Predictive performance of Shock Index for postpartum hemorrhage during cesarean delivery.

BACKGROUND: The Shock Index (SI), defined as heart rate divided by systolic blood pressure, is reportedly an early surrogate indicator for postpartum hemorrhage (PPH). However, most previous studies have used clinical data of women who delivered vaginally. Therefore, we aimed to evaluate the SI pattern during cesarean delivery and determine its usefulness in detecting PPH. METHODS: This was a single-center retrospective study using the clinical data of women (n = 331) who underwent cesarean delivery under spinal anesthesia at term between 2018 and 2021. We assessed the SI pattern stratified by total blood loss and evaluated the predictive performance of each vital sign in detecting PPH (total blood loss ≥1000 mL) based on the area under the receiver operating characteristic curve (AUROC). RESULTS: At 10-15 min after delivery, the mean SI peaked between 0.84 and 0.90 and then decreased to a level between 0.72 and 0.77, which was similar to that upon entering the operating room. Among 331 women, 91 (27.5%) were diagnosed with PPH. There was no correlation between SI and total blood loss (rs = 0.02). The SI had low ability to detect PPH (AUROC 0.54, 95% confidence interval 0.47 to 0.61), which was similar to other vital signs (AUROCs 0.53-0.56). CONCLUSION: We determined the pattern of SI during cesarean delivery. We found no correlation between SI and total blood loss. Unlike in vaginal delivery, the prognostic accuracy of SI for PPH detection in cesarean delivery was low.

Breast cancer surgery in patients with schizophrenia: short-term outcomes from a nationwide cohort.

BACKGROUND: Although patients with schizophrenia have a higher risk of developing breast cancer than the general population, studies that have investigated postoperative complications after breast cancer surgery in patients with schizophrenia are scarce. This study examined associations between schizophrenia and short-term outcomes following breast cancer surgery. METHODS: Patients who underwent surgery for stage 0-III breast cancer between July 2010 and March 2017 were identified from a Japanese nationwide inpatient database. Multivariable analyses were conducted to compare postoperative complications and hospitalization costs between patients with schizophrenia and those without any psychiatric disorder. Three sensitivity analyses were performed: a 1 : 4 matched-pair cohort analysis with matching for age, institution, and fiscal year at admission; analyses excluding patients with schizophrenia who were not taking antipsychotic medication; and analyses excluding patients with schizophrenia who were admitted to hospital involuntarily. RESULTS: The study included 3660 patients with schizophrenia and 350 860 without any psychiatric disorder. Patients with schizophrenia had a higher in-hospital morbidity (odds ratio (OR) 1.37, 95 per cent c.i. 1.21 to 1.55), with more postoperative bleeding (OR 1.34, 1.05 to 1.71) surgical-site infections (OR 1.22, 1.04 to 1.43), and sepsis (OR 1.20, 1.03 to 1.41). The total cost of hospitalization (coefficient €743, 95 per cent c.i. 680 to 806) was higher than that for patients without any psychiatric disorder. All sensitivity analyses showed similar results to the main analyses. CONCLUSION: Although causal inferences remain premature, multivariable regression analyses showed that schizophrenia was associated with greater in-hospital morbidity and higher total cost of hospitalization after breast cancer surgery than in the general population.

Enhanced wound healing by topical application of ointment containing a low concentration of povidone-iodine.

OBJECTIVE: To investigate the effect of a novel topical wound-healing agent, low-concentration povidone-iodine ointment (LPIO) with a hydrophobic white petrolatum-rich base on skin-wound models in rats and rabbits. METHOD: The therapeutic efficacy of topically applied LPIO was compared to that of standard-concentration povidone-iodine ointment (SPIO) and non-treatment control, using a full-thickness skin-wound model in 24 hairless rats and a full-thickness skin-defect model in rabbit earlobes. The animals were kept under standardised conditions at the Central Research Laboratory of Maruishi Pharmaceutical Co. Ltd. (Osaka, Japan). Therapeutic efficacy was evaluated based on macroscopic wound-size reduction, as well as histopathological and immuno-histochemical examinations. RESULTS: LPIO enhanced wound healing in rat full-thickness skin ulcers, reducing wound size and inflammation, when compared with that in SPIO and non-treatment control. LPIO also markedly improved wound healing in rabbit earlobe ulcers by significantly improving re-epithelialisation, compared with that in SPIO. CONCLUSION: The results of this study suggest that LPIO is a useful topical therapy for ulcerative lesions.

Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative).

This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmö, Sweden on 23-24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure (POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms.

Effects of washing of the face with a mild facial cleanser formulated with sodium laureth carboxylate and alkyl carboxylates on acne in Japanese adult males.

BACKGROUND/PURPOSE: Washing the face with a mild cleanser is generally recommended for acne care. Occasionally, the general public has the misconception that acne is exacerbated by cleansers and furthermore it has concerns about inducing skin irritation and xerosis by intensive washing. Recently, we developed a new cleanser based on sodium laureth carboxylate and alkyl carboxylates (AEC/soap) that cleans sebum well without penetrating the stratum corneum. METHODS: We designed a controlled clinical trial conducted on adult Japanese males with moderate or less acne. Twenty subjects washed their faces with AEC/soap base cleanser twice a day for 4 weeks. Assessment of the efficacy was conducted prior to the start of the study, and at the end of weeks 2 and 4. RESULTS: Significant improvement of the acne was observed within 2 weeks, and acne lesions were not detectable in 25% of the subjects at week 4. Sebum secretion levels on the skin significantly increased on the forehead, but significantly decreased on the cheek which correlated with the improvement. No complaints of dryness or irritation occurred during the study. CONCLUSION: Washing the face twice a day with facial cleanser based on AEC/soap is an effective care for moderate or less grade facial acne.

Report from the third international consensus meeting to harmonise core outcome measures for atopic eczema/dermatitis clinical trials (HOME).

This report provides a summary of the third meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in San Diego, CA, U.S.A., 6-7 April 2013 (HOME III). The meeting addressed the four domains that had previously been agreed should be measured in every eczema clinical trial: clinical signs, patient-reported symptoms, long-term control and quality of life. Formal presentations and nominal group techniques were used at this working meeting, attended by 56 voting participants (31 of whom were dermatologists). Significant progress was made on the domain of clinical signs. Without reference to any named scales, it was agreed that the intensity and extent of erythema, excoriation, oedema/papulation and lichenification should be included in the core outcome measure for the scale to have content validity. The group then discussed a systematic review of all scales measuring the clinical signs of eczema and their measurement properties, followed by a consensus vote on which scale to recommend for inclusion in the core outcome set. Research into the remaining three domains was presented, followed by discussions. The symptoms group and quality of life groups need to systematically identify all available tools and rate the quality of the tools. A definition of long-term control is needed before progress can be made towards recommending a core outcome measure.

A new formula for a mild body cleanser: sodium laureth sulphate supplemented with sodium laureth carboxylate and lauryl glucoside.

OBJECTIVE: Sodium laureth sulphate (SLES) is an anionic detergent, which has been used globally for personal care products because of its mildness and good foaming ability. However, SLES is somewhat invasive and stimulatory to the skin, and many consumers with sensitive skin desire milder detergents for daily use skin cleansers. We enhanced the mildness of SLES by formulating it with sodium laureth carboxylate (AEC) and lauryl glucoside (LG). METHODS: In skin soak tests, 5% detergent solutions were applied to the forearms of 10 Japanese healthy volunteers for 30 min followed by washing with tap water once a day for 4 days. Twenty-four hours after the last treatment, cutaneous capacitance measurements and visual analyses were performed. In a controlled usage study, 16 Japanese healthy volunteers used the test body cleanser for 4 weeks. Assessment of efficacy and mildness was conducted prior to the start of the study and at the end of week 4 by cutaneous conductance, dermoscopic evaluation of the stratum corneum and visual assessment by a dermatologist. RESULTS: In soak tests, cutaneous capacitance was significantly decreased on the soap-treated region and on the SLES-treated region. No significant decrease was identified on the SLES/AEC/LG-treated region with less induction of erythema or dryness. In the controlled usage study, no significant changes in cutaneous conductance or texture or damage of corneocytes on the forearm and lower thigh were found. However, visual assessment revealed a significant decrease in scaling and erythema on the lower thigh after 4 weeks of usage with an improvement of the discomfort of the consumer. The favourability rating of this formulated detergent in several questionnaire items was very good. CONCLUSION: The newly formulated skin cleanser with the combination of anionic surfactants SLES and AEC and the non-ionic surfactant LG provides a mild surfactant with a satisfactory cleansing activity for body washing.

