Pan-viral serology implicates enteroviruses in acute flaccid myelitis.

Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)1-6. Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)2. CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM

A nationwide analysis of geriatric proximal humerus fractures: trends, outcomes, and cost

Background In the USA, proximal humerus fractures (PHF) are the third most common fracture among the elderly. Although most geriatric PHF are treated conservatively, surgical management remains an option. This retrospective study compares annual trends, patient outcomes, and hospital costs between operatively and non-operatively managed geriatric PHF.Methods The Healthcare Cost and Utilization Project Nationwide Inpatient Sample was queried from 2012 to 2015. Geriatric patients with PHF were identified and those who underwent operative or non-operative management were compared in trends, outcomes and costs.Results In total, 137 810 patients met inclusion criteria, of which 51 795 (37.6%) underwent operative management. The operative cohort was younger (76.6 vs 80.9, p<0.001) with a greater proportion of females (81.8% vs 77.6%, p<0.001). The operative cohort demonstrated less frailty and lower Elixhauser Comorbidity Scores (both p<0.001). The operative cohort was also more likely to be discharged home (30.4% vs 13.9%, p<0.001). There was no significant linear trend in age-adjusted and sex-adjusted proportions of operative versus non-operative geriatric PHF (p=0.071), but a positive linear trend was statistically significant for total cost of operative geriatric PHF (p<0.001). Multivariable analyses demonstrated similar overall complication rates between cohorts (OR 0.95, 95% CI 0.89 to 1.00; p=0.06), although surgical intervention increased length of stay (LOS) by 0.15 days (95% CI 0.03 to 0.27; p<0.001) and median cost of hospitalization by US$10 684 (95$10 384 to US$10 984; p<0.001).Conclusions This study identifies a positive linear trend in total cost of operatively managed geriatric PHF from 2012 to 2015. Operative management of geriatric PHF is associated with a similar overall complication rate and greater likelihood of being discharged home. Although non-operative management is associated with decreased LOS and hospital expenses, providers should consider surgical PHF treatment options when available and appropriate in the context of patient-focused outcomes, particularly long-term disposition after intervention.Level of Evidence This level IV retrospective study identifies

Penetrating Colorectal Injuries: Diagnostic Performance of Multidetector CT with Trajectography

Purpose To determine the diagnostic performance of multidetector computed tomography (CT) with trajectography for penetrating colorectal injuries. Materials and Methods This institutional review board-approved and HIPAA-compliant study was a 6-year blinded retrospective review by two independent readers of 182 consecutive patients who preoperatively underwent 40- or 64-row multidetector CT for penetrating torso trauma below the diaphragm and had surgically confirmed findings. Colorectal perforation was present in 42 patients. Trajectory analysis with postprocessing software was used for all studies. Additional signs evaluated were rectal contrast agent leak, collections of extruded fecal material, mural defect, wall thickening, abnormal enhancement, free fluid or stranding, and free air. The quality of the colorectal contrast agent administration was recorded. Sensitivity, specificity, predictive values, areas under the receiver operating characteristic curves (AUCs), and Cohen κ were determined. Results In patients with rectal contrast agent administration (n = 151), AUCs were 0.90-0.91, which indicated excellent accuracy. Trajectory was sensitive (88%-91%). For single wounds (n = 104), sensitivity of trajectory was 96% for both readers, but was only 80% for multiple wounds (n = 47). Contrast agent leak was highly specific (96%-98%), but insensitive (42%-46%). Improved diagnostic performance was observed in patients with poor colonic distension or opacification. Accuracy remained high (AUC, 0.86-0.99) in the group without rectal contrast agent administration (n = 31). Conclusion Trajectory had excellent sensitivity, while rectal contrast agent leak was specific but insensitive. Sensitivity of trajectory was lower for multiple wounds. Accuracy remained high in patients without rectal contrast agent administration. RSNA, 2016

Penetrating Colorectal Injuries: Diagnostic Performance of Multidetector CT with Trajectography.

