Hospital surgical volume-outcome relationship in caesarean hysterectomy for placenta accreta spectrum.

OBJECTIVE: To examine the association between hospital surgical volume of caesarean hysterectomy and surgical morbidity in women with placenta accreta spectrum (PAS). DESIGN: Population-based retrospective cohort study. SETTING: National Inpatient Sample, January 2016 to December 2018. POPULATION: Six thousand and ten women with PAS who underwent caesarean hysterectomy in 738 centres. METHODS: (1) Comprehensive modelling for relative hospital surgical volume cut-point selection, (2) multinomial regression analysis for characterising hospital surgical volume, and (3) binary logistic regression analysis to examine the volume-outcome relationship. MAIN OUTCOME MEASURES: Surgical morbidity (haemorrhage, coagulopathy, shock, urinary tract injury, and death). RESULTS: The majority of centres had five surgeries over the 3-year period (468 centres, 63.4%) and were grouped as the low-volume group. Surgical morbidity decreased after a relative hospital surgical volume of 25 cases (24 centres, 3.3%) was reached, grouped as the high-volume group. The remaining centres were grouped as the mid-volume group (246 centres, 33.3%). In multivariable analysis, women in the high-volume group were more likely to be Black, have lower median household income, medical comorbidity, previous caesarean delivery, placenta praevia or placenta percreta, and to have undergone surgeries at large urban teaching hospitals compared with those in the low-volume group (all, P < 0.05). After controlling for patient demographics, hospital characteristics and pregnancy factors, performance of caesarean hysterectomy at high-volume centres was associated with a 22% decreased risk of surgical complications compared with surgery at the low-volume centres (adjusted odds ratio 0.78, 95% CI 0.64-0.94). CONCLUSION: Caesarean hysterectomy for PAS is a rare surgical procedure. Higher hospital surgical volume may be associated with improved surgical outcome in PAS. TWEETABLE ABSTRACT: Higher hospital caesarean hysterectomy volume may be associated with improved surgical outcome in PAS.

In-vitro fertilisation-embryo-transfer complicates the antenatal diagnosis of placenta accreta spectrum using MRI: a retrospective analysis.

AIM: To evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) for the antenatal diagnosis of placenta accreta spectrum (PAS). MATERIALS AND METHODS: Data from 95 patients with placenta previa or low-lying placenta who underwent MRI at Osaka University Hospital for the antenatal diagnosis of PAS between January 2013 and December 2018 were reviewed retrospectively. The antenatal MRI signs suggesting PAS were assessed. Patients were divided into two groups depending on whether they were diagnosed with PAS. Factors that affected PAS diagnosis were identified using multivariate analysis. RESULTS: The diagnostic accuracy of MRI for detecting PAS was as follows: 71.4% sensitivity, 96.4% specificity, and area under the curve (AUC) of 0.839 (95% confidence interval [CI]: 0.73-0.91). The diagnostic accuracy was lower in patients with in-vitro fertilisation with embryo transfer (IVF-ET): 22.2% sensitivity, 93.3% specificity, and AUC=0.578 (95% CI: 0.417-0.724). On multivariate analysis, only IVF-ET showed a significant association with false-positive or -negative MRI diagnosis of PAS (adjusted odds ratio: 26.5; 95% CI: 2.42-289.4; p=0.007). CONCLUSION: IVF-ET affects the antenatal diagnosis of PAS using MRI.

Conservative surgery for ovarian torsion in young women: perioperative complications and national trends.