Inflammatory bone loss in experimental periodontitis induced by Aggregatibacter actinomycetemcomitans in interleukin-1 receptor antagonist knockout mice.

The interleukin-1 receptor antagonist (IL-1Ra) binds to IL-1 receptors and inhibits IL-1 activity. However, it is not clear whether IL-1Ra plays a protective role in periodontal disease. This study was undertaken to compare experimental periodontitis induced by Aggregatibacter actinomycetemcomitans in IL-1Ra knockout (KO) mice and wild-type (WT) mice. Computed tomography (CT) analysis and hematoxylin-and-eosin (H&E) and tartrate-resistant acid phosphatase (TRAP) staining were performed. In addition, osteoblasts were isolated; the mRNA expression of relevant genes was assessed by real-time quantitative PCR (qPCR); and calcification was detected by Alizarin Red staining. Infected IL-1Ra KO mice exhibited elevated (P, <0.05) levels of antibody against A. actinomycetemcomitans, bone loss in furcation areas, and alveolar fenestrations. Moreover, protein for tumor necrosis factor alpha (TNF-α) and IL-6, mRNA for macrophage colony-stimulating factor (M-CSF), and receptor activator of NF-κB ligand (RANKL) in IL-1Ra KO mouse osteoblasts stimulated with A. actinomycetemcomitans were increased (P, <0.05) compared to in WT mice. Alkaline phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OCN)/bone gla protein (BGP), and runt-related gene 2 (Runx2) mRNA levels were decreased (P, <0.05). IL-1α mRNA expression was increased, and calcification was not observed, in IL-1 Ra KO mouse osteoblasts. In brief, IL-1Ra deficiency promoted the expression of inflammatory cytokines beyond IL-1 and altered the expression of genes involved in bone resorption in A. actinomycetemcomitans-infected osteoblasts. Alterations consistent with rapid bone loss in infected IL-Ra KO mice were also observed for genes expressed in bone formation and calcification. In short, these data suggest that IL-1Ra may serve as a potential therapeutic drug for periodontal disease.

Lipopolysaccharide of Aggregatibacter actinomycetemcomitans up-regulates inflammatory cytokines, prostaglandin E2 synthesis and osteoclast formation in interleukin-1 receptor antagonist-deficient mice.