Purpose To determine the diagnostic performance of multidetector computed tomography (CT) with trajectography for penetrating colorectal injuries. Materials and Methods This institutional review board-approved and HIPAA-compliant study was a 6-year blinded retrospective review by two independent readers of 182 consecutive patients who preoperatively underwent 40- or 64-row multidetector CT for penetrating torso trauma below the diaphragm and had surgically confirmed findings. Colorectal perforation was present in 42 patients. Trajectory analysis with postprocessing software was used for all studies. Additional signs evaluated were rectal contrast agent leak, collections of extruded fecal material, mural defect, wall thickening, abnormal enhancement, free fluid or stranding, and free air. The quality of the colorectal contrast agent administration was recorded. Sensitivity, specificity, predictive values, areas under the receiver operating characteristic curves (AUCs), and Cohen κ were determined. Results In patients with rectal contrast agent administration (n = 151), AUCs were 0.90-0.91, which indicated excellent accuracy. Trajectory was sensitive (88%-91%). For single wounds (n = 104), sensitivity of trajectory was 96% for both readers, but was only 80% for multiple wounds (n = 47). Contrast agent leak was highly specific (96%-98%), but insensitive (42%-46%). Improved diagnostic performance was observed in patients with poor colonic distension or opacification. Accuracy remained high (AUC, 0.86-0.99) in the group without rectal contrast agent administration (n = 31). Conclusion Trajectory had excellent sensitivity, while rectal contrast agent leak was specific but insensitive. Sensitivity of trajectory was lower for multiple wounds. Accuracy remained high in patients without rectal contrast agent administration

Broad-Spectrum Antiherpes Activities of 4-Hydroxyquinoline Carboxamides, a Novel Class of Herpesvirus Polymerase Inhibitors

Through broad screening of the compound library at Pharmacia, a naphthalene carboxamide was identified as a nonnucleoside inhibitor of human cytomegalovirus (HCMV) polymerase. Structure-activity relationship studies demonstrated that a quinoline ring could be substituted for naphthalene, resulting in the discovery of a 4-hydroxyquinoline-3-carboxamide (4-HQC) class of antiviral agents with unique biological properties. In vitro assays with the 4-HQCs have demonstrated potent inhibition of HCMV, herpes simplex virus type 1 (HSV-1), and varicella-zoster virus (VZV) polymerases but no inhibition of human α, δ, and γ polymerases. Antiviral cell culture assays have further confirmed that these compounds are active against HCMV, HSV-1, HSV-2, VZV, and many animal herpesviruses. However, these compounds were not active against several nonherpesviruses representing different DNA and RNA virus families. A strong correlation between the viral DNA polymerase and antiviral activity for this class of compounds supports inhibition of the viral polymerase as the mechanism of antiviral activity. Northern blot analysis of immediate-early and late viral transcripts also pointed to a block in the viral life cycle consistent with inhibition of viral DNA replication. In vitro HCMV polymerase assays indicate that the 4-HQCs are competitive inhibitors of nucleoside binding. However, no cross-resistance could be detected with ganciclovir-resistant HCMV or acyclovir-resistant HSV-1 mutants. The unique, broad-spectrum activities of the 4-HQCs may offer new opportunities for treating many of the diseases caused by herpesviruses