OBJECTIVE: To analyse populational trends and perioperative complications following conservative surgery versus oophorectomy in women <50 years of age with ovarian torsion. DESIGN: Population-based retrospective observational study. SETTING: Nationwide Inpatient Sample in the USA (2001-2015). POPULATION: In all, 89 177 ovarian torsions including 20 597 (23.1%) conservative surgeries and 68 580 (76.9%) oophorectomies. METHODS: (1) Trend analysis to assess utilisation of conservative surgery over time, (2) multivariable binary logistic regression to identify independent factors associated with conservative surgery and (3) inverse probability of treatment weighting with a generalised estimating equation to analyze perioperative complications. MAIN OUTCOME MEASURES: Trends, characteristics and complications related to conservative surgery. RESULTS: Performance of conservative surgery increased from 18.9 to 25.1% between 2001 and 2015 (32.8% relative increase, P = 0.001) but decreased steadily after age 15, and sharply declined after age 35 (P < 0.001). On multivariable analysis, younger age exhibited the largest effect size for conservative surgery among the independent factors (adjusted odds ratios 3.39-7.96, P < 0.001). In the weighted model, conservative surgery was associated with an approximately 30% decreased risk of perioperative complications overall (10.0% versus 13.6%, odds ratio 0.73, 95% confidence interval 0.62-0.85, P < 0.001) and was not associated with venous thromboembolism (0.2 versus 0.3%, P = 0.457) or sepsis (0.4 versus 0.3%, P = 0.638). CONCLUSION: There has been an increasing utilisation of conservative surgery for ovarian torsion in the USA in recent years. Our study suggests that conservative surgery for ovarian torsion may not be associated with increased perioperative complications. TWEETABLE ABSTRACT: Conservative surgery for ovarian torsion may not be associated with increased perioperative complications.

Trauma and endometriosis. A review. May we explain surgical phenotypes and natural history of the disease?

OBJECTIVE: The study was performed to evaluate whether trauma is an initial event of development of endometriosis. METHOD: Using Medline database from January 1960 up to December 2014, a systematic review was made of all published studies using the keywords trauma, healing, injury, infection, hyperperistaltism, stretch and endometriosis, adenomyosis and trauma. Studies and review articles written in French and/or in English related to the topic were included and reviewed independently by two authors. RESULTS: The role of trauma is well-established for endometriotic lesions diagnosed in surgical scars. Various traumas including delivery, uterine curettage or incision, intraperitoneal hemorrhage, or occult pelvic inflammatory diseases could be involved to explain other localizations of the disease. Many data suggested that the healing process, particularly growth factors and the associated estrogen production, may facilitate the implantation and the growth of ectopic endometrial cells. After the initial, a traumatic event, the phenotype of the disease would depend on the tissue in which the endometriotic lesion grows. CONCLUSIONS: The present literature review may support a potential role of a trauma as an initial event of endometriosis.

Short interpregnancy interval after B-Lynch uterine compression suture: a case report.

PURPOSE: The influence of the B-Lynch suture technique on subsequent fertility and pregnancy outcomes is not clear. In the present report, the authors describe the case of a very short interpregnancy interval following the successful placement of a B-lynch suture and discuss the associated problems. MATERIALS AND METHODS: A 33-year-old-woman underwent cesarean section after undergoing artificial induction of labor and subsequent atonic postpartum hemorrhage. Placement of a B-Lynch brace suture successfully stopped the bleeding and preserved the uterus. The patient became unexpectedly pregnant only four months later, making the present case the shortest reported interpregnancy interval after a surgery involving the B-Lynch suture. CONCLUSION: In the present case, fertility was not affected, and obstetric complications (abortion, fetal growth restriction, preterm delivery, and placenta previa) were not observed. Adhesions between the abdominal wall and the surface of the uterus along the previous B-Lynch suture line were observed and irregular, large blood vessels were observed on the surface of the uterus. Further reports are expected to determine the influence of the B-Lynch brace suture technique on the subsequent pregnancy.

Cesarean delivery via a transverse uterine fundal incision for the successful management of a low-lying placenta and aplastic anemia.

PURPOSE: To present a case report on the successful management of a low-lying placenta and aplastic anemia. Aplastic anemia is a rare but serious disorder that is often characterized by severe pancytopenia. Because of the rarity of aplastic anemia, a pregnancy complicated by it is rarely encountered by obstetricians. Moreover, placenta previa (low-lying placenta) complicated by aplastic anemia has not been previously reported. MATERIALS AND METHODS: The authors present the first reported case of placenta previa with aplastic anemia in a patient who had undergone a previous cesarean delivery. RESULTS: They successfully managed this case by making a transverse uterine fundal incision during an elective cesarean delivery. This incision minimized blood loss and enabled good visualization of the source of bleeding in the lower uterine segment. Bleeding was stemmed by suturing the source of bleeding. CONCLUSION: The authors propose that this procedure should be considered for patients with low platelet counts and abnormal placentation.

Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma.

BACKGROUND: To examine the effect of the histology of carcinoma and sarcoma components on survival outcome of uterine carcinosarcoma. PATIENTS AND METHODS: A multicenter retrospective study was conducted to examine uterine carcinosarcoma cases that underwent primary surgical staging. Archived slides were examined and histologic patterns were grouped based on carcinoma (low-grade versus high-grade) and sarcoma (homologous versus heterologous) components, correlating to clinico-pathological demographics and outcomes. RESULTS: Among 1192 cases identified, 906 cases were evaluated for histologic patterns (carcinoma/sarcoma) with high-grade/homologous (40.8%) being the most common type followed by high-grade/heterologous (30.9%), low-grade/homologous (18.0%), and low-grade/heterologous (10.3%). On multivariate analysis, high-grade/heterologous (5-year rate, 34.0%, P = 0.024) and high-grade/homologous (45.8%, P = 0.017) but not low-grade/heterologous (50.6%, P = 0.089) were independently associated with decreased progression-free survival (PFS) compared with low-grade/homologous (60.3%). In addition, older age, residual disease at surgery, large tumor, sarcoma dominance, deep myometrial invasion, lymphovascular space invasion, and advanced-stage disease were independently associated with decreased PFS (all, P < 0.01). Both postoperative chemotherapy (5-year rates, 48.6% versus 39.0%, P < 0.001) and radiotherapy (50.1% versus 44.1%, P = 0.007) were significantly associated with improved PFS in univariate analysis. However, on multivariate analysis, only postoperative chemotherapy remained an independent predictor for improved PFS [hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.27-0.43, P < 0.001]. On univariate analysis, significant treatment benefits for PFS were seen with ifosfamide for low-grade carcinoma (82.0% versus 49.8%, P = 0.001), platinum for high-grade carcinoma (46.9% versus 32.4%, P = 0.034) and homologous sarcoma (53.1% versus 38.2%, P = 0.017), and anthracycline for heterologous sarcoma (66.2% versus 39.3%, P = 0.005). Conversely, platinum, taxane, and anthracycline for low-grade carcinoma, and anthracycline for homologous sarcoma had no effect on PFS compared with non-chemotherapy group (all, P > 0.05). On multivariate analysis, ifosfamide for low-grade/homologous (HR 0.21, 95% CI 0.07-0.63, P = 0.005), platinum for high-grade/homologous (HR 0.36, 95% CI 0.22-0.60, P < 0.001), and anthracycline for high-grade/heterologous (HR 0.30, 95% CI 0.14-0.62, P = 0.001) remained independent predictors for improved PFS. Analyses of 1096 metastatic sites showed that carcinoma components tended to spread lymphatically, while sarcoma components tended to spread loco-regionally (P < 0.001). CONCLUSION: Characterization of histologic pattern provides valuable information in the management of uterine carcinosarcoma.

Placenta accreta following laparoscopic adenomyomectomy: a case report.

BACKGROUND: The influence of adenomyomectomy on subsequent pregnancy is unknown. Placenta accreta is most often associated with placenta previa in women with multiple previous cesarean sections. CASE: A 41-year-old woman became pregnant six years after a laparoscopic uterine posterior adenomyomectomy. She was diagnosed with complete placenta previa and considered at a low risk for placenta accreta by ultrasonography. Cesarean section and subsequent hysterectomy were required, and histopathological analysis revealed a posterior placenta accreta. DISCUSSION: The authors discuss the association of adenomyomectomy and placenta accreta on subsequent pregnancy and conclude that previous adenomyomectomy may increase the risk of abnormal placentation. Therefore, careful treatment is required during the pregnancies of patients with previous adenomyomectomy.

Atomoxetine reverses locomotor hyperactivity, impaired novel object recognition, and prepulse inhibition impairment in mice lacking pituitary adenylate cyclase-activating polypeptide.

