Loma Linda University
  • Loma Linda, CA, United States
Recent publications
Introduction Among premature infants, the incidence of inguinal hernias is reported to be as high as 30%. Despite being one of the most commonly performed procedures, the optimal setting of inguinal hernia repair (IHR) that is inpatient versus outpatient remains debatable. We sought to compare the 30-day outcomes of each approach by querying the National Surgical Quality Improvement Program-Pediatric database. Materials and methods A retrospective cohort study comparing inpatient versus outpatient IHR using the National Surgical Quality Improvement Program-Pediatric database from 2013 to 2019 was performed. Demographic and clinical data were initially compared using univariate analysis. Continuous variables are presented as median and interquartile range and categorical variables are presented as n (%). Subsequently, cohorts were propensity matched using clinically and statistically significant patient characteristics. Results 928 patients underwent IHR, 634 (68.3%) while inpatient, 294 (31.7%) following hospital discharge. Inpatient IHR was associated with lower age at the time of surgery (120 versus 147 d; P < 0.0001), younger gestational age (27 versus 33 wk; P < 0.0001), decreased probability of repair in elective setting (87.2% versus 97.3%; P < 0.0001), and increased preoperative supplemental oxygen need (42% versus 4.4%; P < 0.0001). Comparison of propensity matched cohorts revealed that inpatient IHR was associated with increased procedure time (82 versus 51 min; P < 0.0001) and anesthetic duration (146 versus 102 min; P < 0.0001), wound infection rates (3.8% versus 0%; P = 0.007), blood transfusions (4.2% versus 0.5%; P = 0.036), unplanned intubations (2.8% versus 0%; P = 0.03), ventilator days (0 versus 0; range [0,30 versus 0,2]; P = 0.002), reoperation rate (5.6% versus 0%; P < 0.001), postoperative hospital length of stay (4 versus 1 d; P < 0.0001), and unplanned readmissions (8.9% versus 0.9%; P = 0.002). Conclusions Inpatient IHR in premature neonates were associated with different postoperative outcomes than outpatient IHR. At least in the elective setting among premature infants, outpatient IHR can be considered safe in select patients while we await higher quality prospective data.
The marine pathogen Vibrio vulnificus senses and responds to environmental stimuli via two chemosensory systems and 42-53 chemoreceptors. Here we present an analysis of the V. vulnificus Aer2 chemoreceptor, VvAer2, which is the first V. vulnificus chemoreceptor to be characterized. VvAer2 is related to the Aer2 receptors of other gammaproteobacteria, but uncharacteristically contains three PAS domains (PAS1-3), rather than one or two. Using an E. coli chemotaxis hijack assay, we determined that VvAer2, like other Aer2 receptors, senses and responds to O2 . All three VvAer2 PAS domains bound pentacoordinate b-type heme and exhibited similar O2 affinities. PAS2 and PAS3 both stabilized O2 via conserved Iβ-Trp residues, but PAS1, which was easily oxidized in vitro, was unaffected by Iβ-Trp replacement. Our results support a model in which PAS1 is largely dispensable for O2 -mediated signaling, whereas PAS2 modulates PAS3 signaling, and PAS3 signals to the downstream domains. Each PAS domain appeared to be positionally optimized, because PAS swapping caused altered signaling properties, and neither PAS1 nor PAS2 could replace PAS3. Our findings strengthen previous conclusions that Aer2 receptors are O2 sensors, but with distinct N-terminal domain arrangements that facilitate, modulate and tune responses based on environmental signals.
Objectives The goal of this study was to evaluate the long-term impact of repeated (r) mild traumatic brain injury (mTBI) on the healing of fractures in a mouse model. Ten week-old male mice were subjected to r-mTBI once per day for 4 days followed by closed femoral fracture using a three-point bending technique, 1 week post impact and fracture healing phenotype evaluated at 20 weeks of age. Results Micro-CT analysis of the fracture callus region at nine weeks post fracture revealed reduced bone volume (30%, p < 0.05 ) in the r-mTBI fracture group compared to the control-fracture group. The connectivity density of the fracture callus bone was reduced by 40% ( p < 0.01) in the r-mTBI fracture group. Finite element analysis of the fracture callus region showed reduced failure load ( p = 0.08 ) in the r-mTBI group compared to control group. There was no residual cartilage in the fracture callus region of either the r-mTBI or control fracture group. The reduced fracture callus bone volume and mechanical strength of fracture callus in r-mTBI mice 9 weeks post fracture are consistent with negative effects of r-mTBI on fracture healing over a long-term resulting in decreased mechanical strength of the fracture callus.
