Development of an Immunochromatography Assay to Detect Marburg Virus and Ravn Virus.

The recent outbreaks of Marburg virus disease (MVD) in Guinea, Ghana, Equatorial Guinea, and Tanzania, none of which had reported previous outbreaks, imply increasing risks of spillover of the causative viruses, Marburg virus (MARV) and Ravn virus (RAVV), from their natural host animals. These outbreaks have emphasized the need for the development of rapid diagnostic tests for this disease. Using monoclonal antibodies specific to the viral nucleoprotein, we developed an immunochromatography (IC) assay for the rapid diagnosis of MVD. The IC assay was found to be capable of detecting approximately 102-4 50% tissue culture infectious dose (TCID50)/test of MARV and RAVV in the infected culture supernatants. We further confirmed that the IC assay could detect the MARV and RAVV antigens in the serum samples from experimentally infected nonhuman primates. These results indicate that the IC assay to detect MARV can be a useful tool for the rapid point-of-care diagnosis of MVD.

Antibacterial potency of type VI amidase effector toxins is dependent on substrate topology and cellular context.

Members of the bacterial T6SS amidase effector (Tae) superfamily of toxins are delivered between competing bacteria to degrade cell wall peptidoglycan. Although Taes share a common substrate, they exhibit distinct antimicrobial potency across different competitor species. To investigate the molecular basis governing these differences, we quantitatively defined the functional determinants of Tae1 from Pseudomonas aeruginosa PAO1 using a combination of nuclear magnetic resonance and a high-throughput in vivo genetic approach called deep mutational scanning (DMS). As expected, combined analyses confirmed the role of critical residues near the Tae1 catalytic center. Unexpectedly, DMS revealed substantial contributions to enzymatic activity from a much larger, ring-like functional hot spot extending around the entire circumference of the enzyme. Comparative DMS across distinct growth conditions highlighted how functional contribution of different surfaces is highly context-dependent, varying alongside composition of targeted cell walls. These observations suggest that Tae1 engages with the intact cell wall network through a more distributed three-dimensional interaction interface than previously appreciated, providing an explanation for observed differences in antimicrobial potency across divergent Gram-negative competitors. Further binding studies of several Tae1 variants with their cognate immunity protein demonstrate that requirements to maintain protection from Tae activity may be a significant constraint on the mutational landscape of tae1 toxicity in the wild. In total, our work reveals that Tae diversification has likely been shaped by multiple independent pressures to maintain interactions with binding partners that vary across bacterial species and conditions.

The World Health Organization's Frontline Support to Countries During the COVID-19 Pandemic in 2020.

The World Health Organization (WHO) declared the SARS-CoV-2 outbreak a Public Health Emergency of International Concern (PHEIC) on January 30, 2020. WHO rapidly scaled up its response including through its 149 country offices to support Member States prepare for and respond to the COVID-19 pandemic. This article describes the frontline role of the WHO Country Offices (WCOs) and demonstrates that WHO utilized its existing country presence to deliver its global program of work during this unprecedented emergency. Using data collected from the 2020 WHO COVID-19 Strategic Preparedness and Response Plan monitoring and evaluation framework assessments, plus data collected in a quantitative survey completed by 149 WCOs during 2020, this article describes how WHO supported national authorities and partners through leadership, policy dialogue, strategic support, technical assistance, and service delivery, in line with WHO's current 5-year strategic plan, the WHO 13th General Programme of Work 2019-2023. Country level case studies were used to further illustrate actions taken by WCOs. WHO's achievements notwithstanding, the Organization faced several key challenges in the first year of the response. Recommendations to enhance WHO presence in countries for future emergency prevention, preparedness and response, from several independent reviews, were presented to the World Health Assembly in May 2021 and relevant recommendations are presented in this article.

Soluble terminal complement activation fragment sC5b-9: a new serum biomarker for traumatic brain injury?