Attention-deficit/hyperactivity disorder (ADHD) is a complex neurobehavioral disorder that is characterized by attention difficulties, impulsivity, and hyperactivity. A non-stimulant drug, atomoxetine (ATX), which is a selective noradrenaline reuptake inhibitor, is widely used for ADHD because it exhibits fewer adverse effects compared to conventional psychostimulants. However, little is known about the therapeutic mechanisms of ATX. ATX treatment significantly alleviated hyperactivity of pituitary adenylate cyclase-activating polypeptide (PACAP)-deficient (PACAP(-/-)) mice with C57BL/6J and 129S6/SvEvTac hybrid background. ATX also improved impaired novel object recognition memory and prepulse inhibition in PACAP(-/-) mice with CD1 background. The ATX-induced increases in extracellular noradrenaline and dopamine levels were significantly higher in the prefrontal cortex of PACAP(-/-) mice compared to wild-type mice with C57BL/6J and 129S6/SvEvTac hybrid background. These results suggest that ATX treatment-induced increases in central monoamine metabolism may be involved in the rescue of ADHD-related abnormalities in PACAP(-/-) mice. Our current study suggests that PACAP(-/-) mice are an ideal rodent model with predictive validity for the study of ADHD etiology and drug development. Additionally, the potential effects of differences in genetic background of PACAP(-/-) mice on behaviors are discussed.

The protein Ocular albinism 1 is the orphan GPCR GPR143 and mediates depressor and bradycardic responses to DOPA in the nucleus tractus solitarii.

BACKGROUND AND PURPOSE: L-DOPA is generally considered to alleviate the symptoms of Parkinson's disease by its conversion to dopamine. We have proposed that DOPA is itself a neurotransmitter in the CNS. However, specific receptors for DOPA have not been identified. Recently, the gene product of ocular albinism 1 (OA1) was found to exhibit DOPA-binding activity. Here, we have investigated whether OA1 is a functional receptor of DOPA in the nucleus tractus solitarii (NTS). EXPERIMENTAL APPROACH: We examined immunohistochemical expression of OA1 in the NTS, and the effects of DOPA microinjected into the depressor sites of NTS on blood pressure and heart rate in anaesthetized rats, with or without prior knock-down of OA1 in the NTS, using shRNA against OA1. KEY RESULTS: Using a specific OA1 antibody, OA1-positive cells and nerve fibres were found in the depressor sites of the NTS. OA1 expression in the NTS was markedly suppressed by microinjection into the NTS of adenovirus vectors carrying the relevant shRNA sequences against OA1. In animals treated with OA1 shRNA, depressor and bradycardic responses to DOPA, but not those to glutamate, microinjected into the NTS were blocked. Bilateral injections into the NTS of DOPA cyclohexyl ester, a competitive antagonist against OA1, suppressed phenylephrine-induced bradycardic responses without affecting blood pressure responses. CONCLUSION AND IMPLICATIONS: OA1 acted as a functional receptor for DOPA in the NTS, mediating depressor and bradycardic responses. Our results add to the evidence for a central neurotransmitter role for DOPA, without conversion to dopamine.

Chronic exposure to particles caused bronchioloalveolar carcinoma in a patient with cryptogenic organizing pneumonia evaluated by elemental analysis.

An 81-year-old Japanese man had organizing pneumonia (OP), and he had worked as a painter and had a history of exposure of various paints over 20 years. The major features on computed tomography (CT) in patients were cryptogenic organizing pneumonia (COP) showing airspace consolidation, and air bronchograms were consistent finding in consolidation in right lung of S¹°. Such parenchymal abnormalities were clinically and pathologically diagnosed COP and the lesion was improved by corticosteroid therapy. About 1.5 years later, similar shadows emerged in new locations of right S4 and left S8, and these were bronchioloalveolar carcinoma (BAC) classified as adenocarcinoma. BAC causes similar X-ray changes to COP and inflammation accompanying BAC can also respond to corticosteroids, which may lead to delay in the diagnosis of BAC associated with COP. These radiological features lead to difficulty in making a diagnosis of new parenchymal diseases. The present patient had been painter, and metals of carcinogens were proven in both tissue of COP and BAC. Here, we reported a painter with COP and new-onset BAC who had been exposed to particles proven by elemental analysis. The combination of COP with BAC is considered uncommon, but the risk of BAC may increase when there is a history of particle inhalation.

