1.01, p=0.003) were significant determinants of OS. In addition, age (HR 1.11, p=0.002), lymphatic invasion (HR 3.16, p=0.010), stage (HR 6.89, p<0.001), and CLR (HR 1.05, p=0.002) were significant determinants of CSS. Conclusions: Our findings show that CLR could be a determinant of survival in NSCLC patients undergoing curative surgical resection.

Immediate breast reconstruction after salvage mastectomy: Case control outcome comparisons of DIEP flap and DTI reconstruction.

BACKGROUND: Cancer recurrence after breast-conserving therapy is most often managed by salvage mastectomy. Successful breast reconstruction immediately after salvage mastectomy, however, remains challenging because the reconstruction is performed on previously irradiated breast tissue. METHODS: Records of patients who underwent breast reconstruction from June 2010 to June 2019 were reviewed, including their demographic characteristics, methods of breast reconstruction, and early and late outcomes. Deep inferior epigastric perforator (DIEP) flaps and direct-to-implant (DTI) reconstructions following salvage mastectomies were compared with reconstructions following completion or primary mastectomies. Patients who underwent reconstruction followed by postmastectomy radiotherapy (PMRT) and patients followed up for less than 6 months were excluded. RESULTS: DIEP flaps in 27 breasts that underwent salvage mastectomy were compared with DIEP flaps in 32 breasts that underwent completion and 564 that underwent primary mastectomy. Rates of early complications, including microsurgical revision and total flap loss, and of late complications (>6 months after surgery), including fat necrosis and flap volume loss, did not differ significantly. DTI reconstruction in 20 breasts that underwent salvage mastectomy was compared with DTI reconstruction in 12 breasts that underwent completion and 351 that underwent primary mastectomy. Wound healing problems, including wound dehiscence and delayed wound healing (15% vs. 2.6%, P = 0.0022), and capsular contracture (30% vs. 5.4%, P = 0.0000), were significantly more frequent in breasts that underwent salvage than primary mastectomy. CONCLUSIONS: DIEP flap is a successful reconstruction option after salvage mastectomy. DTI reconstruction is associated with higher rates of wound healing problems and capsular contracture after salvage than after primary mastectomy.

Regulatory (FoxP3+) T cells and TGF-ß predict the response to anti-PD-1 immunotherapy in patients with non-small cell lung cancer.

Antitumor immune responses induced by immune checkpoint inhibitors anti-PD-1 or anti-PD-L1 have been used as therapeutic strategies in advanced non-small cell lung cancer (NSCLC) patients over the last decade. Favorable antitumor activity to immune checkpoint inhibitors is correlated with high PD-L1 expression, increased tumor-infiltrating lymphocytes, and decreased suppressive immune cells including Treg cells, myeloid-derived suppressor cells, or tumor-associated macrophages in various cancer types. In this study, we investigated the potential correlation between clinical outcomes and peripheral blood immune cell profiles, specifically focused on FoxP3+ Treg cells, collected at baseline and one week after anti-PD-1 therapy in two independent cohorts of patients with NSCLC: a discovery cohort of 83 patients and a validation cohort of 49 patients. High frequencies of circulating Treg cells one week after anti-PD-1 therapy were correlated with a high response rate, longer progression-free survival, and overall survival. Furthermore, high levels of TGF-ß and Treg cells were associated with favorable clinical outcomes. Our results suggest that higher levels of FoxP3+ Treg cells and TGF-ß can predict a favorable response to anti-PD-1 immunotherapy in patients with advanced NSCLC.

Docetaxel rechallenge in metastatic castration-resistant prostate cancer: A retrospective, single-center study.

