Laparoscopic Sacrohysteropexy for Pelvic Organ Prolapse and the Technique Used for Uterine Preservation: A Case Report.

Pelvic organ prolapse (POP) is prevalent among middle-aged and older women, and its prevalence is expected to increase in Japan in the future. Laparoscopic surgery for POP is covered by insurance and is currently a minimally invasive procedure. There are multiple treatment approaches for the uterus, especially sacrohysteropexy, for patients who wish to preserve their uterus. This approach requires an understanding of its anatomical characteristics, including how the arm is threaded. However, specific techniques for uterine preservation have not yet been thoroughly investigated or reported. Here, we discuss the innovative operative techniques for uterine preservation and mesh application achieved by laparoscopic sacrohysteropexy performed at our hospital. A 34-year-old woman presented at our hospital with a uterine prolapse in the hope of undergoing laparoscopic sacrohysteropexy. The anterior vaginal wall was dissected, the mesh fixed, and the right and left intrauterine foramina next to the cervix were deployed and released. The anterior vaginal wall mesh penetrated the released mesentery and was integrated with the mesh of the posterior vaginal wall. It was fixed to the anterior aspect of the cape angle by using a subperitoneal tunnel. This surgical case is currently under follow-up, with no recurrence to date. We elaborate upon the ingenious insertion site of the port for the preservation of the uterus, the secure fixation of the mesh to the uterus, and the traction method. Unlike laparoscopic sacrocolpopexy and sacrocervicopexy, laparoscopic sacrohysteropexy necessitates at least the aforementioned techniques. At our institution, we perform sacrohysteropexy following the method outlined in this case. A more efficient technique is expected to emerge as larger-scale studies accumulate additional cases, ultimately leading to widespread acceptance and standardization of the approach.

Efficacy of biological agents combined with oral immunotherapy (OIT) for food allergy: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Food allergy affects a large population throughout the world. Recently, oral immunotherapy (OIT) has been reported as an effective treatment for severe food allergy. Although OIT was successful in numerous trials in desensitisation, adverse events including anaphylaxis during OIT frequently occur. Additionally, some patients fail to be desensitised after OIT and the response to treatment is often not sustained. As a further adjunctive therapy to facilitate OIT, the role of biological agents has been identified. For example, efficacy and safety of omalizumab as an adjuvant therapy of OIT has become apparent through some RCTs and observational studies. Interest towards this topic is growing worldwide, and ongoing trials will provide additional data on the biologics in food allergy.We aim to systematically analyse the efficacy and safety of OIT combined with biological agents for food allergy. METHODS AND ANALYSIS: This paper provides a protocol for a systematic review of the relevant published analytical studies using an aggregate approach following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. Two authors will perform a comprehensive search for studies on MEDLINE/PubMed, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) databases. Subsequently, two independent authors will perform abstract screening, full-text screening and data extraction. A meta-analysis will be conducted as appropriate. ETHICS AND DISSEMINATION: The protocol of this systematic review will be provided in a peer-reviewed journal. As the researchers will not identify the individual patients included in the studies, they do not need to acquire ethics approval. PROSPERO REGISTRATION NUMBER: CRD42022373015.

A Behavioral and Electroencephalographic Study of Anesthetic State Induced by MK-801 Combined with Haloperidol, Ketamine and Riluzole in Mice.

