Clinical Course of Residual Ventricular Septal Defects After Congenital Heart Disease Repair.

The clinical course of residual ventricular septal defects after congenital heart disease repair is not completely elucidated in the medical literature. This study assessed the incidence, size, and clinical course of residual defects.This single-center retrospective study included 132 patients who survived after ventricular septal defect patch closure (n = 107) and intracardiac repair of double-outlet right ventricle (n = 16) and tetralogy of Fallot (n = 9). Residual defect was evaluated on transthoracic echocardiogram upon hospital discharge and at outpatient clinic visits.The median age at surgery was 1.2 (0.3-13.9) years. In total, 45 (34.1%) patients presented with residual defects upon hospital discharge. The residual defects were within 2 mm (n = 27), 2-3 mm (n = 15), and > 3 mm (n = 3), and the median size was 1.5 (0.5-3.8) mm. There was no late mortality during a median follow-up of 5.4 years. Among 42 residual defects measuring < 3 mm upon hospital discharge, 37 (82.2%) spontaneously closed. Further, five defects decreased in size (1.8 ± 0.6 mm upon hospital discharge vs1.2 ± 0.8 mm at the latest visits, p = 0.15). However, the size of three residual defects measuring > 3 mm upon hospital discharge increased, and two patients required re-surgery for residual defect.Significant residual defect requiring reoperation was rare. In most cases, residual defects measuring < 3 mm upon hospital discharge spontaneously closed within 5 years, and the size of the other defects decreased.

Efficacy of 18F-Fluorodeoxyglucose positron emission tomography/computed tomography for detecting renal cell carcinoma in patients with end-stage renal disease.

PURPOSE: Dialysis patients are at an increased risk of developing renal cell carcinoma (RCC); however, differentiating between RCC and benign cysts can sometimes be difficult using modalities, such as computed tomography (CT) and ultrasonography. 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET)/CT efficiently detects malignant tumors; however, physiological accumulation of FDG in the kidney limits its efficacy in detecting renal tumors. However, in patients with severely impaired renal function, the renal accumulation of FDG is decreased, possibly improving the detection of renal malignancies in this patient population. This study evaluated the usefulness of FDG-PET/CT as a screening tool for detecting RCC in patients with end-stage renal disease. MATERIALS AND METHODS: This prospective study recruited 150 participants from 2012 to 2016 who were on dialysis or underwent renal transplantation and were on dialysis until transplantation. FDG-PET/CT was performed to screen for RCC. Three radiologists independently evaluated the images. No protocol was defined for the additional management of positive examinations, leaving decisions to the discretion of each participant. Negative examinations were observed until the end of 2019. RESULTS: In total, 150 participants (mean age, 58 ± 13 years; 105 men) underwent FDG-PET/CT. Twenty patients (13.4%) were diagnosed as positive. Fifteen patients underwent additional examinations and/or procedures, and RCC was found in seven patients. Of the four patients who underwent surgical resection, the pathological results were clear cell RCC in one, papillary RCC in one, and acquired cystic disease-associated RCC in two. Two participants were diagnosed with RCC on bone biopsy, and one was diagnosed on dynamic CT but opted for observation. The sensitivity, specificity, and negative predictive value were 100%, 93.9%, and 100%, respectively. CONCLUSION: FDG-PET/CT was useful for detecting RCC in patients with end-stage renal disease. Our findings show the potential use of FDG-PET/CT as a screening tool for RCC in this patient population.

Carbon Ion Radiation Therapy for Nonmetastatic Castration-Resistant Prostate Cancer: A Retrospective Analysis.

