Search

Background: Patient blood management (PBM) is a multidisciplinary and patient-centered treatment approach, comprising the detection and treatment of anemia, the minimization of blood loss, and the rational use of allogeneic transfusions. Pregnancy, delivery, and the puerperium are associated with increased rates of iron deficiency and anemia, which correlates with worse maternal and fetal outcomes and places pregnant women at increased risk of obstetric hemorrhage. Summary: Early screening for iron deficiency before the onset of anemia, as well as the use of oral and intravenous iron to treat iron deficiency anemia, has been shown to be beneficial. Anemia in pregnancy and the puerperium should be treated according to a staged regimen, administering either iron alone or in combination with an off-label use of human recombinant erythropoietin in selected patients. This regimen should be tailored to the needs of each individual patient. Postpartum hemorrhage (PPH) accounts for up to one-third of maternal deaths in both developing and developed countries. Bleeding complications should be anticipated and blood loss reduced by interdisciplinary preventive measures and individually tailored care. It is recommended that facilities have a PPH algorithm, primarily focusing on prevention through use of uterotonics, but also incorporating early diagnosis of the cause of bleeding, optimization of hemostatic conditions, timely administration of tranexamic acid, and integration of point-of-care tests to support the guided substitution of coagulation factors, alongside standard laboratory tests. Additionally, cell salvage has proven beneficial and should be considered for various indications in obstetrics including hematologic disturbances, as well as various forms of placental disorders. Key Message: This article reviews PBM in pregnancy, delivery, and the puerperium. The concept comprises early screening and treatment of anemia and iron deficiency, a transfusion and coagulation algorithm during delivery, as well as cell salvage.

BACKGROUND Viscoelastic hemostatic assays, such as ROTEM or TEG, enable prompt diagnosis and accelerate targeted treatment. However, the complex interpretation of the results remains challenging. Visual Clot - a situation awareness-based visualization technology - was developed to assist clinicians in interpreting viscoelastic tests. OBJECTIVE Following a previous high-fidelity simulation study, we analyzed users' perceptions of the technology to identify its strengths and limitations from clinicians' perspectives. METHODS This is a mixed qualitative-quantitative study consisting of interviews and an online survey. After solving coagulation scenarios using Visual Clot in high-fidelity simulations, we interviewed anesthesia personnel about the perceived advantages and disadvantages of the new tool. We used a template approach to identify dominant themes in interview responses. Out of these themes, we then defined five main statements, which were rated on Likert scales in the online questionnaire. RESULTS We interviewed 77 participants and 23 completed the online survey. We identified nine frequently mentioned topics by analyzing interview responses. The most common themes were ``positive design features``, ``intuitive and easy to learn`` and ``lack of a quantitative component ``. In the online survey, 70% of participants agreed that Visual Clot is easy to learn and that a combination of Visual Clot and ROTEM would help manage complex hemostatic situations. CONCLUSIONS A group of anesthesia care providers found Visual Clot well-designed, intuitive and easy to learn. Participants highlighted its usefulness in emergencies, especially for clinicians inexperienced in coagulation management. However, the lack of quantitative information is an area for improvement.

Prehospital Pain Management: Overview and Potential Improvements

Sağır, Özlem (Balikesir Author), Introduction More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. Methods and analysis EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. Ethics and dissemination EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369. ©

Pre-eclampsia (PE) is a systemic maternal syndrome affecting 2-8% of pregnancies worldwide and involving poor placental perfusion and impaired blood supply to the foetus. It manifests after the 20th week of pregnancy as new-onset hypertension and substantial proteinuria and is responsible for severe maternal and newborn morbidity and mortality. Identifying biomarkers that predict PE onset prior to its establishment would critically help treatment and attenuate outcome severity. MicroRNAs are ubiquitous gene expression modulators found in blood and tissues. Trophoblast cell surface antigen (Trop)-2 promotes cell growth and is involved in several cancers. We assessed the PE predictive ability of maternal miR-125b in the first trimester of pregnancy by measuring its plasma levels in women with normal pregnancies and with pregnancies complicated by PE on the 12th week of gestation. To gain insight into PE pathogenesis we investigated whether Trop-2 is targeted by miR-125b in placental tissue. Data analysis demonstrated a significant association between plasma miR-125b levels and PE, which together with maternal body mass index before pregnancy provided a predictive model with an area under the curve of 0.85 (95% confidence interval, 0.70-1.00). We also found that Trop-2 is a target of miR-125b in placental cells; its localization in the basal part of the syncytiotrophoblast plasma membrane suggests a role for it in the early onset of PE. Altogether, maternal miR-125b proved a promising early biomarker of PE, suggesting that it may be involved in placental development through its action on Trop-2 well before the clinical manifestations of PE.

