Crash Performance of Rear-facing Restraints With a Fracture Type Spica Casted 1-Year-Old Dummy.

BACKGROUND: Motor vehicle crashes represent a significant cause of mortality and morbidity for young children. Safely restraining a child is typically more complicated for special cases such as children treated with a hip spica cast. In the current study, hip spica casts typical for treatment of a femoral fracture were applied to a crash dummy representing the size and weight of a 1-year-old child. This spica casted dummy was used to study the performance of 4 rear-facing car seats in a series of simulated frontal impacts. METHODS: The restrained, rear-facing dummy was subjected to a frontal crash test at 30 mph (48 kph) per federal guidelines. Two of the tested car seats were specifically designed for transporting children with hip spica casts, while the other 2 were conventional seats capable of accommodating the cast. All seats were installed per the manufacturer's instructions. As a control, tests were performed without a cast using the conventional/standard seats. RESULTS: The lowest overall loading of the dummy's head, neck, and chest occurred during tests with the standard seats. While it was easier to seat the casted child in the spica-specific seats, these designs led to greater loading on the dummy's body. In a spica-specific seat, the chest acceleration values exceeded the federal limit in a test where the seat was installed in a reclined orientation that was within the manufacturer's described positioning. CONCLUSIONS: Spica-specific seats more easily accommodate the cast, but conventional seats can provide similar levels of protection in a crash. As cast and seat designs continue to evolve, hospitals might consider having a range of seats available for patient use. It is important to help caregivers make informed decisions on how and when to transport children with hip spica casts.

Acute myeloid leukemia induces protumoral p16INK4a-driven senescence in the bone marrow microenvironment.

Acute myeloid leukemia (AML) is an age-related disease that is highly dependent on the bone marrow (BM) microenvironment. With increasing age, tissues accumulate senescent cells, characterized by an irreversible arrest of cell proliferation and the secretion of a set of proinflammatory cytokines, chemokines, and growth factors, collectively known as the senescence-associated secretory phenotype (SASP). Here, we report that AML blasts induce a senescent phenotype in the stromal cells within the BM microenvironment and that the BM stromal cell senescence is driven by p16INK4a expression. The p16INK4a-expressing senescent stromal cells then feed back to promote AML blast survival and proliferation via the SASP. Importantly, selective elimination of p16INK4a+ senescent BM stromal cells in vivo improved the survival of mice with leukemia. Next, we find that the leukemia-driven senescent tumor microenvironment is caused by AML-induced NOX2-derived superoxide. Finally, using the p16-3MR mouse model, we show that by targeting NOX2 we reduced BM stromal cell senescence and consequently reduced AML proliferation. Together, these data identify leukemia-generated NOX2-derived superoxide as a driver of protumoral p16INK4a-dependent senescence in BM stromal cells. Our findings reveal the importance of a senescent microenvironment for the pathophysiology of leukemia. These data now open the door to investigate drugs that specifically target the "benign" senescent cells that surround and support AML.

Advanced Hodgkin lymphoma in the East of England: a 10-year comparative analysis of outcomes for real-world patients treated with ABVD or escalated-BEACOPP, aged less than 60 years, compared with 5-year extended follow-up from the RATHL trial.

Treatment with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or escalated(e)-BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) remains the international standard of care for advanced-stage classical Hodgkin lymphoma (HL). We performed a retrospective, multicentre analysis of 221 non-trial ("real-world") patients, aged 16-59 years, diagnosed with advanced-stage HL in the Anglia Cancer Network between 2004 and 2014, treated with ABVD or eBEACOPP, and compared outcomes with 1088 patients in the Response-Adjusted Therapy for Advanced Hodgkin Lymphoma (RATHL) trial, aged 18-59 years, with median follow-up of 87.0 and 69.5 months, respectively. Real-world ABVD patients (n=177) had highly similar 5-year progression-free survival (PFS) and overall survival (OS) compared with RATHL (PFS 79.2% vs 81.4%; OS 92.9% vs 95.2%), despite interim positron-emission tomography-computed tomography (PET/CT)-guided dose-escalation being predominantly restricted to trial patients. Real-world eBEACOPP patients (n=44) had superior PFS (95.5%) compared with real-world ABVD (HR 0.20, p=0.027) and RATHL (HR 0.21, p=0.015), and superior OS for higher-risk (international prognostic score ≥3 [IPS 3+]) patients compared with real-world IPS 3+ ABVD (100% vs 84.5%, p=0.045), but not IPS 3+ RATHL patients. Our data support a PFS, but not OS, advantage for patients with advanced-stage HL treated with eBEACOPP compared with ABVD and suggest higher-risk patients may benefit disproportionately from more intensive therapy. However, increased access to effective salvage therapies might minimise any OS benefit from reduced relapse rates after frontline therapy.

