Comparison of respiratory inductive plethysmography versus head-out plethysmography for anesthetized nonhuman primates in an animal biosafety level 4 facility

For inhalational studies and aerosol exposures to viruses, head-out plethysmography acquisition has been traditionally used for the determination of estimated inhaled dose in anesthetized nonhuman primates prior to or during an aerosol exposure. A pressure drop across a pneumotachograph is measured within a sealed chamber during inspiration/exhalation of the nonhuman primate, generating respiratory values and breathing frequencies. Due to the fluctuation of depth of anesthesia, pre-exposure respiratory values can be variable, leading to less precise and accurate dosing calculations downstream. Although an anesthesia infusion pump may help stabilize the depth of sedation, pumps are difficult to use within a sealed head-out plethysmography chamber. Real-time, head-out plethysmography acquisition could increase precision and accuracy of the measurements, but the bulky equipment needed for head-out plethysmography precludes real-time use inside a Class III biological safety cabinet, where most aerosol exposures occur. However, the respiratory inductive plethysmography (RIP) acquisition method measures the same respiratory parameters by detecting movement of the chest and abdomen during breathing using two elastic bands within the Class III biological safety cabinet. As respiratory values are relayed to a computer for software integration and analysis real-time, adjustment of aerosol exposure duration is based on the depth of sedation of the animal. The objective of this study was to compare values obtained using two methodologies (pre-exposure head-out plethysmography and real-time RIP). Transitioning to RIP technology with real-time acquisition provides more consistent, precise, and accurate aerosol dosing by reducing reported errors in respiratory values from anesthesia variability when using pre-exposure head-out plethysmography acquisition.     

Correction: Thrombotic and bleeding events,mortality, and anticoagulant use among 546,656 hospitalized patients with COVID‑19 in the United States: a retrospective cohort study

Journal of Thrombosis and Thrombolysis -     

Re-Validating the Observational Teamwork Assessment for Surgery Tool (OTAS-D): Cultural Adaptation, Refinement, and Psychometric Evaluation

Background

The nontechnical and team skills of surgical teams are critical for safety and efficiency in the operating room. Assessment of nontechnical and team skills can facilitate improvement by encouraging both self-reflection and team reflection, identifying training needs, and informing operating room (OR) team training approaches. The observational teamwork assessment for surgery (OTAS) tool is a well-validated and robust tool for capturing teamwork in the operating room. The aims of the present study were to systematically adapt and refine the OTAS for German-speaking OR staff and to test the adapted assessment tool (OTAS-D) for psychometric properties and metric equivalence.

Methods

The study was carried out in three stages: at stage 1, OTAS was translated into German. At stage 2, experienced German OR experts (surgeons, OR nurses, anesthetists) were interviewed. At stage 3, two blinded assessors observed 11 general surgical operations (general surgical and vascular procedures) and interrater reliability was tested for refined OTAS-D behavioral exemplars and scorings.

Results

The German OR experts confirmed the applicability and content validity of the vast majority of translated behavioral exemplars. After their evaluation, 32 items were changed slightly, six were changed substantially, and one item was added. During observations, perfect and substantial interobserver agreement was found for 77 behavioral exemplars (67.1 % of the items, kappa coefficient >0.60). Rating at all OTAS behaviors showed acceptable levels of reliability (intraclass correlation coefficients >0.72).

Conclusions

The OTAS-D is a tool for valid and reliable assessment of nontechnical skills that contribute to safe and effective surgical performance in ORs staffed by German-speaking professionals. Furthermore, our study serves as an example for systematically adapting and customizing well-established observational tools across different healthcare environments.     

Prevalence of incidental findings in trauma patients detected by computed tomography imaging

Study Objective

The primary intention of spiral computed tomography (SCT) in trauma patients is to identify significant injuries. However, unanticipated information is often discovered. We hypothesize that SCT often identifies clinically significant incidental findings in trauma patients.

Methods

This was a retrospective protocol chart review of consecutive adult trauma patients seen at a level I trauma center. A complete SCT was defined as computed tomography imaging of the head, cervical spine, chest, abdomen, and pelvis, thoracic, and lumbar spine. Incidental findings were classified into 2 categories: type 1, which requires urgent evaluation, and type 2, which requires informing the patient but does not mandate urgent follow-up.

Results

We reviewed 3246 patient charts and 3092 met inclusion criteria. Type 1 findings were reported in 990 (32.0%; 95% confidence interval [CI], 30.4%-33.7%) patients. Type 2 findings were found in 1274 (41.2%; 95% CI, 39.5%-42.9%) patients. Female sex (odds ratio, 1.38; 95% CI, 1.16-1.65) and older age (odds ratio, 2.61; 95% CI, 2.33-2.93) were independently associated with a higher prevalence of type 1 findings. There were 631 incidental findings concerning for neoplasm, which included 196 pulmonary nodules, 99 liver, 36 renal, 23 brain, and 11 breast masses.

Conclusions

A significant number of trauma patients evaluated with SCT are diagnosed with potentially serious incidental findings. For long-term care and medicolegal concerns, physicians need to inform patients of these incidental findings and the need for further evaluation.     

