Thirty-Day Mortality for Proximal Femoral Fractures Treated at a U.K. Elective Center with a Site-Streaming Policy During the COVID-19 Pandemic.

COVID-19 led to the reconfiguration of U.K. orthopaedic trauma services because surgical capacity was threatened in acute centers. We report the 30-day mortality of proximal femoral fractures in older adults treated at an elective orthopaedic center. METHODS: Patients >60 years old who presented with a proximal femoral fracture to any of 4 sites in the regional trauma network were transferred to our elective center for emergency surgery. Care was modeled according to the National Institute for Health and Care Excellence guidelines, and efforts were made to treat all patients within 36 hours. Data were collected prospectively, and mortality outcomes were recorded. RESULTS: Of the 192 patients who presented to the elective orthopaedic center, 167 were treated there. The median age of the latter patients was 88 years (interquartile range, 83 to 79 years). The median Charlson Comorbidity Index was 4 (interquartile range, 4 to 6). The median time from emergency department admission to surgical treatment was 24.5 hours (interquartile range, 18.8 to 34.7 hours). The 30-day rate of mortality was 10.2%. A total of 29 (17.4%) tested positive for COVID-19 during their admission, of whom 10 died, for a case-fatality rate of 34.5%. There were no significant differences in age (p = 0.33) or Charlson Comorbidity Index (p = 0.13) between patients who tested positive and those who did not. There was no significant difference in age between those who tested positive and died and those who tested positive and did not die (p = 0.13), but there was a significant difference in Charlson Comorbidity Index between those subgroups (p = 0.03). CONCLUSIONS: During a pandemic, an elective orthopaedic center can be reconfigured to a surgical center for older patients with proximal femoral fractures with acceptable health-care quality outcomes. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins.

A 73-kilodalton (kD) intracellular protein was found to bind to peptide regions that target intracellular proteins for lysosomal degradation in response to serum withdrawal. This protein cross-reacted with a monoclonal antibody raised to a member of the 70-kD heat shock protein (hsp70) family, and sequences of two internal peptides of the 73-kD protein confirm that it is a member of this family. In response to serum withdrawal, the intracellular concentration of the 73-kD protein increased severalfold. In the presence of adenosine 5'-triphosphate (ATP) and MgCl2, the 73-kD protein enhanced protein degradation in two different cell-free assays for lysosomal proteolysis.

Two subcellular mechanisms underlie calcium-dependent facilitation of bioluminescence.

Epithelial calcium action potentials in Obelia geniculata trigger brief light flashes from specialized cells by direct activation of cytoplasmic calcium-activated photoprotein obelin. During a series of action potentials, sequential flashes undergo characteristic facilitation and decrement with no change in associated spike waveform. Analysis of the subcellular light distribution shows that facilitation results from two processes: recruitment of calcium entry sites and increased light from previously responding localized sites. We propose a model that accounts for the localized flash facilitation and decrement observed in vivo and is based upon the kinetics of calcium binding and emission of obelin. In this model, obelin emits light only when three calcium ions are bound. Changes in flash intensity during successive action potentials result from calcium bound persistently to unexpended obelin, effectively lowering the number of calcium ions required for subsequent activation. Accordingly, facilitation or decrement results from the time-dependent availability of singly and doubly bound obelin.

Do radiological and functional outcomes correlate for fractures of the distal radius?

AIMS: We conducted a study to determine whether radiological parameters correlate with patient reported functional outcome, health-related quality of life and physical measures of function in patients with a fracture of the distal radius. PATIENTS AND METHODS: The post-operative palmar tilt and ulnar variance at six weeks and 12 months were correlated with the Patient Rated Wrist Evaluation, Disabilities of the Arm, Shoulder and Hand, and EuroQol scores, grip strength, pinch strength and range of movement at three, six and 12 months for 50 patients (mean age 57 years; 26 to 85) having surgical fixation, with either percutaneous pinning or reconstruction with a volar plate, for a fracture of the distal radius. RESULTS: Radiological parameters were found to correlate poorly with the patient reported outcomes (r = 0.00 to 0.47) and physical measures of function (r = 0.01 to 0.51) at all intervals. CONCLUSION: This study raises concerns about the use of radiological parameters to determine management, and to act as a surrogates for successful treatment, in patients with a fracture of the distal radius. Restoration of 'normal' radiographic parameters may not be necessary to achieve a satisfactory functional outcome for the patient. Cite this article: Bone Joint J 2017;99-B:376-82.

Is it time to revisit the AO classification of fractures of the distal radius? Inter- and intra-observer reliability of the AO classification.

