Multiplex analysis for the identification of plasma protein biomarkers for predicting lung cancer immunotherapy response.

Background: Programmed death-ligand (PD-L1) expression serves as a predictive biomarker for immune checkpoint inhibitor (ICI) sensitivity in non-small cell lung cancer (NSCLC). Nevertheless, the development of biomarkers that reliably predict ICI response remains an ongoing endeavor due to imperfections in existing methodologies. Objectives: ICIs have led to a new paradigm in the treatment of NSCLC. The current companion PD-L1 diagnostics are insufficient in predicting ICI response. Therefore, we sought whether the Olink platform could be applied to predict response to ICIs in NSCLC. Design: We collected blood samples from patients with NSCLC before ICI treatment and retrospectively analyzed proteomes based on their response to ICI. Methods: Overall, 76 NSCLC patients' samples were analyzed. Proteomic plasma analysis was performed using the Olink platform. Intraplate reproducibility, validation, and statistical analyses using elastic net regression and generalized linear models with clinical parameters were evaluated. Results: Intraplate coefficient of variation (CV) assays ranged from 3% to 6%, and the interplate CV was 14%. In addition, the Pearson correlation coefficient of the Olink Normalized Protein eXpression data was validated. No statistical differences were observed in the analyses of progressive disease and response to ICIs. Furthermore, no single proteome showed prognostic value in terms of progression-free survival. Conclusion: In this study, the proximity extension assay-based approach of the Olink panel could not predict the patient's response to ICIs. Our proteomic analysis failed to achieve predictive value in both response or progression to ICIs and progression-free survival (PFS).

Nomogram Using Prostate Health Index for Predicting Prostate Cancer in the Gray Zone: Prospective, Multicenter Study.

PURPOSE: To create a nomogram that can predict the probability of prostate cancer using prostate health index (PHI) and clinical parameters of patients. And the optimal cut-off value of PHI for prostate cancer was also assessed. MATERIALS AND METHODS: A prospective, multi-center study was conducted. PHI was evaluated prior to biopsy in patients requiring prostate biopsy due to high prostate-specific antigen (PSA). Among screened 1,010 patients, 626 patients with clinically suspected prostate cancer with aged 40 to 85 years, and with PSA levels ranging from 2.5 to 10 ng/mL were analyzed. RESULTS: Among 626 patients, 38.82% (243/626) and 22.52% (141/626) were diagnosed with prostate cancer and clinically significant prostate cancer, respectively. In the PSA 2.5 to 4 ng/mL group, the areas under the curve (AUCs) of the nomograms for overall prostate cancer and clinically significant prostate cancer were 0.796 (0.727-0.866; p<0.001), and 0.697 (0.598-0.795; p=0.001), respectively. In the PSA 4 to 10 ng/mL group, the AUCs of nomograms for overall prostate cancer and clinically significant prostate cancer were 0.812 (0.783-0.842; p<0.001), and 0.839 (0.810-0.869; p<0.001), respectively. CONCLUSIONS: Even though external validations are necessary, a nomogram using PHI might improve the prediction of prostate cancer, reducing the need for prostate biopsies.

Preoperative low muscle mass and early postoperative outcomes in children undergoing living donor liver transplantation: A retrospective study.

