bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Affecting Household Disaster Preparedness Among Foreign Residents in Japan
Authors: GREEN David , LINLEY Matthew , WHITNEY Justin , SANO Yae
Published: September 2020

Japan is a country known both for its devastating natural disasters and its high level of community preparedness. However, while demographic pressures stemming from an aging society have led to a growing foreign population, scholars have paid little attention to understanding the levels of disaster preparedness exhibited by this group. Using representative data from the 2015 Nagoya City Foreign Resident Survey, this article is the first to explore variations in household disaster preparedness among Japan’s foreign residents. Although numerous factors were found to affect preparedness, the most important appear to be national origin, experience with disaster training, and exposure to disaster information. Japanese language proficiency, perhaps surprisingly, was of minor importance. We thus argue that a person’s cultural background and their exposure to information about local hazards affect their ability to identify and assess risk, which increases the likelihood that they will prepare their household for emergencies. This study not only provides insight into what might drive preparedness activities within foreign populations but also helps explain how migrants obtain disaster information. Its main implication is that Japan’s disparate migrant populations require a strategically varied approach when considering interventions to address disaster vulnerability.
Incidence of Traumatic Spinal Fractures in the Netherlands
Authors: Smits Arjen J. , Ouden Lars P. den , Deunk Jaap , Bloemers Frank W.
Published: September 2020

Study Design.

Retrospective database study based on prospectively collected data.

Objective.

The aim of this study was to describe the current incidence and epidemiology of traumatic spinal fractures in the Netherlands

Summary of Background Data.

Traumatic spinal fractures may lead to severe disability and have considerable consequences on healthcare capacity and costs. Several studies have reported a large and increasing share of fractures in elderly. Currently, a reliable, detailed, and up to date incidence of these injuries in the Netherlands is lacking. These numbers could aid in the composition of preventative measures.

Methods.

All patients from 2010 to 2017 that were admitted with a spinal fracture were included. Patients were selected based on Abbreviated Injury Scores (AIS) codes. Collected data consisted of patient- and injury characteristics, afflicted spine-region, associated injury, referral- and discharge location, and geographic region of admittance.

Results.

Overall, 29,637 patients were included in this study. The incidence of spinal fractures increased from 2010 to 2017 (from 21.5 to 24.0 per 100,000 inhabitants). Most patients were injured by a (low-energy) fall from the same level followed by (high-energy) traffic accidents. Elderly patients (≥65 years of age) made up 42% of all patients. The proportion of elderly increased significantly faster over the years compared to younger patients. More than half of polytrauma (injury severity score ≥16) patients had fractures in multiple spine regions. 5,5% of all patients suffered spinal cord injury (SCI), most often associated with cervical fractures in polytrauma patients. Regional differences were found mainly in presentation through referral and low- and high-energy falls.

Conclusion.

The incidence of patients with spinal fractures increased and elderly made up a large part. Preventative measures could be regional dependent and should focus on low-energy falls, traffic accidents, and bicycle accidents in specific. In polytraumatized patients there should be special attention for any additional spine fractures and SCI.

Level of Evidence: 3
Restoration of Thoracic Kyphosis in Adolescent Idiopathic Scoliosis Over a Twenty-year Period: Are We Getting Better?
Authors: Bodendorfer Blake M. , Shah Suken A. , Bastrom Tracey P. , Lonner Baron S. , Yaszay Burt , Samdani Amer F. , Miyanji Firoz , Cahill Patrick J. , Sponseller Paul D. , Betz Randal R. , Clements David H. , Lenke Lawrence G. , Shufflebarger Harry L. , Marks Michelle C. , Newton Peter O.
Published: September 2020

Study Design.

A multicenter, prospectively collected database of 20 years of operatively treated adolescent idiopathic scoliosis (AIS) was utilized to retrospectively examine pre- and postoperative thoracic kyphosis at 2-year follow-up.

Objective.

To determine if the adoption of advanced three-dimensional correction techniques has led to improved thoracic kyphosis correction in AIS.

Summary of Background Data.

Over the past 20 years, there has been an evolution of operative treatment for AIS, with more emphasis on sagittal and axial planes. Thoracic hypokyphosis was well treated with an anterior approach, but this was not addressed sufficiently in early posterior approaches. We hypothesized that patients with preoperative thoracic hypokyphosis prior to 2000 would have superior thoracic kyphosis restoration, but the learning curve with pedicle screws would reflect initially inferior restoration and eventual improvement.

Methods.

From 1995 to 2015, 1063 patients with preoperative thoracic hypokyphosis (<10°) were identified. A validated formula for assessing three-dimensional sagittal alignment using two-dimensional kyphosis and thoracic Cobb angle was applied. Patients were divided into 1995–2000 (Period 1, primarily anterior), 2001–2009 (Period 2, early thoracic pedicle screws), and 2010–2015 (Period 3, modern posterior) cohorts. Two-way repeated measures analysis of variance and post-hoc Bonferroni corrections were utilized with P < 0.05 considered significant.

Results.

Significant differences were demonstrated. Period 1 had excellent restoration of thoracic kyphosis, which worsened in Period 2 and improved to near Period 1 levels during Period 3. Period 3 had superior thoracic kyphosis restoration compared with Period 2.

Conclusion.

Although the shift from anterior to posterior approaches in AIS was initially associated with worse thoracic kyphosis restoration, this improved with time. The proportion of patients restored to >20° kyphosis with a contemporary posterior approach has steadily improved to that of the era when anterior approaches were more common.