BACKGROUND: Ketamine is an intravenous anesthetic that acts as a channel blocker on the N-methyl-d-aspartate (NMDA) receptor, a glutamate receptor subtype. MK-801 is the most potent compound among noncompetitive NMDA receptor antagonists. Ketamine induces loss of the righting reflex (LORR) in rodents, which is one of the indicators of unconsciousness, whereas high doses of MK-801 produce ataxia, but not LORR. In contrast, we previously reported that MK-801 combined with a low dose of the dopamine receptor antagonist haloperidol-induced LORR in mice. To assess a neurophysiologically distinct brain state and demonstrate unconsciousness, electroencephalograms (EEG) need to be examined together with LORR. Therefore, we herein investigated EEG changes after the systemic administration of MK-801 alone or in combination with haloperidol, and compared them with those induced by ketamine, the glutamate release inhibitor riluzole, and the γ-aminobutyric acid type A receptor agonist propofol. METHODS: All drugs were intraperitoneally administered to adult male ddY mice (n = 168). General anesthesia was evaluated based on the righting reflex test. Animals who exhibited no righting for more than 30 seconds were considered to have LORR. In a separate group of mice, EEG of the primary visual cortex was recorded before and after the administration of MK-801 (3.0 mg/kg) alone or in combination with haloperidol (0.2 mg/kg), ketamine (150 mg/kg), riluzole (30 mg/kg), or propofol (240 mg/kg). The waveforms recorded were analyzed using EEG power spectra and spectrograms. RESULTS: The high dose of MK-801 alone did not induce LORR, whereas MK-801 combined with haloperidol produced LORR in a dose-dependent manner. Ketamine, riluzole, and propofol also dose-dependently induced LORR. In the EEG study, MK-801 alone induced a significant increase in δ power, while MK-801 plus haloperidol exerted similar effects on not only δ, but also θ and α power during LORR, suggesting that increases in δ, θ, and α power were necessary for LORR. The results obtained on MK-801 plus haloperidol were similar to those on ketamine in the behavioral and EEG studies, except for an increase in γ power by ketamine during LORR. Propofol significantly increased δ, θ, α, and ß power during LORR. However, the EEG results obtained using riluzole, which produced a unique pattern of lower amplitude activity spanning most frequencies, markedly differed from those with the other drugs. CONCLUSIONS: This study revealed differences in EEG changes induced by various sedatives. The results obtained on MK-801 alone and MK-801 plus haloperidol suggest the importance of dopamine transmission in maintaining the righting reflex.

Evaluation of levator ani muscle elasticity after vaginal delivery and cesarean section using shear wave elastography.

PURPOSE: The risk of pelvic floor muscle injury is commonly considered to be higher in vaginal than in cesarean delivery. This study aimed to compare levator ani muscle (LAM) elasticity after vaginal and cesarean delivery using shear wave elastography (SWE). METHODS: Postpartum women who underwent a single SWE evaluation 1 month after their first delivery were divided into vaginal and cesarean delivery groups. The elastic moduli of both sides of the LAM were measured in a horizontal section and compared between the groups. In addition, a subgroup analysis was performed to compare LAM elasticity according to the delivery method within the vaginal delivery group-normal vaginal delivery, episiotomy, and operative vaginal delivery. RESULTS: Sixty-two women were included (vaginal delivery, n = 47; elective cesarean section, n = 15). Multiple regression analysis revealed that the LAM elastic modulus was significantly lower in the vaginal delivery group than in the cesarean delivery group (right LAM: 44.2 vs. 72.7 kPa, p = 0.0036; left LAM 40.4 vs. 82.7 kPa, p < 0.0001). In the subgroup analysis, the right LAM elastic modulus was significantly lower in the operative vaginal delivery subgroup than in the normal vaginal delivery subgroup (p = 0.0131). However, there was no significant difference in the left LAM elastic modulus between the three subgroups. CONCLUSION: LAM elasticity was significantly lower after vaginal delivery than after cesarean delivery. Furthermore, the elasticity of the right LAM was lower after operative vaginal delivery than after normal vaginal delivery. SWE has the potential to provide an objective quantitative assessment of postpartum pelvic floor muscle recovery.

Repetitive pain experiences modulate feedforward control of hemodynamics and modification by nitrous oxide/oxygen inhalation in humans.