Frontal Crash Injury Metrics Are Below Mandated Limits for a Spica Casted Child Dummy in Currently Available Restraints.

BACKGROUND: There is a paucity of data defining safe transport protocols for children treated with hip spica casting. Although restraint devices for casted children are available, all federally mandated testing uses a noncasted anthropomorphic test device (ATD or crash dummy). The purpose of this study was to evaluate current restraint options in simulated frontal crash testing using a casted pediatric ATD to determine injury risk to the head, cervical spine, chest, and pelvis. METHODS: Using a 3-year-old ATD, dynamic crash sled tests simulating frontal crash were performed in accordance with government safety standards. The ATD was casted in a double-leg spica and the following restraint devices were tested: a seat designed for spica casted children, a restraint vest-harness, a traditional booster seat, and 2 traditional forward-facing car seats. RESULTS: Although the presence of the cast increased many of the injury metrics measured, all seats passed current federal guidelines for the head and chest. No single seat performed best in all metrics. The greatest magnitude of neck loading and second-highest head injury criterion values were observed for the booster seat. The vest-harness produced the highest head injury criterion and the chest compression exceeded proposed federal limits. CONCLUSIONS: The results suggest safe transport in commercially available seats is possible with the child properly restrained in a correctly fitting seat. However, parents should not assume a child restraint system is appropriate for use just based on fit as, for example, seats with harnesses outperformed an easy to fit booster seat. CLINICAL RELEVANCE: Each child and the position of the child's cast are unique and discharge planning involves consideration of safe transportation. Although this study suggests several seats used to transport spica casted children pass the federal head and chest injury prevention requirements, it is important to recognize that some children may still require emergency vehicle transport.

Prescribing and Consumption of Opioids After Primary, Unilateral Total Hip and Knee Arthroplasty in Opioid-Naive Patients.

BACKGROUND: This cohort study was designed to determine the discrepancy between the quantity of opioid prescribed vs that which was consumed after total knee arthroplasty (TKA) and total hip arthroplasty (THA) in opioid-naive patients. METHODS: Seven hundred twenty-three opioid-naive patients (426 TKAs and 297 THAs) from 7 hospitals in Michigan were contacted within 3 months of their surgery. Opioid prescribing and self-reported consumption was calculated in oral morphine equivalents (OMEs). Secondary outcomes included opioid refill in the first 90 days, pain in the first 7 days post-operatively, and satisfaction with pain care. RESULTS: For TKA, the mean prescribing was 632 mg OME (±229), and the mean consumption was 416 mg (±279). For THA, the mean prescribing was 584 mg OME (±335), and the mean consumption was 285 mg (±301). There were no associations between the amount of opioid prescribed and the likelihood of refill, post-operative pain, or satisfaction with pain control. The amount of opioid prescribed was associated with increased consumption, such that each increase of 1 pill was associated with approximately an additional half pill consumed after adjusting for other covariates. Moreover, 48.2% felt that they received "More" or "Much more" opioid than they needed. CONCLUSION: We recommend no more than 50 tablets of 5 mg oxycodone or its equivalent after TKA and 30 tablets after THA. Although dose reductions in other surgeries have not resulted in harm, continued assessment is needed to ensure that there are no unintended effects of opioid reduction, including worsened pain, decreased satisfaction, emergency department visits, or hospital readmissions. LEVEL OF EVIDENCE: Level III; Retrospective, cohort study.