Level of Evidence: 3
Physical Performance Tests Provide Distinct Information in Both Predicting and Assessing Patient-Reported Outcomes Following Lumbar Spine Surgery
Authors: Master Hiral , Pennings Jacquelyn S. , Coronado Rogelio A. , Henry Abigail L. , O’Brien Michael T. , Haug Christine M. , Skolasky Richard L. , Riley Lee H. , Neuman Brian J. , Cheng Joseph S. , Aaronson Oran S. , Devin Clinton J. , Wegener Stephen T. , Archer Kristin R.
Published: September 2020

Study Design.

Secondary analysis of randomized controlled trial data.

Objective.

The aim of this study was to examine whether preoperative physical performance is an independent predictor of patient-reported disability and pain at 12 months after lumbar spine surgery.

Summary of Background Data.

Patient-reported outcome measures (PROMs) are commonly used to assess clinical improvement after lumbar spine surgery. However, there is evidence in the orthopedic literature to suggest that PROMs should be supplemented with physical performance tests to accurately evaluate long-term outcomes.

Methods.

A total of 248 patients undergoing surgery for degenerative lumbar spine conditions were recruited from two institutions. Physical performance tests (5-Chair Stand and Timed Up and Go) and PROMs of disability (Oswestry Disability Index: ODI) and back and leg pain (Brief Pain Inventory) were assessed preoperatively and at 12 months after surgery.

Results.

Physical performance tests and PROMs significantly improved over 12 months following lumbar spine surgery (P < 0.01). Weak correlations were found between physical performance tests and disability and pain (ρ = 0.15 to 0.32, P < 0.05). Multivariable regression analyses controlling for age, education, preoperative outcome score, fusion, previous spine surgery, depressive symptoms, and randomization group found that preoperative 5-Chair Stand test was significantly associated with disability and back pain at 12-month follow-up. Each additional 10 seconds needed to complete the 5-Chair Stand test were associated with six-point increase in ODI (P = 0.047) and one-point increase in back pain (P = 0.028) scores. The physical performance tests identified an additional 14% to 19% of patients as achieving clinical improvement that were not captured by disability or pain questionnaires.

Conclusion.

Results indicate that physical performance tests may provide distinct information in both predicting and assessing clinical outcomes in patients undergoing lumbar spine surgery. Our findings suggest that the 5-Chair Stand test may be a useful test to include within a comprehensive risk assessment before surgery and as an outcome measure at long-term follow-up.

Level of Evidence: 3
Orbital Cellulitis in Chagas Disease: An Unusual Presentation
Authors: Hernandez-Bogantes Erick , Campos-Fuentes Erick , Barrantes-Dominguez Mario , Wu Lihteh
Published: September 2020

Chagas disease is an inflammatory, infectious disease caused by the parasite Trypanosoma cruzi found in the feces of the triatomine bug, which can cause a sudden, brief acute illness, or it may become a long-lasting chronic condition. Chagas disease is common in South America and Central America, however, the constantly expanding global community has brought Chagas disease to the forefront of non-endemic areas, particularly the United States and Europe. The authors present a case of a 47-year-old healthy farmer diagnosed with a right orbital cellulitis refractory to systemic antibiotics. Based on clinical symptoms, the patient’s medical/demographical history and a proper differential diagnosis, an acute phase of Chagas disease was diagnosed. After antiparasitic treatment, the patient had a proper recovery and continued with a regular follow-up to monitor the possible development of a chronic phase.
Histopathologic Observations of Eyes in Exenterated Orbits After Neoadjuvant Intra-Arterial Cytoreductive Chemotherapy for Adenoid Cystic Carcinoma of the Lacrimal Gland
Authors: Liao Sophie D. , Erickson Benjamin P. , Kapila Neha , Dubovy Sander R. , Tse David T.
Published: September 2020

Purpose:

To assess whether exenteration specimens obtained after neoadjuvant intra-arterial cytoreductive chemotherapy (IACC) for adenoid cystic carcinoma of the lacrimal gland demonstrate significant ocular histopathologic alterations that might preclude future pursuit of globe-preserving therapy.

Methods:

Retrospective histopathologic analysis of globes in IACC-treated exenteration specimens among the same cohort of patients whose survival outcomes have been reported.

Results:

Twenty patients had specimens available. Nineteen globes revealed no abnormalities of the iris, ciliary body, lens, retinal pigment epithelium, choroid, or chorioretinal vasculature. Eighteen globes showed no optic nerve abnormalities. One globe from a patient who refused exenteration until adenoid cystic carcinoma recurrence supervened demonstrated optic nerve edema with a peripapillary hemorrhage and cotton wool spot, as well as hemorrhage and necrosis within an extraocular muscle. Eighteen globes showed no retinal abnormalities attributable to intra-arterial chemotherapy. Three globes showed incidental retinal findings: 2 globes contained 1 to 2 small peripheral retinal hemorrhages and 1 had a pigmented retinal hole. Seven demonstrated mild, chronic extraocular muscle inflammation, and 13 had unremarkable musculature. The single patient who received IACC via the internal carotid rather than the external carotid artery developed ophthalmic artery occlusion with orbital apex syndrome prior to exenteration, and diffuse necrosis and hemorrhage were evident histopathologically.