Most cardiac imaging conferences have adopted social media as a means of disseminating conference highlights to a global audience well beyond the confines of the conference location. A deliberate and thoughtful social media campaign has the potential to increase the reach of the conference and allow for augmented engagement. The coronavirus disease 2019 (COVID-19) pandemic triggered a radical transformation in not just the delivery of healthcare but also the dissemination of science within the medical community. In the past, in-person medical conferences were an integral annual tradition for most medical professionals to stay up to date with the latest in the field. Social distancing requirements of the COVID-19 pandemic resulted in either cancelling medical conferences or shifting to a virtual format. Following suit, for the first time in its history, the 2021 Society for Cardiovascular Magnetic Resonance (SCMR) annual meeting was an all-virtual event. This called for a modified social media strategy which aimed to re-create the sociability of an in-person conference whilst also promoting global dissemination of the science being presented. This paper describes the employment of social media as well as the evolution through the SCMR scientific sessions for 2020 and 2021 that serves as a model for future cardiovascular conferences.
Breast Cancer (BrC) is a common malignancy with genetically diverse subtypes. There is evidence that specific BrC subtypes originate from particular normal mammary cell populations. However, the cell populations that give rise to most BrC subtypes are unidentified. Several human breast scRNAseq datasets are available. In this research, we utilized a robust human scRNAseq dataset to identify population-specific marker genes and then identified the expression of these marker genes in specific BrC subtypes. In humans, several BrC subtypes, HER2-enriched, basal-like, and triple-negative (TN), are more common in women who have had children. This observation suggests that cell populations that originate during pregnancy give rise to these BrCs. The current human datasets have few normal parous samples, so we supplemented this research with mouse datasets, which contain mammary cells from various developmental stages. This research identified two novel normal breast cell populations that may be the origin of the basal-like and HER2-overexpressing subtypes, respectively. A stem cell-like population, SC, that expresses gestation-specific genes has similar gene expression patterns to basal-like BrCs. A novel luminal progenitor cell population and HER2-overexpressing BrCs are marked by S100A7, S100A8, and S100A9 expression. We bolstered our findings by examining SC gene expression in TN BrC scRNAseq datasets and S100A7-A9 gene expression in BrC cell lines. We discovered that several potential cancer stem cell populations highly express most of the SC genes in TN BrCs and confirmed S100A8 and A9 overexpression in a HER2-overexpressing BrC cell line. In summary, normal SC and the novel luminal progenitor cell population likely give rise to basal-like and HER2-overexpressing BrCs, respectively. Characterizing these normal cell populations may facilitate a better understanding of specific BrCs subtypes.
Alpha(α)Klotho, a soluble transmembrane protein, facilitates calcium-phosphorus homeostasis through feedback between bone and kidney and is a potential systemic biomarker for bone-kidney health during spaceflight. We determined if: (1) plasma αKlotho was reduced after both spaceflight aboard the ISS and hindlimb unloading (HU); and (2) deficiency could be reversed with exercise. Both spaceflight and HU lowered circulating plasma αKlotho: plasma αKlotho recovered with exercise after HU.
The 25th Society for Cardiovascular Magnetic Resonance (SCMR) Annual Scientific Sessions saw 1524 registered participants from more than 50 countries attending the meeting virtually. Supporting the theme “CMR: Improving Cardiovascular Care Around the World”, the meeting included 179 invited talks, 52 sessions including 3 plenary sessions, 2 keynote talks, and a total of 93 cases and 416 posters. The sessions were designed so as to showcase the multifaceted role of cardiovascular magnetic resonance (CMR) in identifying and prognosticating various myocardial pathologies. Additionally, various social networking sessions as well as fun activities were organized. The major areas of focus for the future are likely to be rapid efficient and high value CMR exams, automated and quantitative acquisition and post-processing using artificial intelligence and machine learning, multi-contrast imaging and advanced vascular imaging including 4D flow.