The ubiquitin ligase parkin mediates resistance to intracellular pathogens.

Ubiquitin-mediated targeting of intracellular bacteria to the autophagy pathway is a key innate defence mechanism against invading microbes, including the important human pathogen Mycobacterium tuberculosis. However, the ubiquitin ligases responsible for catalysing ubiquitin chains that surround intracellular bacteria are poorly understood. The parkin protein is a ubiquitin ligase with a well-established role in mitophagy, and mutations in the parkin gene (PARK2) lead to increased susceptibility to Parkinson's disease. Surprisingly, genetic polymorphisms in the PARK2 regulatory region are also associated with increased susceptibility to intracellular bacterial pathogens in humans, including Mycobacterium leprae and Salmonella enterica serovar Typhi, but the function of parkin in immunity has remained unexplored. Here we show that parkin has a role in ubiquitin-mediated autophagy of M. tuberculosis. Both parkin-deficient mice and flies are sensitive to various intracellular bacterial infections, indicating parkin has a conserved role in metazoan innate defence. Moreover, our work reveals an unexpected functional link between mitophagy and infectious disease.

Sensing of Mycobacterium tuberculosis and consequences to both host and bacillus.

Mycobacterium tuberculosis (Mtb), the primary causative agent of human tuberculosis, has killed more people than any other bacterial pathogen in human history and remains one of the most important transmissible diseases worldwide. Because of the long-standing interaction of Mtb with humans, it is no surprise that human mucosal and innate immune cells have evolved multiple mechanisms to detect Mtb during initial contact. To that end, the cell surface of human cells is decorated with numerous pattern recognition receptors for a variety of mycobacterial ligands. Furthermore, once Mtb is ingested into professional phagocytes, other host molecules are engaged to report on the presence of an intracellular pathogen. In this review, we discuss the role of specific mycobacterial products in modulating the host's ability to detect Mtb. In addition, we describe the specific host receptors that mediate the detection of mycobacterial infection and the role of individual receptors in mycobacterial pathogenesis in humans and model organisms.

Heme Oxygenase-1 Regulates Inflammation and Mycobacterial Survival in Human Macrophages during Mycobacterium tuberculosis Infection.

Mycobacterium tuberculosis, the causative agent of tuberculosis, is responsible for 1.5 million deaths annually. We previously showed that M. tuberculosis infection in mice induces expression of the CO-producing enzyme heme oxygenase (HO1) and that CO is sensed by M. tuberculosis to initiate a dormancy program. Further, mice deficient in HO1 succumb to M. tuberculosis infection more readily than do wild-type mice. Although mouse macrophages control intracellular M. tuberculosis infection through several mechanisms, such as NO synthase, the respiratory burst, acidification, and autophagy, how human macrophages control M. tuberculosis infection remains less well understood. In this article, we show that M. tuberculosis induces and colocalizes with HO1 in both mouse and human tuberculosis lesions in vivo, and that M. tuberculosis induces and colocalizes with HO1 during primary human macrophage infection in vitro. Surprisingly, we find that chemical inhibition of HO1 both reduces inflammatory cytokine production by human macrophages and restricts intracellular growth of mycobacteria. Thus, induction of HO1 by M. tuberculosis infection may be a mycobacterial virulence mechanism to enhance inflammation and bacterial growth.

Characterization of patient population receiving bioactive glass bone graft substitute as intraoperative treatment for orthopaedic trauma fractures.