Influence of tissue particles on Fas expression in idiopathic interstitial pneumonia.

Idiopathic interstitial pneumonia (IIP) is a progressive fibrosing interstitial pneumonia of unknown etiology with a poor prognosis. The aim of this study is to prove the occurrence of particle deposition and particle-induced tissue damage in IIP by examining proapoptotic Fas expression with in-air microparticle induced X-ray emission (in-air micro-PIXE) analysis. A total of 21 patients were enrolled. Lung tissues from 12 IIP patients and nontumorous lung tissues from 9 lung cancer patients (as a control) were subjected to in-air micro-PIXE analysis. The distribution of particles in lung tissue was compared with the localization of Fas expression by immunohistochemistry. Silicon (Si) was identified in 58.3% of IIP samples and 44.4% of control samples. Iron (Fe) was identified 25% in IIP samples and 11.1% in control samples. The mean lung tissue content of Si and Fe relative to S did not differ between IIP and control patients. Only two IIP patients showed the co-localization of Si and Fe deposition with Fas expression. Adaptation of this method would contribute to assess the influence of particles on IIP.

Molecular mechanism of kallikrein-related peptidase 8/neuropsin-induced hyperkeratosis in inflamed skin.

BACKGROUND: Hyperkeratosis and acanthosis occur in inflamed skin. Proliferation and differentiation of keratinocytes are important processes during epidermal repair after inflammation. Neuropsin and its human homologue kallikrein-related peptidase 8 (KLK8) have been reported to be involved in epidermal proliferation and differentiation, but the involved molecular mechanisms are obscure. OBJECTIVES: To explore the molecular mechanism of KLK8/neuropsin-induced hyperkeratosis and acanthosis in inflamed skin. METHODS: The molecular mechanism involved in KLK8/neuropsin-induced hyperkeratosis and acanthosis in inflamed skin was investigated both in vivo and in vitro using neuropsin knockout mice and KLK8 knockdown human keratinocytes. Neuropsin-related genes were identified by differential gene display. The localization and functional relationship of the molecules affected downstream of KLK8/neuropsin in normal and inflamed skin were analysed by in situ hybridization and immunohistochemistry. RESULTS: Hyperkeratosis and acanthosis in sodium lauryl sulphate-stimulated skin were markedly inhibited in neuropsin knockout mice. Knockdown of KLK8/neuropsin increased transcription factor activator protein-2α (AP-2α) expression and decreased keratin 10 expression in human keratinocytes and mouse skin, respectively. AP-2α has been reported to inhibit epidermal proliferation and keratin 10 expression. Distributional analysis showed that KLK8/neuropsin was expressed in the stratum spinosum, AP-2α was expressed in the stratum basale and the lower part of the stratum spinosum, and keratin 10 was expressed throughout the stratum spinosum. CONCLUSIONS: The above findings suggest the following mechanism of events underlying KLK8/neuropsin-induced hyperkeratosis: (i) skin inflammation increases KLK8/neuropsin expression in the stratum spinosum; (ii) the released KLK8/neuropsin inhibits AP-2α expression in the cells of the stratum basale and stratum spinosum; (iii) the decrease in AP-2α results in cell proliferation in the stratum basale and cell differentiation in the stratum spinosum, with an increase in keratin 10 expression.

DISC1 regulates cell-cell adhesion, cell-matrix adhesion and neurite outgrowth.