BACKGROUND AND OBJECTIVE: The interleukin (IL)-1 receptor antagonist (Ra) binds to IL-1 receptors and inhibits IL-1 activity. However, it is unclear whether the IL-1Ra plays a protective role in periodontal disease. The purpose of this study was to compare IL-1Ra knockout (KO) and wild-type (WT) mice in regard to proinflammatory cytokine production, osteoclast formation and bone resorption in response to periodontal bacterial lipopolysaccharide (LPS). MATERIAL AND METHODS: Peritoneal macrophages (Mφs) were obtained from 13-wk-old IL-1Ra KO and WT mice. Peritoneal Mφs were cultured with or without 10 µg/mL of Aggregatibacter actinomycetemcomitans LPS for 24 h. The levels of IL-1alpha (IL-1α), IL-1beta (IL-1ß), tumor necrosis factor-α (TNF-α) and IL-6 were measured in periotoneal Mφs supernatant fluid (PM-SF) using an ELISA. Bone marrow cells were obtained from the mice and stimulated with PM-SF for 9 d, then stained with TRAP. The frequency of TRAP-positive multinucleated giant cell formation was calculated based on a fusion index. PM-SF-stimulated calvarial bone resorption was analyzed using micro-computed tomography, and calvarial histological analysis was performed using hematoxylin and eosin and TRAP staining. The expression of cyclooxygenase-2 (Cox2), prostanoid receptor EP4 (Ep4) and Rank mRNAs in bone marrow cells were measured using real-time quantitative PCR, while prostaglandin E2 (PGE2 ) production was determined by ELISA. RESULTS: The levels of IL-1α, IL-1ß, TNF-α and IL-6 in IL-1Ra KO mice PM-SF stimulated with A. actinomycetemcomitans LPS were significantly increased by approximately 4- (p < 0.05), 5- (p < 0.05), 1.3- (p < 0.05) and 6- (p < 0.05) fold, respectively, compared with the levels in WT mice. Moreover, osteoclast formation, expression of Rank, Ep4 and Cox2 mRNAs and production of PGE2 were significantly increased by approximately 2- (p < 0.05), 1.6- (p < 0.05), 2.5- (p < 0.05), 1.6- (p < 0.05) and 1.9- (p < 0.05) fold, respectively, in IL-1Ra KO mice stimulated with A. actinomycetemcomitans LPS compared with WT mice. CONCLUSION: IL-1Ra regulates IL-1 activity and appears to reduce the levels of other inflammatory cytokines, including TNF-α and IL-6, while it also reduces expression of the EP4 receptor related to prostanoid sensitivity and osteoclast formation. These results suggest that IL-1Ra is an important molecule for inhibition of inflammatory periodontal bone resorption.

Enzastaurin has anti-tumour effects in lung cancers with overexpressed JAK pathway molecules.

BACKGROUND: Enzastaurin, an oral serine-threonine kinase inhibitor, was initially developed as an ATP-competitive selective inhibitor against protein kinase Cß. However, the mechanism by which enzastaurin contributes to tumourigenesis remains unclear. METHODS: We analysed the anti-tumour effects of enzastaurin in 22 lung cancer cell lines to ascertain the potential for enzastaurin-based treatment of lung cancer. To identify molecules or signalling pathways associated with this sensitivity, we conducted a gene, receptor tyrosine kinases phosphorylation and microRNA expression profiling study on the same set of cell lines. RESULTS: We identified eight genes by pathway analysis of molecules having gene-drug sensitivity correlation, and used them to build a support vector machine algorithm model by which sensitive cell lines were distinguished from resistant cell lines. Pathway analysis revealed that the JAK/STAT signalling pathway was one of the main ones involved in sensitivity to enzastaurin. Overexpression of JAK1 was observed in the sensitive cells by western blotting. Simultaneous administration of enzastaurin and JAK inhibitor inhibited enzastaurin-induced cell growth-inhibitory effect. Furthermore, lentiviral-mediated JAK1-overexpressing cells were more sensitive to enzastaurin than control cells. CONCLUSION: Our results suggested that the JAK1 pathway may be used as a single predictive biomarker for enzastaurin treatment. The anti-tumour effect of enzastaurin should be evaluated in lung cancer with overexpressed JAK pathway molecules.

Heat-killed bacillus Calmette-Guérin and Mycobacterium kansasii antigen 85B combined vaccination ameliorates dermatitis in a mouse model of atopic dermatitis by inducing regulatory T cells.