Low skeletal muscle mass may develop in children with end-stage liver disease, affecting postoperative outcomes. We retrospectively investigated whether preoperative low muscle mass was associated with early postoperative outcomes in pediatric patients undergoing living donor liver transplantation (LDLT). Electronic medical records of children (age below 12 y) who underwent LDLT between February 1, 2007, and January 31, 2018, were reviewed. The cross-sectional areas of psoas, quadratus lumborum, and erector spinae muscles at the level of fourth-fifth lumbar intervertebral disks were measured using abdominal CT images, divided by the square of the height and were added to obtain the total skeletal muscle index (TSMI). The patients were divided into two groups according to the median TSMI in the second quintile (1859.1 mm 2 /m 2 ). Complications in the early postoperative period (within 30 d after surgery) classified as Clavien-Dindo grade 3 or higher were considered major complications. Logistic regression analyses were performed to determine the association between preoperative low muscle mass and early postoperative outcomes. In the study population of 123 patients (median age, 14 mo; range, 8-38 mo) who underwent LDLT, 29% and 71% were classified in the low (mean TSMI, 1642.5 ± 187.0 mm 2 /m 2 ) and high (mean TSMI 2188.1 ± 273.5 mm 2 /m 2 ) muscle mass groups, respectively. The rates of major complications, mechanical ventilation >96 hours, intensive care unit stay >14 days, hospital stay >30 days, and in-hospital mortality were not significantly different between the 2 groups. Additionally, adverse outcomes according to pediatric end-stage liver disease scores and sex were not significantly different between the 2 groups. In conclusion, preoperative low muscle mass defined by TSMI was not associated with early postoperative outcomes in pediatric patients undergoing LDLT.

Inhalation of Origanum majorana L. essential oil while working reduces perceived stress and anxiety levels of nurses in a COVID-19 intensive care unit: a randomized controlled trial.

Background: Nurses caring for patients with coronavirus disease 2019 (COVID-19) experience higher psychosocial distress than other healthcare workers, and this can adversely affect the quality of patient care. There is evidence that inhalation of essential oil from marjoram (Origanum majorana L.) has calming effects, suggesting this intervention may help to reduce the stress and anxiety of nurses working in a COVID-19 intensive care unit (ICU). This study aimed to investigate the effect of inhalation of marjoram essential oil at work on the stress and anxiety levels of nurses in a COVID-19 ICU. Methods: Nurses (n = 57) working in a single COVID-19 ICU were randomly assigned to inhale 3% marjoram essential oil (marjoram group, n = 29) or almond oil (control group, n = 28) for 2 h while at work. Mean arterial pressure (MAP), heart rate, state anxiety score, and score on a visual analog scale for anxiety (VAS-anxiety) and stress (VAS-stress) were measured before and after the intervention. Results: The two groups had similar baseline variables. MAP did not have within-group or between-group differences. Heart rate increased significantly in the marjoram group after the intervention (p = 0.031), but it remained within the normal range and the increase was not clinically meaningful. There was no significant between-group difference in the state-anxiety or VAS-anxiety score after the intervention, but the marjoram group had a significantly lower state-anxiety (p = 0.001) and VAS-anxiety (p = 0.037) score at posttest vs. pretest. The VAS-stress score was significantly lower in the marjoram group at the posttest vs. the pretest (p = 0.026). Conclusion: Nurses caring for patients in a COVID-19 ICU experience significant stress, and strategies are needed to address this important issue. Inhalation of 3% marjoram essential oil while caring for patients in a COVID-19 ICU may be a simple and effective intervention that reduces perceived stress and anxiety in nurses.Clinical Trial Registration: https://cris.nih.go.kr/, KCT0007543.

HDAC5-mediated exosomal Maspin and miR-151a-3p as biomarkers for enhancing radiation treatment sensitivity in hepatocellular carcinoma.

