The polymyxin-B direct hemoperfusion OPTimal Initiation timing with Catecholamine PMX-OPTIC study: A multicenter retrospective observational study.

BACKGROUND: Polymyxin-B direct hemoperfusion (PMX-DHP) is an endotoxin adsorption column-based blood purification therapy. Since one of the most potent effects of PMX-DHP is blood pressure elevations, it may be the most effective when it is introduced at the time when the need for vasopressors is the greatest, which, in turn, may reduce mortality. METHODS: A multicenter retrospective study was conducted at 24 ICUs in Japan. In each ICU, the 20 most recent consecutive cases of septic shock treated with PMX-DHP were analyzed. The duration between the time of the peak vasopressive agent dose, expressed as the noradrenaline equivalent dose (NEq), and the time of PMX initiation was evaluated. The primary outcome was 28-day mortality, and a multivariable analysis was performed to investigate factors associated with mortality. RESULTS: A total of 480 septic shock patients were included in the analysis. Among all patients, the 28-day mortality group was older, more severely ill, and had a higher body mass index. The NEq peak and NEq on PMX-DHP initiation were both higher in deceased patients. Regarding the timing of PMX-DHP initiation from the NEq peak, -4 << 4 h had more survivors (229/304, 75.3%) than ≤-4 h (50/75, 66.7%) and ≥4 h (66/101, 65.4%) (p = 0.085). When -4 << 4 h was assigned as a reference, the timing of PMX-DHP initiation from the NEq peak of ≤-4 h had an odds ratio of 1.96 (1.07-3.58), p = 0.029, while ≥4 h had an odds ratio of 1.64 (0.94-2.87), p = 0.082 for 28-day mortality, in the multivariable regression analysis. A spline curve of the relationship between the probability of death and the timing of PMX-DHP initiation from the NEq peak showed a downward convex curve with a nadir at timing = 0. The odds ratios of the timing of PMX-DHP initiation other than -4 << 4 h were significantly higher in an older age, male sex, lower BMI, more severe illness, and higher oxygenation. CONCLUSIONS: The induction of PMX-DHP at the time of the peak vasopressor dose correlated with lower mortality. PMX-DHP is one of the options available for elevating blood pressure in septic shock, and its initiation either too early or late for shock peak may not improve the outcome.

Impact of salvage cytotoxic chemotherapy on prognosis in patients with recurrence after radical cystectomy: a multi-institutional retrospective study.

BACKGROUND: In patients experiencing disease recurrence after radical cystectomy (RC) for bladder cancer, data about the impact of clinicopathologic factors, including salvage treatment using cytotoxic chemotherapy, on the survival are scarce. We investigated the prognostic value of clinicopathologic factors and the treatment effect of salvage cytotoxic chemotherapy (SC) in such patients. METHODS: In this retrospective study, we evaluated the clinical data for 86 patients who experienced recurrence after RC. Administration of SC or of best supportive care (BSC) was determined in consultation with the urologist in charge and in accordance with each patient's performance status, wishes for treatment, and renal function. Statistical analyses explored for prognostic factors and evaluated the treatment effect of SC compared with BSC in terms of cancer-specific survival (CSS). RESULTS: Multivariate analyses showed that liver metastasis after RC (hazard ratio [HR] 2.13; 95% confidence interval [CI] 1.17 to 3.85; P = 0.01) and locally advanced disease at RC (HR 1.92; 95% CI 1.06 to 3.46; P = 0.03) are independent risk factors for worse CSS in patients experiencing recurrence after RC. In a risk stratification model, patients were assigned to one of two groups based on liver metastasis and locally advanced stage. In the high-risk group, which included 68 patients with 1-2 risk factors, CSS was significantly better for patients receiving SC than for those receiving BSC (median survival duration: 9.4 months vs. 2.4 months, P = 0.005). The therapeutic effect of SC was not related to a history of adjuvant chemotherapy. CONCLUSIONS: The present study indicated the potential value of 1st-line SC in patients experiencing recurrence after RC even with advanced features, such as liver metastasis after RC and locally advanced disease at RC.