PURPOSE: To assess the efficacy and safety of docetaxel rechallenge in the salvage setting in metastatic castration-resistant prostate cancer (mCRPC) patients. MATERIALS AND METHODS: Clinicopathologic data from patients treated with docetaxel rechallenge were collected from a single-center cancer registry. Among 227 patients who received first-line docetaxel for mCRPC between January 2011 and June 2019, 23 undergo rechallenge docetaxel after failure to androgen receptor targeting agents and/or cabazitaxel treatment. Endpoints included radiologic progression-free survival (PFS), treatment duration, and prostate-specific antigen (PSA) response and safety. RESULTS: Overall, 30%, 44%, 13%, and 13% of patients received docetaxel rechallenge as either the third, fourth, fifth, or sixth-line therapy, respectively, at a median of 23.6 months after stopping first-line docetaxel. With first-line docetaxel and rechallenge, median treatment duration was 6.4 and 3.3 months, respectively. With docetaxel rechallenge, PSA response was 35% (95% confidence interval [CI], 15% to 54%) and median PFS was 4.5 months (95% CI, 1.9 to 7.1 months). The median OS was 24.3 months (95% CI, 4.6 to 44.0 months). There were 7 severe adverse events (grade 3 or more) including anemia (8.7%), neutropenia, thrombocytopenia, leukopenia, diarrhea, and nausea (4.3% each). CONCLUSIONS: Docetaxel rechallenge showed meaningful anti-tumor activity with acceptable toxicity in heavily pretreated patients with mCRPC.

Effects of a Lifestyle Intervention Based on Type D Personality in Overweight and Obese Middle-Aged Women: A Feasibility Study.

BACKGROUND: Obesity is an important public health problem, particularly among middle-aged women. Type D personality, characterized by negative affectivity and social inhibition, is prevalent among obese and overweight middle-aged women and has been linked to maladaptive health-related behaviors and unhealthy lifestyle. Lifestyle interventions based on type D personality could be a first step in combatting obesity in middle-aged women. AIM: To identify the effects of a lifestyle intervention based on type D personality on health-promoting lifestyle behaviors, psychological distress, type D personality, and body composition in overweight and obese middle-aged women. METHODS: A total of 36 overweight and obese middle-aged women participated in a quasi-experimental design using a non-equivalent control group pretest-posttest. The experimental group received a total of eight sessions of a lifestyle intervention program based on type D personality over the course of four weeks. Outcomes were measured health-promoting lifestyle behaviors, psychological distress, type D personality, and body composition (body weight, body mass index, body fat, and abdominal fat). RESULTS: Following the intervention, the experimental group scored significantly higher than the control group for health-promoting lifestyle behaviors, and significantly lower than the control group for psychological distress and type D personality. Body weight and body mass index decreased significantly in the experimental group compared to the control group. LINKING EVIDENCE TO ACTION: Further research on various intervention programs for overweight and obese middle-aged women is warranted, including lifestyle interventions based on type D personality.

MDSC subtypes and CD39 expression on CD8+ T cells predict the efficacy of anti-PD-1 immunotherapy in patients with advanced NSCLC.

The major suppressive immune cells in tumor sites are myeloid derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and Treg cells, and the major roles of these suppressive immune cells include hindering T-cell activities and supporting tumor progression and survival. In this study, we analyzed the pattern of circulating MDSC subtypes in patients with non-small cell lung cancer (NSCLC) whether those suppressive immune cells hinder T-cell activities leading to poor clinical outcomes. First, we verified PMN-MDSCs, monocytic-MDSCs (M-MDSCs), and Treg cells increased according to the stages of NSCLC, and MDSCs effectively suppressed T-cell activities and induced T-cell exhaustion. The analysis of NSCLC patients treated with anti-PD-1 immunotherapy demonstrated that low PMN-MDSCs, M-MDSCs, and CD39+ CD8+ T cells as an individual and all together were associated with longer progression free survival and overall survival, suggesting PMN-MDSCs, M-MDSCs, and CD39+ CD8+ T cells frequencies in peripheral blood might be useful as potential predictive and prognostic biomarkers.

Public Health Emergency and Crisis Management: Case Study of SARS-CoV-2 Outbreak.

The SARS-CoV-2 pandemic has caused an unparalleled public health crisis, delivering an immense shock to humanity. With the virus's health consequences largely unknown, different health systems around the globe have pursued various avenues of crisis management. South Korea, troubled early by the virus, was once the second most affected nation in the world. Arrays of measures in South Korea, such as large-scale diagnostic testing and technology-based comprehensive contact tracing, have brought about debates among public health experts and medical professionals. This case study describes the major cluster transmissions in SARS-CoV-2 hotspots in South Korea (such as a religious sect, a call center, logistics facilities, and nightclubs) and offers early observations on how South Korean public health authorities acted in response to the initial outbreak of the virus and to the new waves prompted by re-opening economies. We then discuss the way in which South Korea's experience can act as a reference for shaping other countries' public health strategies in pandemic crisis management.