BACKGROUND: Tumor-derived exosomes are critical elements of the cell-cell communication response to various stimuli. This study aims to reveal that the histone deacetylase 5 (HDAC5) and p53 interaction upon radiation in hepatocellular carcinoma intricately regulates the secretion and composition of exosomes. METHODS: We observed that HDAC5 and p53 expression were significantly increased by 2 Gy and 4 Gy radiation exposure in HCC. Normal- and radiation-derived exosomes released by HepG2 were purified to investigate the exosomal components. RESULTS: We found that in the radiation-derived exosome, exosomal Maspin was notably increased. Maspin is known as an anti-angiogenic gene. The expression of Maspin was regulated at the cellular level by HDAC5, and it was elaborately regulated and released in the exosome. Radiation-derived exosome treatment caused significant inhibition of angiogenesis in HUVECs and mouse aortic tissues. Meanwhile, we confirmed that miR-151a-3p was significantly reduced in the radiation-derived exosome through exosomal miRNA sequencing, and three HCC-specific exosomal miRNAs were also decreased. In particular, miR-151a-3p induced an anti-apoptotic response by inhibiting p53, and it was shown to induce EMT and promote tumor growth by regulating p53-related tumor progression genes. In the HCC xenograft model, radiation-induced exosome injection significantly reduced angiogenesis and tumor size. CONCLUSIONS: Our present findings demonstrated HDAC5 is a vital gene of the p53-mediated release of exosomes resulting in tumor suppression through anti-cancer exosomal components in response to radiation. Finally, we highlight the important role of exosomal Maspin and mi-151a-3p as a biomarker in enhancing radiation treatment sensitivity. Therapeutic potential of HDAC5 through p53-mediated exosome modulation in radiation treatment of hepatocellular carcinoma.

Prognostic significance of 25-hydroxyvitamin D levels in patients with peripheral T-cell lymphoma.

Vitamin D insufficiency has been linked to unfavourable outcomes in diverse malignancies. However, the prognostic significance of vitamin D levels in peripheral T-cell lymphoma (PTCL) remains unclear. In this study, we thus aimed to assess the prognostic relevance of 25-hydroxyvitamin D [25(OH)D] levels in patients newly diagnosed with PTCL. The analysis included 144 patients with PTCL treated from March 2015 to May 2020. The median 25(OH)D level was 12.2 (1.7-48.8) ng/mL, and 59 (41%) patients had vitamin D deficiency. Patients with vitamin D deficiency demonstrated significantly worse event-free survival (EFS) and overall survival (OS). In the multivariate analysis, vitamin D was independently associated with OS, with a hazard ratio of 1.66 (95% confidence interval, 1.05-2.63, p = 0.030). These findings suggest that vitamin D deficiency significantly correlates with poor survival outcomes in patients with PTCL.

An ensemble machine learning approach to predict postoperative mortality in older patients undergoing emergency surgery.

BACKGROUND: Prediction of preoperative frailty risk in the emergency setting is a challenging issue because preoperative evaluation cannot be done sufficiently. In a previous study, the preoperative frailty risk prediction model used only diagnostic and operation codes for emergency surgery and found poor predictive performance. This study developed a preoperative frailty prediction model using machine learning techniques that can be used in various clinical settings with improved predictive performance. METHODS: This is a national cohort study including 22,448 patients who were older than 75 years and visited the hospital for emergency surgery from the cohort of older patients among the retrieved sample from the Korean National Health Insurance Service. The diagnostic and operation codes were one-hot encoded and entered into the predictive model using the extreme gradient boosting (XGBoost) as a machine learning technique. The predictive performance of the model for postoperative 90-day mortality was compared with those of previous frailty evaluation tools such as Operation Frailty Risk Score (OFRS) and Hospital Frailty Risk Score (HFRS) using the receiver operating characteristic curve analysis. RESULTS: The predictive performance of the XGBoost, OFRS, and HFRS for postoperative 90-day mortality was 0.840, 0.607, and 0.588 on a c-statistics basis, respectively. CONCLUSIONS: Using machine learning techniques, XGBoost to predict postoperative 90-day mortality, using diagnostic and operation codes, the prediction performance was improved significantly over the previous risk assessment models such as OFRS and HFRS.

A New Prognostic Index for Extranodal Natural Killer/T-Cell Lymphoma:Incorporation of Serum ß-2 Microglobulin to PINK.