Background: Repetitive experiences of certain stresses evoke feedforward cardiovascular responses via central command (CC)--central signals from the higher brain. However, it is unclear whether the anticipatory cardiovascular responses before pain stimulation occur after repetitive pain experiences and how nitrous oxide/oxygen inhalation (N2O), a sedative widely used in dentistry, affects the responses. We tested the hypothesis that the repetitive cold pressor test (CPT) alters the anticipatory cardiovascular responses, which are attenuated by N2O. Materials and methods: Beat-to-beat systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), and finger arterial stiffness (ß-stiffness) were measured during the 5-min rest, 30-s countdown (CD) before CPT, 2-min CPT, and 3-min recovery (CPT[1st]) in 15 young adults [age, 28 ± 4 years]. The same protocols were repeated randomly with the second CPT (CPT + CC) or placebo test (PLCB + CC). Results: SBP and DBP increased from baseline in CPT[1st] and CPT + CC under room air (RA) and 40 % N2O, while SBP was lower under N2O than under RA in CPT[1st]. HR in CPT[1st] was lower under N2O than under RA. The change (Δ) in HR was smaller during CPT[1st] than during CPT + CC under N2O, and a similar trend was observed under RA. ΔSBP by CD was lower under N2O than under RA in CPT[1st] but not in CPT + CC. HR increased with CD in CPT + CC but not in CPT[1st] under both RA and N2O. ß-stiffness increased by CD regardless of the pain experience, while it was lower under N2O. Conclusion: Repetitive pain experiences induce a feedforward HR increase. 40 % N2O decreases vascular stiffness, which may attenuate the anticipatory pressor response only when the feedforward HR increase does not exist.

Palatal microbiota associated with membranous substances in older Japanese individuals undergoing tube feeding in long-term care: A cross-sectional study.

Objective: Tube feeders are prone to membranous substance formation on the palate, and those with membranous substances have a risk of fever, with the probable involvement of their oral bacteria. However, the palatal microbiota of those with membranous substances has not been elucidated. Therefore, we evaluated the differences in palatal microbiota between tube-fed individuals with and without membranous substances to clarify the microbiota. Materials and methods: This study included 19 participants aged 65 years who required tube feeding. The participants' characteristics were collected from nursing records and oral examinations. If membranous materials were found on the palate, a specimen was collected. Membranous substances were defined as keratotic degeneration observed under a microscope. Additionally, we performed a comprehensive microbiome analysis by extracting DNA from the samples and performing 16 S rRNA gene sequencing. Finally, we compared the participant demographics and oral microbiota between patients with and without membranous substances. Results: A total of 11 participants had membranous substances associated with "mouth dryness" (p < 0.001) and "constant mouth opening" (p = 0.020). Palatal microbiota differed between those with and without membranous substances. Among the bacteria with a relative abundance greater than 1.0%, the abundance of Streptococcus (p = 0.007), Fusobacterium (p = 0.041), Streptococcus agalactiae (p = 0.009), and Fusobacterium nucleatum subsp. vincentii (p = 0.026) was significantly higher in the membranous substance group than in the non-membranous substance group. Conclusions: The palatal microbiota of individuals undergoing tube feeding differed depending on the presence or absence of membranous substances. Membrane substance formation associated with dry mouth purportedly alters the palatal microbiota. Streptococcus, Fusobacterium, S. agalactiae, and F. nucleatum subsp. vincentii were more abundant in the oral microbiota of patients with membranous substances. Thus, preventing this formation may help in controlling the growth of these microbes.

Comparison of dental plaque flora between intellectually disabled patients and healthy individuals: a cross-sectional study.

Periodontal diseases, including gingivitis, are highly prevalent in individuals with intellectual disability (ID). In particular, gingivitis can be difficult to cure owing to the lack of patient cooperation. Here, we evaluated differences in the oral bacterial flora between individuals with ID (n = 16) and healthy controls (n = 14) to facilitate the development of strategies for the prevention of periodontal disease in people with ID. Our results showed no significant difference in the number of decayed, missing, and filled teeth between the two groups. However, there were significant differences in the median papillary-marginal-attached index, plaque index, and gingival index between groups (P < 0.0001). Additionally, the mean probing depth in the ID group was significantly higher than that in the control group (P < 0.0001). The diversity of oral flora in people with ID and concurrent gingivitis was significantly lower than that of healthy individuals without periodontal disease. The relative abundances of Tannerella spp. and Treponema spp. were significantly higher in the ID group than in the control group at the genus level (P = 0.0383 and 0.0432, respectively), whereas that of Porphyromonas spp. was significantly lower in the ID group (P < 0.0001). Overall, our findings provided important insights into differences in the oral microbiota between patients with ID and healthy controls.