Outcomes of artificial urinary sphincter implantation in patients with diabetes mellitus: A subgroup analysis.

OBJECTIVES: To estimate the surgical and quality-of-life outcomes of artificial urinary sphincter implantation in patients with diabetes mellitus (DM). Subanalyses were performed using the same population as that in our previous multicenter, prospective, observational study. METHODS: A total of 135 male patients who underwent primary artificial urinary sphincter implantation were divided into two groups: those with and without DM. The revision-free rates, that is, the percentage of patients who did not require revision surgery, were compared between patients with and without DM. The number of urinary pads required per day, International Consultation on Incontinence Questionnaire-Short Form, and King's Health Questionnaire were used to compare the continence status and quality of life (QOL) between the two groups preoperatively and at 1, 3, and 12 months after surgery. RESULTS: Revision-free rates were significantly lower in the DM group (83.9%, 77.4%, and 67.8% at 1, 2, and 3 years after implantation, respectively) than in the non-DM group (95.5%, 92.5%, and 85.5% at 1, 2, and 3 years after implantation, respectively). Both continence status and QOL, assessed by questionnaires, markedly improved after surgery in patients with and without DM. CONCLUSIONS: Despite differences in the durability of the artificial urinary sphincters, patients with DM can obtain as much benefit from artificial urinary sphincter implantation regarding continence and quality-of-life improvement as patients without DM. Therefore, DM was not considered a comorbidity that contraindicated artificial urinary sphincter implantation. Additional large-scale studies are required to verify our findings.

First dorsal metacarpal artery perforator-based propeller flap: functional anatomy and clinical application in soft-tissue defects of the dorsal hand and digits.

BACKGROUND: Many approaches have been reported to repair soft-tissue defects of the hand using dorsal metacarpal artery flaps. Use of a perforator-based propeller flap from the first intermetacarpal space to the dorsum of the hand has been described. The aim of this study was to confirm the functional anatomy of a first dorsal metacarpal artery (FDMA) perforator flap. METHODS: Twenty-nine fixed cadaveric hands were dissected to determine the origin, course, and branches of the FDMA. Clinically, five cases of soft tissue defects of the hand underwent reconstructive surgery using an FDMA perforator-based propeller flap. RESULTS: The FDMA was found in 27 specimens (93%). The ulnar branch of the FDMA always supplied the cutaneous perforator (mean ± SD, 4.3 ± 1.6), and the most distal cutaneous perforating branch was found along the metacarpal long axis within 25 mm of the tip of the metacarpal head with high frequency (28/29, 97%). In the two hands that had aplasia of the FDMA, well-developed perforators arose directly from the radial artery and advanced to the metacarpal head. Seven hands (24%) had perforators arising from the palmar arterial system, penetrating through or passing close by the second metacarpal bone. In clinical application, all the flaps survived completely without major complications. CONCLUSIONS: The FDMA perforator-based propeller flap is minimally invasive and technically simple. It is expected to be a new option for hand reconstruction.

Relationship between Facial Color Changes and Psychological Problems Associated with Lower Back Pain.

Background and Objectives: The aim of this study was to determine whether a non-contact sensor that detects complexion changes can be used to assess the psychological state of patients with chronic lower back pain (LBP). Materials and Methods: Twenty-six patients with LBP (LBP group; mean age = 68.0 ± 13.9 years) and 18 control subjects without LBP (control group; mean age = 60.8 ± 16.1 years) were included in the study. All the subjects in the two groups wore headphones when asked LBP-related and LBP-unrelated questions. During questioning, the facial image of the subjects was captured using a video camera, and the complexion of the subjects was converted into red, green, and blue (RGB) values. RGB correlation coefficients (RGBCCs; range: 0-1) represent the difference in complexion between LBP-related and LBP-unrelated questions. A high RGBCC indicates that the brain is more activated by LBP-related questions than by LBP-unrelated questions. We also noted the scores of subjects on the Numerical Rating Scale (NRS), Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ), Pain Catastrophizing Scale (PCS), and Hospital Anxiety and Depression Scale (HADS). Results: There were no significant differences in RGBCC between the control and LBP groups (0.64 versus 0.56, p = 0.08). In the LBP group, no correlation was observed between RGBCC and each examination item of NRS, JOABPEQ, and HADS. In contrast, a correlation was observed between RGBCC and the rumination subscale of PCS in the LBP group (Spearman's rank correlation coefficient = 0.40, p = 0.04). Conclusions: The complexion of patients with catastrophic thinking changes when the patients are asked LBP-related questions.