We conducted an observational radiographic study to determine the inter- and intra-observer reliability of the AO classification of fractures of the distal radius. Plain posteroanterior and lateral radiographs of 456 patients with an acute fracture of the distal radius were classified by a consultant orthopaedic hand specialist and two specialist trainees, and the k coefficient for the inter- and intra-observer reliability of the type, group and subgroup classification was calculated. Only the type of fracture (A, B or C) was found to provide substantial intra-observer reliability (k type 0.65). The inclusion of 'group' and 'subgroup' into the classification reduced the inter-observer reliability to fair (kgroup 0.29, ksubgroup = 0.28) and the intra-observer reliability to moderate (kgroup 0.53, ksubgroup 0.49). Disagreement was found to arise between specific subgroups, which may be amenable to clarification.

Novel mutations of the RPGR gene in RP3 families.

X-linked retinitis pigmentosa is a severe retinal degeneration characterized by night blindness and visual field constriction, leading to complete blindness within the third decade of life. Mutations in the RPGR gene (retinitis pigmentosa GTPase regulator), located on Xp21.1 in the RP3 region, have been associated with an RP phenotype. Further to our previous mutation screening of RPGR in families segregating with the RP3 locus, we have expanded this study to include other 8 RP3 pedigrees. Here we report the results of this expanded study and the identification of five mutations in RPGR, four of which are novel (IVS6+5 G>A, 950-951delAA, 963 T>C, EX8del) and one of which occurs in the donor splice site of intron 1 (IVS1+1 G>A). These findings bring the proportion of "RP3 genotypes" with a mutation in this gene to 27% (10/37). Hum Mutat 15:386, 2000.

Novel frameshift mutations in the RP2 gene and polymorphic variants.

Mutations in the RP2 gene located on Xp11.23 are associated with X-linked retinitis pigmentosa (XLRP), a severe form of progressive retinal degeneration which leads to complete loss of vision in affected males. To date, 14 different mutations in the RP2 gene have been reported to cause XLRP, the majority of which lead to a coding frameshift within the gene and predicted truncation of the protein product. We here report two novel frameshift mutations in RP2 identified in XLRP families by PCR-SSCP and direct sequencing, namely 723delT and 796-799del. Four single nucleotide polymorphisms (SNPs) within the coding region of RP2 are also described (105A>T, 597T>C, 844C>T, 1012G>T), the first polymorphisms to be reported within this gene of unknown function, two of which alter the amino acid sequence. The current study extends the XLRP mutation profile of RP2 and highlights non-pathogenic coding sequence variations which may facilitate both functional studies of the gene and analysis of intragenic allelic contribution to the phenotype.

NRL S50T mutation and the importance of 'founder effects' in inherited retinal dystrophies.

The aim of this work was to identify NRL mutations in a panel of 200 autosomal dominant retinitis pigmentosa (adRP) families. All samples were subjected to heteroduplex analysis of the three exons of the NRL gene, and HphI restriction digest analysis of exon 2 (to identify the S50T mutation). Families found to have the S50T mutation, and six additional larger pedigrees (which had previously been excluded from the other nine adRP loci) underwent linkage analysis using polymorphic markers located in the region of 14q11. HphI restriction analysis followed by direct sequencing of the amplified NRL exon 2 product demonstrated the presence of the NRL S50T sequence change in three adRP families. Comparison of marker haplotypes in affected individuals from these families with those of affected members of the original 14q11 linked family revealed a common disease haplotype for markers within the adRP locus. Recombination events observed in these families define an adRP critical interval of 14.9 cM between D13S72 and D14S1041. Linkage analysis enabled all six of the larger adRP pedigrees to be excluded from the 14q11 locus. The NRL S50T mutation represents another example of a 'founder effect' in a dominantly inherited retinal dystrophy. Identification of such 'founder effects' may greatly simplify diagnostic genetic screening and lead to better prognostic counselling. The exclusion of several adRP families from all ten adRP loci indicates that at least one further adRP locus remains to be found.

Molecular recognition of amiloride analogs: a molecular electrostatic potential analysis. 1. Pyrazine ring modifications.