BACKGROUND: Atopic dermatitis (AD) is a recurrent inflammatory skin disease characterized by dominant T-helper (Th) 2 cytokine response. Bacillus Calmette-Guérin (BCG) has been used for preventing tuberculosis, and is regarded as a strong Th1 cytokine inducer. Antigen (Ag) 85B is a secretory protein present in Mycobacterium species that induces Th1 cytokine production. OBJECTIVES: We investigated the effects of combined vaccination of heat-killed BCG (hkBCG) and Mycobacterium kansasii Ag85B in an AD mouse model. METHODS: For the AD model, keratin 14 promoter-derived caspase-1 overexpressing mice (KCASP1Tg) were used. The mice received a combination therapy of hkBCG at age 3 weeks and Ag85B twice weekly for 11 weeks from the 4th week; Ag85B monotherapy from the 4th week; hkBCG monotherapy at the 3rd week; or control saline. Areas of skin lesions, cytokine mRNA expression and serum interleukin (IL)-18 and immunoglobulin (Ig) E levels were analysed. Inducible Foxp3+ regulatory T cells (iTreg), IL-10-producing T cells (Tr1), and interferon (IFN)-γ/IL-4/IL-17-producing T cells were evaluated in the spleen. RESULTS: Saline-treated mice and hkBCG monotherapy mice spontaneously developed severe dermatitis. However, combined therapy with hkBCG and Ag85B significantly suppressed the development of skin lesions and mast cell infiltrations. Elevations of the serum IgE and IL-18 levels were significantly suppressed with combined therapy. Mice treated with hkBCG and Ag85B had a normal number of iTreg in the spleen, and decreased number of both IL-4- and IL-17-producing CD4+ T cells. The effect of Ag85B monotherapy was limited. CONCLUSIONS: Combined vaccination with hkBCG and Ag85B decreases AD skin lesions by inducing regulatory T cells, suggesting that this vaccination is a potent and novel therapeutic strategy for AD.

Time-action profiles of insulin detemir in normal and diabetic dogs.

Insulin detemir is the first member of a new class of long-acting soluble insulin analogues capable of maintaining the basal level of insulin in humans. In this preliminary study, we investigated the time-action profiles of insulin detemir in normal and diabetic dogs since the use of insulin detemir in canines has yet to be determined. Eight animals were used in our study (three normal and five insulin dependent diabetic dogs). Time-action profiles of insulin detemir were monitored in normal dogs using an artificial pancreas apparatus under euglycemic condition. Blood sampling was performed at 2h intervals post feeding, with insulin administration, in insulin dependent diabetic dogs. Time-action profiles of insulin detemir, in normal dogs, demonstrated that insulin detemir is a long-lasting preparation similar to what has been observed in humans. A pronounced peak was detected at 8-10h while the glucose-lowering effect lasted for over 24h after insulin injection, thus illustrating its longer prolonged peak activity time. Furthermore, intensive glycemic control was achieved with insulin detemir in insulin dependent diabetic dogs, using a lower dosage than NPH insulin and insulin glargine therapeutic doses. Our results indicate that insulin detemir has a greater effect than either NPH insulin or insulin glargine in canines, requiring a lower dose than either insulin preparation. However, using insulin detemir also carries a higher risk of inducing hypoglycemia as compared to either NPH insulin or insulin glargine.

1,24-Dihydroxyvitamin D3 (tacalcitol) prevents skin T-cell infiltration.

BACKGROUND: 1,24-Dihydroxyvitamin D3 (tacalcitol), a vitamin D(3) compound, has been used to treat T cell-mediated inflammatory skin diseases such as psoriasis, prurigo and vitiligo. The best-known mechanism of action of this compound is inhibition of the abnormal proliferation of keratinocytes and subsequent maturation; however, its effects on skin T-cell recruitment have not yet been evaluated. Cutaneous lymphocyte-associated antigen (CLA), a surface glycoprotein expressed on T cells, plays a critical role in skin T-cell infiltration. We recently reported that 1,25-dihydroxyvitamin D3 inhibits skin infiltration of CD4+ T cells by suppressing CLA expression on T cells. OBJECTIVES: In this study, we investigated the effect of tacalcitol on CLA epitope decoration and on the levels of gut or lymph node homing receptor expression in human T cells. METHODS: We cultured human T cells with tacalcitol and analysed the effect on CLA expression and skin-homing ability, and evaluated glycosyltransferase mRNAs. We also performed an in vivo study using an antigen-dependent delayed-type hypersensitivity (DTH) mouse model and investigated the effect of tacalcitol on skin-infiltrating CD4+ T cells. RESULTS: Tacalcitol downregulated the expression of CLA and, in parallel, the E- and P-selectin ligand function; however, it exerted no effect on other homing receptors. Subcutaneously and intraperitoneally administered tacalcitol downregulated skin infiltration of effector CD4+ T cells in an in vivo DTH mouse model. CONCLUSIONS: These findings suggest that tacalcitol reduces skin inflammation by partially downregulating CLA expression levels.