Posterior urethral obstruction. Prenatal sonographic findings and clinical outcome in fourteen cases

Fourteen cases of fetal urethral obstruction were reviewed retrospectively. The purpose of this study was to emphasize the following: 1) prenatal sonographic findings: 2) clinical outcome: and 3) associated congenital anomalies. Decreased amniotic fluid volume complicated 12 pregnancies (86%). A dilated posterior urethra was identified in nine fetuses (64%) and an enlarged bladder in 13 (93%). Evaluation of the fetal kidneys revealed hydronephrosis in 81%, increased parenchymal echogenicity in 73% and macroscopic renal cysts in 15%. There were seven live births, but only two neonates survived beyond 5 weeks. Pulmonary hypoplasia contributed to the five postnatal deaths. Associated congenital anomalies were noted at autopsy in six cases.     

Evaluation of Sagittal Spinopelvic Balance in Spinal Cord Stimulator Patients

ObjectiveSpinal cord stimulation (SCS) has become a popular nonopioid pain intervention. However, the treatment failure rate for SCS remains significantly high and many of these patients have poor sagittal spinopelvic balance, which has been found to correlate with increased pain and decreased quality of life. The purpose of this study was to determine if poor sagittal alignment is correlated with SCS treatment failure.Materials and MethodsComparative retrospective analysis was performed between two cohorts of patients who had undergone SCS placement, those who had either subsequent removal of their SCS system (representing a treatment failure cohort) and those that underwent generator replacement (representing a successful treatment cohort). The electronic medical record was used to collect demographic and surgical characteristics, which included radiographic measurements of lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). Also included were data on pain medication usage including opioid and nonopioid therapies.ResultsEighty-one patients met inclusion criteria, 31 had complete removal, and 50 had generator replacements. Measurement of sagittal balance parameters demonstrated that many patients had poor alignment, with 34 outside normal range for LL (10 vs 24 in removal and replacement cohorts, respectively), 30 for PI (12 [38.7%] vs 18 [36.0%]), 46 for PT (18 [58.1%] vs 28 [56.0%]), 38 for SS (18 [58.1%] vs 20 [40.0%]), and 39 for PI-LL mismatch (14 [45.2%] vs 25 [50.0%]). There were no significant differences in sagittal alignment parameters between the two cohorts.ConclusionsThis retrospective cohort analysis of SCS patients did not demonstrate any relationship between poor sagittal alignment and failure of SCS therapy. Further studies of larger databases should be performed to determine how many patients ultimately go on to have additional structural spinal surgery after failure of SCS and whether or not those patients go on to have positive outcomes.     

Land-Based Healing: Toward Understanding the Role of Elders

Building on prior research on Indigenous land-based healing from the viewpoints of community members, this qualitative study sought to learn the perspectives of Elders regarding land-based interventions within a Mushkegowuk community in northern Ontario. While previous studies have shown the importance to community members of Elders’ involvement with land-based initiatives, the current project aimed to understand, via conversations with Elders, their broad view of land-based healing. Employing Indigenous and phenomenological methods, the authors conducted and summarized interviews with three Elders regarding their views on key components, challenges, and steps in transferring knowledge of land-based programming. Elders spoke about learning in a natural context, strengthening bonds between youth and Elders as well as ancestors, and preparing food in a traditional manner as important aspects of healing. They also underscored the benefits of enhancing a sense of community, cultural pride, and spirituality, as well as connecting with nature. Challenges discussed included funding, permits, parental support and participation, and participants’ reliance on technology. Conversations regarding the process of knowledge transfer revealed the significance of misunderstanding for non-Indigenous researchers working within Indigenous communities.

     

Identification of small-molecule inhibitors of autotaxin that inhibit melanoma cell migration and invasion

Autotaxin (ATX) is a prometastatic enzyme initially isolated from the conditioned medium of human melanoma cells that stimulates a myriad of biological activities, including angiogenesis and the promotion of cell growth, survival, and differentiation through the production of lysophosphatidic acid (LPA). ATX increases the aggressiveness and invasiveness of transformed cells, and ATX levels directly correlate with tumor stage and grade in several human malignancies. To study the role of ATX in the pathogenesis of malignant melanoma, we developed antibodies and small-molecule inhibitors against recombinant human protein. Immunohistochemistry of paraffin-embedded human tissue shows that ATX levels are markedly increased in human primary and metastatic melanoma relative to benign nevi. Chemical screens identified several small-molecule inhibitors with binding constants ranging from nanomolar to low micromolar. Cell migration and invasion assays with melanoma cell lines show that ATX markedly stimulates melanoma cell migration and invasion, an effect suppressed by ATX inhibitors. The migratory phenotype can be rescued by the addition of the enzymatic product of ATX, LPA, confirming that the observed inhibition is linked to suppression of LPA production by ATX. Chemical analogues of the inhibitors show structure-activity relationships important for ATX inhibition and indicate pathways for their optimization. These studies suggest that ATX is an approachable molecular target for the rational design of chemotherapeutic agents directed against malignant melanoma.