Vertical transmission of methicillin-resistant Staphylococcus aureus at delivery and its clinical impact: An observational, prospective cohort study.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) infection has a significant clinical impact on both pregnant women and neonates. The aim of this study was to assess accurately the vertical transmission rate of MRSA and its clinical impacts on both pregnant mothers and neonates. MATERIAL AND METHODS: We conducted a prospective observational cohort study of 898 pregnant women who were admitted to our department and 905 neonates from August 2016 to December 2017. MRSA was cultured from nasal and vaginal samples taken from the mothers at enrollment and from nasal and umbilical surface swabs taken from neonates at the time of delivery. We examined the vertical transmission rate of MRSA in mother-neonate pairs. We used multivariable logistic regression to identify risk factors for maternal MRSA colonization and maternal/neonatal adverse outcomes associated with maternal MRSA colonization. RESULTS: The prevalence of maternal MRSA colonization was 6.1% (55 of 898) at enrollment. The independent risk factors were multiparity and occupation (healthcare provider) (odds ratio [OR] 2.35, 95% confidence interval [CI] 1.25-4.42 and OR 2.58, 95% CI 1.39-4.79, respectively). The prevalence of neonatal MRSA colonization at birth was 12.7% (7 of 55 mother-neonate pairs) in the maternal MRSA-positive group, whereas it was only 0.12% (one of 843 pairs) in the maternal MRSA-negative group (OR 121, 95% CI 14.6-1000). When maternal vaginal samples were MRSA-positive, vertical transmission was observed in four of nine cases (44.4%) in this study. Skin and soft tissue infections developed more frequently in neonates in the maternal MRSA-positive group than in the MRSA-negative group (OR 7.47, 95% CI 2.50-22.3). CONCLUSIONS: The prevalence of MRSA in pregnant women was approximately 6%. Vertical transmission caused by maternal vaginal MRSA colonization was observed in four of nine cases (44.4%). Although our study includes a limited number of maternal MRSA positive cases, the vertical transmission of MRSA may occur in up to 44% of neonates of mothers with vaginal MRSA colonization. Maternal MRSA colonization may be associated with increased development of skin and soft tissue infections in neonates via vertical transmission.

The effects of inhaling hydrogen gas on macrophage polarization, fibrosis, and lung function in mice with bleomycin-induced lung injury.

BACKGROUND: Acute respiratory distress syndrome, which is caused by acute lung injury, is a destructive respiratory disorder caused by a systemic inflammatory response. Persistent inflammation results in irreversible alveolar fibrosis. Because hydrogen gas possesses anti-inflammatory properties, we hypothesized that daily repeated inhalation of hydrogen gas could suppress persistent lung inflammation by inducing functional changes in macrophages, and consequently inhibit lung fibrosis during late-phase lung injury. METHODS: To test this hypothesis, lung injury was induced in mice by intratracheal administration of bleomycin (1.0 mg/kg). Mice were exposed to control gas (air) or hydrogen (3.2% in air) for 6 h every day for 7 or 21 days. Respiratory physiology, tissue pathology, markers of inflammation, and macrophage phenotypes were examined. RESULTS: Mice with bleomycin-induced lung injury that received daily hydrogen therapy for 21 days (BH group) exhibited higher static compliance (0.056 mL/cmH2O, 95% CI 0.047-0.064) than mice with bleomycin-induced lung injury exposed only to air (BA group; 0.042 mL/cmH2O, 95% CI 0.031-0.053, p = 0.02) and lower static elastance (BH 18.8 cmH2O/mL, [95% CI 15.4-22.2] vs. BA 26.7 cmH2O/mL [95% CI 19.6-33.8], p = 0.02). When the mRNA levels of pro-inflammatory cytokines were examined 7 days after bleomycin administration, interleukin (IL)-6, IL-4 and IL-13 were significantly lower in the BH group than in the BA group. There were significantly fewer M2-biased macrophages in the alveolar interstitium of the BH group than in the BA group (3.1% [95% CI 1.6-4.5%] vs. 1.1% [95% CI 0.3-1.8%], p = 0.008). CONCLUSIONS: The results suggest that hydrogen inhalation inhibits the deterioration of respiratory physiological function and alveolar fibrosis in this model of lung injury.