Disrupted-in-schizophrenia 1 (DISC1) is a promising susceptibility gene for major mental illness. Recent studies have implicated DISC1 in key neurodevelopmental processes, including neurite outgrowth, neuronal migration and proliferation. Here, we report that DISC1 regulates cell-cell and cell-matrix adhesion and neurite outgrowth. DISC1 overexpression increased expression of the adherence junction protein N-cadherin and enhanced cell-cell adhesion. The increased N-cadherin accumulated in the areas of cell-cell contact. DISC1 overexpression also enhanced cell-matrix adhesion by inducing expression of beta1-integrin protein. In the presence of nerve growth factor (NGF), DISC1 overexpression increased beta1-integrin expression at the cell membrane and growth cone. NGF-induced neurite extension was enhanced by DISC1, and anti-beta1-integrin antibody reduced the neurite outgrowth of DISC1-overexpressing cells to the control level. Furthermore, DISC1 also regulated N-cadherin and beta1-integrin expression at the cell membrane in primary neurons. We conclude that DISC1 regulates cell-cell adhesion and cell-matrix adhesion by regulating the expression of adhesion molecules.

Analysis on the co-localization of asbestos bodies and Fas or CD163 expression in asbestos lung tissue by in-air micro-pixe.

To prevent and control disease caused by exposure to various agents, it is necessary to determine the harmful level of intervention and to establish a method for measuring that level. In-air microparticle-induced X-ray emission (in-air micro-PIXE) analysis is based on irradiation of specimens with a proton ion microbeam, and has been modified for biological application. Two-dimensional analysis and quantitative analysis using the system confirmed that asbestos induced apoptosis by upregulating Fas expression and also revealed the accumulation of CD163-expressing macrophages in the lungs of patients with asbestosis. By quantitative comparison of the area of Fas or CD163 expression and the Fas- or CD163-negative area in asbestos lung tissue, the harmful levels which caused the expression of Fas or CD163 could be estimated on Silica, Ferrous iron, and Magnesium (the components of asbestos) deposition. These results indicate that the system could be useful for investigating the pathogenesis of inhaled particle-induced immune reactions and for determining harmful levels of exogenous agents.

Putative occurrence of lysine decarboxylase isoforms in soybean (Glycine max) seedlings.

The activity of lysine decarboxylase was studied in 3-day-old soybean (Glycine max (L.) Meer cv. Sakai) seedlings also in relation to light conditions. Lysine decarboxylase activity was mainly localized in the roots and to a lesser extent in the hypocotyls and was detectable in both the soluble and particulate fractions. The enzyme activity levels were similar during germination under light and dark conditions. With respect to lysine concentration, the initial decarboxylation rate of the soluble fraction showed a saturating curve. Conversely, the initial decarboxylation rate of the particulate fraction showed a sigmoidal curve. These results could suggest that at least two isoforms of lysine decarboxylase are present in different organs of soybean seedlings. In the root soluble fraction, the suicide inhibitor alpha-difluoromethyl-lysine suppressed the activity of lysine decarboxylase and of ornithine decarboxylase to the same extent, but had no effect on arginine decarboxylase activity.

Clinical significance of LAMB3 and COL7A1 mRNA in esophageal squamous cell carcinoma.

AIMS: LAMB3 and COL7A1 genes code for the laminin-5beta3 chain and type VII collagen, respectively. They constitute the major components of the basement membrane zone. The aim of the current study was to clarify the clinical significance of LAMB3 and COL7A1 mRNA expression in esophageal squamous cell carcinoma (ESC). METHODS: We quantitated the expression of LAMB3 mRNA and COL7A1 mRNA in malignant esophageal tissues (T) and corresponding normal tissues (N) by real-time quantitative reverse transcription-polymerase chain reaction assays. The clinicopathologic significance of LAMB3 and COL7A1 expression was also determined. Paired T and N tissues were obtained from 66 patients who underwent curative esophagectomy. RESULTS: The expression levels of LAMB3 and COL7A1 mRNAs were higher in malignant tissues than in the corresponding normal tissues. The level of LAMB3 expression was significantly correlated with the depth of invasion and venous invasion (p=0.007 and 0.001, respectively). COL7A1 expression was significantly correlated with depth of tumor invasion and lymphatic invasion (p=0.046, 0.013, respectively). The five-year survival rate was better in the 22 patients with relatively low expression of both LAMB3 and COL7A1 in comparison with the other 44 cases (p<0.05). CONCLUSION: The evaluation of LAMB3 and COL7A1 mRNA expression is useful for predicting the malignant properties of ESC and may prove valuable in predicting the future course of the disease.