Time needed to intubate and suction a manikin prior to instituting positive pressure ventilation: a simulation trial

Tracheal suctioning in non-vigorous newborn delivered through meconium-stained amniotic fluid (MSAF) is supposed to delay initiation of positive pressure ventilation (PPV), but the magnitude of such delay is unknown. To compare the time of PPV initiation when performing immediate laryngoscopy with intubation and suctioning vs. performing immediate PPV without intubation in a manikin model. Randomized controlled crossover (AB/BA) trial comparing PPV initiation with or without endotracheal suctioning in a manikin model of non-vigorous neonates born through MSAF. Participants were 20 neonatologists and 20 pediatric residents trained in advanced airway management. Timing of PPV initiation was longer with vs. without endotracheal suctioning in both pediatric residents (mean difference 13\ua0s, 95% confidence interval 8 to 18\ua0s; p\ua0< 0.0001) and neonatologists (mean difference 12\ua0s, 95% confidence interval 8 to 16\ua0s; p < 0.0001). The difference in timing of PPV initiation was similar between pediatric residents and neonatologists (mean difference 12 1\ua0s, 95% confidence interval 12 7 to 6\ua0s; p\ua0= 0.85). Conclusions: Performing immediate laryngoscopy with intubation and suctioning was associated with longer\u2014but not clinically relevant\u2014time of initiation of PPV compared with immediate PPV without intubation in a manikin model. While suggesting negligible delay in starting PPV, further studies in a clinical setting are warranted. Registration: clinicaltrial.gov NCT04076189.What is Known:\u2022 Management of the non-vigorous newborn delivered through meconium-stained amniotic fluid remains still controversial.\u2022 Tracheal suctioning in non-vigorous newborn delivered through meconium-stained amniotic fluid is supposed to delay initiation of positive pressure ventilation, but the magnitude of such delay is unknown.What is New:\u2022 Performing immediate ventilation without intubation was associated with shorter\u2014but not clinically relevant\u2014time of initiation of ventilation compared to immediate laryngoscopy with intubation and suctioning in a manikin model.\u2022 Further studies in a clinical setting are warranted

A comparison of the effectiveness of three LED phototherapy machines, single- and double-sided, for treating neonatal jaundice in a low resource setting

© 2018 Arnolda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction Neonatal jaundice is one of the most common reasons for hospital admission in low resource settings. Treatment is frequently inadequate as conventional phototherapy requires frequent bulb changes. LED phototherapy has comparable efficacy to conventional phototherapy, and the bulbs last over 40,000 hours. This observational study compares the effectiveness of three LED machines, two single-sided and one double-sided in routine use in Vietnam. Methods We included all infants weighting 1500g and with jaundice diagnosed visually or by Total Serum Bilirubin (TSB) measurement at The Da Nang Hospital for Women and Children (Da Nang, Vietnam). The primary endpoint was the average hourly change in TSB over the first six hours of treatment. The secondary endpoints were duration of treatment; average hourly change in TSB over treatment, and length of stay in the neonatal unit. Multivariable analysis and bootstrap methods was performed to compare outcomes, adjusting for potential confounders. Results All outcomes were comparable in the two single-sided machines. The double-sided machine showed 54% increase in the hourly speed of TSB reduction (1.3 μmol/L/hr, 95% CI 0.3-2.3), with a 45% increase in the speed of TSB reduction over the duration of treatment (0.9 μmol/ L/hr, 95% CI 0.6-1.3). In addition, the double-sided machine was associated with 21% reduction in the duration of treatment (14 hours, 95% CI 5-22) and 16% reduction of length of stay (14 hours, 95% CI 3-25). Conclusion The results confirm and quantify the benefits of increasing surface-area exposure during phototherapy. Adjusted for multiple potential confounders, use of double-sided phototherapy can substantially increase the speed of TSB reduction, and substantially decrease the duration of treatment and length of stay in the NCU

Shielding efficiency and E(J) characteristics measured on large melt cast Bi-2212 hollow cylinders in axial magnetic fields

We show that tubes of melt cast Bi-2212 used as current leads for LTS magnets can also act as efficient magnetic shields. The magnetic screening properties under an axial DC magnetic field are characterized at several temperatures below the liquid nitrogen temperature (77 K). Two main shielding properties are studied and compared with those of Bi-2223, a material that has been considered in the past for bulk magnetic shields. The first property is related to the maximum magnetic flux density that can be screened, Blim; it is defined as the applied magnetic flux density below which the field attenuation measured at the centre of the shield exceeds 1000. For a cylinder of Bi-2212 with a wall thickness of 5 mm and a large ratio of length over radius, Blim is evaluated to 1 T at T = 10 K. This value largely exceeds the Blim value measured at the same temperature on similar tubes of Bi-2223. The second shielding property that is characterized is the dependence of Blim with respect to variations of the sweep rate of the applied field, dBapp/dt. This dependence is interpreted in terms of the power law E = Ec(J/Jc)^n and allows us to determine the exponent n of this E(J) characteristics for Bi-2212. The characterization of the magnetic field relaxation involves very small values of the electric field. This gives us the opportunity to experimentally determine the E(J) law in an unexplored region of small electric fields. Combining these results with transport and AC shielding measurements, we construct a piecewise E(J) law that spans over 8 orders of magnitude of the electric field.Comment: 16 pages, 7 figure

Mismatch-repair protein expression in high-grade gliomas: A large retrospective multicenter study