Luminal preloading with hydrogen-rich saline ameliorates ischemia-reperfusion injury following intestinal transplantation in rats.

Prolonged intestinal cold storage causes considerable mucosal breakdown, which could bolster bacterial translocation and cause life-threatening infection for the transplant recipient. The intestine has an intraluminal compartment, which could be a target for intervention, but has not yet been fully investigated. Hydrogen gas exerts organ protection and has used been recently in several clinical and basic research studies on topics including intestinal transplantation. In this study, we aimed to investigate the cytoprotective efficacy of intraluminally administered hydrogen-rich saline on cold IR injury in intestinal transplantation. Isogeneic intestinal transplantation with 6 hours of cold ischemia was performed on Lewis rats. Hydrogen-rich saline (H2 concentration at 5 ppm) or normal saline was intraluminally introduced immediately before preservation. Graft intestine was excised 3 hours after reperfusion and analyzed. Histopathological analysis of control grafts revealed blunting of the villi and erosion. These mucosal changes were notably attenuated by intraluminal hydrogen. Intestinal mucosa damage caused by IR injury led to considerable deterioration of gut barrier function 3 h post-reperfusion. However, this decline in permeability was critically prevented by hydrogen treatment. IR-induced upregulation of proinflammatory cytokine mRNAs such as IL-6 was mitigated by hydrogen treatment. Western blot revealed that hydrogen treatment regulated loss of the transmembrane protein ZO-1. Hydrogen-rich saline intraluminally administered in the graft intestine modulated IR injury to transplanted intestine in rats. Successful abrogation of intestinal IR injury with a novel strategy using intraluminal hydrogen may be easily clinically applicable and will compellingly improve patient care after transplantation.

Oncologic Outcomes of Salvage Chemotherapy in Patients with Recurrent or Metastatic Lesions after Radical Nephroureterectomy: A Multi-Institutional Retrospective Study.

BACKGROUND: Radical nephroureterectomy (RNU) is the standard treatment for patients with upper tract urothelial carcinoma (UTUC). However, approximately 25% of patients experience recurrence or metastasis after RNU. This study evaluated the clinical outcome and efficacy of salvage chemotherapy (SC) after recurrence or metastasis. PATIENTS AND METHODS: Of the 441 nonmetastatic UTUC patients who underwent RNU, 147 patients with recurrent or metastatic lesions were analyzed; patients with bladder cancer recurrence were excluded. Time from disease recurrence or metastasis to cancer-specific survival (CSS) was estimated by the Kaplan-Meier method. Multivariate analyses were performed with the Cox proportional hazards regression model, controlling for the effects of clinicopathological factors. RESULTS: The median time from RNU to disease recurrence or metastasis was 13.2 months. In the recurrent or metastatic sites, 31 cases (21%) were liver. In multivariate analyses, pT stage (≥pT3), time to recurrence (<12 months), and liver metastasis were independently predictive factors. In the risk stratification model for CSS after recurrence, patients were categorized into 2 groups based on pT stage, time to recurrence, and liver metastasis. The low-risk group (0-1 risk factors) included 87 patients, and the high-risk group (2-3 risk factors) included 60 patients. In the high-risk group, 27 patients received SC. The probability of CSS after recurrence or metastasis was higher in patients in the SC group compared to the non-SC group (9.5 vs. 3.7 months; p < 0.001). CONCLUSION: Two or more risk factors defined the high-risk group for patients with recurrence or metastasis after RNU. SC was associated with improved survival in patients with high-risk UTUC.