Conclusions:

Neoadjuvant IACC does not cause significant histopathologic damage to key ocular structures or compromise visual function in patients receiving intra-arterial chemotherapy through the external carotid artery. However, delivering chemotherapy through the internal carotid artery may result in visually significant thrombotic vascular events. The generally benign histopathological findings in these exenteration specimens support the concept of IACC delivery through the external carotid system as the cornerstone of a future globe-preserving strategy for lacrimal gland adenoid cystic carcinoma.
Transnasal Endoscopic Sclerotherapy for Orbital Apex Lymphatic Malformation
Authors: Cheung Stephanie S. L. , Lam Stacey C. , Yuen Hunter K. L.
Published: September 2020

Orbital lymphatic malformations are benign, slowly progressive vascular malformations. Management of these malformations is challenging due to their infiltrative and diffuse nature. The authors present a case with orbital apex lymphatic malformation treated with transnasal endoscopic sclerotherapy.
Ocular Perfusion Following Orbital Apex Exenteration
Authors: Gallo Ryan A. , Pirakitikulr Nathan , Tse David T. , Rong Andrew J.
Published: September 2020

A 68-year-old man with a history of type 2 diabetes mellitus and kidney transplantation on chronic immunosuppression presented with right-sided proptosis and vision loss. He was hospitalized 4 months prior for invasive sinus aspergillosis. MRI revealed abnormal enhancement in the right orbital apex, inferior medial right orbit, anterior cranial fossa floor, and anterior aspect of the falx cerebri. The patient was successfully managed with extensive sinus surgery, bifrontal craniotomy with resection of dura, cribriform plate resection, and a right orbital apex exenteration. The globe and anterior orbital structures were preserved to cover the large surgical sinodural-orbital defect and avoid complex reconstructive surgery. Orbital perfusion was maintained by exploiting the robust anastomoses between branches of external carotid and ophthalmic artery.
Orbital Crystal-Storing Histiocytosis: A Clinicopathologic Study of 4 Cases
Authors: Wilde Caroline , Amin Sepideh , Poitelea Cornelia , Uddin Jimmy , Rose Geoffrey E. , Sherafat Hooman
Published: September 2020

The authors report the clinicopathological features of crystal-storing histiocytosis (CSH) that involved the orbit and conjunctiva and review published cases of CSH. Cases of histologically proven CSH were identified from archives at the Institute of Ophthalmology, London, and a retrospective review of clinical details and pathology was performed for cases between 1997 and 2017. Four cases of CSH were identified: 1 might have arisen from an inflammatory reaction to a silicone retinal buckle and 3 others occurred with localized B-cell lymphomas. Two patients presented with a conjunctival mass, and 2 had an orbital mass causing proptosis and hypoglobus. One case was associated with amyloid deposition and another had an earlier diagnosis of IgG4-related disease. In the patient without underlying lymphoma, the condition settled with removal of the explant and orbital mass, and the 3 with lymphoma underwent orbital radiotherapy with cessation of disease progression. All patients retained good vision. Ocular CSH is rare, can present in several ways, and should prompt investigation for an underlying lymphoproliferative disorder.
Evaluation of the Initiation Timing of Hydrocortisone in Adult Patients With Septic Shock
Authors: Sacha Gretchen L. , Chen Alyssa Y. , Palm Nicole M. , Duggal Abhijit
Published: September 2020

Introduction:

Clinical studies evaluating the use of hydrocortisone in patients with septic shock are heterogeneous in design with conflicting results. The appropriate time in which to initiate hydrocortisone after shock onset is unknown. This study sought to compare clinical outcomes including vasopressor duration and mortality in patients with septic shock who received hydrocortisone based on timing of initiation after shock onset.

Methods:

Retrospective cohort study of patients between 2011 and 2017 admitted to 10 medical, surgical, and neurosciences intensive care units (ICUs) at a large, tertiary care academic medical center. Adult patients with vasopressor-dependent septic shock who received hydrocortisone were included. Patients were divided into five timing cohorts based on time after shock onset: 0–6, 6–12, 12–24, 24–48, or >48 h. The primary outcome was days alive and free from vasopressors.

Results:

One thousand four hundred seventy patients were included: 567 (38.6%) received hydrocortisone between 0 and 6 h, 231 (15.7%) 6 and 12 h, 260 (17.7%) 12 and 24 h, 195 (13.3%) 24 and 48 h, and 217 (14.8%) >48 h after shock onset. Patients who received hydrocortisone earlier were sicker at baseline with higher APACHE III scores, lactate concentrations, and norepinephrine requirements. On univariate analysis, days alive and free from vasopressors did not significantly differ amongst the timing groups (median 3.3 days for 0–6 h; 1.9 for 6–12 h; 1.9 for 12–24 h; 0 for 24–48 h; 0 for >48 h; P = 0.39); similarly, ICU mortality did not differ. On multivariable linear regression, timing of hydrocortisone was independently associated with more days alive and free from vasopressors when comparing initiation within 0 to 6 h with >48 h (beta-coefficient 2.8 days [95% CI 0.8–4.7]), 6–12 h with >48 h (2.5 days [95% CI 0.2–4.7]), and 12–24 h with >48 h (2.3 days [95% CI 0.2–4.5]). On multivariable logistic regression, timing of hydrocortisone was associated with reduced ICU mortality when comparing receipt within 0 to 6 h of shock onset to >48 h after shock onset (OR 0.6, 95% CI 0.4–0.8).