Transvaginal vesicovaginal fistula closure: A retrospective study of 28 cases at a single facility in Japan.

OBJECTIVES: We aimed to report the background of patients with vesicovaginal fistulas (VVFs) at our center, which has treated a relatively large number of such patients in Japan, as well as the ingenuity and outcomes of vesicovaginal fistula closure (VVFC). We also investigated the causes of VVFs. METHODS: A retrospective review was performed for 28 patients with VVFs treated at our center. Age, body mass index, etiology, site of fistula, and postoperative outcomes were investigated. RESULTS: Twenty-one (75%) fistulas occurred following hysterectomy. The overall success rate of VVFC was 85.7%, and the success rate limited to the first attempt was 89.5%. In 68% of cases, no bladder injury suspected as the cause of VVF was noticed during the surgery. Energy devices were used in all 12 patients for whom information on the type of device used for hysterectomy was confirmed. CONCLUSIONS: To our knowledge, this is the first report to evaluate a relatively large number of VVFCs in Japan. Although VVF is thought to be caused by bladder injury during hysterectomy, delayed thermal damage might also result in this pathology, even if there is no apparent intraoperative bladder injury.

N-methyl-d-aspartate receptors and glycinergic transmission, respectively, mediate muscle relaxation and immobility of pentobarbital in mice.

Pentobarbital-induced anesthesia is believed to be mediated by enhancement of the inhibitory action of γ-aminobutyric acid (GABA)ergic neurons in the central nervous system. However, it is unclear whether all components of anesthesia induced by pentobarbital, such as muscle relaxation, unconsciousness, and immobility in response to noxious stimuli, are mediated only through GABAergic neurons. Thus, we examined whether the indirect GABA and glycine receptor agonists gabaculine and sarcosine, respectively, the neuronal nicotinic acetylcholine receptor antagonist mecamylamine, or the N-methyl-d-aspartate receptor channel blocker MK-801 could enhance pentobarbital-induced components of anesthesia. Muscle relaxation, unconsciousness, and immobility were evaluated by grip strength, the righting reflex, and loss of movement in response to nociceptive tail clamping, respectively, in mice. Pentobarbital reduced grip strength, impaired the righting reflex, and induced immobility in a dose-dependent manner. The change in each behavior induced by pentobarbital was roughly consistent with that in electroencephalographic power. A low dose of gabaculine, which significantly increased endogenous GABA levels in the central nervous system but had no effect on behaviors alone, potentiated muscle relaxation, unconsciousness, and immobility induced by low pentobarbital doses. A low dose of MK-801 augmented only the masked muscle-relaxing effects of pentobarbital among these components. Sarcosine enhanced only pentobarbital-induced immobility. Conversely, mecamylamine had no effect on any behavior. These findings suggest that each component of anesthesia induced by pentobarbital is mediated through GABAergic neurons and that pentobarbital-induced muscle relaxation and immobility may partially be associated with N-methyl-d-aspartate receptor antagonism and glycinergic neuron activation, respectively.

Greater resting muscle sympathetic nerve activity reduces cold pressor autonomic reactivity in older women, but not older men.