Background: Bioactive glass synthetic bone grafts are used to treat osseous defects in orthopaedic surgery. Characterization of the clinical scenarios associated with bioactive glass use in the context of orthopaedic trauma, are not well established. This study aims to characterize population demographics, operative variables, as well as postoperative variables, for patients who required bone grafting for treatment of traumatic orthopaedic injuries and received a bioactive glass bone substitute intraoperatively. Methods: The electronic medical record at a large Level I trauma center was queried for fracture patients between January 1st, 2019, and April 30th, 2022. Our retrospective cohort included fracture patients who received Fibergraft Matrix or Fibergraft Putty intraoperatively, and their respective control groups. This study ascertained patient demographic variables, operative variables, and postoperative variables. Differences in categorical variables were tested with Fischer's Exact Tests, while differences in continuous variables were tested with ANOVA. Statistical significance was determined as P < 0.05. If the overall Group model was significant for a given variable, post-hoc Fischer's Exact or Tukey HSD tests were used to assess pairwise significance between individual Group pairs. Results: A total of four categories across our analysis of demographic, operative, and postoperative variables displayed significant differences amongst subject Groups (P ≤ 0.03). Individual groups were compared such that significant differences between subject groups could be appreciated for a specific variable. FM subjects had greater length of surgery, billable costs, and vitamin D supplementation at the time of surgery compared to FM controls. Similarly, FP subjects had greater length of surgery, billable cost, and implants used intraoperatively compared to FP controls. Conclusion: This analysis revealed Fibergraft patients to have greater length of surgery and billable cost, with respect to their matched controls. These data suggest that Fibergraft patients had more severe orthopaedic fractures compared to matched controls.

Safe transport of spica casted infants: Reducing the risk of traumatic injury in side impact collisions.

BACKGROUND: There is limited data on transporting small children in hip spica casts used to treat pediatric femur fractures. Specific challenges include the fixed position of the body in the casted position and the increased size of the child due to cast thickness. Additionally, children less than 2 years old are recommended to be rear facing during transportation. This traveling position requires seats that are specifically designed to accommodate the small size of the child as well as accommodate the rear facing position. While seats able to accommodate casted children are available, it is unclear if they provide adequate protection in side impact collisions for rear facing spica casted infants. Therefore, the aim of this study was to evaluate traumatic injury metrics in a side impact collision model where a spica casted infant crash dummy was restrained in currently available car seats. METHODS: Two seats designed for spica casted children (R82 Quokka, Merritt Wallenberg) and two traditional car seats (Britax Emblem, Graco Sequel) able to accommodate a casted one-year-old crash test dummy were identified. Side impact collision testing was performed with the dummy positioned in the rear facing position and injury metrics recorded. RESULTS: Testing identified contact between the dummy's head and the door panel for a specialty spica car seat without protective side-wings for the head. All other seats contained side wings and prevented door-head contact. CONCLUSIONS: Casted children should be transported in a seat able to accommodate the cast and safely restrain them. Our results demonstrate the importance of side wing protection in any seat used to transport these children as side bolsters may help decrease the potential for head contact with the door and lower the risk of severe head injury.

Real-world study of children and young adults with myeloproliferative neoplasms: identifying risks and unmet needs.

Myeloproliferative neoplasms (MPNs) are uncommon in children/young adults. Here, we present data on unselected patients diagnosed before 25 years of age included from 38 centers in 15 countries. Sequential patients were included. We identified 444 patients, with median follow-up 9.7 years (0-47.8). Forty-nine (11.1%) had a history of thrombosis at diagnosis, 49 new thrombotic events were recorded (1.16% patient per year [pt/y]), perihepatic vein thromboses were most frequent (47.6% venous events), and logistic regression identified JAK2V617F mutation (P = .016) and hyperviscosity symptoms (visual disturbances, dizziness, vertigo, headache) as risk factors (P = .040). New hemorrhagic events occurred in 44 patients (9.9%, 1.04% pt/y). Disease transformation occurred in 48 patients (10.9%, 1.13% pt/y), usually to myelofibrosis (7.5%) with splenomegaly as a novel risk factor for transformation in essential thrombocythemia (ET) (P= .000) in logistical regression. Eight deaths (1.8%) were recorded, 3 after allogeneic stem cell transplantation. Concerning conventional risk scores: International Prognostic Score for Essential Thrombocythemia-Thrombosis and new International Prognostic Score for Essential Thrombocythemia-Thrombosis differentiated ET patients in terms of thrombotic risk. Both scores identified high-risk patients with the same median thrombosis-free survival of 28.5 years. No contemporary scores were able to predict survival for young ET or polycythemia vera patients. Our data represents the largest real-world study of MPN patients age < 25 years at diagnosis. Rates of thrombotic events and transformation were higher than expected compared with the previous literature. Our study provides new and reliable information as a basis for prospective studies, trials, and development of harmonized international guidelines for the specific management of young patients with MPN.