Introduction Lower screening rates and poorer outcomes for colorectal cancer have been associated with Hispanic ethnicity and Spanish-speaking status, respectively. Methods We reviewed sequential colorectal cancer patients evaluated by the surgical service at a safety-net hospital (SNH) (2016-2019). Insurance type, stage, cancer type, surgery class (elective/urgent), initial surgeon contact setting (outpatient clinic/inpatient consult), operation (resection/diversion), and follow-up were compared by patient-reported primary spoken language. Results Of 157 patients, 85 (54.1%) were men, 91 (58.0%) had colon cancer, 67 (42.7%) primarily spoke Spanish, and late stage (III or IV) presentations occurred in 83 (52.9%) patients. The median age was 58 y, cancer resection was completed in 48 (30.6%) patients, and 51 (32.5%) patients were initially seen as inpatient consults. On univariate analysis, Spanish-speaking status was significantly associated with female sex, Medicaid insurance, being seen as an outpatient consult, and undergoing elective and resection surgery. On multivariable logistic regression, Spanish-speaking patients had higher odds of having Medicaid insurance (AOR 2.28, P = 0.019), receiving a resection (AOR 3.96, P = 0.006), and undergoing an elective surgery (AOR 3.24, P = 0.025). Spanish-speaking patients also had lower odds of undergoing an initial inpatient consult (AOR 0.34, P = 0.046). Conclusions Spanish-speaking status was associated with a lower likelihood of emergent presentation and need for palliative surgery among SNH colorectal cancer patients. Further research is needed to determine if culturally competent infrastructure in the SNH setting translates into Spanish-speaking status as a potentially protective factor.
Introduction The average body weight is smaller in Asian patients compared with Western patients, but influence of body weight in antibiotic dosing is unknown. This study was to predict the optimal ceftazidime, cefepime, meropenem, piperacillin/tazobactam doses in Asian patients undergoing continuous venovenous hemofiltration (CVVH). Methods Monte Carlo simulations (MCS) were performed using published Asian demographics and pharmacokinetics parameters in 5000 virtual patients at three CVVH effluent rates (Qeff; 20, 30, 40 mL/kg/h). Various dosing regimens were assessed for the probability of target attainments using 60% fT > 1 × MIC or 4xMIC and neurotoxicity risk at 48-h using suggested neurotoxicity thresholds. Results Ceftazidime 1 g q12h, meropenem 1 g q12h, and piperacillin/tazobactam 3.375 g q6h were optimal for all Qeff settings against fT > 1 × MIC. Cefepime 2 g q24h and 2 g q12h were optimal at 20 and 30–40 mL/kg/h respectively. For the aggressive PD target (4 × MIC), optimal ceftazidime regimens were 1.25 g q8h (20–30 mL/kg/h) and 1.5 g q8h (40 mL/kg/h). Cefepime 2 g q8h and meropenem 1 g q8h were optimal at all Qeff settings. No simulated piperacillin doses attained the aggressive PD target. Increased neurotoxicity risk was predicted with ceftazidime and cefepime doses attaining the efficacy. Conclusion MCS enabled the prediction of optimal β-lactam dosing regimens for Asian patients receiving CVVH at varying Qeff. Clinical validation is warranted.
Introduction Chest trauma is a major contributor to injury morbidity and mortality, and understanding trends is a crucial part of addressing this burden in low- and middle-income countries. This study reports the characteristics and emergency department (ED) management of chest trauma patients presenting to Rwanda's national teaching hospital in Kigali. Methods This descriptive analysis included a convenience sample of patients presenting to a single tertiary hospital ED with chest trauma from June to December 2017. Demographic data were collected as well as injury mechanism, thoracic and associated injuries, types of imaging obtained, and treatments performed. Chart review was conducted seven days post-admission to follow up on outcomes and additional diagnoses and interventions. Incidences were calculated with Microsoft Excel. Results Among the 62 patients included in this study, 74% were male, and mean age was 35 years. Most patients were injured in road traffic crashes (RTCs) (68%). Common chest injuries included lung contusions (79% of cases), rib fractures (44%), and pneumothoraces (37%). Head trauma was a frequent concurrent extra-thoracic injury (61%). Diagnostic imaging primarily included E-FAST ultrasound (92%) and chest x-ray (98%). The most common therapies included painkillers (100%), intravenous fluids (89%), and non-invasive oxygen (63%), while 29% underwent invasive intervention in the form of thoracostomy. The majority of patients were admitted (81%). Pneumonia was the most common complication to occur in the first seven days (32% of admitted patients). Ultimately, 40% of patients were discharged home within seven days of presentation, 50% remained hospitalized, and 5% died. Conclusion This study on the epidemiology of chest trauma in Rwanda can guide injury prevention and medical training priorities. Efforts should target prevention in young males and those involved in RTCs. ED physicians in Rwanda need to be prepared to diagnose and treat a variety of chest injuries with invasive and noninvasive means.