Purpose: Treatment outcomes of definitive photon radiation therapy for nonmetastatic castration-resistant prostate cancer (nmCRPC) are reportedly unsatisfactory. Carbon ion radiation therapy (CIRT) has shown favorable tumor control in various malignancies, including radioresistant tumors. Therefore, we retrospectively evaluated the clinical outcomes of CIRT for nmCRPC. Methods and Materials: Patients with nmCRPC (N0M0) treated with CIRT at a total dose of 57.6 Gy (relative biologic effectiveness) in 16 fractions or 51.6 Gy (relative biologic effectiveness) in 12 fractions were included. The castration-resistant status received a diagnosis based on prostate-specific antigen kinetics showing a monotonic increase during primary androgen deprivation therapy or the need to change androgen deprivation therapy. Clinical factors associated with patient prognosis were explored. Twenty-three consecutive patients were identified from our database. The median follow-up period was 63.6 months (range, 14.1-120). Results: Seven patients developed biochemical relapse, 6 had clinical relapse, and 4 died of the disease. The 5-year overall survival, local control rate, biochemical relapse-free survival, and clinical relapse-free survival were 87.5%, 95.7%, 70.3%, and 75.7%, respectively. One patient with diabetes mellitus requiring insulin injections and taking antiplatelet and anticoagulant drugs developed grade 3 hematuria and bladder tamponade after CIRT. None of the patients developed grade 4 or worse toxicity. Conclusions: The present findings indicate the acceptable safety and favorable efficacy of CIRT, encouraging further research on CIRT for nmCRPC.

Chemoattractant receptor signaling in humoral immunity.

Efficient induction of humoral immune responses depends on orchestrated migration of B cells within lymphoid organs, which is governed by G protein-coupled receptors (GPCRs) responding to chemoattractants, represented by chemokines. After ligand binding, GPCRs are phosphorylated by different GPCR kinases (GRKs) at distinct sites on the receptor C termini, which dictates functional outcomes of ß-arrestin-mediated signaling, ranging from receptor inactivation to effector molecule activation. However, the molecular mechanisms by which individual GRKs are selectively targeted to GPCRs have been poorly understood. Our recent study revealed that a protein complex consisting of copper metabolism MURR1 domain-containing (COMMD) 3 and 8 (COMMD3/8 complex) functions as an adaptor that recruits a specific GRK to chemoattractant receptors and plays an important role in the control of B cell migration during humoral immune responses. In this review, we summarize the current understanding of chemoattractant receptor signaling in the context of humoral immunity and discuss the potential of the COMMD3/8 complex as a therapeutic target for autoimmune diseases.

Association of homocysteine with white matter dysconnectivity in schizophrenia.

Several studies have shown white matter (WM) dysconnectivity in people with schizophrenia (SZ). However, the underlying mechanism remains unclear. We investigated the relationship between plasma homocysteine (Hcy) levels and WM microstructure in people with SZ using diffusion tensor imaging (DTI). Fifty-three people with SZ and 83 healthy controls (HC) were included in this retrospective observational study. Tract-Based Spatial Statistics (TBSS) were used to evaluate group differences in WM microstructure. A significant negative correlation between plasma Hcy levels and WM microstructural disruption was noted in the SZ group (Spearman's ρ = -.330, P = 0.016) but not in the HC group (Spearman's ρ = .041, P = 0.712). These results suggest that increased Hcy may be associated with WM dysconnectivity in SZ, and the interaction between Hcy and WM dysconnectivity could be a potential mechanism of the pathophysiology of SZ. Further, longitudinal studies are required to investigate whether high Hcy levels subsequently cause WM microstructural disruption in people with SZ.

Non-destructive visualization of internal structural changes in humidified magnesium oxide tablets using X-ray computed tomography.

Detailed examinations of the internal structure of tablets are imperative for comprehending their formulation, physical attributes, and ensuring their safe utilization. While X-ray computed tomography (CT) is valuable for noninvasively analyzing internal structural changes, the influence of humidity on these structural changes remains unexplored. Accordingly, we aimed to assess the viability of X-ray CT in non-destructively evaluating the internal structure of humidified magnesium oxide (MgO) tablets. MgO tablets were subjected to conditions of 40 °C and 75% humidity for 7 days, weighed pre- and post-humidification, and subsequently stored at room temperature (22-27 °C) until day 90. Their internal structure was evaluated using X-ray CT. We observed a substantial increase in the weight of MgO tablets concomitant with moisture absorption, with minimal changes observed upon storage at room temperature. The skewness reduced immediately post-moisture absorption, remained almost the same post-storage at room temperature, and failed to revert to pre-humidification levels during the storage period. These findings highlight the utility of X-ray CT as an effective tool for non-destructive, three-dimensional, and detailed evaluation of internal structural transformations in MgO tablets.