Ab initio molecular electrostatic potential (MEP) patterns are used to determine the electrostatic requirements for the formation of a stable blocking complex between amiloride analogs and the epithelial sodium channel of Rana ridibunda. MEP maps calculated in the 3-21G(*) and STO-3G basis sets for amiloride and analogs with pyrazine ring modifications are used to interpret differences in the microscopic rate constants for analog-channel binding determined by Li et al. MEP maps of the protonated analogs are correlated to differences in the value of kon, the microscopic association constant. Those analogs with kon values similar to amiloride are found to have a MEP maximum that is localized over the side chain, as well as strong, distinguishing minima in the MEP pattern off the carbonyl oxygen and positions 3, 4, and 5 of the pyrazine ring. MEP maps of a model-encounter complex (protonated analog and formic acid anion) are correlated to differences in koff, the microscopic dissociation constant. The major conclusions of this work are that (1) a stable blocking complex is formed with analogs which have a deep, localized minimum off the 6 position of the pyrazine ring, (2) the stability of the blocking complex is directly related to the depth of that minimum, (3) substitution at position 5 affects not only the depth but also the location and size of the minimum off position 6, and (4) steric factors may influence the optimal binding of the 6-position ligand to the ion channel. The MEP analysis also suggests that the distance between the proton donors of the chelating guanidinium moiety and the deep, localized minimum off position 6 of the pyrazine ring may define an important spatial requirement for all those analogs which form a stable blocking complex with the channel.

In vivo modulation of CD26 (dipeptidyl peptidase IV) in the mouse: effects of polyreactive and monoreactive antibodies.

We previously reported that intravenous injections in rabbits or guinea pigs of divalent antibodies to purified protein or carbohydrate antigens located mainly on endothelial cells induce acute pulmonary edema, which is often lethal. Surviving animals develop resistance to the injurious effect of subsequent injection of antibodies (adaptation), associated with shedding of antigen-antibody complexes from endothelial cells. In the present study, we investigated and compared in mice the effects of 3-day multiple injections of two different rabbit antibody (IgG) preparations against antigens expressed mainly at the surface of epithelial cells. The first preparation contained antibodies to a single transmembrane protein, CD26 (dipeptidyl peptidase IV [DPP IV]) (monoreactive anti-DPP IV IgG); the second contained antibodies against multiple antigens of the renal tubular brush border (BB), including DPP IV (polyreactive anti-BB IgG). Both IgG preparations caused loss of DPP IV from the organs studied, as shown by reduction in enzyme activity in tissue homogenates and by immunofluorescence microscopy, which showed loss of DPP IV from cell surface. However, the monoreactive anti-DPP IV IgG induced considerably greater reduction than polyreactive anti-BB IgG. Loss of DPP IV from the cell surface probably occurred by shedding of immune complexes into vascular and extravascular fluids, including bile and urine. The results may have relevance to hyperacute rejection of xenografts, as from pigs to primates. Since human natural antibodies that bind to porcine cells are polyreactive, a new prophylactic strategy for hyperacute rejection might be based on down-regulation of the major xenogeneic antigen, alpha-galactosyl, by injecting donor animals with monoreactive alpha-galactosyl antibodies before transplantation.

Intrafamilial variation of phenotype in Stargardt macular dystrophy-Fundus flavimaculatus.

PURPOSE: To evaluate the intrafamilial phenotypic variation in Stargardt macular dystrophy-Fundus flavimaculatus (SMD-FFM). METHODS: Thirty-one siblings from 15 families with SMD-FFM were examined. Age of onset, visual acuity, and clinical features on fundus examination and fundus autofluorescence images, including presence or absence of central and peripheral atrophy and distribution of flecks, were recorded. In addition, electrophysiological studies were undertaken. RESULTS: Large differences between siblings in age of onset (median, 12 years; range, 5-23 years) were observed in six of the 15 families studied, whereas in 9 families differences in age of onset between siblings were small (median, 1 year; range, 0-3 years). Visual acuity varied two or more lines among siblings in nine families. In 10 families (67%) siblings were found to have different clinical appearance on fundus examination and fundus autofluorescence images, whereas in 5 families (33%), affected siblings had similar clinical features. Electrodiagnostic tests were performed on affected members of 12 families and disclosed similar qualitative findings among siblings. In nine families there was loss of central function only; in two, global loss of cone function; and in one, global loss of cone and rod function. CONCLUSIONS: In this series, although differences in age of onset, visual acuity, and fundus appearance were observed between siblings, electrophysiological studies demonstrated intrafamilial homogeneity in retinal function. The findings are difficult to reconcile with expression studies showing ABCR transcripts in rod photoreceptors but not in cones.

A method for testing the toxicity of temporary crown and bridge materials.

A realistic method for testing the toxicity of a temporary crown and bridge material in vivo is described. The results are compared with a previous study. It is stressed that temporary crown and bridge materials should never be used as a temporary filling material.