PURPOSE: Prognostic Index for Natural Killer Lymphoma (PINK) is the most widely accepted prognostic model for patients withextranodal natural killer/T-cell lymphoma (ENKTL) treated with non-anthracycline-based therapy. We aimed to evaluate the prognostic implications of serum ß-2 microglobulin (ß2M) in the context of PINK and proposed a new prognostic model. MATERIALS AND METHODS: A total of 138 patients who were newly diagnosed with ENKTL and treated with non-anthracycline-based chemotherapy were identified. The cut-off value of high serum ß2M was calculated by maximal-chi square methods (4.1 mg/L). A new prognostic model incorporating serum ß2M into PINK was proposed and validated in an independent validation cohort (n=88). RESULTS: The patients' median age was 53.5 years (range, 19 to 80 years). Patients with high serum ß2M levels had significantly worse overall survival (OS) and progression-free survival (PFS). In multivariate analysis, high serum ß2M was an independent adverse prognostic factor for OS. A new PINK-B (Prognostic Index for Natural Killer Lymphoma-serum ß-2 microglobulin) model stratifiedpatients into three groups with distinct OS and PFS in the training cohort (3-year OS, 84.1% [95% confidence interval, 75.1 to 94.2], 46.8% [36.1 to 60.8] and 17.6% [6.3 to 49.2] for the low-, intermediate, and high-risk groups, respectively; 3-year PFS, 70.6% [59.4 to 83.8], 35.9% [25.9 to 49.8], and 7.35% [1.1 to 46.7] for the low-, intermediate-, and high-risk groups, respectively). The PINK-B model was further validated in an independent cohort. CONCLUSION: Serum ß2M is an independent prognostic factor for ENKTL patients. The new serum ß2M-based prognostic model may be useful for identifying ultra-high-risk patients, and it can easily be adopted into daily clinical practice.

Simultaneous robot-assisted approach in a super-elderly patient with urothelial carcinoma and synchronous contralateral renal cell carcinoma: A case report.

BACKGROUND: It is rare for urothelial and renal cell carcinomas to coexist in the same patient, and even rarer for them to be detected simultaneously. Because of this rarity, a standard treatment has not been established and studies about overall survival are scarce. Therefore, physicians must modify treatments according to the individual's situation and the stage of each disease. In recent years, with advances in the instruments and techniques, minimal invasive robotic surgeries have become available for advanced-stage or high-risk patients. CASE SUMMARY: An 85-year-old woman with a medical history of hypertension and hyperlipidemia visited our institution. She had visited her local hospital complaining of intermittent, painless, gross hematuria that had started 3 mo earlier. On computed tomography, a right renal mass and left proximal ureteral mass with hydronephrosis were found simultaneously. We decided to perform robot-assisted surgery on both sides during one operation. Considering renal function and kidney loading, right partial nephrectomy was performed first, followed by left nephroureterectomy with bladder cuff excision. At the 6-mo follow-up, no specific symptoms were reported and dialysis was not considered. There were no unusual findings in the imaging study, and regular follow-up and imaging studies are scheduled. CONCLUSION: This case report assessed the feasibility of simultaneous minimal invasive robotic surgery as an alternative to conventional open or laparoscopic surgery.

A study of quantitative indicators for slice sorting in cine-mode 4DCT.

The uncertainties of four-dimensional computed tomography (4DCT), also called as residual motion artefacts (RMA), induced from irregular respiratory patterns can degrade the quality of overall radiotherapy. This study aims to quantify and reduce those uncertainties. A comparative study on quantitative indicators for RMA was performed, and based on this, we proposed a new 4DCT sorting method that is applicable without disrupting the current clinical workflow. In addition to the default phase sorting strategy, both additional amplitude information from external surrogates and the quantitative metric for RMA, investigated in this study, were introduced. The comparison of quantitative indicators and the performance of the proposed sorting method were evaluated via 10 cases of breath-hold (BH) CT and 30 cases of 4DCT. It was confirmed that N-RMSD (normalised root-mean-square-deviation) was best matched to the visual standards of our institute's regime, manual sorting method, and could accurately represent RMA. The performance of the proposed method to reduce 4DCT uncertainties was improved by about 18.8% in the averaged value of N-RMSD compared to the default phase sorting method. To the best of our knowledge, this is the first study that evaluates RMA indicators using both BHCT and 4DCT with visual-criteria-based manual sorting and proposes an improved 4DCT sorting strategy based on them.