Comparison of sexual function after robot-assisted radical prostatectomy and carbon-ion radiotherapy for Japanese prostate cancer patients using propensity score matching.

BACKGROUND: The quality of life of patients is an important consideration when selecting treatments for localized prostate cancer (PCa). We retrospectively compared sexual function after robot-assisted radical prostatectomy (RARP) and carbon-ion radiotherapy (CIRT) using propensity score matching. METHODS: In total, 127 Japanese PCa patients treated with RARP and 190 treated with CIRT monotherapy were evaluated. We evaluated the Expanded Prostate Cancer Index Composite (EPIC) score before treatment and 12 and 24 months after treatment. After propensity score matching, data from 101 patients from each group were analyzed. The study protocol was approved by the Institutional Review Board of Gunma University Hospital (no. IRB2020-050, 1839). RESULTS: After propensity score matching, the mean EPIC sexual function summary scores in the RARP and CIRT groups were 46.4 and 48.2, respectively. At 12 and 24 months after treatment, these scores were 27.9 (39.9% decrease) and 28.2 (39.2% decrease) in the RARP group and 41.4 (14.1% decrease) and 41.6 (13.7% decrease) in the CIRT group, respectively. Both groups demonstrated significantly decreased scores after 12 and 24 months of treatment compared to before treatment (all p < 0.05). At 12 and 24 months, the sexual function summary score was significantly higher in the CIRT group than in the RARP group (p < 0.001). CONCLUSIONS: There was a smaller decrease in the EPIC sexual function score in the CIRT group than in the RARP group. These results provide useful information for treatment decision-making of Japanese PCa patients.

A large iliopsoas abscess due to colon cancer complicated by bowel obstruction: A case report.

INTRODUCTION: Iliopsoas abscesses (IPAs) associated with bowel obstruction due to colon cancer are rare, and there is no consensus regarding treatment strategies. PRESENTATION OF CASE: A 63-year-old man presented with swelling and pain in the right iliac region. Imaging studies revealed an IPA expanding from the psoas major muscle and retroperitoneal space subcutaneously around the right ilium. After percutaneous drainage, the patient developed bowel obstruction secondary to colon cancer. Hemicolectomy and preventive ileostomy were performed at the gastrointestinal surgery department, and chemotherapy was administered at the medical oncology department after ileostomy closure. Three months later, local recurrence was confirmed in the right iliac region, and the recurrent lesion, including the ilium, was widely resected. One and a half years after the reoperation, there was no recurrence. DISCUSSION: An IPA due to colorectal cancer without obvious perforation can also occur, and the treatment of IPAs depends on their size, location, shape, and presence of gas. Minimally invasive and staged treatment is preferable for IPAs due to colorectal cancer because the surgical mortality rate for colorectal cancer with local abscesses is high. CONCLUSION: Colorectal cancer should be considered as a cause of IPAs. Treatment of IPAs caused by colon cancer should be performed in a less invasive manner after considering their size, location, shape, and the presence of gas. Cooperation between gastrointestinal surgeons and oncologists is essential for managing patients with an IPA due to colon cancer complicated by bowel obstruction.

L-type amino acid transporter 1 inhibitor JPH203 prevents the growth of cabazitaxel-resistant prostate cancer by inhibiting cyclin-dependent kinase activity.

L-type amino acid transporter 1 (LAT1, SLC7A5) is an amino acid transporter expressed in various carcinomas, and it is postulated to play an important role in the proliferation of cancer cells through the uptake of essential amino acids. Cabazitaxel is a widely used anticancer drug for treating castration-resistant prostate cancer (CRPC); however, its effectiveness is lost when cancer cells acquire drug resistance. In this study, we investigated the expression of LAT1 and the effects of a LAT1-specific inhibitor, JPH203, in cabazitaxel-resistant prostate cancer cells. LAT1 was more highly expressed in the cabazitaxel-resistant strains than in the normal strains. Administration of JPH203 inhibited the growth, migration, and invasive ability of cabazitaxel-resistant strains in vitro. Phosphoproteomics using liquid chromatography-mass spectrometry to comprehensively investigate changes in phosphorylation due to JPH203 administration revealed that cell cycle-related pathways were affected by JPH203, and that JPH203 significantly reduced the kinase activity of cyclin-dependent kinases 1 and 2. Moreover, JPH203 inhibited the proliferation of cabazitaxel-resistant cells in vivo. Taken together, the present study results suggest that LAT1 might be a valuable therapeutic target in cabazitaxel-resistant prostate cancer.

