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Frostbite is a high morbidity injury caused by soft tissue freezing, which can lead to digit necrosis requiring amputation. Rapid rewarming is a first-line treatment method that involves placing affected digits into a warm water bath. This study aims to assess the clinical practices for frostbite at facilities outside of dedicated burn centers, and any impact these practices have on tissue salvage. Retrospective chart review at a single burn center identified frostbite patients admitted directly or as transfers over a 7-year period. Records were reviewed to identify initial treatment strategies. If given, time to thrombolytics from admit was noted. Tissue salvage rates were calculated from radiologically derived tissue at-risk scores and final amputation scores. One-hundred patients were transferred from outside facilities, and 108 were direct admissions (N = 208). There was no significant difference in group demographics. Rapid rewarming was the initial treatment modality more commonly in direct admit patients (P = .016). The use of rapid rewarming did not correlate with tissue salvage (P = .112). Early use of thrombolytics had a positive impact on tissue salvage (P = .003). Thrombolytics were given 1.2 hours earlier in direct admit patients (P = .029), however there was no difference in tissue salvage rates between the groups (P = .127). Efforts should focus on larger scale study to further assess the effectiveness of rapid rewarming. Although rapid rewarming did not significantly impact tissue salvage in this study, we continue to recommend its use over less studied treatment methods, and continue to view it as an important bridge to burn center transfer and administration of thrombolytic therapy., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The data are insufficient to support standardized treatment of all patients with frostbite with thrombolytic therapy. The following guidelines, however, should be applied to all patients with cyanosis persisting proximal to the distal phalanx (Grade 3 or 4 frostbite injury) and demonstrated loss of perfusion at or proximal to the middle phalanx immediately after rewarming., (© American Burn Association 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A pharmacokinetic (PK) model was developed for nusinersen, an antisense oligonucleotide (ASO) that is the first approved treatment for spinal muscular atrophy (SMA). The model was built with data from 92 nonhuman primates (NHPs) following intrathecal doses (0.3-7 mg) and characterized the PK in cerebrospinal fluid (CSF), plasma, total spinal cord, brain, and pons. The estimated volumes were 13.6, 937, 4.5, 53.8, and 2.11 mL, respectively. Global sensitivity analysis demonstrated that the CSF-to-plasma drug distribution rate (0.09 hour -1 ) is a major determinant of the maximum nusinersen concentration in central nervous system (CNS) tissues. Physiological age-based and body weight-based allometric scaling was implemented with exponent values of -0.08 and 1 for the rate constants and the volume of distribution, respectively. Simulations of the scaled model were in agreement with clinical observations from 52 pediatric phase I PK profiles. The developed model can be used to guide the design of clinical trials with ASOs., (© 2018 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Although the overall incidence of and mortality rate associated with burn injury have decreased in recent decades, burns remain a significant source of morbidity and mortality in children. Children with major burns require emergent resuscitation. Resuscitation is similar to that for adults, including pain control, airway management, and administration of intravenous fluid. However, in pediatrics, fluid resuscitation is needed for burns greater than or equal to 15% of total body surface area (TBSA) compared with burns greater than or equal to 20% TBSA for adults. Unique to pediatrics is the additional assessment for non-accidental injury and accurate calculation of the percentage of total burned surface area (TBSA) in children with changing body proportions are crucial to determine resuscitation parameters, prognosis, and disposition., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Cold exposure that leads to frostbite puts patients at high risk for extremity amputations. Recent treatment advances, such as thrombolytic administration, have decreased amputation rates. However, little is known about patient outcomes with early mobilization of affected limbs. A retrospective review of 41 patients admitted for lower extremity frostbite was performed at an urban hospital burn unit. All patients received the institution's standard frostbite treatment protocol. The study group was allowed to bear weight within 72 hours, while the control group was immobilized beyond this time frame. No significant differences were found between groups when comparing total tissue loss, complications, or hospital length of stay. Previous treatment of frostbite at our institution involved strict avoidance of weight bearing to the affected extremity due to concern for repeat trauma and associated complications. Our findings show that patients who ambulated sooner had comparable outcomes to those immobilized for longer time periods. Larger studies would be useful to determine a standard time to mobilization in frostbite treatment protocols.