Multi-center validation of machine learning model for preoperative prediction of postoperative mortality.

Accurate prediction of postoperative mortality is important for not only successful postoperative patient care but also for information-based shared decision-making with patients and efficient allocation of medical resources. This study aimed to create a machine-learning prediction model for 30-day mortality after a non-cardiac surgery that adapts to the manageable amount of clinical information as input features and is validated against multi-centered rather than single-centered data. Data were collected from 454,404 patients over 18 years of age who underwent non-cardiac surgeries from four independent institutions. We performed a retrospective analysis of the retrieved data. Only 12-18 clinical variables were used for model training. Logistic regression, random forest classifier, extreme gradient boosting (XGBoost), and deep neural network methods were applied to compare the prediction performances. To reduce overfitting and create a robust model, bootstrapping and grid search with tenfold cross-validation were performed. The XGBoost method in Seoul National University Hospital (SNUH) data delivers the best performance in terms of the area under receiver operating characteristic curve (AUROC) (0.9376) and the area under the precision-recall curve (0.1593). The predictive performance was the best when the SNUH model was validated with Ewha Womans University Medical Center data (AUROC, 0.941). Preoperative albumin, prothrombin time, and age were the most important features in the model for each hospital. It is possible to create a robust artificial intelligence prediction model applicable to multiple institutions through a light predictive model using only minimal preoperative information that can be automatically extracted from each hospital.

Application of the New Preoperative Frailty Risk Score in Elderly Patients Undergoing Emergency Surgery.

BACKGROUND: Predicting preoperative frailty risk in emergency surgery is difficult with limited information because preoperative evaluation is not commonly performed properly. A recent study attempted to predict preoperative frailty risk using only diagnostic and surgical codes that can be extracted from the electronic medical records system. OBJECTIVE: This study aimed to validate whether the prediction model of preoperative frailty risk presented in the previous study is well applied to other medical hospitals' data. METHODS: This is a retrospective cohort study including 1,557 patients (≥75 years old) who were admitted to a single institution for emergency operations between January 1, 2010, and December 31, 2019, for study analysis. The Charlson comorbidity index, Hospital Frailty Risk Score, and the recently developed Operation Frailty Risk Score (OFRS) were calculated using the patient's diagnostic and operation codes. The predictive performances of these calculated risk scores and the American Society of Anesthesiologists-Physical Status classification for postoperative 90-day mortality were compared by using the receiver operating characteristic curve analysis. FINDINGS: The predictive performance of the OFRS, Charlson comorbidity index, American Society of Anesthesiologists-Physical Status, and Hospital Frailty Risk Score for postoperative 90-day mortality was 0.81, 0.630, 0.699, and 0.549 on a c-statistics basis, respectively. CONCLUSIONS: The OFRS using diagnostic and operation codes may show the best predictive performance for 90-day mortality compared to other risk scores, and it can be the clinically applicable model to evaluate the preoperative frailty risk in elderly patients undergoing emergency surgery.

Radiation-induced C-reactive protein triggers apoptosis of vascular smooth muscle cells through ROS interfering with the STAT3/Ref-1 complex.