PURPOSE: Terminal complement pathway activation after traumatic brain injury (TBI) leads to formation of the membrane attack complex (MAC/C5b-9) which induces neuronal cell death and host-mediated secondary brain injury. Serum levels of soluble MAC (sC5b-9) have not been previously determined in patients with isolated TBI. METHODS: A prospective observational cohort study was performed during a 5-year time-period on adult patients with isolated TBI admitted to an academic level I trauma center in the United States. Controls consisted of patients with femur shaft fractures with or without TBI to mitigate the effect of systemic complement activation by peripheral trauma. Healthy volunteers served as internal controls. The sC5b-9 serum concentrations were measured on the day of admission by enzyme-linked immunosorbent assay (ELISA) and compared between the study cohorts. Univariate analysis was performed to determine independent predictive variables of major complications during hospital admission. RESULTS: Serum sC5b-9 levels were significantly elevated in patients with isolated TBI (n = 42), compared to patients with isolated femoral shaft fractures (n = 36) or combined TBI and femoral shaft fractures (n = 30; p < 0.05). There was no significant difference in serum sC5b-9 levels between the femur group and the combined injury group, compared to the healthy volunteers (n = 21). Univariate analysis revealed serum sC5b-9 levels as an independent predictor of major postinjury complications after isolated TBI (p < 0.01). CONCLUSION: The soluble terminal complement complex sC5b-9 represents a potential novel serum biomarker specific for isolated head injuries, since peripheral trauma did not appear to affect the serum sC5b-9 levels.

Preperitoneal Pelvic Packing Is Not Associated With an Increased Risk of Surgical Site Infections After Internal Anterior Pelvic Ring Fixation.

OBJECTIVE: To investigate the risk of postoperative surgical site infections after plate fixation of the anterior pelvic ring subsequent to preperitoneal pelvic packing (PPP). DESIGN: Retrospective observational cohort study. SETTING: Level I academic trauma center. PATIENTS: Adult trauma patients with unstable pelvic ring injuries requiring surgical fixation of the anterior pelvic ring. INTERVENTION: Pelvic plate fixation was performed as a staged procedure after external fixation and PPP/depacking (PPP group; n = 25) or as a single-stage primary internal fixation (control group; n = 87). MAIN OUTCOME MEASURE: Incidence of postoperative surgical site infections of the pelvic space. RESULTS: Anterior pelvic plate fixation was performed in 112 patients during a 5-year study period. The PPP group had higher injury severity scores and transfused packed red blood cells than the control group (injury severity score: 46 ± 12.2 vs. 29 ± 1.5; packed red blood cells: 13 ± 10 vs. 5 ± 2; P < 0.05). The mean time until pelvic depacking was 1.7 ± 0.6 days (range: 1-3 days) and 3.4 ± 3.7 days (range: 0-15 days) from depacking until pelvic fracture fixation. Two patients in the PPP group and 8 patients in the control group developed a postoperative infection requiring a surgical revision (8.0% vs. 9.2%; n.s.). Both PPP patients with a pelvic space infection had undergone anterior plate fixation for associated acetabular fractures. CONCLUSIONS: These data support the safety of the PPP protocol for bleeding pelvic ring injuries due to the lack of increased infection rates after fracture fixation. Caution should be applied when considering PPP in patients with associated acetabular fractures. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Wound complications after open reduction and internal fixation of tibial plateau fractures in the elderly: a multicentre study.

PURPOSE: The incidence of wound complications after open reduction with internal fixation (ORIF) of tibial plateau fractures in young patients has been reported to range from approximately 5 to 15%. Reports on wound complication rates in the elderly patients are limited. This study investigates the incidence of post-operative wound complications in elderly patients undergoing ORIF of their tibial plateau fractures. METHODS: A retrospective study was performed within three accredited level 1 trauma centres. Patients > 60 years of age undergoing open reduction and internal fixation of their tibial plateau fractures were included. The primary outcome measure was wound complications of the surgical site. These were divided into superficial infections versus deep infections. RESULTS: One hundred two patients matched the inclusion criteria. Of these, 16 patients (15.7%) developed a post-operative wound infection. The analysis of underlying co-morbidities and risk factors revealed that patients with American Society of Anaesthesiologists (ASA) classes 3 and 4 were at significantly increased risk of sustaining a wound complications as compared to ASA classes 1 and 2 (23.7 versus 5.1%, p = 0.015). CONCLUSIONS: The overall infection rates in elderly patients undergoing ORIF for tibial plateau fractures is in a similar range to published data on younger patient populations. In particular, elderly patients without significant co-morbidities seem to be appropriate candidates for ORIF of their tibial plateau fractures. However, elderly patients with significant co-morbidities must be considered as high risk and alternative treatment options, such as nonoperative treatment or less invasive surgical options, should be explored in these patients.

Association Between 6-Week Postdischarge Risk Classification and 12-Month Outcomes After Orthopedic Trauma.