Baseline characteristics may impact treatment duration of cabazitaxel in patients with mCRPC: a subanalysis of data from a post-marketing surveillance.

OBJECTIVE: Cabazitaxel has demonstrated improvements in overall survival among patients with metastatic castration-resistant prostate cancer (mCRPC) in the pivotal comparison clinical trials TROPIC, PROSELICA and CARD. However, these trials include mCRPC patients with similar characteristics, and there are limited data on how baseline characteristics affect treatment discontinuation in the patient population. METHODS: To assess individual factors that may impact the discontinuation rate of cabazitaxel treatment, we conducted a post hoc analysis of data from a nationwide all-case, post-marketing surveillance of cabazitaxel in Japan. Patients were grouped according to the number of cabazitaxel treatment cycles received (1-2 and ≥3 cycles). Predictive factors were identified through multivariate logistic regression analysis. RESULTS: Across 660 patients with metastatic castration-resistant prostate cancer, 70.2% received ≥3 cycles of cabazitaxel treatment. Those receiving 1-2 cycles of cabazitaxel had a greater proportion of patients with poorer Eastern Cooperative Oncology Group Performance Status, presence of lung and liver metastases, higher prostate-specific antigen level and prior radiation therapy at baseline. Regardless of the number of cabazitaxel cycles received, the primary reason for discontinuation was progression of disease rather than adverse events. Compared with those receiving 1-2 cycles, a lower proportion of patients receiving 3-10 and ≥11 cycles of cabazitaxel treatment experienced adverse events. Multivariate analysis showed a significant association between early discontinuation and presence of liver lesions, poorer Eastern Cooperative Oncology Group Performance Status and higher prostate-specific antigen level at baseline. CONCLUSIONS: Post-marketing surveillance data suggest physicians should individualize cabazitaxel treatment based on certain patient characteristics at baseline.

Simvastatin Enhances the Radiosensitivity of Androgen-independent Prostate Cancer Cells via Inhibition of RAD51 Expression.

BACKGROUND/AIM: Statins exert antitumor effects via various mechanisms. Additionally, the recurrence rate of prostate cancer after radiation therapy is lower in patients taking statins. This study investigated the efficacy of combination therapy with statins and irradiation in androgen-independent prostate cancer cells. MATERIALS AND METHODS: PC-3 and LNCaP human prostate cancer cell lines were used in this study. We developed androgen-independent LNCaP cells (LNCaP-LA) by gradually replacing fetal bovine serum (FBS) with charcoal-stripped FBS. Microarray analysis was performed, followed by Ingenuity Pathway Analysis. Cell viability was determined using the MTS assay. RESULTS: Simvastatin alters gene expressions in PC-3 cells. Microarray data showed that the number of differentially expressed genes was the highest in the pathway of "Role of BRCA1 in DNA Damage Response". In the validation, the expression of RAD51, listed in "Role of BRCA1 in DNA Damage Response", decreased significantly by simvastatin in PC-3 cells. Reduction in RAD51 expression following siRNA transfection increased the cytocidal effects of X-ray therapy in PC-3 and LNCaP-LA cells. The combination of simvastatin and irradiation further inhibited cell proliferation compared with monotherapy with either therapy in PC-3 or LNCaP-LA cells. In addition, compared with X-ray monotherapy, the combination of simvastatin and irradiation further enhanced the expression of γH2AX, which is reported to be one of the accurate markers of DNA damage in PC-3 cells. CONCLUSION: Simvastatin decreased the expression of RAD51 in androgen-independent prostate cancer cells. The combination of irradiation and drugs that reduce RAD51 expression can potentially affect androgen-independent prostate cancer growth.

Successful embolization of subcutaneous mesenteric varices within an ileal conduit in a patient with liver cirrhosis.