Conclusions:

In patients in whom hydrocortisone is prescribed for vasopressor-dependent septic shock, timing is crucial and hydrocortisone should be started within the first 12 h after shock onset.
COVID-19 Associated Hypercoagulability: Manifestations, Mechanisms, and Management
Authors: Mazzeffi Michael A. , Chow Jonathan H. , Tanaka Kenichi
Published: September 2020

Patients with severe coronavirus disease-2019 (COVID-19) frequently have hypercoagulability caused by the immune response to the severe acute respiratory syndrome coronavirus-2 infection. The pathophysiology of COVID-19 associated hypercoagulability is not fully understood, but characteristic changes include: increased fibrinogen concentration, increased Factor VIII activity, increased circulating von Willebrand factor, and exhausted fibrinolysis. Anticoagulant therapy improves outcomes in mechanically ventilated patients with COVID-19 and viscoelastic coagulation testing offers an opportunity to tailor anticoagulant therapy based on an individual patient's coagulation status. In this narrative review, we summarize clinical manifestations of COVID-19, mechanisms, monitoring considerations, and anticoagulant therapy. We also review unique considerations for COVID-19 patients who are on extracorporeal membrane oxygenation.
Group A emergency-release plasma in trauma patients requiring massive transfusion
Authors: de Roulet Amory , Kerby Jeffrey D. , Weinberg Jordan A. , Lewis Richard H. , Hudgins Jay P. , Shulman Ira A. , Fox Erin E. , Holcomb John B. , Brasel Karen J. , Bulger Eileen M. , Cohen Mitchell Jay , Cotton Bryan A. , Fabian Timothy C. , O’Keeffe Terence , Rizoli Sandro , Scalea Thomas M. , Schreiber Martin A. , Inaba Kenji ,   the PROPPR Study Group
Published: September 2020

BACKGROUND

Both groups A and AB plasma have been approved for emergency-release transfusion in acutely bleeding trauma patients before blood grouping being performed. The safety profile associated with this practice has not been well characterized, particularly in patients requiring massive transfusion.

METHODS

This secondary analysis of the Pragmatic, Randomized, Optimal Platelet and Plasma Ratios trial examined whether exposure to group A emergency-release plasma (ERP) was noninferior to group AB ERP. We also examined patients whose blood groups were compatible with group A ERP versus patients whose blood groups were incompatible with group A ERP. Outcomes included 30-day mortality and complication rates including systemic inflammatory response syndrome, infection, renal injury, pulmonary dysfunction, and thromboembolism.

RESULTS

Of the 680 patients predicted to receive a massive transfusion, 584 (85.9%) received at least 1 U of ERP. Of the 584 patients analyzed, 462 (79.1%) received group AB and 122 (20.9%) received group A ERP. Using a hazard ratio (HR) of 1.35 as the noninferiority margin, transfusion with group A versus group AB ERP was not associated with increased thromboembolic rates (HR, 0.52; 95% confidence interval [CI], 0.31–0.90). Mortality (HR, 1.15; 95% CI, 0.91–1.45) and nonfatal complication rates (HR, 1.24; 95% CI, 0.87–1.77) were inconclusive. In the subgroup analysis, transfusion with incompatible ERP (group B or AB patients receiving group A ERP) was not associated with increased nonfatal complications (HR, 1.02; 95% CI, 0.80–1.30). There were no reported hemolytic transfusion reactions.

CONCLUSION

The use of ERP is common in patients requiring massive transfusion and facilitates the rapid balanced resuscitation of patients who have sustained blood loss. Group A ERP is an acceptable option for patients requiring massive transfusion, especially if group AB ERP is not readily available.

LEVEL OF EVIDENCE

Therapeutic/Care Management, level IV; Prognostic, level III.
Association of timing of initiation of pharmacologic venous thromboembolism prophylaxis with outcomes in trauma patients
Authors: Hecht Jason P. , Han Emily J. , Cain-Nielsen Anne H. , Scott John W. , Hemmila Mark R. , Wahl Wendy L.
Published: September 2020

BACKGROUND

Patients are at a high risk for developing venous thromboembolism (VTE) following traumatic injury. We examined the relationship between timing of initiation of pharmacologic prophylaxis with VTE complications.

METHODS

Trauma quality collaborative data from 34 American College of Surgeons Committee on Trauma–verified levels I and II trauma centers were analyzed. Patients were excluded if they were on anticoagulant therapy at the time of injury, had hospitalization <48 hours, or received no or nonstandard pharmacologic VTE prophylaxis (heparin drip). Patient comparison groups were based on timing of initiation of VTE prophylaxis relative to hospital presentation (0 to <24 hours, 24 to <48 hours, ≥48 hours). Risk-adjusted rates of VTE events were calculated accounting for patient factors including type of pharmacologic agent in addition to standard trauma patient confounders. A sensitivity analysis was performed excluding patients who received blood in the first 4 hours and/or patients with a significant traumatic brain injury.

RESULTS

Within the 79,386 patients analyzed, there were 1,495 (1.9%) who experienced a VTE complication and 1,437 (1.8%) who died. After adjusting for type of prophylaxis and patient factors, the risk of a VTE event was significantly increased in the 24- to <48-hour (odds ratio, 1.26; 95% confidence interval, 1.09–1.47; p = 0.002) and ≥48-hour (odds ratio, 2.35; 95% confidence interval, 2.04–2.70; p < 0.001) cohorts relative to patients initiated at 0 to <24 hours. These VTE event findings remained significant after exclusion of perceived higher-risk patients in a sensitivity analysis.

CONCLUSION

Early initiation of pharmacologic VTE prophylaxis in stable trauma patients is associated with lower rates of VTE.