Human trophoblast cell surface antigen 2 (Trop-2) is a 40-kDa transmembrane glycoprotein that was first identified as a marker of human trophoblast cells. Trop-2 acts on cell proliferation, adhesion, and migration by activating a number of intracellular signalling pathways. Elevated Trop-2 expression has been demonstrated in several types of cancer and correlated with aggressiveness and poor prognosis. Since no data are available on Trop-2 in bladder cancer (BC), the purpose of the study was to determine its levels in tissue specimens from normal individuals and patients with BC at different stages. Moreover, since according to recent evidence Trop-2 is a miR-125b target, miR-125b expression was also assessed in tissue specimens. Finally, the effect of the Trop-2/miR-125b axis on the proliferation and migration of BC cells was evaluated in vitro. The Trop-2/miR-125b axis was seen to be differentially expressed in normal urothelium, non-invasive BC and invasive BC tissue. Significant miR-125b down-regulation was associated with a significant increase in Trop-2 protein levels in BC tissue and correlated with disease severity. In vitro analysis confirmed the role of miR-125b in down-modulation of Trop-2 protein levels and showed that Trop-2/miR-125b axis affects cellular proliferation in bladder tissue. In conclusion, our findings highlight a role for the Trop-2/miR-125b axis in BC progression and suggest Trop-2 and miR-125b as diagnostic/prognostic marker candidates as well as druggable targets for innovative therapeutic approaches.

Uterine leiomyomas (fibroids or myomas) are the most common benign tumors of premenopausal women and new medical treatments are needed. This study aimed to determine the effects of omega-3 fatty acids on the lipid profile, membrane architecture and gene expression patterns of extracellular matrix components (collagen1A1, fibronectin, versican, or activin A), mechanical signaling (integrin β1, FAK, and AKAP13), sterol regulatory molecules (ABCG1, ABCA1, CAV1, and SREBF2), and mitochondrial enzyme (CYP11A1) in myometrial and leiomyoma cells. Myometrial tissues had a higher amount of arachidonic acid than leiomyoma tissues while leiomyoma tissues had a higher level of linoleic acid than myometrial tissues. Treatment of primary myometrial and leiomyoma cells with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) reduced the monounsaturated fatty acid (MUFA) content and increased the polyunsaturated fatty acid (PUFA) content in both cell types. Myometrial and leiomyoma cell membranes were in the liquid-crystalline phase, but EPA- and DHA-treated cells had decreased membrane fluidity. While we found no changes in the mRNA expression of ECM components, EPA and DHA treatment reduced levels of ABCG1, ABCA1, and AKAP13 in both cell types. EPA and DHA also reduced FAK and CYP11A1 expression in myometrial cells. The ability of omega-3 fatty acids to remodel membrane architecture and downregulate the expression of genes involved in mechanical signaling and lipid accumulation in leiomyoma cells offers to further investigate this compound as preventive and/or therapeutic option.

Introduction Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary systemic vascular disorder. Granular osmiophilic material (GOM) is its ultrastructural marker. We reviewed tissue biopsies from CADASIL patients to establish whether ultrastructural observations help clarify the pathogenic mechanism of CADASIL. Given the resemblance of the GOM deposits to the immunoglobulin deposits seen in glomerulonephritis and focal segmental glomerulosclerosis (FSGS), their morphologies were investigated and compared. Methods Skin, skeletal muscle, kidney, and pericardium tissue biopsies from 13 patients with a clinical and molecular diagnosis of CADASIL, and kidney biopsies from five patients with IgA nephropathy and five patients with primary FSGS were subjected to ultrastructural examination. Results In CADASIL patients, several GOM deposits from all sites were partially or totally surrounded by an electron-lucent halo. The deposits frequently had a more electron-dense portion with a regular outline on the inner side and a less osmiophilic, looser outer side displaying a less regular profile. The uniformly dense deposits tended to be more osmiophilic if located close to the cell membrane and less osmiophilic if laid farther away from it. The immunoglobulin deposits from the glomerulonephritis and FSGS patients lacked both the granular pattern and the halo. Conclusions This study demonstrates that GOM deposits may have a nonuniform morphology and describes in detail an electron-lucent halo surrounding several of them. It is conceivable that the halo is the morphological evidence and possibly the cause of an aberrant NOTCH3 processing, already suspected to be involved in CADASIL.