Background: DNA mismatch repair (MMR) is a system for repairing errors in DNA replication. Cancer cells with MMR deficiency can have immunohistochemical loss of MMR protein expression leading to a hypermutable phenotype that may correlate with anti-PD1 efficacy. Scant data exist about immunohistochemical loss of MMR protein expression in high-grade gliomas (HGG). Materials and Methods: We performed a large multicenter retrospective study to investigate the frequency and the prognostic role of immunohistochemical loss of MMR protein expression in HGG patients; we nevertheless evaluated the association between this status and clinical or molecular characteristics. Immunohistochemical loss of MMR protein expression was recorded as partial or complete loss of at least 1 MMR protein. Results: We analyzed the expression of MMR proteins in tumor tissue of 355 consecutive patients. Partial and complete immunohistochemical loss of MMR proteins was found in 43/355 samples (12.1%) and among these, 15 cases (4.2%) showed a complete loss of at the least one MMR protein. Alteration of MSH2 expression was found in 55.8%, MSH6 in 46.5%, PMS2 in 34.9%, and MLH1 in 30.2%. Alteration of MMR protein expression was statistically more frequent in anaplastic gliomas, in recurrent disease, in patients treated with temozolomide, and in IDH-mut gliomas. Immunohistochemical loss of MMR proteins was not associated with survival, adjusting for clinically relevant confounders. Conclusions: MMR protein expression status did not affect survival in HGG patients. We identified clinical and molecular characteristics correlating with immunohistochemical loss of MMR proteins expression. A large study should be performed to analyze its predictive role of immune checkpoint inhibitor efficacy in these subgroups of patients

Definition of the Prognostic Role of MGMT Promoter Methylation Value by Pyrosequencing in Newly Diagnosed IDH Wild‐Type Glioblastoma Patients Treated with Radiochemotherapy: A Large Multicenter Study

Background. O6‐methylguanine (O6‐MeG)‐DNA methyltransferase (MGMT) methylation status is a predictive factor for alkylating treatment efficacy in glioblastoma patients, but its prognostic role is still unclear. We performed a large, multicenter study to evaluate the association between MGMT methylation value and survival. Methods. We evaluated glioblastoma patients with an assessment of MGMT methylation status by pyrosequencing from nine Italian centers. The inclusion criteria were histological diagnosis of IDH wild‐type glioblastoma, Eastern Cooperative Oncology Group Performance Status (ECOG‐PS) ≤2, and radio‐chemotherapy treatment with temozolomide. The relationship between OS and MGMT was investigated with a time‐dependent Receiver Operating Characteristics (ROC) curve and Cox regression models. Results. In total, 591 newly diagnosed glioblastoma patients were analyzed. The median OS was 16.2 months. The ROC analysis suggested a cut‐off of 15% for MGMT methylation. The 2‐year Overall Survival (OS) was 18.3% and 51.8% for MGMT methylation &lt;15% and ≥15% (p &lt; 0.0001). In the multivariable analysis, MGMT methylation &lt;15% was associated with impaired survival (p &lt;0.00001). However, we also found a non‐linear association between MGMT methylation and OS (p = 0.002): median OS was 14.8 months for MGMT in 0–4%, 18.9 months for MGMT in 4–40%, and 29.9 months for MGMT in 40– 100%. Conclusions. Our findings suggested a non‐linear relationship between OS and MGMT promoter methylation, which implies a varying magnitude of prognostic effect across values of MGMT promoter methylation by pyrosequencing in newly diagnosed IDH wild‐type glioblastoma patients treated with chemoradiotherapy

Antitumorigenesis of antioxidants in a transgenic Rac1 model of Kaposi's sarcoma

Kaposi's sarcoma (KS) is the major AIDS-associated malignancy. It is characterized by the proliferation of spindle cells, inflammatory infiltrate, and aberrant angiogenesis caused by Kaposi's sarcoma herpesvirus (KSHV) infection. Small GTPase Rac1, an inflammatory signaling mediator triggering reactive oxygen species (ROS) production by NADPH-oxidases, is implicated in carcinogenesis and tumor angiogenesis. Here, we show that expression of a constitutively active Rac1 (RacCA) driven by the α-smooth muscle actin promoter in transgenic mice is sufficient to cause KS-like tumors through mechanisms involving ROS-driven proliferation, up-regulation of AKT signaling, and hypoxia-inducible factor 1-α–related angiogenesis. RacCA-induced tumors expressed KS phenotypic markers; displayed remarkable transcriptome overlap with KS lesions; and were, like KS, associated with male gender. The ROS scavenging agent N-acetyl-cysteine inhibited angiogenesis and completely abrogated transgenic RacCA tumor formation, indicating a causal role of ROS in tumorigenesis. Consistent with a pathogenic role in KS, immunohistochemical analysis revealed that Rac1 is overexpressed in KSHV+ spindle cells of AIDS-KS biopsies. Our results demonstrate the direct oncogenicity of Rac1 and ROS and their contribution to a KS-like malignant phenotype, further underscoring the carcinogenic potential of oxidative stress in the context of chronic infection and inflammation. They define the RacCA transgenic mouse as a model suitable for studying the role of oxidative stress in the pathogenesis and therapy of KS, with relevance to other inflammation-related malignancies. Our findings suggest host and viral genes triggering Rac1 or ROS production as key determinants of KS onset and potential KS chemopreventive or therapeutic targets

Adaptabilidade e estabilidade de híbridos de sorgo biomassa semeados em três locais na safra 2021/2022.

O objetivo desse trabalho foi avaliar a adaptabilidade e estabilidade para a produtividade (t.ha-1) de 25 híbridos de sorgo destinadas à produção de biomassa.Evento híbrido