LEVEL OF EVIDENCE

Diagnostic, level III.
Computed tomography angiography in the “no-zone” approach era for penetrating neck trauma: A systematic review
Authors: Ibraheem Kareem , Wong Sunnie , Smith Alison , Guidry Chrissy , McGrew Patrick , McGinness Clifton , Duchesne Juan , Taghavi Sharven , Harris Charles , Schroll Rebecca
Published: September 2020

BACKGROUND

Penetrating neck trauma (PNT) continues to present a diagnostic dilemma. Practice guidelines advocate the use of computed tomography angiography (CTA) for suspected vascular or aerodigestive injuries in all neck zones. There is also an evolving evidence of “no-zone” approach where the decision to obtain a CTA is guided by physical examination findings and clinical presentation. The aim of this systematic review was to examine existing literature on the diagnostic accuracy of CTA as an integral component of the no-zone approach in stable patients with PNT.

METHODS

We performed a systematic review using an electronic search of three databases (PubMed, Medline, Cochrane Review) from 2000 to 2017.

RESULTS

A total of 5 prospective and 8 retrospective studies were included. The sensitivity of CTA ranged from 83% to 100%; specificity, from 61% to 100%; positive predictive value, from 30% to 100%; and negative predictive value, from 90% to 100%. Three studies reported high sensitivity and specificity for the detection of vascular injuries but low specificity for aerodigestive tract injuries. When stratified by clinical presentation, CTA had a sensitivity of 89.5% to 100% and specificity of 61% to 100% in stable patients presenting with soft signs (SSs). In a combined group of stable patients with either hard signs (HSs) or SSs, the sensitivity of CTA was 94.4% to 100% and the specificity was 96.7% to 100%. Among patients presenting with HSs, the sensitivity of CTA was 78.6% to 90% and the specificity was 100%.

CONCLUSIONS

This is the first systematic review to examine the role of CTA in PNT. In combination with physical examination, CTA demonstrated a reliable high sensitivity and specificity for detecting injuries in PNT in stable patients with SSs of injury and select patients with HSs of injury. These results support the management of PNT using no-zone approach based on physical examination and the use of CTA in stable patients.

LEVEL OF EVIDENCE

Systematic review, level IV.
Quantifying the expense of deferring surgical stabilization of rib fractures: Operative management of rib fractures is associated with significantly lower charges
Authors: Coleman Julia R. , Leasia Kiara , Douglas Ivor S. , Hosokawa Patrick , Lawless Ryan A. , Moore Ernest E. , Pieracci Fredric
Published: September 2020

INTRODUCTION

Surgical stabilization of rib fractures (SSRF) remains a relatively controversial operation, which is often deferred because of concern about expense. The objective of this study was to determine the charges for SSRF versus medical management during index admission for rib fractures. We hypothesize that SSRF is associated with increased charge as compared with medical management.

METHODS

This is a retrospective chart review of a prospectively maintained database of patients with ≥3 displaced rib fractures admitted to a level 1 trauma center from 2010 to 2019. Patients who underwent SSRF (operative management [OM]) were compared with those managed medically (nonoperative management [NOM]). The total hospital charge between OM and NOM was compared with univariate analysis, followed by backward stepwise regression and mediation analysis.

RESULTS

Overall, 279 patients were included. The majority (75%) were male, the median age was 54 years, and the median Injury Severity Scale score (ISS) was 21. A total of 182 patients underwent OM, whereas 97 underwent NOM. Compared with NOM, OM patients had a lower ISS (18 vs. 22, p = 0.004), less traumatic brain injury (14% vs. 31%, p = 0.0006), shorter length of stay (10 vs. 14 days, p = 0.001), and decreased complications. After controlling for the differences between OM and NOM patients, OM was significantly associated with decreased charges (β = US $35,105, p = 0.01). Four other predictors, with management, explained 30% of the variance in charge (R
2 = 0.30, p < 0.0001): scapular fracture (β = US $471,967, p < 0.0001), ISS per unit increase (β = US $4,139, p < 0.0001), long bone fracture (β = US $52,176, p = 0.01), bilateral rib fractures (β = US $34,392, p = 0.01), and Glasgow Coma Scale per unit decrease (β = US $17,164, p < 0.0001). The difference in charge between NOM and OM management was most strongly, although only partially, mediated by length of stay.

CONCLUSION

Our analysis found that OM, as compared with NOM, was independently associated with decreased hospital charges. These data refute the prevailing notion that SSRF should be withheld because of concerns for increased cost.

LEVEL OF EVIDENCE

Economic, level II.
Protein and Microbial Biomarkers in Sputum Discern Acute and Latent Tuberculosis in Investigation of Pastoral Ethiopian Cohort
Authors: HaileMariam Milkessa , Yu Yanbao , Singh Harinder , Teklu Takele , Wondale Biniam , Worku Adana , Zewde Aboma , Monaud Stephanie , Tsitrin Tamara , Legesse Mengistu , Ameni Gobena , Pieper Rembert
Published: September 2020