Effect of glimepiride and nateglinide on serum insulin and glucose concentration in healthy cats.

Glimepiride and nateglinide are two common oral hypoglycemic agents currently being used with humans suffering from Type 2 diabetes mellitus. Neither drug has been tested with cats thus far and it is currently unknown whether either of these drugs exert any effect in cats or not. The objective of this study was to determine the effect of glimepiride and nateglinide on glucose and insulin responses in healthy control cats, in order to determine their potential use in diabetic cats. The intravenous glucose tolerance tests was carried out since it is an excellent test for evaluating pancreatic beta-cell function for insulin secretion. Alterations in the insulin secretion pattern can be perceived as the earliest sign of beta-cell dysfunction in many species, including cats. Nateglinide demonstrated a quick action/short duration type effect with serum glucose nadiring and insulin response peaking at 60 and 20 minutes, respectively. Alternatively, glimepiride is medium-to-long acting with serum glucose nadiring and insulin response peaking at 180 minutes and 60 minutes, respectively. Nateglinide's potency was evident allowing it to induce a 1.5-2 higher preliminary insulin peak (3.7 +/- 1.1 pg/ml) than glimepiride's (2.5 +/- 0.1 pg/ml), albeit only for a short period of time. Because glimepiride and nateglinide have a shared mode of action, no significant differences in overall glucose AUC(0-360 min) (24,435 +/- 2,940 versus 24,782 +/- 2,354 mg min/dl) and insulin AUC(0-360 min) (410 +/- 192 versus 460 +/- 159) in healthy control cats were observed. These findings may provide useful information when choosing a hypoglycemic drug suited for the treatment of diabetic cats depending on the degree of diabetes mellitus the cat is suffering from.

Infusion requirements and reversibility of rocuronium at the corrugator supercilii and adductor pollicis muscles.

BACKGROUND: The aim of this study is to compare the infusion rates required to maintain a constant neuromuscular block and the reversibility of rocuronium at the corrugator supercilii muscle (CSM) and the adductor pollicis muscle (APM). METHODS: We randomly allocated 30 female patients into two groups of 15 patients each to monitor neuromuscular block at either the CSM or the APM. After induction of anaesthesia and laryngeal mask insertion, contraction of the CSM to the facial nerve stimulation or that of the APM to the ulnar nerve stimulation was quantified using an acceleromyograph during 1.0-1.5% end-tidal sevoflurane anaesthesia. All the patients received a bolus of 1 mg/kg rocuronium. When the first twitch (T1) of train-of-four (TOF) recovered to 10% of the control, rocuronium infusion was commenced and maintained at T1 of 10% of the control at the CSM or APM for 120 min. Immediately after rocuronium infusion was discontinued, the time required for 0.04 mg/kg neostigmine-facilitated recovery to a TOF ratio of 0.9 was recorded. RESULTS: Rocuronium infusion dose after a lapse of 120 min was significantly larger in the CSM than in the APM [7.1 (2.3) vs. 4.7 (2.6) microg/kg/min; P=0.001]. The time for facilitated recovery was shorter in the CSM than in the APM [11.4 (3.8) vs. 16.2 (6.0) min; P=0.016]. CONCLUSION: A larger rocuronium infusion dose was required to maintain a constant neuromuscular block at the CSM. Neostigmine-mediated reversal was faster at the CSM.