Introduction: Venous hemorrhage from ectopic varices is potentially fatal. This report describes a rare case in which bleeding from mesenteric varices in an ileal conduit was treated successfully by embolization therapy. Case presentation: The patient was an 82-year-old man who had previously undergone total pelvic exenteration for colon cancer with creation of an ileal conduit for urinary diversion. He subsequently developed liver cirrhosis and underwent partial hepatectomy for hepatocellular carcinoma. 9 years after his colon surgery, he was admitted with gross hematuria. Computed tomography revealed subcutaneous mesenteric varices in the ileal conduit and hemorrhage as a result of rupture of the varices. The bleeding continued despite repeated manual compression but was eventually stopped by embolization therapy. Conclusion: Embolization therapy may be helpful for hemostasis in the event of intractable bleeding from mesenteric varices in an ileal conduit.

Simvastatin Induces Autophagy and Inhibits Proliferation in Prostate Cancer Cells.

BACKGROUND/AIM: Statin has recently been studied for its effects on inducing cell death and inhibiting metastasis. Nevertheless, the precise mechanism of its anti-tumor effect is not yet fully understood. We conducted research on statin as a novel treatment for castration-resistant prostate cancer (CRPC). This study focused on autophagy in prostate cancer cells and assessed the effects of simvastatin. MATERIALS AND METHODS: After administering simvastatin to PC-3 cells, we conducted a microarray analysis. Simvastatin was administered to prostate cancer cell lines (PC-3, LNCaP-LA; cultured under androgen-depleted conditions, DU145, 22RV1), and the tumor proliferation inhibition was evaluated using the MTS assay and cell count. Autophagy was measured by observing autophagosome staining under a fluorescence microscope and quantifying LC-3 protein using western blot. We also investigated the effects of rapamycin, an autophagy inducer, and chloroquine as an inhibitor. RESULTS: Simvastatin demonstrated a significant concentration-dependent growth inhibition effect on prostate cell lines. Moreover, a significant increase in autophagy was observed in all cell lines following simvastatin administration. When we administered simvastatin with rapamycin at a concentration that did not show a tumor growth inhibitory effect, it significantly enhanced autophagy induction compared to simvastatin alone, and also significantly enhanced the growth inhibition effect on PC-3 cells. CONCLUSION: Simvastatin induced autophagy and inhibited the proliferation of prostate cancer cell lines. The combination of simvastatin and rapamycin significantly induced autophagy and enhanced the inhibitory effect of simvastatin on proliferation. This mechanism may serve as a novel therapeutic target.

Association between Children's Difficulties, Parent-Child Sleep, Parental Control, and Children's Screen Time: A Cross-Sectional Study in Japan.

Children's screen time may affect their growth and development. However, differences in the impact of various psychiatric and psychological factors on children's screen time is a research gap. This study aimed to explore the differences in the influence of related factors affecting children's screen time based on their sleep, difficulties, and parental control among Japanese elementary and junior high school students. A cross-sectional survey was conducted among parents in Japan. Data on screen time duration, parent-child background, strengths and difficulties, sleep variables, and parental control types were collected from 225 households. A regression analysis revealed that high Strengths and Difficulties Questionnaire (SDQ) scores (ß = 0.166, p = 0.008), sleep duration (ß = -0.281, p < 0.001), and parental control (ß = -0.204, p = 0.001) were significantly related to children's screen time. Additionally, it was found that parents' late bedtimes affect children's screen time by mediating children's sleep duration. This study, together with previous research, provides comprehensive insights into design interventions to decrease the screen time of children in the Japanese context.

Predictive models of long-term survival outcomes following radical cystectomy.