Impact of maintenance therapy using a half dose of the bacillus Calmette-Guérin Tokyo strain on recurrence of intermediate and high-risk nonmuscle invasive bladder cancer: a retrospective single-center study.

BACKGROUND: Data are scarce regarding intravesical maintenance therapy (MT) with the low-dose bacillus Calmette-Guérin (BCG) Tokyo strain. We investigated the efficacy and safety of MT with a half dose of the Tokyo strain for patients following transurethral resection of nonmuscle invasive bladder cancer (NMIBC). METHODS: This study retrospectively reviewed clinical data on 78 patients diagnosed with intermediate or high-risk NMIBC followed by either MT (n = 38) or IT alone (n = 40) between January 2012 and March 2018. Statistical analysis was performed to compare recurrence-free survival (RFS) and adverse effects between the two groups. BCG was instilled once weekly for 6 weeks as IT, then once weekly in 2-week for a total of 20 instillations over 3 years. RESULTS: Kaplan-Meier analyses showed that patients undergoing MT had significantly better RFS than did those undergoing IT alone (hazard ratio (HR):0.32, 95% confidence interval (CI):0.12-0.89, P = 0.02). The 3-year RFS was 65.0% in the IT group and 89.5% in the MT group. Multivariate analysis showed that MT was associated with a reduced risk of recurrence (HR: 0.32, 95% CI:0.11-0.93, P = 0.03). One MT patient (2.6%) exhibited progression. CONCLUSIONS: The BCG Tokyo strain showed acceptable efficacy and safety in patients undergoing MT; thus, it is a potential treatment for preventing bladder cancer recurrence.

Prognostic impact of preoperative renal function in patients treated with radical cystectomy: a multi-institutional retrospective study.

BACKGROUND: Little data on the preoperative prognostic factors in radical cystectomy (RC) patients have made it difficult to choose the appropriate type of urothelial diversion (UD). This study aimed to investigate the prognostic role of UD, with a subgroup analysis of that of preoperative renal function. METHODS: From 1990 to 2015, 279 patients underwent RC for bladder cancer at six hospitals affiliated with Kitasato University in Japan. All patients were divided into three groups: cutaneous ureterostomy (CU; n = 54), ileal conduit (IC; n = 139), and orthotopic neobladder (NB; n = 86). Patients were also stratified into three groups based on preoperative estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2): normal eGFR (> 60 mL/min/1.73 m2; n = 149), moderately reduced eGFR (45-60 mL/min/1.73 m2; n = 66), and severely reduced eGFR (< 45 mL/min/1.73 m2; n = 37). Statistical analyses were performed to investigate prognostic values of UD and preoperative eGFR. RESULTS: Kaplan-Meier analyses showed that progression-free survival (PFS) and cancer-specific survival (CSS) did not differ between the three types of UD groups. With regard to renal function, the preoperative severely reduced group had significantly worse PFS and CSS than the other groups. The multivariate analysis showed that severely reduced preoperative eGFR was an independent risk factor of worse PFS and worse CSS. CONCLUSION: The present study demonstrated that preoperative severe renal function was shown as an independent risk factor of both PFS and CSS.

Histologic variants associated with biological aggressiveness and poor prognosis in patients treated with radical cystectomy.