Previous work demonstrates augmented muscle sympathetic nerve activity (MSNA) responses to the cold pressor test (CPT) in older women. Given its interindividual variability, however, the influence of baseline MSNA on CPT reactivity in older adults remains unknown. Sixty volunteers (60-83y; 30 women) completed testing where MSNA (microneurography), blood pressure (BP), and heart rate (HR) were recorded during baseline and a 2-min CPT (~4°C). Participant data were terciled by baseline MSNA (n=10/group); comparisons were made between the high baseline men (HM) and women (HW), and low baseline men (LM) and women (LW). By design, HM and HW, vs. LM and LW, had greater baseline MSNA burst frequency (37±5 and 38±3 vs. 9±4 and 15±5 bursts/min) and burst incidence (59±14 and 60±8 vs. 16±10 and 23±7 bursts/100hbs; both P<0.001). However, baseline BP and HR were not different between the groups (all P>0.05). During the CPT, there were no differences in the increase in BP and HR (all P>0.05). Conversely, ΔMSNA burst frequency was lower in HW vs. LW (8±9 vs. 22±12 bursts/min; P=0.012) yet was similar in HM vs. LM (17±12 vs. 19±10 bursts/min, P=0.994). Further, ΔMSNA burst incidence was lower in HW vs. LW (9±13 vs. 28±16 bursts/100hbs; P=0.020), with no differences between HM vs. LM (21±17 vs. 31±17 bursts/100hbs; P=0.455). Our findings suggest that heightened baseline activity in older women attenuates the typical CPT-mediated increase in MSNA without changing cardiovascular reactivity. While the underlying mechanisms remain unknown, altered sympathetic recruitment or neurovascular transduction may contribute to these disparate responses.

Metastatic prostate cancer with low PSA levels diagnosed after holmium laser enucleation of the prostate.

Holmium laser enucleation of the prostate is a widely accepted surgical treatment method for benign prostate hyperplasia, but its effect on prostate cancer remains unclear. In this study, we report the cases of two patients with metastatic prostate cancer diagnosed during follow-up after holmium laser enucleation of the prostate. Case 1 was a 74 year-old man who underwent holmium laser enucleation of the prostate. Prostate-specific antigen levels declined from 4.3 to 1.5 ng/mL at 1 month after surgery, but after 19 months, they increased to 6.6 ng/mL. Based on pathological and radiological findings, he was diagnosed as having prostate cancer, with Gleason score 5 + 4 with neuroendocrine differentiation, cT3bN1M1a. Case 2 was a 70 year-old man who also underwent holmium laser enucleation of the prostate. Prostate-specific antigen levels declined from 7.2 to 2.9 ng/mL at 6 months after surgery, but after 12 months, they increased to 12 ng/mL. Based on pathological and radiological findings, he was diagnosed as having prostate cancer, with Gleason score 4 + 5 with intraductal carcinoma of the prostate, cT3bN1M1a. This report suggests that advanced prostate cancer may be newly diagnosed after holmium laser enucleation of the prostate. Even if prostate cancer had not been demonstrated in the enucleated specimen, and postoperative PSA levels were below the standard values, physicians should regularly monitor prostate-specific antigen levels after holmium laser enucleation of the prostate, and further examination should be considered keeping in mind prostate cancer progression.

Effects of remote facilitation on ankle joint movement: Focusing on occlusal strength and balance.

Background: Remote facilitation refers to teeth occlusion-activated spinal cord activity resulting in increased trunk and limb muscle strength. Facilitation depends on dentition-related pressure during occlusion and masticatory muscle contraction strength. Aims: This study aimed to clarify the neurophysiological phenomenon and mechanisms by which occlusal strength and balance affect leg muscle activity and smooth joint movement execution. Materials & Methods: To examine occlusal strength, three conditions were set: no contact between teeth and Moderate- and Maximum-strength occlusion (No-bite, Moderate, and Max conditions, respectively). To assess occlusal balance, we measured occlusal forces and calculated the left-right force ratio. We designated the sides with higher and lower occlusal pressure as hypertonic and hypotonic, respectively. We assessed ankle dorsiflexion movements with joint movement and isometric tasks. Results: The rate of joint development and peak ankle dorsiflexion torque were significantly higher under occlusion (moderate and max compared to No-bite conditions), and the joint movement performance time was significantly shorter under Moderate compared to No-bite conditions. The joint movement execution time change rate from No-bite to Moderate condition was significantly lower on the Hypertonic side. Joint movement function was most improved under Moderate conditions. Discussion: While remote facilitation improves with higher occlusal strength, leading to increased muscle strength, there is optimal occlusion intensity in joint movement. Moreover, an occlusal balance-dependent imbalance exists in remote facilitation between the Hyper- and Hypotonic sides. Conclusion: Thus, low-intensity occlusion is optimal for smooth joint movement, and unbalanced occlusion results in asymmetrical motor function facilitation.