BACKGROUND: Identifying the likelihood of life-threatening recurrence after radical cystectomy by reliable and user-friendly predictive models remains an unmet need in the clinical management of invasive bladder cancer. METHODS: A total of 204 consecutive patients undergoing open radical cystectomy (ORC) for bladder cancer were retrospectively enrolled between May 2005 and August 2020. Clinicopathological and peri-ORC therapeutic data were extracted from clinical records. We explored predictive factors that significantly affected the primary endpoint of overall survival (OS) and secondary endpoints of cancer-specific survival (CSS) and recurrence-free survival (RFS). RESULTS: During a median follow-up of 3.9 years, 42 (20.6%) and 10 (4.9%) patients died due to bladder cancer and other causes, respectively. Five-year RFS, CSS, and OS were 66.5%, 77.6%, and 75.4%, respectively. Pathological T and N categories and lymphovascular invasion (LVI) significantly affected RFS by Cox regression analysis. Accordingly, clinical T and pathological N categories and LVI significantly affected CSS. Clinical T and pathological N categories, LVI, age, and ORC tumor grade significantly affected OS. Based on the assessment score for each independent risk factor, we developed the Gunma University Oncology Study Group (GUOSG) score, which predicts RFS, CSS, and OS. The GUOSG score classified four groups for RFS, three for CSS, and five for OS, with statistically significant distribution for nearly all comparisons. CONCLUSIONS: The GUOSG model is helpful to show individualized prognosis and functions as a risk-stratified historical cohort for assessing the lifelong efficacy of new salvage treatment regimens.

Small Extracellular Vesicles from adipose-derived stem cells suppress cell proliferation by delivering the let-7 family of microRNAs in ovarian cancer.

INTRODUCTION: Ovarian cancer is the leading cause of death among women with gynecological cancer, and novel treatment options are urgently needed. Extracellular vesicles (EVs), including exosomes, may be one of the most promising therapeutic tools for various diseases. In this study, we aimed to investigate the therapeutic effects of adipose-derived stem cell-derived EVs (ADSC-EVs) on ovarian cancer cell lines. MATERIALS AND METHODS: ADSCs and the ovarian cancer cell lines SKOV3 and OV90 were used for analysis. ADSC-EVs were isolated through ultracentrifugation and validated using a cryotransmission electron microscope, nanoparticle tracking analysis, and western blotting. Then, the effect of ADSC-EVs on ovarian cancer cells was investigated using IncuCyte and microRNA sequencing. Moreover, the potential functions of miRNAs were evaluated by gain-of function analysis and in silico analysis. RESULTS: ADSC-EVs suppressed SKOV3 and OV90 cell proliferation. In particular, small EVs (sEVs) from ADSCs exhibited a stronger antitumor effect than ADSC-medium/large EVs (m/lEVs). Comparison of the miRNA profiles between ADSC-sEVs and ADSC-m/lEVs, along with downstream pathway analysis, suggested the involvement of the let-7 family. Overexpression of hsa-let-7b-5p and hsa-let-7e-5p significantly suppressed the proliferation of SKOV3 cells. In silico analysis revealed that four potential target genes of hsa-let-7b-5p and hsa-let-7e-5p were significantly associated with the prognoses of the patients. CONCLUSION: ADSC-sEVs had a stronger antitumor effect than ADSC-m/lEVs. Hsa-let-7b-5p and hsa-let-7e-5p, which are highly abundant in ADSC-sEVs, suppressed cell proliferation. These findings may open up new possibilities for therapeutic approaches using ADSC-sEVs.

Glucuronic acid is a novel source of pentosidine, associated with schizophrenia.

Pentosidine (PEN) is an advanced glycation end-product (AGEs), where a fluorescent cross-link is formed between lysine and arginine residues in proteins. Accumulation of PEN is associated with aging and various diseases. We previously reported that a subpopulation of patients with schizophrenia showed PEN accumulation in the blood, having severe clinical features. PEN is thought to be produced from glucose, fructose, pentoses, or ascorbate. However, patients with schizophrenia with high PEN levels present no elevation of these precursors of PEN in their blood. Therefore, the molecular mechanisms underlying PEN accumulation and the molecular pathogenesis of schizophrenia associated with PEN accumulation remain unclear. Here, we identified glucuronic acid (GlcA) as a novel precursor of PEN from the plasma of subjects with high PEN levels. We demonstrated that PEN can be generated from GlcA, both in vitro and in vivo. Furthermore, we found that GlcA was associated with the diagnosis of schizophrenia. Among patients with high PEN, the proportion of those who also have high GlcA is 25.6%. We also showed that Aldo-keto reductase (AKR) activity to degrade GlcA was decreased in patients with schizophrenia, and its activity was negatively correlated with GlcA levels in the plasma. This is the first report to show that PEN is generated from GlcA. In the future, this finding will contribute to understanding the molecular pathogenesis of not only schizophrenia but also other diseases with PEN accumulation.

