The Perioperative Effect of Increased Body Mass Index on Peripheral Nerve Blockade: an Analysis of 528 Ultrasound Guided Interscalene Blocks

SummaryBackground and objectivesObese patients can pose a unique perioperative anesthetic challenge, making regional anesthetic techniques an intriguing means of providing analgesia for this population. Ultrasound guidance has been touted recently as being beneficial for this population in which surface landmarks can become obscured. In this study, the effect of increased Body Mass Index (BMI) on ultrasound guided interscalene peripheral nerve blockade is investigated.Material and methodsThis study is a retrospective review of 528 consecutive patients who received preoperative ultrasound-guided interscalene nerve blocks at the University of Wisconsin Hospital and Clinics. We examined the association between BMI and the following parameters: time required for block placement; presence of Postoperative Nausea and Vomiting (PONV); postoperative Post Anesthesia Care Unit (PACU) pain scores; volume of local anesthetic injected; acute complications; and opioid administration preoperatively, intraoperatively, and postoperatively. Univariate and multivariate least squares and logistic regression models were used.ResultsAn elevated BMI was associated with an increased: time required for block placement (p-value=0.025), intraoperative fentanyl administration (p-value<0.001), peak PACU pain scores (p-value<0.001), PACU opioid administration (p-value<0.001), PACU oral opioid administration (p-value<0.001), total PACU opioid administration (p-value<0.001) and incidence of PACU nausea (p-value=0.025)ConclusionsUltrasound guided interscalene nerve blocks for perioperative analgesia can be safely and effectively performed in the obese patient but they may be more difficult to perform and analgesia may not be as complete

A compilation of global bio-optical in situ data for ocean colour satellite applications – version three

A global in situ data set for validation of ocean colour products from the ESA Ocean Colour Climate Change Initiative (OC-CCI) is presented. This version of the compilation, starting in 1997, now extends to 2021, which is important for the validation of the most recent satellite optical sensors such as Sentinel 3B OLCI and NOAA-20 VIIRS. The data set comprises in situ observations of the following variables: spectral remote-sensing reflectance, concentration of chlorophyll-a, spectral inherent optical properties, spectral diffuse attenuation coefficient, and total suspended matter. Data were obtained from multi-project archives acquired via open internet services or from individual projects acquired directly from data providers. Methodologies were implemented for homogenization, quality control, and merging of all data. Minimal changes were made on the original data, other than conversion to a standard format, elimination of some points, after quality control and averaging of observations that were close in time and space. The result is a merged table available in text format. Overall, the size of the data set grew with 148 432 rows, with each row representing a unique station in space and time (cf. 136 250 rows in previous version; Valente et al., 2019). Observations of remote-sensing reflectance increased to 68 641 (cf. 59 781 in previous version; Valente et al., 2019). There was also a near tenfold increase in chlorophyll data since 2016. Metadata of each in situ measurement (original source, cruise or experiment, principal investigator) are included in the final table. By making the metadata available, provenance is better documented and it is also possible to analyse each set of data separately. The compiled data are available at https://doi.org/10.1594/PANGAEA.941318 (Valente et al., 2022)

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Efeito perioperatório do índice de massa corporal elevado no bloqueio do nervo periférico: uma análise de 528 bloqueios interescalênicos guiados por ultrassom

JUSTIFICATIVA E OBJETIVOS: Os pacientes obesos podem representar um desafio anestésico perioperatório único, tornando as técnicas anestésicas regionais um meio desafiador de oferecer analgesia para esta população. A orientação por ultrassom foi recentemente elogiada como sendo benéfica para esta população na qual os limites anatômicos de superfície podem ser obscurecidos. Neste estudo, é investigado o efeito do Índice de Massa Corporal (IMC) elevado no bloqueio interescalênico do nervo periférico guiado por ultrassom. MATERIAL E MÉTODOS: Este estudo é uma análise retrospectiva de 528 pacientes consecutivos que receberam bloqueios nervosos interescalênicos pré-operatórios guiados por ultrassom no Hospital e Clínica da University of Wisconsin. Examinamos a associação entre IMC e os parâmetros: tempo exigido para localização do bloqueio; presença de náuseas e vômitos pós-operatórios (NVPO); pontuações de dor pós-operatória na sala de recuperação pós-anestésica (SRPA); volume de anestésico local injetado; complicações agudas; e administração de opioides antes, durante e depois da cirurgia. Foram utilizadas regressões univariada e multivariada com estimativa dos mínimos quadrados e logística. RESULTADOS: Um IMC elevado foi associado a maiores: tempo exigido para localização do bloqueio (p = 0,025), administração de fentanil durante a cirurgia (p < 0,001), pico de pontuações de dor em SRPA (p < 0,001), administração de opioide na SRPA (p < 0,001), administração oral de opioide na SRPA (p < 0,001), administração total de opioide na SRPA (p < 0,001) e incidência de náusea em SRPA (p = 0,025). CONCLUSÕES: Os bloqueios nervosos interescalênicos guiados por ultrassom para analgesia perioperatória podem ser executados de forma segura e efetiva em pacientes obesos, mas o procedimento pode ser mais difícil e a analgesia talvez não seja complet

Aberrant DNMT3B7 expression correlates to tissue type, stage, and survival across cancers.