Background: The EmboTrap Recanalization Device is a novel stent retriever for thrombectomy in the setting of acute ischemic stroke due to large-vessel occlusion. Purpose: Our aim was to summarize the safety and efficacy of the EmboTrap Recanalization Device in acute ischemic stroke-large-vessel occlusion through a systematic review and meta-analysis. Data sources: Medline, EMBASE, the Cochrane Library, Web of Science, and Google Scholar were searched up to April 2022. Study selection: Nine observational studies using the EmboTrap Recanalization Device were selected. Data analysis: We adapted effect size with 95% CIs for dichotomous data. P value <.05 was statistically significant. Data synthesis: The estimated rate of successful recanalization (modified TICI 2b-3) was 90% (95% CI, 86%-95%; I 2 = 82.4%); 90-day favorable outcome (mRS 0-2), 53% (95% CI, 42%-63%; I 2 = 88.6%); modified first-pass effect, 43% (95% CI, 35%-51%; I 2 = 63.7%); and first-pass effect, 36% (95% CI, 29%-46%; I 2 = 10.7%). The rate of any intracerebral hemorrhage was 19% (95% CI, 16%-22%; I 2 = 0.0%); symptomatic intracerebral hemorrhage, 5% (95% CI, 1%-8%; I 2 = 84.6%); and 90-day mortality, 14% (95% CI, 9%-19%; I 2 = 79.3%). Subgroup analysis showed higher rates of complete recanalization for EmboTrap II than for the EmboTrap System. Limitations: The included studies are single-arm without direct comparison with other stent retrievers. Some of the studies recruited had a small sample size and were limited by the retrospective study design. In addition, the uncertain heterogeneity among studies was high. Conclusions: The EmboTrap Recanalization Device is safe and efficient in treating acute ischemic stroke due to large-vessel occlusion.
Introduction: Congenital high airway obstruction syndrome (CHAOS) is a rare condition that can progress to fetal hydrops and demise in utero or at birth unless interventions are undertaken to alleviate the tracheal obstruction. While the ex-utero intrapartum treatment (EXIT) procedure for airway stabilization is technically feasible, abnormal pulmonary development as a result of the antenatal obstructive process may result in severe postnatal respiratory complications. Case presentation: We describe a case of CHAOS with secondary hydrops treated in utero at 24 0/7 weeks' gestation by fetoscopic tracheal decompression via laser perforation of the airway obstruction. Interval imaging after the fetoscopic operation demonstrated resolution of the fetal hydrops. Tracheostomy for airway stabilization was performed at the time of the EXIT procedure near term (36 0/7 weeks). The patient underwent tracheal reconstruction and decannulation at 3 years of life. Discussion/conclusion: The primary goal of fetoscopic airway evaluation and intervention is not necessarily to perform definitive stabilization of the airway but rather to achieve sufficient decompression of the trachea to reverse fetal hydrops and salvage pulmonary development. In utero fetoscopic treatment may allow for prolongation of the pregnancy with delivery at or near term via EXIT procedure for definitive neonatal airway stabilization.
Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose To describe the benefits of pharmacist integration into a community rheumatology clinic in terms of clinical outcomes, patient and provider satisfaction, and clinic time efficiency. Methods A 6-month study was conducted at a community rheumatology clinic to compare clinical and patient and provider satisfaction outcomes before and after a clinical pharmacist (CP) was integrated into the clinic staff to assist with providing medication counseling, ordering and monitoring laboratory tests, monitoring adverse effects and medication adherence, and titrating medication doses. The primary outcome was the change in Routine Assessment of Patient Index Data 3 (RAPID-3) scores from baseline to 3 and 6 months after CP integration. Secondary outcomes included the change in monthly pain scores from baseline to 6 months, the change in patient satisfaction scores from baseline to 6 months, and time saved for the rheumatology providers after pharmacist integration into the clinic. Results The mean difference in RAPID-3 scores from baseline to 3 months (N = 55) was an improvement of 5.58 points (P < 0.001), while the mean change in weighted RAPID-3 scores was an improvement of 1.87 (P < 0.001). The mean change in RAPID-3 scores from baseline to 6 months (n = 25) was an improvement of 5.13 (P = 0.003), and the mean change in weighted RAPID-3 scores was 1.78 (P = 0.003). Conclusion The results of this quality improvement project suggest that the integration of a CP in the rheumatology clinic improved patient-reported outcomes, as quantified by patients’ pain scores and RAPID-3 scores. The integration of the CP also appeared to enhance patient and provider satisfaction.
The increasing incidence of physiologic/pathologic conditions that impair the otherwise routine healing of endochondral bone fractures and the occurrence of severe bone injuries necessitate novel approaches to enhance clinically challenging bone fracture repair. To promote the healing of nonunion fractures, we tested an approach that used two small molecules to sequentially enhance cartilage development and conversion to bone in the callus of a murine femoral segmental defect nonunion model of bone injury. Systemic injections of SAG21k were used to stimulate chondrogenesis through the activation of the hedgehog (SHH) pathway early in bone repair, while injections of the prolyl hydroxylase domain (PHD)2 inhibitor, IOX2, were used to stimulate hypoxia signaling‐mediated endochondral bone formation. The expression of SHH pathway genes and Phd2 target genes was increased in chondrocyte cell lines in response to SAG21k and IOX2 treatment, respectively. The segmental defect responded to sequential systemic administration of these small molecules with increased chondrocyte expression of PTCH1, GLI1, and SOX9 in response to SAG and increased expression of HIF‐1α and VEGFA in the defect tissues in response to IOX2. At six weeks post‐surgery, the combined SAG‐IOX2 therapy produced increased bone formation in the defect with bony union over the injury. This article is protected by copyright. All rights reserved.
Aims Although cardiovascular (CV) mortality increased during the COVID-19 pandemic, little is known about how these patterns varied across key subgroups, include age, sex, and race and ethnicity, as well as by specific cause of CV death. Methods and Results The Centers for Disease Control WONDER database was used to evaluate trends in age-adjusted CV mortality between 1999 and 2020 among US adults aged 18 and older. Overall, there was a 4.6% excess CV mortality in 2020 compared to 2019, which represents an absolute excess of 62 802 deaths. The relative CV mortality increase between 2019 and 2020 was higher for adults under 55 years of age (11.9% relative increase), versus adults aged 55–74 (7.9% increase) and adults 75 and older (2.2% increase). Hispanic adults experienced a 9.4% increase in CV mortality (7 400 excess deaths) versus 4.3% for non-Hispanic adults (56 760 excess deaths). Black adults experienced the largest % increase in CV mortality at 10.6% (15 477 excess deaths) versus 3.5% increase (42 907 excess deaths) for White adults. Among individual causes of CV mortality, there was an increase between 2019 and 2020 of 4.3% for ischemic heart disease (32 293 excess deaths), 15.9% for hypertensive disease (13 800 excess deaths), 4.9% for cerebrovascular disease (11 218 excess deaths), but a decline of 1.4% for heart failure mortality. Conclusion The first year of the COVID pandemic in the United States was associated with a reversal in prior trends of improved CV mortality. Increases in CV mortality were most pronounced among Black and Hispanic adults.
The last sentence of the third paragraph on page 497 should be phrased as: Even when remembered in the literature they are often referred to as Arabs and/or Moslems, contrary to their national identity as Assyrians and Chaldeans (the indigenous people of Mesopotamia) and contrary to their religious identity as Christians.
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Nathan R. Wall
  • Department of Basic Sciences, Center for Health Disparities Research & Mol. Medicine
Vladimir A Bashkirov
  • Department of Basic Sciences
Aruni Wilson
  • Division of Microbiology
Carlos Casiano
  • Center for Health Disparities & Molecular Medicine
Penelope Duerksen-Hughes
  • Department of Basic Sciences
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