Predicting Recidivism Among Defendants in an Expedited Domestic Violence Court.

Specialized domestic violence courts are presumed to be more effective than general case processing in understanding and addressing the unique issues associated with this crime type, which should lead to reduced recidivism among offenders. Research, however, is less clear about whether and how domestic violence courts reduce recidivism. This study analyzes data from a misdemeanor, expedited domestic violence court in southeast Texas to assess whether defendant characteristics and court processing characteristics influence recidivism among offenders processed through the specialty docket. Results indicate that case processing time was a significant predictor of rearrest for domestic violence. Offenders who had a prior domestic violence arrest were twice as likely to have a subsequent domestic violence arrest. Offenders who received a jail sentence were significantly more likely to have a subsequent domestic violence arrest. Policy implications and future research needs are also discussed.

Gastric lymphoma at high risk of perforation successfully managed with chemotherapy alone.

We report the case of a previously healthy 49-year-old woman who presented with upper gastrointestinal bleeding, which was found at laparotomy to be due to high-grade B cell gastric lymphoma. CT scans showed that this was partially adherent to the spleen, with erosion of the gastric wall and suggested impending perforation. Given the risk of perforation, further surgical intervention (gastrectomy and splenectomy) was considered; however, after multidisciplinary team discussion, we chose to offer chemotherapy and careful inpatient observation instead.Our patient made a full recovery with no perforation.The message from our experience and literature review is that medical management may lead to a more favourable outcome in gastric lymphoma than surgery, despite radiological appearances suggesting impending perforation. This approach avoids the risk of the lymphoma progressing at other anatomical sites secondary to delays in giving chemotherapy. If this approach is followed, the patient must be carefully monitored.

Venetoclax and Daratumumab combination treatment demonstrates pre-clinical efficacy in mouse models of Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) remains an incurable malignancy despite recent advances in treatment. Recently a number of new therapies have emerged for the treatment of AML which target BCL-2 or the membrane receptor CD38. Here, we show that treatment with Venetoclax and Daratumumab combination resulted in a slower tumor progression and a reduced leukemia growth both in vitro and in vivo. These data provide evidence for clinical evaluation of Venetoclax and Daratumumab combination in the treatment of AML.

Developing an interactive microsimulation method in pharmacology.

Pharmacology decision making requires clinical judgment. The authors created interactive microsimulation applying drug information to varying patients' situations. The theory-based microsimulation requires situational analysis for each scenario. The microsimulation uses an interactive format that allows the participant to navigate through three separate virtual clients' situations. Correct clinical decisions are rewarded by sounds and by video footage of the patient improving. Conversely, incorrect choices show video footage of the patient decompensating. This micro-simulation was developed to help students learn from the consequences of incorrect medication decision making in the virtual world without harming patients. The feedback of watching an incorrect decision on a patient helps students associate cause and effect on patient outcomes. The microsimulation reinforces the ease with which medication errors can occur and the extent of possible sequalae. The development process used to incorporate the technology in the nursing curriculum is discussed.

Dissecting dementia, depression, and drug effects in older adults.

As adults age, many changes in functioning occur, and dementia and/or depression may develop. Medications used to manage dementia and depression include selective serotonin reuptake inhibitors. The challenge for nurses is recognizing which behaviors, signs, and symptoms are the result of the dementia or depression and which are the result of the drug therapy. The purpose of this article is to present information to increase awareness of the complexities of care for older adults with dementia and/or depression and identify possible implications for practicing nurses.

Analysis of restraint use in pregnant versus non-pregnant populations involved in motor vehicle collisions.