The Brain-Dead Organ Donor

Addressing all aspects of brain death and thoroughly detailing how a potential organ donor should be maintained to ensure maximum use of the organs and cells, The Brain-Dead Organ Donor: Pathophysiology and Management is a landmark addition to the literature. This first-of-its-kind, multidisciplinary volume will be of interest to a large section of the medical community. The first section of the book reviews the historical, medical, legal, and ethical aspects of brain death. That is followed by two chapters on the pathophysiology of brain death as investigated in small and large animal models. This includes a review of the many hormonal changes, including the neuroendocrine- adrenergic ‘storm’, that takes place during and following the induction of brain death, and how they impact metabolism. The next section of the book reviews various effects of brain death, namely its impact on thyroid function, the inflammatory response that develops, and those relating to innate immunity. The chapters relating to assessment and management of potential organ donors will be of interest to a very large group of transplant surgeons and physicians as well as critical care and neurocritical care physicians and nurses. Neurologists, endocrinologists, neurosurgeons, and pathologists will also be interested, especially in the more basic science sections on various aspects of brain-death and hormonal therapy. Organ procurement organizations and transplant coordinators worldwide will also be interested in this title. Other chapters will be of interest to medical historians, medico-legal experts, and ethicists.CONTENIDO: Introduction, Dimitri Novitzky, David K. C. Cooper, Pages 1-6 -- Historical Aspects of the Diagnosis of Death, Félix Bacigalupo, Daniela A. Huerta Fernández, Pages 7-11 -- The Determination of Brain Death, Curtis M. Keller, Boris Chulpayev, Michael Hoffmann, Pages 13-19 -- Legal Aspects of Brain Death and Organ Donorship, Ricky T. Munoz, Mark D. Fox, Pages 21-35 -- Ethical Issues in Organ Donation from Brain-Dead Donors, Mark D. Fox, Ricky T. Munoz, Pages 37-53 -- Pathophysiology of Brain Death in Small Animal Models, Bernhard Floerchinger, Nicholas L. Tilney, Stefan G. Tullius, Pages 55-64 -- Pathophysiology of Brain Death and Effects of Hormonal Therapy in Large Animal Models, Dimitri Novitzky, Winston N. Wicomb, David K. C. Cooper, Pages 65-90 -- The Efficacy of Thyroid Hormone Therapy in Brain-Dead Heart Donors: A Review of Thyroid Function in Health and Disease, Lawrence E. Shapiro, Tatiana Baron, Pages 91-105 -- The Inflammatory Response to Brain Death, Anne Barklin, Christine Lodberg Hvas, Else Toennesen, Pages 107-119 -- The Influence of Brain Death and Intensive Care Management on Donor Organs: Assessment of Inflammatory Markers, Wayel Jassem, Susan V. Fuggle, Pages 121-129 -- Brain Death-Induced Inflammation: Possible Role of the Cholinergic Anti-inflammatory Pathway, Simone Hoeger, Benito A. Yard, Pages 131-138 -- Innate Immunity and Injury During Brain Death: Opportunities for Intervention, Marc A. Seelen, Henri G. D. Leuvenink, Rutger J. Ploeg, Pages 139-145 -- Selection of the Brain-Dead Potential Organ Donor, Kadiyala V. Ravindra, Keri E. Lunsford, Paul C. Kuo, Pages 147-154 -- Infectious Disease Aspects of the Brain-Dead Potential Organ Donor, Nicole M. Theodoropoulos, Michael G. Ison, Pages 155-176 -- Malignancy in the Brain-Dead Organ Donor, Michael A. Nalesnik, Ron Shapiro, Michael G. Ison, Pages 177-189 -- Early Clinical Experience of Hormonal Therapy in the Brain-Dead Potential Organ Donor, Dimitri Novitzky, Burcin Ekser, David K. C. Cooper, Pages 191-207 -- Assessment, Monitoring, and Management of Brain-Dead Potential Organ Donors in the USA, Demetrios Demetriades, Lydia Lam, Pages 209-216 -- Assessment, Monitoring, and Management of Brain-Dead Potential Organ Donors in Europe, Gabriel J. Echeverri, Bruno G. Gridelli, Pages 217-235 -- Assessment, Monitoring, and Management of Brain-Dead Potential Organ Donors in Australia, Peter S. Macdonald, Anders E. M. Aneman, Deepak Bhonagiri, Daryl A. Jones, Gerry O’Callaghan, Helen I. Opdam et al., Pages 237-249 -- Management of the Brain-Dead Organ Donor: Perspectives of the Transplant Coordinator, Nicole T. Farina, David K. C. Cooper, Pages 251-261 -- Surgical Aspects of Thoracic and Abdominal Organ Procurement from Brain-Dead Donors, Michael J. Anstadt, Paul C. Kuo, Kadiyala V. Ravindra, Pages 263-281 -- Impact of Brain Death on Storage of the Heart, Winston N. Wicomb, David K. C. Cooper, Pages 283-288 -- Impact of Brain Death on Abdominal Organs and Allograft Preservation Strategies, Coney Bae, Anthony Watkins, Scot D. Henry, James V. Guarrera, Pages 289-298 -- Functional Repair of Brain Death-Induced Injury, Henri G. D. Leuvenink, Marc A. Seelen, Rutger J. Ploeg, Pages 299-310 -- Functional Repair of Brain Death-Injured Donor Lungs, Jonathan C. Yeung, Marcelo Cypel, Shaf Keshavjee, Pages 311-320 -- Thyroid Hormone Therapy to the Recipient of a Heart from a Brain-Dead Donor, Dimitri Novitzky, David K. C. Cooper, Pages 321-331 -- Current and Potential Future Trends in the Management of the Brain-Dead Organ Donor, Octavio E. Pajaro, James K. Kirklin, Pages 333-341 -- Maximizing Utilization of the Potential Deceased Donor: The Challenge Continues,Eliezer Katz,Pages 343-35