BACKGROUND: The prognostic value of histologic variants (HV) after radical cystectomy (RC) remains controversial. We evaluated the clinicopathological features and prognosis in patients with pure urothelial carcinoma (UC) and HV following RC. METHODS: From 1990 to 2015, 286 patients with bladder cancer were treated with RC at six Kitasato University-affiliated hospitals. All patients were divided into two groups: pure UC and HV, which contained pure variants and mixed-type UC with variant pattern. A comparison of patient characteristics between the two groups was made to assess the clinicopathological features, and statistical analyses were performed to investigate prognosis in the two groups. RESULTS: Of the 286 patients, 226 (79%) had pure UC, while 60 (21%) had HV. Of all HV, pure variants accounted for 45% (n = 27). The prevalence of lymph node involvement, locally advanced stage (≥ pT3), positive soft tissue surgical margin and lymphovascular invasion were significantly higher in patients with HV than in those with pure UC. Patients with HV showed worse disease-free survival and cancer-specific survival than those with pure UC (P = 0.009 and 0.003, respectively). In multivariate analysis, HV and lymph node involvement were independent predictors of worse disease-free survival (P = 0.017 and 0.001, respectively). HV, locally advanced stage, lymph node involvement, and positive soft tissue surgical margin were also confirmed as independent predictors of worse cancer-specific survival (P = 0.011, 0.012, 0.003 and 0.010, respectively.). CONCLUSIONS: HV was associated with greater biological aggressiveness and worse prognosis than pure UC.

Impact of histologic variants on the oncological outcomes of patients with upper urinary tract cancers treated with radical surgery: a multi-institutional retrospective study.

BACKGROUND: No definitive evidence exists regarding the clinical significance of histologic variants (HV) in upper urinary tract cancer. We investigated the impact of HV on prognosis in patients with upper urinary tract cancer following radical surgery. PATIENTS AND METHODS: We retrospectively analyzed 451 patients with upper urinary tract cancer who underwent radical nephroureterectomy at six affiliated hospitals from 1990 to 2015. Patients with distant metastatic disease prior to surgery and those who received neoadjuvant chemotherapy were excluded, leaving 441 eligible patients. Patients were classified into two groups: pure urothelial carcinoma (UC) and HV. The clinicopathological variables of each group were examined using Kaplan-Meier plots and proportional Cox hazard ratios (HR) to compare the oncological outcomes between the two groups. RESULTS: HV included 37 patients (8%). Compared with the pure UC patients, HV patients had significantly worse recurrence-free survival (RFS) and cancer-specific survival (CSS; RFS p = 0.0002, CSS p = 0.0001). Multivariate analysis for RFS revealed HV were independent predictors (HR 1.92; p = 0.026), but the association did not remain significant for CSS. There was no significant difference in CSS between the adjuvant chemotherapy (AC) group and the non-AC group for all HV patients, except in patients with ≥ pT3 tumor or positive lymph node status where the AC group had significantly favorable CSS. CONCLUSIONS: HV in upper urinary tract cancer are independent predictors for RFS, but not for CSS. AC improved CSS for HV patients with ≥ pT3 tumor or positive lymph node status.

[Dermatomyositis-Like Symptoms Useful for Diagnosis of Ureteral Cancer].

We here report a case of dermatomyositis associated with ureteral cancer. A 69-year-old male presented to our hospital complaining of a rash on his whole body, which resulted in a clinical diagnosis of dermatomyositis. Right ureteral cancer was suspected on computed tomographic CT examination during the investigation for the underlying malignancy. The patient was treated with prednisolone and right nephroureterectomy with bladder cuffing for dermatomyositis and ureteral cancer, respectively. One year after surgery, the dermatomyositis worsened, and CT examination showed local recurrence and lymph node metastasis. Chemotherapy was performed, and CT examination 3 months after treatment showed that the tumor had shrunk. Skin symptoms were also ameliorated. Chemotherapy was given intermittently thereafter. The tumor then increased and skin symptoms reappeared ; 3 years after surgery the patient's general condition deteriorated, resulting in death. Ureteral cancer with dermatomyositis is rare, but dermatomyositis complicated with malignancy has a poor prognosis. Careful whole body search may be useful for early detection of malignancy.

Surgical and Patient Reported Outcomes of Artificial Urinary Sphincter Implantation: A Multicenter, Prospective, Observational Study.