A case series title: femoral nerve injury with an episode of motor neuropathy caused by gynecological surgery: a case series.

Background: Although iatrogenic nerve injury is sometimes diagnosed after gynecological surgery, its incidence is underestimated because most cases are self-limiting and underreported. Herein, we report on six cases of femoral nerve injury after gynecological surgery with both sensory and motor neuropathy. Methods: We retrospectively analyzed 785 patients with gynecological cancer requiring surgery, including lymph node dissection, between 2012 and 2016 at our center. The functional damage due to femoral nerve injury was postoperatively assessed and classified according to the Medical Research Council (MRC) scale by an orthopedist and a physiatrist. The eligibility criteria were grade 3 or less hip joint bending and muscular weakness due to nerve injury. Patients were excluded if they had been diagnosed with an isolated sensory disorder. Results: We found six cases (0.76%) of femoral motor neuropathy resulting from gynecological surgery. All six patients underwent laparotomy using energy devices under general anesthesia with epidural anesthesia in the lithotomy position. Four of them recovered fully within 8 months from surgery with either physical therapy or no treatment, while the other two died within a year post-treatment; thus, recovery evaluation could not be accurately performed. Conclusion: Postoperative femoral nerve injury can be diagnosed based on gait disturbances and difficulties climbing stairs. It is difficult to identify risk factors for femoral nerve injury as they may involve a combination of features, such as intraoperative compression with self-retaining retractors, the lithotomy position, and the use of energy devices. The surgeon should be familiar with the nature of energy devices, make every effort to understand the necessary anatomy, and make every effort to avoid femoral nerve injury. Iatrogenic femoral nerve injury caused by gynecological surgery should be further investigated regarding the patients' quality of life postoperatively.

Blood Concentration of Cabazitaxel in a Patient Whose General Condition Worsened with Concomitant Use of Clarithromycin.

We encountered a case in which the general condition of a patient receiving cabazitaxel worsened with concomitant use of clarithromycin. Cabazitaxel is metabolized mainly by CYP3A4, and the frequency of adverse events is known to increase with increasing exposure. Although these drugs are not often quantified in daily practice, we quantified them because we considered it possible that the blood concentration of cabazitaxel had increased due to CYP3A4 inhibition of clarithromycin and that cabazitaxel-related adverse events had occurred. However, the concentration of cabazitaxel was not increased and we attributed the patient's deterioration to decreased tolerability of cabazitaxel. At least at a trough concentration of 70 ng/mL, which is the trough concentration when a normal dose of clarithromycin is administered, clarithromycin does not appear to have a significant effect on the blood concentration of cabazitaxel. This case suggests that the administration of the normal dose of clarithromycin might be relatively safe in patients receiving cabazitaxel.

Orexin receptor antagonists versus antipsychotics for the management of delirium in intensive care unit patients with cardiovascular disease: A retrospective observational study.

OBJECTIVE: Although antipsychotics are often used in the pharmacological treatment of delirium, recent reports suggest the efficacy of orexin receptor antagonists. This study investigated whether orexin receptor antagonists could be a possible treatment option for delirium. METHOD: A nonblinded nonrandomized routine clinical treatment was performed. Patients treated in intensive care units (ICU) for cardiovascular disease and receiving psychiatric intervention were studied retrospectively. The scores from the Intensive Care Delirium Screening Checklist (ICDSC) were compared between patients treated with orexin receptor antagonists and those treated with antipsychotics. RESULTS: The mean (standard deviation) ICDSC scores were 4.5 (1.8) at day -1 and 2.6 (2.6) at day 7 for orexin receptor antagonist group (n = 25) and 4.6 (2.4) at day -1 and 4.1 (2.2) at day 7 for antipsychotic group (n = 28). The orexin receptor antagonist group showed significantly lower ICDSC scores than the antipsychotic group (p = 0.021). CONCLUSION: While precise efficacy cannot be determined from our retrospective, observational, and uncontrolled pilot study, this analysis encourages a future double-blind randomized placebo-controlled trial of orexin-antagonists for delirium treatment.