Effect of Lacticaseibacillus rhamnosus L8020 on the abundance of periodontal pathogens in individuals with intellectual disability: a randomized clinical trial.

OBJECTIVES: Gingivitis refers to inflammation of the gingiva and its connective tissues. Research has revealed a higher prevalence of gingivitis in individuals with intellectual disability than in healthy individuals. Milk fermented with Lacticaseibacillus rhamnosus L8020 (L8020 yogurt) inhibits the accumulation of periodontal disease-related pathogens in vitro and alleviates the symptoms of periodontal disease. The aim of this study was to investigate the influence of L8020 yogurt on oral microbiota and the abundance of four periodontal pathogens (Tannerella forsythia, Porphyromonas gingivalis, Prevotella intermedia, and Treponema denticola) and on the microbiota in individuals with intellectual disability and gingivitis. METHOD AND MATERIALS: Forty-one outpatients with intellectual disability participated in this study. To examine the effects of daily consumption of L8020 yogurt, the patients were randomly divided into L8020 (test group, n = 21) and placebo (n = 20) yogurt groups. All patients consumed 80 g of yogurt for 12 weeks. Oral examination was performed before the first intake of yogurt and dental plaque was collected before and after the intake of yogurt. DNA was extracted from dental plaque and subjected to next-generation sequencing. RESULTS: The relative abundance of T forsythia was significantly lower in the test group than in the placebo group. Additionally, the relative abundance of the four pathogens reduced after 84 days of consuming L8020 yogurt compared with that after consuming placebo yogurt. CONCLUSION: Mixing L rhamnosus L8020 with probiotic products that are consumed daily would be effective in suppressing the increase in periodontal disease-causing bacteria and beneficial for individuals with intellectual disability.

Differential regulation of sympathetic neural burst frequency and amplitude throughout normal pregnancy: a longitudinal study.

Sympathetic activation is a hallmark of pregnancy. However, longitudinal assessments of muscle sympathetic nerve activity (MSNA) in pregnancy are scarce and have primarily focused on burst occurrence (frequency) at rest, despite burst strength (amplitude) representing distinct characteristics of sympathetic outflow. Thus, we assessed MSNA burst amplitude distributions in healthy women to determine the impact of normal pregnancy on neural discharge patterns in response to orthostatic stress. Twenty-six women were studied longitudinally during pre-, early- (4-8 wk of gestation), and late (32-36 wk) pregnancy, as well as postpartum (6-10 wk after delivery). MSNA, blood pressure (BP), and heart rate (HR) were measured in the supine posture and during graded head-up tilt (30° and 60° HUT). Mean and median MSNA burst amplitudes were used to characterize burst amplitude distribution. In late pregnancy, women demonstrated smaller increases in HR (P < 0.001) during 60° HUT and larger increases in systolic BP (P = 0.043) throughout orthostasis, compared with prepregnancy. The increase in MSNA burst frequency during late- relative to prepregnancy (Late: Δ14[10] vs. Pre: Δ21[9] bursts/min; P = 0.001) was smaller during 60° HUT, whereas increases in burst incidence were smaller in late- relative to prepregnancy throughout orthostasis (P = 0.009). Nonetheless, median burst amplitude was smaller throughout orthostasis in late compared with prepregnancy (P = 0.038). Thus, while supine MSNA burst frequency was greater in late pregnancy, increases in burst frequency and strength during orthostasis were attenuated. These smaller, orthostatically induced MSNA increases may reflect natural adaptions of pregnancy serving to prevent sympathetic hyper-reactivity that is common in pathological states.

Posture-related changes in sympathetic baroreflex sensitivity during normal pregnancy.