Damage to normal tissue can occur over a long period after cancer radiotherapy. Free radical by radiation can initiate or accelerate chronic inflammation, which can lead to atherosclerosis. However, the underlying mechanisms remain unclear. Vascular smooth muscle cells (VSMCs) proliferate in response to JAK/STAT3 signalling. C-reactive protein (CRP) can induce VSMCs apoptosis via triggering NADPH oxidase (NOX). Apoptotic VSMCs promote instability and inflammation of atherosclerotic lesions. Herein, we identified a VSMCs that switched from proliferation to apoptosis through was enhanced by radiation-induced CRP. NOX inhibition using lentiviral sh-p22phox prevented apoptosis upon radiation-induced CRP. CRP overexpression reduced the amount of STAT3/Ref-1 complex, decreased JAK/STAT phosphorylation and formed a new complex of Ref-1/CRP in VSMC. Apoptosis of VSMCs was further increased by CRP co-overexpressed with Ref-1. Functional inhibition of NOX or p53 also prevented apoptotic activity of the CRP-Ref-1 complex. Immunofluorescence showed co-localization of CRP, Ref-1 and p53 with α-actin-positive VSMC in human atherosclerotic plaques. In conclusion, radiation-induced CRP increased the VSMCs apoptosis through Ref-1, which dissociated the STAT3/Ref-1 complex, interfered with JAK/STAT3 activity, and interacted with CRP-Ref-1, thus resulting in transcription-independent cell death via p53. Targeting CRP as a vascular side effect of radiotherapy could be exploited to improve curability.

Prognostic significance of serum ß2-microglobulin levels in patients with peripheral T-cell lymphoma not otherwise specified.

We aimed to investigate the prognostic value of serum ß2-microglobulin in patients with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS). A cohort study of PTCL-NOS patients (n = 147) was conducted. An elevated serum ß2-microglobulin level was associated with the presence of previously identified predictors of a poor prognosis for PTCL-NOS. Patients with an elevated serum ß2-microglobulin level exhibited a significantly worse progression-free survival (PFS) and overall survival (OS). Multivariate analyses revealed that an elevated serum ß2-microglobulin level was independently associated with a shorter PFS and OS. A new prognostic index incorporating the serum ß2-microglobulin level allowed for the stratification of patients into three distinct risk subgroups. The index was validated to stratify patients with distinct survival outcomes in an independent cohort of PTCL-NOS (n = 89). In conclusion, serum ß2-microglobulin level is an independent prognostic factor in patients with PTCL-NOS. Our ß2-microglobulin-based prognostic index for PTCL-NOS deserves further investigation and validation.

BCL2 super-expressor diffuse large B-cell lymphoma: a distinct subgroup associated with poor prognosis.

Overexpression of the BCL2 protein has been reported as a poor prognostic factor for diffuse large B-cell lymphoma (DLBCL). However, there are currently no standardized criteria for evaluating BCL2 protein expression. We aimed to evaluate the prognostic value of BCL2 expression determined by immunohistochemistry (IHC), incorporating both the staining intensity and proportion, in patients with de novo DLBCL who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as first-line treatment. We defined tumors with BCL2 expression in nearly all tumor cells with a uniformly strong intensity by IHC as BCL2 super-expressor. The BCL2 super-expressors (n = 35) showed significantly worse event-free survival (EFS; HR, 1.903; 95% CI, 1.159-3.126, P = 0.011) and overall survival (OS; HR, 2.467; 95% CI, 1.474-4.127, P = 0.001) compared with the non-BCL2 super-expressors (n = 234) independent of the international prognostic index (IPI), cell of origin (COO), and double expressor status in the training set (n = 269). The adverse prognostic impact of BCL2 super-expression was confirmed in the validation set (n = 195). When the survival outcomes were evaluated in the entire cohort (n = 464), BCL2 super-expressor group was significantly associated with inferior EFS and OS regardless of IPI, COO, MYC expression, and stages. BCL2 super-expressors had genetic aberrations enriched in the NOTCH and TP53 signaling pathways. This study suggests that the BCL2 super-expressor characterizes a distinct subset of DLBCL with a poor prognosis and warrants further investigation as a target population for BCL-2 inhibitors.

Robot-Assisted Laparoscopic Paravaginal Repair and Sacrocolpopexy in Patients With Pelvic Organ Prolapse.