The primary target organ for uptake of systemically administered phosphorothioate oligonucleotides is the kidney cortex and the proximal tubular epithelium in particular. To determine the effect of oligonucleotide uptake on renal function, a detailed renal physiology study was performed in cynomolgus monkeys treated with 10-40 mg/kg/week ISIS 113715 for 4 weeks. The concentrations of oligonucleotide in the kidney cortex ranged from 1400 to 2600 μg/g. These concentrations were associated with histologic changes in proximal tubular epithelial cells that ranged from the appearance of cytoplasmic basophilic granules to atrophic and degenerative changes at higher concentrations. However, there were no renal functional abnormalities as determined by the typical measurements of blood urea nitrogen, serum creatinine, creatinine clearance, or urine specific gravity. Nor were there changes in glomerular filtration rate, or renal blood flow. Specific urinary markers of tubular epithelial cell damage, such as N-acetyl-glucosaminidase, and α-glutathione-s-transferase were not affected. Tubular function was further evaluated by monitoring the urinary excretion of amino acids, β(2)-microglobulin, or glucose. Renal function was challenged by administering a glucose load and by examining concentrating ability after a 4-h water deprivation. Neither challenge produced any evidence of change in renal function. The only change observed was a low incidence of increased urine protein/creatinine ratio in monkeys treated with ≥40 mg/kg/week which was rapidly reversible. Collectively, these data indicate that ISIS 113715-uptake by the proximal tubular epithelium has little or no effect on renal function at concentrations of 2600 μg/g., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The goals in this study were several-fold. First, to optimize the in vivo phage display methodology by incorporating phage pharmacokinetic properties, to isolate peptides that target the brain microvasculature, and then to build focused libraries to obtain structure activity relationship information in vivo to identify the optimal targeting motif., Materials and Methods: The blood pharmacokinetics of filamentous and T7 phage were evaluated to choose the optimal platform. A randomized peptide library with a motif CX(10)C was constructed in T7 phage and used for in vivo panning. Focused peptide libraries around each structural element of the brain-specific peptide were constructed to perform kinetic structure activity relationship (kSAR) analysis in vivo. To determine potential function, sepsis was induced in mice by LPS administration and four hours later the effect of GST-peptide on adhesion of rhodamine-labelled lymphocytes or CFDA-labelled platelets to pial microvasculature was observed by intravital microscopy., Results: The blood phamacokinetics of T7 was rapid (half-life of 12 min) which aids the clearance of non-specific phage. In vivo panning in brain enriched for isolates expressing the motif CAGALCY. Kinetic analysis of focused libraries built around each structural element of the peptide provided for rapid pharmacophore mapping. The computer modeling data suggested the peptide showed similarities to peptide mimetics of adhesion molecule ligands. GST-CAGALCY but not GST control protein was able to inhibit the rolling and adhesion of labeled platelets to inflamed pial vasculature. GST-CAGALCY had no effect on lymphocyte adhesion., Conclusions: Incorporating normal blood phamacokinetics of T7 phage into in vivo phage display improves the ability to recover targeting peptide motifs and allows effective lead optimization by kSAR. This approach led to the isolation of a brain-specific peptide, CAGALCY, which appears to function as an effective antagonist of platelet adhesion to activated pial microvasculature.

A community outbreak of at least 16 cases of hepatitis A is described. Salivary antibody testing of 126 children within a school in that community showed only one case of undiagnosed previous infection. Three other children had received hepatitis A vaccine previously, and this was reflected in their antibody titres. For the schools serving the community control measures included advice on good hygiene (supervised handwashing and additional cleaning in the schools). All close contacts of cases (household and childminding contacts and all staff in one school) were given active immunisation, though two subsequently developed hepatitis A, 17 and 27 days after vaccination. The use of human normal immunoglobulin (HNIG) was fully discussed with contacts, but was declined in all cases. The low prevalence of previous infection found in the schoolchildren implies that, in future, few adults will be immune. Public concern about blood products after the recent Department of Health decision to stop using British-sourced plasma may be a factor in limiting the uptake of HNIG, especially as there is now a perceived safer alternative, namely hepatitis A vaccine. Lack of evidence of spread of disease within the schools involved demonstrates that good hygiene, especially handwashing, remains the most important element in the control of hepatitis A.

Cases and, particularly, clusters of meningococcal meningitis often create high levels of public concern and attract the interest of news media. We describe below our experience of managing intense local and national media interest during a community outbreak of meningococcal disease in Derbyshire. Our learning is set out as ten key recommendations. Four of these are around managing the media, including using a proactive press release, providing detailed briefings, using a single spokesperson and coordination of the response by a press officer experienced in media management. Another four describe how to deliver an appropriate on-site response, often requested during community intervention programmes. The two final recommendations relate to ensuring good communication and supporting staff during what is an intensely stressful period. We hope our experiences may help others if faced with a similar problem.

Two brothers presented with meningococcal infection in a five day period, the first with a rifampicin sensitive strain and the second, who had received rifampicin chemoprophylaxis, with a resistant strain. Secondary cases of meningococcal disease can occur despite chemoprophylaxis, and may be rifampicin resistant. Close contacts should be informed of the early symptoms of meningococcal disease and of the need to seek medical advice urgently if they occur.

Physicians are facing the same competitive pressures as hospitals. As local distributors of health care, physicians need to compete on the basis of quality, price, convenience and access; however, they often do not have the requisite skills. This article details one hospital's strategies for mutually beneficial cooperative marketing.

The amino acids of collagenous and elastic connective tissue of beef and pork and of commercial meat products were determined by gaschromatography. A correlation was established between hydroxyproline and glycine and also between hydroxyproline and proline. Thus the content of elastic connective tissue in meat products is quite constant and compared with the amount of collagenous material insignificant.--Determination of amount of connective tissue in meat products from the amount of hydroxyproline this is suitable for the needs of food control.

Identifying and meeting physician needs is the focus of many hospital efforts today. Various informal and formal methods have been used in this endeavor. Surveys and focus groups are the traditional methodologies; and the responses have included various types of physician liaison programs. The author of this article reviews these methodologies and offers recommendations for securing accurate information and ensuring the success of programs to meet the needs thus identified.