Importance: Numerous studies have demonstrated that long-term outcomes after orthopedic trauma are associated with psychosocial and behavioral health factors evident early in the patient's recovery. Little is known about how to identify clinically actionable subgroups within this population. Objectives: To examine whether risk and protective factors measured at 6 weeks after injury could classify individuals into risk clusters and evaluate whether these clusters explain variations in 12-month outcomes. Design, Setting, and Participants: A prospective observational study was conducted between July 16, 2013, and January 15, 2016, among 352 patients with severe orthopedic injuries at 6 US level I trauma centers. Statistical analysis was conducted from October 9, 2017, to July 13, 2018. Main Outcomes and Measures: At 6 weeks after discharge, patients completed standardized measures for 5 risk factors (pain intensity, depression, posttraumatic stress disorder, alcohol abuse, and tobacco use) and 4 protective factors (resilience, social support, self-efficacy for return to usual activity, and self-efficacy for managing the financial demands of recovery). Latent class analysis was used to classify participants into clusters, which were evaluated against measures of function, depression, posttraumatic stress disorder, and self-rated health collected at 12 months. Results: Among the 352 patients (121 women and 231 men; mean [SD] age, 37.6 [12.5] years), latent class analysis identified 6 distinct patient clusters as the optimal solution. For clinical use, these clusters can be collapsed into 4 groups, sorted from low risk and high protection (best) to high risk and low protection (worst). All outcomes worsened across the 4 clinical groupings. Bayesian analysis shows that the mean Short Musculoskeletal Function Assessment dysfunction scores at 12 months differed by 7.8 points (95% CI, 3.0-12.6) between the best and second groups, by 10.3 points (95% CI, 1.6-20.2) between the second and third groups, and by 18.4 points (95% CI, 7.7-28.0) between the third and worst groups. Conclusions and Relevance: This study demonstrates that during early recovery, patients with orthopedic trauma can be classified into risk and protective clusters that account for a substantial amount of the variance in 12-month functional and health outcomes. Early screening and classification may allow a personalized approach to postsurgical care that conserves resources and targets appropriate levels of care to more patients.

Introducing the "Bone-Screw-Fastener" for improved screw fixation in orthopedic surgery: a revolutionary paradigm shift?

BACKGROUND: Conventional screws used for fracture fixation in orthopedic surgery continue to rely on the historic buttress thread design. While buttress screws generally provide solid resistance against unidirectional axial loading forces, their design suffers from several limitations, as the buttress thread does not adequately resist multiaxial forces. Furthermore, the buttress screw is prone to stripping at the bone-screw interface and can cause microfracturing of the surrounding bone due to its thread design. Standard buttress screws are therefore at risk of adverse postoperative outcomes secondary to failure of bone fixation. A new patented Bone-Screw-Fastener was recently designed that is based on an interlocking thread technology. This new fastener provides distributive forces from the threads onto the bone and therefore resists loads in multiple directions. The underlying concept is represented by a "female thread" bone cutting technology designed to maximize bone volume, preserve bone architecture, and create a circumferential interlocking interface between the implant and bone that protects the thread from stripping and from failing to multiaxial forces. PRESENTATION OF THE HYPOTHESIS: We hypothesize that the new Bone-Screw-Fastener overcomes the classic shortcomings of conventional orthopedic screws with buttress threads by ease of insertion, improved bone preservation, increased resistance to off-axis multidirectional loading forces and to stripping of the threads. These advanced biomechanical and biological properties can potentially mitigate the classic limitations of conventional buttress screws by providing better resistance to implant failure under physiological loads, preserving bone biology, and thus potentially improving patient outcomes in the future. TESTING THE HYPOTHESIS: The presumed superiority of the new fastener will require testing and validation in well-designed prospective multicenter randomized controlled trials (RCTs), using the conventional buttress screw as control. IMPLICATIONS OF THE HYPOTHESIS: Once validated in multicenter RCTs, the new Bone-Screw-Fastener may drive a change in paradigm with regard to its innovative biomechanical principles and biologic bone preservation for surgical applications requiring screw fixation.

Work-hour restrictions and orthopaedic resident education: a systematic review.