Differential diagnosis of tuberculosis (TB) and latent TB infection (LTBI) remains a public health priority in high TB burden countries. Pulmonary TB is diagnosed by sputum smear microscopy, chest X-rays, and PCR tests for distinctMycobacterium tuberculosis(Mtb) genes. Clinical tests to diagnose LTBI rely on immune cell stimulation in blood plasma with TB-specific antigens followed by measurements of interferon-γ concentrations. The latter is an important cytokine for cellular immune responses against Mtb in infected lung tissue. Sputum smear microscopy and chest X-rays are not sufficiently sensitive while both PCR and interferon-γ release assays are expensive. Alternative biomarkers useful for developing diagnostic tests to discern TB disease states are desirable. This study’s objective was to discover biomarkers in sputum, assessing the proteomes and microbiomes of 74 TB patients, 46 individuals with LTBI, and 51 negative community controls (NCC). Study participants were from the South Omo province, a pastoral region in southern Ethiopia. A total of 161 and 115 samples were used to determine the 16S rRNA sequence-based bacterial taxonomies and proteomic profiles, respectively. Sputum microbiota did not reveal statistically significant differences in α-diversity comparing the three groups. The genusMycobacterium, representing Mtb, was only identified for the TB group. The latter featured reduced abundance of the genusRothiain comparison to the LTBI and NCC groups.Rothiais a human respiratory tract commensal and may be sensitive to the inflammatory milieu caused by TB infection. Proteomic data strongly supported innate immune responses against Mtb in subjects with pulmonary TB. Ferritin, an iron storage protein released by damaged host cells, was markedly increased in abundance in TB sputum compared to the LTBI and NCC groups, along with α-1-acid glycoproteins ORM1 and ORM2. These proteins are acute phase reactants and inhibit excessive neutrophil activation. Proteomic data also supported effector roles of neutrophils in the anti-Mtb response which was not observed for LTBI cases. Less abundant in sputum of the LTBI group versus the NCC group were two immunomodulatory proteins, mitochondrial TSPO and the extracellular ribonuclease T2. If validated, these proteins are of interest as diagnostic biomarkers for LTBI.
Vaccination for some childhood diseases may impact the outcome of covid-19 infections
Authors: Gobe Irene , Koto Garesego F , Mokomane Margaret , Molebatsi Kesaobaka , Kasvosve Ishmael , Motswaledi Modisa S
Published: September 2020

Background

COVID-19 found the world in a state of unpreparedness. While research efforts to develop a vaccine are on-going, others have suggested the use of available vaccines to boost innate immunity.

Objective

We analysed three databases: UNICEF Immunization Coverage, Worldometer Corona Virus Updates and World Bank List of Economies to establish the association, if any, between vaccination for various diseases and COVID-19 death rates and recoveries across world economies.

Results

Mean percentage death rates were lower in countries that vaccinated for Hepatitis-B birth dose (2.53% vs 3.79%, p = 0.001), Bacille Calmette-Guérin Vaccine (2.93% vs 5.10%, p = 0.025) and Inactivated Polio Vaccine 1st dose (2.8% vs 4.01%, p = 0.022) than those which did not report vaccination. In high income countries, a significant negative correlation with death rates was observed with vaccination for Measles-containing vaccine 2nd dose (r = –0.290, p = 0.032), Rubella-containing vaccine 1st dose (r = –0.325, p = 0.015), Hepatitis B 3rd dose (r = –0.562, p = 3.3 x10−5), Inactivated Polio vaccine 1st dose (r = –0.720, p = 0.008). Inactivated Polio Vaccine 1st dose and Measles-containing vaccine 2nd dose also correlated with better recoveries. In Low Income countries, only Rubella-containing vaccine correlated with lower deaths while Yellow fever vaccine was associated with poorer recoveries.

Conclusion

Our analysis corroborates the potential benefit of vaccination and warrant further research to explore the rationale for repurposing other vaccines to fight COVID-19.
Discrete TrkB-expressing neurons of the dorsomedial hypothalamus regulate feeding and thermogenesis
Authors: Houtz Jessica , Liao Guey-Ying , Xu Baoji
Published: September 2020

Mutations in the TrkB neurotrophin receptor lead to profound obesity in humans, and expression of TrkB in the dorsomedial hypothalamus (DMH) is critical for maintaining energy homeostasis. However, the functional implications of TrkB-expressing neurons in the DMH (DMHTrkB) on energy expenditure are unclear. Additionally, the neurocircuitry underlying the effect of DMHTrkBneurons on energy homeostasis has not been explored. In this study, we show that activation of DMHTrkBneurons leads to a robust increase in adaptive thermogenesis and energy expenditure without altering heart rate or blood pressure, while silencing DMHTrkBneurons impairs thermogenesis. Furthermore, we reveal neuroanatomically and functionally distinct populations of DMHTrkBneurons that regulate food intake or thermogenesis. Activation of DMHTrkBneurons projecting to the raphe pallidus stimulates thermogenesis and increased energy expenditure, whereas DMHTrkBneurons that send collaterals to the paraventricular hypothalamus and preoptic area inhibit feeding. Together, our findings provide evidence that DMHTrkBneuronal activity plays an important role in regulating energy expenditure and delineate distinct neurocircuits that underly the separate effects of DMHTrkBneuronal activity on food intake and thermogenesis.

Brief summary

This study shows that TrkB-expressing DMH neurons stimulate thermogenesis through projection to raphe pallidus, while inhibiting feeding through collaterals to paraventricular hypothalamus and preoptic area.
Mutation in position of 32 (G>U) of S2M differentiate human SARS-CoV2 from Bat Coronavirus
Authors: Vahed Majid , Vahed Mohammad , Sweeney Aaron , Shirazi Farshad H , Mirsaeidi Mehdi
Published: September 2020