OBJECTIVE: To evaluate the surgical effects of robotic paravaginal repair and sacrocolpopexy in patients diagnosed with lateral cystocele due to paravaginal defect. PATIENTS AND METHODS: Robotic paravaginal repair and sacrocolpopexy were performed contemporaneously in 43 patients with high-grade pelvic organ prolapse combined with a lateral or mixed cystocele. To objectively evaluate prolapse correction, the Pelvic Organ Prolapse Quantification (POP-Q) test was performed at the 12-month visit and the results compared to those of the preoperative period. Subjective satisfaction was scored using the Patient Global Impression of Improvement (PGI-I) questionnaire. RESULTS: POP-Q measurement results before and after surgery, an objective indicator of surgery, the Ba and C scores improved significantly from 2.1 ± 1.2 preoperatively to -2.0 ± 1.1 postoperatively (P <.01), and from 0.3 ± 1.3 preoperatively to -4.3 ± 1.1 postoperatively (P <.01), respectively. In PGI-I questionnaire, the numbers of patients who awarded scores of 1 and 2 (evidencing high-level symptom improvement) were 33 at 1 month (76.7%), 30 at 3 months (69.8%), and 28 (65.1%) at 12 months. When respondents awarding 3 points (a little improvement) were included, the numbers rose to 38 (88.4%) at 1 and 3 months and 35 (81.4%) at 12 months, indicating satisfaction with symptom improvement. There were no critical complications during and after surgery, but complications such as de novo stress urinary incontinence that lower patient satisfaction occurred in some cases. CONCLUSION: Robot-assisted paravaginal repair and sacrocolpopexy can be safely performed in patients with cystocele-predominant pelvic organ prolapse and good surgical results can be expected with excellent effects.

Prostate cancer specific mortality after 5α-reductase inhibitors medication in benign prostatic hyperplasia patients: systematic review and meta-analysis.

BACKGROUND: Our study was conducted to investigate the effect of 5-ARI on the death rate from prostate cancer by means of an updated meta-analysis using related data. METHODS: We did comprehensive literature searches using the PubMed, Embase, and Cochrane databases through July 2019. We evaluated the risk of bias in such studies using the ROBINS-I tool and analyzed deaths from cancer and deaths from all causes using HR. RESULTS: The meta-analysis included 11 studies. The pooled overall HRs for cancer-specific deaths between 5-ARI treatment versus non-exposed groups were 0.937 (95% CI: 0.730, 1.201). In the subgroup moderator analysis, the number of patients and additional medication variables were significantly associated with deaths from all causes (p = 0.022 and p = 0.005, respectively). For detecting the publication bias or small-study effect in the included studies, we performed Begg and Mazumdar's correlation test (0.851 and 0.573) and Egger's regression coefficient test (0.035 and 0.245) and ​suggested that there was no evidence of publication bias or small-study effect in this meta-analysis. CONCLUSIONS: Our study indicated that exposure to 5-ARI had no close association between the overall death rate or cancer-specific deaths. To confirm these results, well-designed prospective studies with large samples are required.

ß-Defensin 2, an Antimicrobial Peptide, as a Novel Biomarker for Ulcerative Interstitial Cystitis; Can ß-Defensin 2 Suspect the Dysbiosis of Urine Microbiota?

As urine is not sterile, inflammatory reactions caused by dysbiosis of the urinary microbiota may induce interstitial cystitis. A study was conducted to determine whether ß-defensin 2 (BD-2), a specific antimicrobial peptide in the bladder, could be used as a novel diagnostic marker for ulcerative interstitial cystitis (IC). Urine samples from three female groups were examined: healthy controls (n = 34, Control group), non-Hunner type IC (n = 40, NHIC group), and Hunner type IC (n = 68, HIC group). Urine samples were collected via a transurethral catheter and assayed for BD-2 levels using enzyme linked immunosorbent assay. Under general or regional anesthesia, cystoscopy with diagnostic and therapeutic hydrodistension was performed in NHIC and HIC groups patients. These patients underwent a biopsy of the bladders. Based on the urinary specimens from 142 patients, BD-2 expression was found to be 18-fold higher in patients with Hunner type IC than in patients with non-Hunner type IC. The enhanced secretion of BD-2 exhibited a strong correlation with increased mast cell counts associated with bladder IC pathology. Enhanced urinary secretion of the antimicrobial peptide BD-2 from Hunner type IC patients associated with clinical phenotypes and demonstrated relatively robust levels to be used as a potential biomarker. Moreover, the increased urinary level of BD-2 may suggest a new possibility of biomarkers caused by dysbiosis of the urinary microbiota in ulcerative IC.