PURPOSE: The ACGME (US) and The European Working Time Directive (UK) placed work-hour restrictions on medical trainees with the goal of improved patient safety. However, there has been concern over a potential decrease in medical education. Orthopaedic training is the focus of this study. We examined previously published subjective and objective data regarding education and work-hour restrictions and developed the questions: Do specific perceptions emerge within the subjective studies examined? Are there objective differences in educational measures before and after work-hour restrictions? Is there a difference between the subjective and objective data? METHODS: A systematic review was conducted via MedLine, regarding orthopaedic studies in the USA and UK, with reference to work-hour restrictions and education. RESULTS: Subjective survey studies demonstrate that residents and attending physicians have a negative response to work-hour restrictions because of the perceived impact on their overall education and operating room experience. Conversely, limited objective studies demonstrated no change in operative volume before or after implementation of restrictions. CONCLUSIONS: This review highlights the need for more objective studies on the educational implications of work-hour restrictions. Studies to date have not demonstrated a measurable difference based on case logs or training scores. Opinion-based surveys demonstrate an overall negative perception by both residents and attending physicians, on the impact of work-hour restrictions on orthopaedic education. Current published data is limited and stronger evidence-based data are needed before definitive conclusions can be reached.

Acute lower-leg compartment syndrome.

Acute compartment syndrome remains a challenging problem for orthopedic surgeons because its diagnosis is not always straightforward and it has a high risk of associated limb morbidity if left undiagnosed or untreated. Failure to diagnose and treat acute compartment syndrome is one of the most common causes of successful medical liability claims. The authors review the current literature concerning the diagnosis of acute compartment syndrome and discuss new non-invasive technologies that may allow for earlier and more accurate diagnosis of impending acute compartment syndrome.

Improving health services for residents through community-based participatory research: a public housing leadership perspective.

BACKGROUND: In response to feedback from a health forum, resident leaders of public housing in Washington, DC, were inspired to create a health survey for and by the residents. OBJECTIVE: The survey was designed to document residents' concerns about health, health care, and environmental threats. It also explored tobacco use and support for smoke-free housing. METHODS: A newly created Health Planning Committee of the Citywide Advisory Board, including residents, academics, and representatives of health and housing organizations, facilitated the creation of a health needs assessment. Questionnaires were initially mailed, then hand-delivered to every public housing household. More than 1,000 completed questionnaires have now been returned. LESSONS LEARNED: This project highlights a model that places resident leaders in charge of health issues, including leading advocacy efforts for policies to reduce health disparities in public housing. It identifies research challenges and ways to overcome them and empowers the community for continued research.

Fatal hemorrhagic fever caused by West Nile virus in the United States.

BACKGROUND: Most West Nile virus (WNV) infections in humans are asymptomatic; severe disease occurs in relatively few patients and typically manifests as encephalitis, meningitis, or acute flaccid paralysis. A few cases of life-threatening disease with diffuse hemorrhagic manifestations have been reported in Africa; however, this clinical presentation has not been documented for any of the >16,700 cases of WNV disease reported in the United States during 1999-2004. We describe a case of fulminant WNV infection in a 59-year-old Florida man who died following a brief illness that resembled hemorrhagic disease caused by Rickettsia reckettsii, dengue virus or yellow fever virus. METHODS: Traditional and contemporary diagnostic assays, including culture isolation, electron microscopic examination, reverse-transcriptase polymerase chain reaction amplification, and immunohistochemical stains, were used to confirm systemic WNV infection in the patient. RESULTS: WNV was isolated in a cell culture from a skin biopsy specimen obtained from the patient shortly prior to death. Electron microscopic examination identified the isolate as a flavivirus, and reverse-transcriptase polymerase chain reaction amplified specific WNV sequences from the isolate and patient tissue. Quantitative polymerase chain reaction identified approximately 1x10(7) viral copies/mL in the patient's serum. WNV antigens were detected by immunohistochemical stains in intravascular mononuclear cells and endothelium in skin, lung, liver, kidney, spleen, bone marrow, and central nervous system; no viral antigens were identified in neurons or glial cells of the central nervous system. CONCLUSIONS: Although hemorrhagic disease is a rare manifestation of WNV infection, the findings provided by this report may offer new insights regarding the clinical spectrum and pathogenesis of WNV disease in humans.

Intracranial tuberculoma in a liver transplant patient: first reported case and review of the literature.

A 66-year-old female who had undergone an orthotopic liver transplant two years before admission was admitted with fever and neurological symptoms of several days' duration. Following an extensive work-up, which revealed positive intracranial lesions on computed typography and magnetic resonance imaging, the patient was begun on broad spectrum antimicrobials including corticosteroids. The patient responded though the etiology of infection remained unclear. After a stereotactic biopsy was performed revealing granulomas and acid-fast bacilli, the patient was started on antituberculous medications. A review of the literature reveals that the rare occurrence of intracranial tuberculoma should be considered in an orthotopic liver transplant (OLT) patient with central nervous system pathology.