PURPOSE: We performed a multicenter, prospective, observational study to assess outcomes, including changes in continence status and quality of life, after artificial urinary sphincter implantation. MATERIALS AND METHODS: Prospectively enrolled in this study were 135 patients who underwent primary AMS 800™ implantation between 2011 and 2014 at 1 of 5 institutions. Perioperative complications were categorized according to the Clavien-Dindo classification. We estimated the revision-free rate, that is the incidence of patients who did not undergo artificial urinary sphincter revision surgery. Cox regression analysis was performed to identify patient risk factors for revision surgery. The number of pads needed per day, ICIQ-SF (International Consultation on Incontinence Questionnaire-Short Form) and KHQ (King's Health Questionnaire) were used to estimate continence status and quality of life preoperatively, and 1, 3 and 12 months postoperatively. RESULTS: The artificial urinary sphincter was implanted without major complications. The revision-free rate 1, 2 and 3 years after implantation was 94%, 88% and 81%, respectively. Diabetes mellitus and poor preoperative American Society of Anesthesiologists® physical status were significant risk factors for revision surgery. Continence status and quality of life were markedly improved after surgery. However, ICIQ-SF and some KHQ items showed slight but significant deterioration at 12 months compared with scores 1 month after surgery. CONCLUSIONS: Artificial urinary sphincter implantation is a safe and durable procedure that substantially improves patient continence status and quality of life soon after surgery. Our results indicate that patients start to experience slight but noticeable deterioration in continence status and quality of life relatively early (within 1 year) after surgery. This finding might be helpful with appropriately counseling patients who undergo artificial urinary sphincter implantation.

Portal Venous Gas Following Ingestion of Hydrogen Peroxide Successfully Treated with Hyperbaric Oxygen Therapy.

The primary toxicity of hydrogen peroxide results from its interaction with catalase, which liberates water and oxygen. We report the case of a 14-year-old Japanese girl with portal venous gas that was caused by oxygen liberated from intentionally ingested hydrogen peroxide. Although she had a past history of atrial septal defect, recovery without cardiac or neurological sequelae was achieved using hyperbaric oxygen therapy. Emergency physicians must be aware of the danger of liberated oxygen due to hydrogen peroxide ingestion.

GLIPR1-ΔTM synergizes with docetaxel in cell death and suppresses resistance to docetaxel in prostate cancer cells.

BACKGROUND: Docetaxel is the first chemotherapy agent approved for treatment of metastatic castration-resistant prostate cancer (mCRPC). The limited survival benefit associated with the quick emergence of resistance and systemic toxicity diminished its efficacy. JNK-mediated apoptosis is one of the mechanisms of docetaxel activity whereas ERK1/2-c-Myc-CXCR4 signaling is implicated in the development of resistance and induction of migration. The aim of this study was to evaluate the hypothesis that the combination treatment with docetaxel and GLIPR1-ΔTM will synergistically induce greater cell death and inhibit the emergence of resistance and development of metastatic potential in prostate cancer (PCa) cells. METHODS: The synergistic effects of the docetaxel and GLIPR1-ΔTM were evaluated with DNA fragmentation, DAPI staining and MTS using paired t-test and isobologram study. The effects of the drugs on JNK and ERK1/2-c-Myc-CXCR4 signaling were evaluated with Western blot, DNA fragmentation, and MTS assays using the JNK inhibitor SP600125, and CXCR4 siRNA. The results of docetaxel and GLIPR1-ΔTM combination on migration were examined with scratch assay using the CXCR4 inhibitor AMD3100 while our hypothesis was examined in vivo using VCaP orthotopic xenograft model. RESULTS: We found that GLIPR1-ΔΤΜ synergized with docetaxel to induce apoptosis in VCaP and PC-3 PCa cells through induction of JNK signaling and concomitant inhibition of ERK1/2-c-Myc-CXCR4 signaling. We showed that JNK activation mediates the apoptotic effects of the drug combination and that CXCR4 knockdown increases its efficacy. We also found that the addition of GLIPR1-ΔΤΜ to docetaxel decreases the migration of VCaP and PC-3 cells. The combination treatment with docetaxel and GLIPR1-ΔTM inhibited tumor growth and decreased metastatic potential in VCaP xenografts more than single agents did. CONCLUSIONS: Our data suggested that addition of GLIPR1-ΔTM treatment in PCa cells increases the efficacy of docetaxel and may inhibit the emergence of drug resistance; potentially permitting a decrease of docetaxel dose for patients with mCRPC eliminating its systemic toxicities.