Postoperative Pulmonary Complications after Transcatheter Aortic Valve Implantation under Monitored Anesthesia Care versus General Anesthesia: Retrospective Analysis at a Single Large Volume Center.

Few studies to date have assessed the postoperative pulmonary complications after transcatheter aortic valve implantation (TAVI) according to the anesthesia method. The present study aims to compare the effects of general anesthesia (GA) or monitored anesthesia care (MAC) on postoperative outcomes in patients undergoing TAVI. This retrospective cohort study included 578 patients who underwent TAVI through the trans-femoral approach between August 2011 and May 2019 at a single tertiary academic center. The primary outcome was postoperative pulmonary complications, which were defined as the occurrence of one or more pulmonary complications, such as respiratory failure, respiratory infection, and radiologic findings, within 7 days after TAVI. Secondary outcomes included postoperative delirium, all-cause 30-day mortality rate, 30-day readmission rate, reoperation rate, vascular complications, permanent pacemaker/implantable cardioverter-defibrillator insertion, length of stay in the ICU, hospital stay, and incidence of stroke. Of the 589 patients, 171 underwent TAVI under general anesthesia (GA), and 418 under monitored anesthesia care (MAC). The incidence of postoperative pulmonary complications was significantly higher in the GA than in the MAC group (17.0% vs. 5.3%, p < 0.001). Anesthetic method significantly affected the occurrence of postoperative pulmonary complications, but not of delirium. ICU stay was significantly shorter in the MAC group, as were operation time, the volume of fluid administered during surgery, heparin dose, transfusion, and inotrope requirements. TAVI under MAC can increase the efficiency of medical resources, reducing the lengths of ICU stay and the occurrence of postoperative pulmonary complications, compared with TAVI under GA.

Safety and efficacy of 10-fraction hypofractionated radiation therapy for non-small cell lung cancer.

PURPOSE: To investigate the safety and efficacy of hypofractionated radiation therapy (HFRT) in patients with non-small cell lung cancer who are unfit for surgery or stereotactic body radiation therapy (SBRT) at our institution. MATERIALS AND METHODS: From May 2007 to December 2018, HFRT was used to treat 68 lesions in 64 patients who were unsuitable for SBRT because of central tumor location, large tumor size, or contiguity with the chest wall. The HFRT schedule included a dose of 50-70 Gy delivered in 10 fractions over 2 weeks. The primary outcome was freedom from local progression (FFLP), and the secondary endpoints included overall survival (OS), disease-free survival, and toxicities. RESULTS: The median follow-up period was 25.5 months (range, 5.3 to 119.9 months). The FFLP rates were 79.8% and 67.8% at 1 and 2 years, respectively. The OS rates were 82.8% and 64.1% at 1 and 2 years, respectively. A larger planning target volume was associated with lower FFLP (p = 0.023). Dose escalation was not associated with FFLP (p = 0.964). Four patients (6.3%) experienced grade 3-5 pulmonary toxicities. Tumor location, central or peripheral, was not associated with either grade 3 or higher toxicity. CONCLUSION: HFRT with 50-70 Gy in 10 fractions demonstrated acceptable toxicity; however, the local control rate can be improved compared with the results of SBRT. More studies are required in patients who are unfit for SBRT to investigate the optimal fractionation scheme.