Normal pregnancy is associated with vast adjustments in cardiovascular autonomic control. Sympathetic baroreflex sensitivity has been reported to be attenuated during pregnancy in animal models, but most studies in humans are cross-sectional and findings from longitudinal case studies are inconclusive. It remains unclear how sympathetic baroreflex sensitivity is altered longitudinally during pregnancy within an individual in different body postures. Therefore, this study examined the impact of posture on sympathetic baroreflex sensitivity in 24 normal-weight normotensive pregnant women. Spontaneous sympathetic baroreflex sensitivity was assessed during early (6-11 weeks) and late (32-36 weeks) pregnancy and 6-10 weeks postpartum in the supine posture and graded head-up tilt (30° and 60°). In addition, data from the postpartum period were compared with (and no different to) 18 age-matched non-pregnant women to confirm that the postpartum period was reflective of a non-pregnant condition (online supplement). When compared with postpartum (-3.8 ± 0.4 bursts/100 heartbeats/mmHg), supine sympathetic baroreflex sensitivity was augmented during early pregnancy (-5.9 ± 0.4 bursts/100 heartbeats/mmHg, P < 0.001). However, sympathetic baroreflex sensitivity at 30° or 60° head-up tilt was not different between any phase of gestation (P > 0.05). When compared to supine, sympathetic baroreflex sensitivity at 60° head-up tilt was significantly blunted during early (Δ2.0 ± 0.7 bursts/100 heartbeats/mmHg, P = 0.024) and late (Δ1.5 ± 0.6 bursts/100 heartbeats/mmHg, P = 0.049) pregnancy but did not change postpartum (Δ0.4 ± 0.6 bursts/100 heartbeats/mmHg, P = 1.0). These data show that time-course changes in sympathetic baroreflex sensitivity are dependent on the posture it is examined in and provides a foundation of normal blood pressure regulation during pregnancy for future studies in women at risk for adverse pregnancy outcomes.

[Re-Administration of Pembrolizumab for Urothelial Carcinoma after immune-Related Myasthenia Gravis : A Case Report].

Immune checkpoint inhibitors (ICIs) provide excellent benefits to the treatment of various cancer types, including urothelial carcinoma. Conversely, they can cause immune-related adverse events (irAEs), and some of them are severe or fatal. Furthermore, evidence on the safety and effectiveness of the readministration of ICIs after the occurrence of irAEs is limited. In this case report, a 78-year-old man who suffered from metastatic right renal pelvic cancer was treated with pembrolizumab. He had a partial response to pembrolizumab, but he developed grade 3 myasthenia gravis. The myasthenia gravis symptoms were immediately relieved by corticosteroids and intravenous immunoglobulin therapy. When the disease rapidly progressed, he was treated again with pembrolizumab. After 5 days, a chest radiograph showed shrinkage of pulmonary metastases. Unfortunately, he died of multiple brain infarctions 7 days after the readministration. We report this case with a literature review on the efficacy and safety of the readministration of ICIs after the occurrence irAEs including myasthenia gravis.

Appropriate Patient Status for Ra-223 Treatment in the Treatment Sequence for Castration-resistant Prostate Cancer.

BACKGROUND/AIM: Radium (Ra)-223 is widely used for treating castration-resistant prostate cancer (CRPC) with bone metastasis based on evidence of increased survival and decreased skeletal-related events. However, the timing of Ra-223 use in the treatment sequence of CRPC remains controversial. Therefore, this study aimed to explore the appropriate patient status for Ra-223 use in the CRPC treatment sequence by examining patients treated with Ra-223 from the time of CRPC diagnosis until death. PATIENTS AND METHODS: The medical records of 67 CRPC patients with bone metastasis who were treated with Ra-223 at two institutes were retrospectively analysed. The impact of 13 factors from the time of CRPC diagnosis until death was analysed using univariate and multivariate Cox hazard ratio models to evaluate the appropriate patient status for Ra-223 treatment. RESULTS: The median survival time following CRPC diagnosis for all the patient groups was 3.82 years. Univariate analysis identified a higher-than-normal alkaline phosphatase (ALP) level, bone scan indexes ≥2, and prostate-specific antigen (PSA) doubling time <3 months before Ra-223 treatment as predominant adverse prognostic factors. Ra-223 therapy discontinuation was not a significant factor. The survival of CRPC patients with these factors was significantly worse than that of patients without these factors. In the multivariate analysis, a higher-than-normal ALP level at the start of treatment was identified as a poor prognostic factor for mortality. CONCLUSION: The appropriate patient status for Ra-223 use includes low bone metastasis burden and well-controlled PSA levels.