The new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a zoonotic pathogen that has rapidly mutated and become transmissible to humans. There is little existing data on the mutations in SARS-CoV-2 and the impact of these polymorphisms on its transmission and viral load. In this study, the SARS-CoV-2 genomic sequence was analyzed to identify variants within the 3’UTR region of its cis-regulatory RNA elements. A 43-nucleotide genetic element with a highly conserved stem-loop II-like motif (S2M), was discovered. The research revealed 32 G>U and 16 G>U/A mutations located within the S2M sequence in human SARS-CoV-2 models. These polymorphisms appear to make the S2M secondary and tertiary structures in human SARS-CoV-2 models less stable when compared to the S2M structures of bat/pangolin models. This grants the RNA structures more flexibility, which could be one of its escape mechanisms from host defenses or facilitate its entry into host proteins and enzymes. While this S2M sequence may not be omnipresent across all human SARS-CoV-2 models, when present, its sequence is always highly conserved. It may be used as a potential target for the development of vaccines and therapeutic agents.
Effect of Renin-Angiotensin-Aldosterone System inhibitors on outcomes of COVID-19 patients with hypertension: Systematic review and Meta-analysis
Authors: Beressa Tamirat Bekele , Sahilu Tamiru , Deyno Serawit
Published: September 2020

Objective

This research aimed to systematically review and summarize the influence of Renin-Angiotensin-Aldosterone System(RAAS) inhibitors on the outcome of COVID_19 patients with hypertension.

Methods

Electronic databases; PubMed/Medline, CINAHL, the Cochrane Central Register of Controlled Trials, clinical trial.gov, and Google Scholar were searched from 2019 to June 1, 2020. Additionally, the references of identified articles were also searched.

Results

A total of 9 articles comprising 3,823 patients were incorporated; 1416 patients on RAAS inhibitors and 3469 on non-RAAS inhibitors. The study demonstrated that the taking of RAAS inhibitors in COVID_19 patients with hypertension significantly reduced mortality where patients on RAAS inhibitors had a 27% decrease of mortality (RR = 0.73 [95% CI: 0.63- 0.85, p< 0.0001, I2= 0%, random-effects model]) compared to those not taking ACEI/ARB. No significant association were observed in disease severity (RR = 0.92 (95% CI: 0.74- 1.14) and hospitalization (WMD = –2.33[95% CI: –5.60, 0.75]), random-effects model.

Conclusion

This study supports RAAS inhibitors’ safe use among COVID_19 patients with hypertension.
Is tumor mutational burden predictive of response to immunotherapy?
Authors: Gurjao Carino , Tsukrov Dina , Imakaev Maxim , Luquette Lovelace J. , Mirny Leonid A.
Published: September 2020

Cancer immunotherapy by checkpoint blockade (ICB) is effective for various cancer types, yet its clinical use is encumbered by a high variability of patient response. Several studies have reported that the number of non-synonymous mutations (Tumor Mutational Burden, TMB), can predict patient response to ICB. This belief has become widespread and led to the FDA approval of immunotherapy patient prioritization based on TMB levels. The notion that TMB is predictive of response to immunotherapy is rooted in the neoantigen theory. It stipulates that cancer-specific mutations can form neoantigens recognized by the immune system; the more mutations a tumor has, the more likely the immune response is triggered. Here we revisit the data underlying the reported association of TMB with response, and the neoantigen theory. First we assembled the largest pan-cancer dataset of immunotherapy patients with sequencing and clinical data. Surprisingly, we find little evidence that TMB is predictive of response to ICB. We demonstrate that associations similar to the ones reported previously can be observed in shuffled data, suggesting that previous studies suffered from a lack of correction for multiple hypotheses testing and confounding disease subtypes.

Second, we develop a model that expands the neoantigen theory and can be consistent with both immunogenicity of neoantigens and the lack of association between TMB and response. Our analysis shows that the use of TMB in clinical practice is not supported by available data and can deprive patients of treatment to which they are likely to respond.
Role of ERK activation inH. pylori-induced disruption of cell-cell tight junctions
Authors: Sekar Amita , Ho Bow
Published: September 2020

Background

Tight junctions, a network of claudins and other proteins, play an important role in maintaining barrier function and para-cellular permeability.H. pylori, the major etiological agent of various gastroduodenal diseases, is known to cause tight junction disruption. However, the molecular events that triggered cell-cell tight junction disruption inH. pylori-infected cells, remain largely elusive.

Materials and Methods

Trans-epithelial electrical resistance (TEER) and FITC-Dextran permeability measurement were performed to determine the barrier function inH. pylori88-3887-infected polarized MKN28 cells. For visualization of tight junction protein localization, immunofluorescence and immunoblotting techniques were used. To examine the role of ERK activation in tight junction disruption, U0126, a MEK inhibitor, was employed. To further support the study, computational analyses ofH. pylori-infected primary gastric cells were carried out to decipher the transcriptomic changes.

Results

The epithelial barrier of polarized MKN28 cells when infected withH. pyloridisplayed disruption of cell-cell junctions as shown by TEER & FITC-dextran permeability tests. Claudin-4 was shown to delocalize from host cytoplasm to nucleus inH. pylori-infected cells. In contrast, delocalization of claudin-4 was minimized when ERK activation was inhibited. Interestingly, transcriptomic analyses revealed the upregulation of genes associated with cell-junction assembly and ERK pathway forming a dense interacting network of proteins.