Preliminary studies on the in vivo morphogenetic properties of dentine matrix proteins.

Two fractions of isolated noncollagenous extracellular matrix proteins from dentine have been implanted into the base of exposed cavities in ferret canine teeth. After sealing the cavities, reparative dentinogenesis was assessed histologically after 14 and 28 days as compared to control cavities. Reparative dentinogenesis was enhanced in the presence of these matrix proteins with evidence of tubular dentine along the walls of the exposure and on the cavity floor demonstrating the in vivo morphogenetic properties of the dentine matrix proteins.

Assessment of the phenotypic range seen in Doyne honeycomb retinal dystrophy.

OBJECTIVE: Using molecular genetics as the basis for diagnosis, to assess the phenotype in the family originally described as having dominantly inherited Doyne honeycomb retinal dystrophy (DHRD) linked to chromosome 2p16. DESIGN: Clinical examination including fluorescein angiography was undertaken in 107 family members. Nine affected patients underwent electroretinography, perimetry, dark adaptometry, color-contrast sensitivity measurement, and autofluorescent fundus imaging. PATIENTS: The disease-associated haplotype used to allocate disease status was based on our further refinement of the DHRD locus to between loci D2S2739 and D2S378. The study identified 50 affected patients. In addition, previously published information on a further 8 individuals was used. The study population represented 6 generations of a 9-generation pedigree. RESULTS: Three types of deposits were seen: large, soft drusen at the macula and abutting the optic nerve head; small, hard deposits that in some patients radiated from the macula; and autofluorescent deposits. Most younger affected individuals exhibited small hard drusen only at the macula and had normal visual function. Information on 2 patients suggested that DHRD can be a cause of childhood-onset blindness. Advanced disease was associated with severe visual loss and posterior pole atrophy without signs of drusen. Advanced age was not invariably associated with severe visual loss. CONCLUSIONS: Previously identified characteristics of DHRD were confirmed and new features identified. Contrary to previous reports, the constancy and severity of radial (basal laminar) drusen seen clinically are the only features that can be used to differentiate between DHRD and malattia leventinese. The highly variable phenotype suggests that the influence of the DHRD-mutant gene may be modulated by other genetic and/or environmental factors.

Odontoblast stimulation in ferrets by dentine matrix components.

The possible effects of isolated dentine matrix components on odontoblast secretory activity were investigated in vivo by implantation of lyophilized fractions of these components into cavities prepared in ferret canine teeth. After implantations as short as 14 days there was significant deposition of reactionary dentine by the odontoblasts beneath the cavity and this response increased in a non-linear manner with time of implantation. In contrast, control cavities lacking the dentine matrix components showed no evidence of reactionary dentine deposition. Examination of teeth at early periods of implantation (2 and 5 days) indicated that odontoblast death had not occurred as a result of the operative procedures and that the response was one of stimulation of existing odontoblasts rather than that of induction of a new generation of odontoblast-like cells. The mechanisms of odontoblast stimulation by the dentine matrix components remain to be elucidated, but could be mediated by growth factors within the dentine matrix preparations.

A study of the relationship among pulpal response, microbial microleakage, and particle heterogeneity in a glass-ionomer-base material.

This investigation was designed to study the pulpal responses to glass-ionomer base materials that differ in particle size distribution. The study was carried out according to the BSI (1980) recommendations for testing restorative materials in vivo. The base materials caused more pulpal inflammation than the control material, Kalzinol, although by an indirect mechanism. A significant association was demonstrated in the statistical model between bacterial presence within the experimental cavity and pulpal inflammation. The type of restorative material has no direct association with the degree of inflammation, although the model suggests that it exerts an indirect influence via its antibacterial properties, and hence its influence on microbial microleakage. The base material, with a heterogeneous particle distribution, was associated with greater bacterial microleakage. Particle size distribution, therefore, has some effect upon bacterial microleakage, but, because of its complex effect upon several physical properties of materials, further studies are indicated.

An evaluation of a rapid setting glass ionomer cement in general dental practice.

Forty-five general dental practitioners evaluated the clinical handling properties and performance of a newly formulated glass ionomer cement of the powder/water type. Seven hundred and ninety restorations were placed and 457 were reviewed after seven months. This formulation set rapidly. Approximately 95 per cent of the restorations performed well over the period of assessment. The results of this trial were compared with those of a trial on an earlier glass ionomer cement. The main advantage of the new formulation was the improved handling properties, notably the speed of set. Misuse of the material was the major factor responsible for poor clinical performance.