Magnetic resonance imaging evaluation of the effectiveness of FemiCushion in pelvic organ prolapse.

AIMS: FemiCushion (FC) is a supportive device for pelvic organ prolapse (POP), but its effectiveness has not been evaluated with imaging studies. This study utilized magnetic resonance imaging (MRI) to evaluate the anatomic changes induced by FC use in patients with severe POP. METHODS: This prospective study examined patients with stage 3 or 4 POP who underwent treatment with FC and received a diagnostic MRI. Measurements were made in the midsagittal plane at rest and during straining with and without FC. The vertical distances from the lowest points of the anterior and posterior vaginal wall (A; P), uterine cervix or vaginal stump (C), and perineal body (PB) to the Pelvic Inclination Correction System line were measured, along with the lengths of the urogenital (UGH) and levator hiatus (LH). RESULTS: Twelve patients were included in the study. The median age was 72 (range, 56-84) years. All reference points were positioned significantly higher with the FC than without the FC (median ΔA: 11 mm, p = 0.005; ΔC: 14 mm, p = 0.011; ΔP: 6 mm, p = 0.008; ΔPB: 7 mm, p = 0.002). Median UGH and LH lengths during straining were significantly shorter with the FC than without the FC (UGH: 44 mm vs. 53 mm, p = 0.002; LH: 60 vs. 65 mm, p = 0.021). CONCLUSIONS: This is the first report on the use of MRI to measure the performance of FC. Our study demonstrates that FC effectively repositioned the organs involved in POP.

Predictive urodynamic factors for de novo stress urinary incontinence after laparoscopic sacrocolpopexy for pelvic organ prolapse.

OBJECTIVES: Laparoscopic sacrocolpopexy is often performed to treat pelvic organ prolapse. Preoperative stress urinary incontinence (SUI) can improve after laparoscopic sacrocolpopexy. In contrast, some patients without incontinence preoperatively develop SUI after pelvic organ prolapse repair (ie, de novo SUI). This study aimed to identify the preoperative predictive factors of de novo SUI after laparoscopic sacrocolpopexy. METHODS: A total of 858 patients underwent laparoscopic sacrocolpopexy between January 2013 and November 2017 at Kameda Medical Center. Urodynamic studies were performed pre- and postoperatively on 75 patients. This retrospective study included 43 of 75 patients who did not have SUI preoperatively. We assessed urethral function according to functional profile length and maximum urethral closure pressure. We evaluated voiding function in terms of maximum flow rate, detrusor pressure at maximum flow rate, and postvoid residual volume. Furthermore, each factor was compared between de novo SUI-positive and SUI-negative groups. RESULTS: After laparoscopic sacrocolpopexy, 30 (69.8%) patients presented with SUI. The preoperative maximum urethral closure pressure was significantly lower in the de novo SUI-positive group (36.0 cmH2 O) than in the de novo SUI-negative group (50.5 cmH2 O, P = .020). More patients with maximum urethral closure pressure <40 cmH2 O had de novo SUI than patients with maximum urethral closure pressure ≥40 cmH2 O (P = .004). There were no significant differences between preoperative maximum urethral closure pressure and postoperative maximum urethral closure pressure in either group. CONCLUSIONS: Low preoperative maximum urethral closure pressure, particularly maximum urethral closure pressure <40 cmH2 O, is a predictor of de novo SUI after laparoscopic sacrocolpopexy.