BACKGROUND: Traumatic injuries obtained by pregnant females in motor vehicle collisions present unique treatment challenges for trauma and orthopaedic surgeons. Understanding safety choices in this population can help physicians and public safety advocates in delivering effective and targeted safety messages. METHODS: A publicly available, de-identified national data set that documents crash information (NASS-CDS) was examined to identify cohorts of pregnant and non-pregnant vehicle occupants and regression analysis employed to identify factors associated with belt non-use. RESULTS: Pregnant women were found to have significantly lower rates of belt use compared to non-pregnant females (70.0% vs. 90.3%, Rao-Scott Sample Weighted Chi-Square p = 0.0265). Logistic regression identified younger age and sitting in the back seat as associated with lower rates of belt use. CONCLUSION: Pregnant women wear belts at significantly lower frequencies than non-pregnant women and youth and second row seating increase noncompliance rates. This work suggests the need for targeted intervention strategies to improve belt compliance.

Injury metrics are altered in spica-casted versus non-casted child ATDs in side-impact collisions with door intrusion.

Objective: There is little data defining safe transport protocols for spica-casted children. A single earlier study demonstrated the presence of a body cast alters kinematics and injury metrics during simulated side-impact crashes. Since then, the National Highway Transportation Safety Administration (NHTSA) proposed a new side-impact test protocol for evaluating child restraints. This test is more severe than the earlier tests, as it simulates an impact with a door intruding into the occupant space. As no currently available child restraint system (CRS) able to accommodate a spica-casted child has been evaluated using these updated testing criteria, the objective of this study was to evaluate current restraint options in simulated side-impact collisions using an anthropomorphic test device (ATD) modeled after a 3-year-old.Methods: Four commercially available CRSs able to accommodate a spica-casted Q3s side-impact ATD were selected for testing. Side-impact testing was performed using casted and uncasted ATDs in compliance with the NHTSA proposed side-impact test. High-speed photography and ATD instrumentation were used to measure selected injury criteria.Results: HIC15 values were highest in CRSs with less robust side wings, such as the Merritt WallenburgTM (HIC15 = 1,373), which allow for the occupant to interact with the intruding door panel. Head contact with the door panel was found to correspond with high resultant neck peak force. Pelvic acceleration magnitudes were greatest for the uncasted tests. Casted tests with a CRS that included an armrest were associated with greater torso rotation in the frontal plane with the left shoulder moving toward the door panel.Conclusions: The presence of a spica cast alters injury metrics in side-impact testing. Spica specific child safety seats are not yet optimized for side-impact with door intrusion. This is due to a lack of adequate side cushion wings, which may place both casted and uncasted occupants at increased likelihood for injury through head contact with an intruding door. Additional work is needed to improve the safety of CRSs for both casted and uncasted children in side-impact collisions.

Treating Patients As People: What Do Hospital Patients Want Clinicians to Know About Them As a Person?

BACKGROUND: There is little understanding or focus on the patient's personal communicative perspective during their experience of clinical treatment. An exploratory study and a follow-up study were conducted at a large safety net hospital to determine whether and what patients wanted clinicians to know more about them as a person. STUDY DESIGN: A convenience sample of 230 patients was selected from 9 different clinical units within the hospital for exploratory interviews to determine whether patients wanted their clinical team to know about them as a person. Based on these findings, additional personal preference data of patients were collected from a census sample of 387 patients selected from 2 intensive care unit units and 2 medical-surgical units. FINDINGS: The majority of patients in the exploratory study reported they wanted to tell their doctors/nurses some personal information about themselves, thought doctors/nurses could provide better care to them if they knew more about them as a person, and that communication between themselves and their doctors/nurses would improve if they knew more about them as a person. The follow-up study found that a majority of patients preferred that their clinicians call them by their first name and identified specific personal information they wanted to share with the clinical care team. The data also showed a meaningful number of patients who did not want to share this information with others. This split in patient preferences is an important reminder that being aware of personal preferences of patients does not necessarily mean an invitation to increase intimacy in all clinician-patient communications.