[A Case of Holmium: YAG Laser Resection of Superficial Bladder Tumor (HoLRBT)].

We present a case of holmium : YAG laser resection of superficial bladder tumor (HoLRBT). A 73-year-old male was referred to our hospital with elevated prostatic specific antigen. Due to difficulty of urination, holmium : YAG laser enucleation of the prostate was performed under the diagnosis of benign prostatic hyperplasia. During the surgery, superficial bladder tumor was incidentally identified, and HoLRBT was performed. After the operation, histopathological examination revealed urothelial carcinoma, G2 ＞ G1, pTa. The patient has been subsequently followed up for 9 months, and there areno evidence of recurrence. Changing the holmium : YAG laser energy setting can potentially be effective and safe to approach a superficial bladder tumor.

Systemic GLIPR1-ΔTM protein as a novel therapeutic approach for prostate cancer.

GLIPR1 is a p53 target gene known to be downregulated in prostate cancer, and increased endogenous GLIPR1 expression has been associated with increased production of reactive oxygen species, increased apoptosis, decreased c-Myc protein levels and increased cell cycle arrest. Recently, we found that upregulation of GLIPR1 in prostate cancer cells increases mitotic catastrophe through interaction with heat shock cognate protein 70 (Hsc70) and downregulation of Aurora kinase A and TPX2. In this study, we evaluated the mechanisms of recombinant GLIPR1 protein (glioma pathogenesis-related protein 1-transmembrane domain deleted [GLIPR1-ΔTM]) uptake by prostate cancer cells and the efficacy of systemic GLIPR1-ΔTM administration in a prostate cancer xenograft mouse model. GLIPR1-ΔTM was selectively internalized by prostate cancer cells, leading to increased apoptosis through reactive oxygen species production and to decreased c-Myc protein levels. Interestingly, GLIPR1-ΔTM was internalized through clathrin-mediated endocytosis in association with Hsc70. Systemic administration of GLIPR1-ΔTM significantly inhibited VCaP xenograft growth. GLIPR1-ΔTM showed no evidence of toxicity following elimination from mouse models 8 hr after injection. Our results demonstrate that GLIPR1-ΔTM is selectively endocytosed by prostate cancer cells, leading to increased reactive oxygen species production and apoptosis, and that systemic GLIPR1-ΔTM significantly inhibits growth of VCaP xenografts without substantial toxicity.

Mean lung pressure during adult high-frequency oscillatory ventilation: an experimental study using a lung model.

In adult high-frequency oscillatory ventilation (HFOV), stroke volume (SV) and mean lung pressure (PLung) are important for lung protection. We measured the airway pressure at the Y-piece and the lung pressure during HFOV using a lung model and HFOV ventilators for adults (R100 and 3100B). The lung model was made of a 20-liter, airtight rigid plastic container (adiabatic compliance: 19.3 ml/cmH2O) with or without a resistor (20 cmH2O/l/sec). The ventilator settings were as follows: mean airway pressure (MAP), 30 cmH2O; frequency, 5-15 Hz (every 1 Hz); airway pressure amplitude (AMP), maximum;and % of inspiratory time (IT), 50% for R100, 33% or 50% for 3100B. The measurements were also performed with an AMP of 2/3 or 1/3 maximum at 5, 10 and 15 Hz. The PLung and the measured MAP were not consistently identical to the setting MAP in either ventilator, and decreasing IT decreased the PLung in 3100B. In conclusion, we must pay attention to the possible discrepancy between the PLung and the setting MAP during adult HFOV.