Objective To investigate the presence of Raf kinase inhibitor protein (RKIP) in human myometrium and leiomyoma as well as to determine the effect of locostatin (RKIP inhibitor) on extracellular matrix (ECM) production, proliferation, and migration in human myometrial and leiomyoma cells. Design Laboratory study. Setting Human myometrium and leiomyoma. Patient(s) Thirty premenopausal women who were admitted to the hospital for myomectomy or hysterectomy. Intervention(s) Myometrial and leiomyoma tissues were used to investigate the localization and the expression level of RKIP through immunohistochemistry and Western blotting. Myometrial and leiomyoma cells were treated with locostatin (10 μM) to measure ECM expression by real-time polymerase chain reaction, GSK3β expression by Western blotting, cell migration by wound-healing assay, and cell proliferation by MTT assay and immunocytochemistry. Main Outcome Measure(s) The expression of RKIP in human myometrial and leiomyoma tissue; ECM components and GSK3β expression, migration, and proliferation in myometrial and leiomyoma cells. Result(s) RKIP is expressed in human myometrial and leiomyoma tissue. Locostatin treatment resulted in the activation of the mitogen-activated protein kinase (MAPK) signal pathway (ERK phosphorylation), providing a powerful validation of our targeting protocol. Further, RKIP inhibition by locostatin reduces ECM components. Moreover, the inhibition of RKIP by locostatin impaired cell proliferation and migration in both leiomyoma and myometrial cells. Finally, locostatin treatment reduced GSK3β expression. Therefore, even if the activation of MAPK pathway should increase proliferation and migration, the destabilization of GSK3β leads to the reduction of proliferation and migration of myometrial and leiomyoma cells. Conclusion(s) Our results indicate that RKIP may be involved in leiomyoma pathophysiology.

Diabet. Med. 28, 1388–1394 (2011) Abstract Objective The key goal of diabetes management is to prevent complications. While the patho-physiological mechanisms responsible for diabetes complications have been extensively studied, at present it is impossible to predict which patient with diabetes could develop complications. In recent years, the role of leukocyte telomere length in the pathogenesis of cardiovascular disease and Type 2 diabetes has been investigated. However, studies aiming to investigate the role of telomeres in the development and progression of Type 2 diabetes, as well as diabetic complications, are still lacking. As a consequence, this study aimed to verify whether leukocyte telomere length is associated with the presence and the number of diabetic complications in a sample of patients with Type 2 diabetes. Methods This is a cross-sectional study. Nine hundred and one subjects were enrolled, including 501 patients with Type 2 diabetes, of whom 284 had at least one complication and 217 were without complications, and 400 control subjects. Leukocyte telomere length was measured by quantitative real-time PCR. Results Patients with diabetes complications had significantly shorter leukocyte telomere length than both patients without diabetes complications and healthy control subjects. Moreover, among patients with diabetes complications, leukocyte telomere length became significantly and gradually shorter with the increasing number of diabetes complications. The magnitude of the effect of the decrease of the abundance of telomeric template vs. a single-copy gene length (T/S ratio) on complications is described by the estimated odds ratio OR = 5.44 (95% CI 3.52–8.42). Conclusions The results of the study support the hypothesis that telomere attrition may be a marker associated with the presence and the number of diabetic complications.

Objective Comparison of climbing versus no treatment to treat chronic low back pain. Design Prospective randomized controlled trial. Setting Tertiary. Participants A total of 30 patients with chronic low back pain were recruited and randomly assigned to 2 different groups: climbing and control. The inclusion criteria were defined as chronic low back pain, age between 18 and 45 years, body mass index lower than 25, and no climbing experience. Interventions Patients in the climbing group were instructed to climb 5 different climbing routes. A climbing activity of 10 sessions in 8 weeks, at least once a week with a minimum duration of 1 hour, was mandatory. Main outcome measures The participants were examined before (T0) and after therapy (8 weeks, T8) and after another 6 weeks (T14). The outcome was evaluated using Oswestry Disability Index, Visual Analog Scale (VAS), Likert scale, and magnetic resonance imaging (MRI). Radiologists evaluating MRI were blinded. The study was performed as a single-center study. Results Evaluating the Oswestry Disability Index, a significant difference in the time course between the 2 groups was detected (P = 0.022). Significant improvements comparing climbing and control group were also found when assessing VAS in a minimal finger-floor-distance position (P = 0.048). Patients in the climbing group showed a reduction in size of disc protrusion. Conclusions Climbing may be an effective and low-cost therapy option for people with chronic low back pain. Clinical relevance Low back pain is a very common disease but still a challenge to treat. Therapy strategies vary from conservative ones, pharmacological treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and weak opioids, to invasive treatment with acupuncture, injections, and operative reconstruction. Some can be costly and not without risks. For instance, many people who use NSAIDs are at risk of common side effects such as gastrointestinal complications (irritation, ulcers, and bleeding) that may lead to hospitalization. Climbing could offer reduction of pain and better performance in daily life, because it offers a closed chain muscle training that has the potential to improve posture, perception of the trunk midline, and muscle control. Climbing may also lead to a better adherence to continuing treatment than traditional physical therapy and exercise due to a more exciting aspect of the sports activity.