Conclusion

Taken together, evidence from this study indicates thatH. pyloriregulates ERK pathway triggering cell-cell junction disruption, contributing to host pathogenesis. It indicates the vital role of ERK in regulating key events associated with the development ofH. pylori-induced gastroduodenal diseases.
Neuronal perception of the social environment intergenerationally controls germline development and generation time inC. elegans
Authors: Perez Marcos Francisco , Shamalnasab Mehrnaz , Mata-Cabana Alejandro , Valle Simona Della , Olmedo María , Francesconi Mirko , Lehner Ben
Published: September 2020

An old and controversial question in biology is whether information perceived by the nervous system of an animal can ‘cross the Weismann barrier’ to alter the phenotypes and fitness of their progeny. Here we show that such intergenerational transmission of sensory information occurs in the model organism,C. elegans, with a major effect on fitness. Specifically, that perception of social pheromones by chemosensory neurons controls the post-embryonic timing of development of one tissue – the germline – relative to others in an animal’s progeny. Neuronal perception of the social environment thus intergenerationally controls the generation time of this animal.
qFit 3: Protein and ligand multiconformer modeling for X-ray crystallographic and single-particle cryo-EM density maps
Authors: Riley Blake T. , Wankowicz Stephanie A. , de Oliveira Saulo H. P. , van Zundert Gydo C. P. , Hogan Daniel , Fraser James S. , Keedy Daniel A. , van den Bedem Henry
Published: September 2020

New X-ray crystallography and cryo-electron microscopy (cryo-EM) approaches yield vast amounts of structural data from dynamic proteins and their complexes. Modeling the full conformational ensemble can provide important biological insights, but identifying and modeling an internally consistent set of alternate conformations remains a formidable challenge. qFit efficiently automates this process by generating a parsimonious multiconformer model. We refactored qFit from a distributed application into software that runs efficiently on a small server, desktop, or laptop. We describe the new qFit 3 software and provide some examples. qFit 3 is open-source under the MIT license, and is available athttps://github.com/ExcitedStates/qfit-3.0.
Development of SARS-CoV-2 Nucleocapsid Specific Monoclonal Antibodies
Authors: Terry James S. , Anderson Loran BR , Scherman Michael S. , McAlister Carley E. , Perera Rushika , Schountz Tony , Geiss Brian J.
Published: September 2020

The global COVID-19 pandemic has caused massive disruptions in every society around the world. To help fight COVID-19, new molecular tools specifically targeting critical components of the causative agent of COVID-19, SARS-Coronavirus-2 (SARS-CoV-2), are desperately needed. The SARS-CoV-2 nucleocapsid protein is a major component of the viral replication processes, integral to viral particle assembly, and is a major diagnostic marker for infection and immune protection. Currently available antibody reagents targeting the nucleocapsid protein were primarily developed against the related SARS-CoV virus and are not specific to SARS-CoV-2 nucleocapsid protein. Therefore, in this work we developed and characterized a series of new mouse monoclonal antibodies against the SARS-CoV-2 nucleocapsid protein. The anti-nucleocapsid monoclonal antibodies were tested in ELISA, western blot, and immunofluorescence analyses. The variable regions from the heavy and light chains from five select clones were cloned and sequenced, and preliminary epitope mapping of the sequenced clones was performed. Overall, the new antibody reagents described here will be of significant value in the fight against COVID-19.
Emergence of stable motifs in consumer-resource communities
Authors: Amarasekare Priyanga , Brose Ulrich , Chase Jonathan , Knight Tiffany , Clark Adam
Published: September 2020

Understanding how and why complex communities can be stable has preoccupied ecologists for over a century. Data show that real communities tend to exhibit characteristic motifs and topologies. Despite a large body of theory investigating both ecological (niche partitioning) and evolutionary (speciation and extinction) mechanisms, a general explanation for why particular motifs are more common than others remains elusive. Here we develop a mechanistic framework that investigates the set of possible motifs that can emerge under minimal conditions of a nutrient-limited system with no external inputs, and no spatial heterogeneity. Focusing on consumer-resource communities structured by competition and predation, we find that the emergent motifs under these minimal conditions are vertical trophic chains that maximize energy transfer and biomass production. Not only are such motifs stable to perturbations of species’ abundances, but they are also robust to species additions and removals. Our findings provide a mechanistic explanation for why tri-trophic chains are overrepresented in real food webs. They suggest that, because they maximize energy transfer, and can emerge and persist under minimal conditions, vertical trophic chains may constitute the fundamental architecture of consumer-resource communities.
Identification, Localization and Expression of NHE Isoforms in the Alveolar Epithelial Cells
Authors: Kinaneh Safa , Knany Yara , Khoury Emad , Ismael-Badarneh Reem , Hammoud Shadi , Berger Gidon , Abassi Zaid , Azzam Zaher S.
Published: September 2020

Na+/H+ exchangers (NHEs), encoded by Solute Carrier 9A (SLC9A) genes in human, are ubiquitous integral membrane ion transporters that mediate the electroneutral exchange of H+ with Na+ or K+. NHEs, found in the kidney and intestine, play a major role in the process of fluid reabsorption together via Na+,K+-ATPase pump and Na+ channels. Nevertheless, the expression pattern of NHE in the lung and its role in alveolar fluid homeostasis has not been addressed. Therefore, we aimed to examine the expression of NHE specific isoforms in alveolar epithelium cells (AECs), and assess their role in congestive heart failure.

Three NHE isoforms were identified in AEC and A549 cell line, at the level of protein and mRNA; NHE1, NHE2 and mainly NHE8, the latter was shown to be localized in the apical membrane of AEC. Treating A549 cells with angiotensin (Ang) II for 1 and 3 hours displayed a significant reduction in NHE8 protein abundance and to lesser extent at 5 hours; however, there was no effect at 24 hours. Moreover, A549 treated overnight with Ang II downregulated NHE8 protein abundance.

CHF rats held for 1 week had increased abundance of NHE8 compared to sham operated rats. However, lower abundance of NHE8 was observed in CHF rats held for 4 weeks.

Herein we show, for the first time, the expression of a novel NHE isoform by AEC, namely NHE8. Besides being negatively affected by Ang II, NHE8 protein levels were distinctly affected in CHF rats, which may be related to CHF severity.