Cancer cells are known for aberrant methylation patterns leading to altered gene expression and tumor progression. DNA methyltransferases (DNMTs) are responsible for regulating DNA methylation in normal cells. However, many aberrant versions of DNMTs have been identified to date and their role in cancer continues to be elucidated. It has been previously shown that an aberrant version of a de novo methylase, DNMT3B7, is expressed in many cancer cell lines and has a functional role in the progression of breast cancer, neuroblastoma, and lymphoma. It is clear that DNMT3B7 is important to tumor development in vitro and in vivo, but it is unknown if expression of the transcript in all of these cell lines translates to relevant clinical results. In this study, a bioinformatics approach was utilized to test the hypothesis that DNMT3B7 expression corresponds to tumor progression in patient samples across cancer types. Gene expression and clinical data were obtained from the Genomic Data Commons for the 33 cancer types available and analyzed for DNMT3B7 expression with relation to tissue type in matched and unmatched samples, staging of tumors, and patient survival. Here we present the results of this analysis indicating a role for DNMT3B7 in tumor progression of many additional cancer types. Based on these data, future in vitro and in vivo studies can be prioritized to examine DNMT3B7 in cancer and, hopefully, develop novel therapeutics to target this aberrant transcript across multiple tumor types

Catalytic activity and stability of laccase entrapped in sol-gel silica with additives

This study investigated the effects of different additives and precursors on the catalytic activity of laccase entrapped in sol-gel silica. It was found that the laccase catalytic activity and stability of sol-gel laccase could be enhanced if the entrapment was performed in the presence of additives such as PVA, PEG and APTS. The use of TEOS as a precursor showed slightly higher laccase catalytic activity compared to TMOS. The PVA as an additive showed a better catalytic activity enhancement compared to the PEG and APTMS with the optimum PVA concentration of 0.03 mg/mL. The optimal temperatures of sol-gel laccase without and with additives were found to be at 40 and 27°C, respectively. After 70 days of storage at 27°C, the catalytic activity of the immobilized sol-gel laccase with additives maintained its catalytic activity compared to only 30% of its original catalytic activity for the sol-gel laccase without additives

Expression of <i>DNMT3B7</i> in normal and tumor patient samples.

<p>Representative graphs of 6 different tumor samples showing relative <i>DNMT3B7</i> expression, as measured by reads per kilobase per million (RPKM) or RNA-Seq by Expectation Maximization (RSEM), in unmatched normal and tumor tissues in (A) HNSC, (B) UCEC, and (C) THCA. Expression of <i>DNMT3B7</i> in matched patient samples is shown in (D) LIHC and (E) LUAD. <i>DNMT3B7</i> expression in primary and recurrent tissues in (F) LGG (<i>p</i> = 0.005) was assessed when normal samples were not available. All samples shown here were significant, <i>p</i> < 0.001, unless otherwise stated.</p

Relative <i>DNMT3B7</i> expression correlates to clinical staging.

<p><i>DNMT3B7</i> expression was compared to clinical stage and shown to be significantly different in (A) ESCA, <i>p</i> = 0.012; (B) KIRC, <i>p</i> = 0.010; (C) KIRP, <i>p</i> = 0.02; (D) LUSC, <i>p</i> = 0.003; (E) TGCT, <i>p</i><0.001; and (F) LAML, <i>p</i><0.001. For (E) TGCT, there were no patient samples with a stage IV diagnosis. (F) LAML staging was measured using the French-American-British (FAB) classifications.</p

Patients with high levels of <i>DNMT3B7</i> expression have lower survival rates than those with low expression levels.

<p>The median <i>DNMT3B7</i> expression for each individual tumor was determined to divide patients with that tumor into “high” (gray, dotted line) and “low” (black, solid line) expression groups. Kaplan-Meier curves were generated and statistical significance was determined for (A) CESC, <i>p</i> = 0.025; (B) KIRC, <i>p</i> = 0.009; (C) LAML, <i>p</i> = 0.035; (D) MESO, <i>p</i> = 0.013; (E) SARC, <i>p</i> = 0.003; and (F) SKCM, <i>p</i> = 0.003.</p