Randomized clinical trial of intraoperative autotransfusion in surgery for abdominal aortic aneurysm

BACKGROUND: Perioperative homologous blood transfusion (HBT) is associated with adverse reactions and risks transmission of infection. It has also been implicated as an immunosuppressive agent. Intraoperative autotransfusion (IAT) is a potential method of autologous transfusion. METHODS: This was a single-centre randomized clinical trial of IAT in surgery for abdominal aortic aneurysm. Forty patients were randomized to IAT and 41 underwent surgery with HBT only. Patients in both groups received HBT to maintain haemoglobin levels above 8 g/dl. Transfusion requirements, and incidence of systemic inflammatory response syndrome (SIRS) and infection, were compared. RESULTS: Significantly fewer patients in the IAT group required HBT (21 versus 31; P = 0.038) and the median blood requirement per patient was 2 units lower (P = 0.012). There was a higher incidence of chest infection (12 versus four patients; P = 0.049) and SIRS (20 versus nine patients; P = 0.020) in the HBT group. Risk of SIRS was related to aortic cross-clamp time in the IAT group only. CONCLUSION: Use of autotransfusion effectively reduced the need for HBT and was associated with a reduced incidence of postoperative SIRS and infective complications.     

Late reconstruction of chronic distal biceps tendon ruptures using fascia lata autograft and suture anchor fixation

Distal biceps tendon ruptures are a rare injury, and surgical reconstruction is typically recommended for chronic ruptures. There is no consensus regarding the most appropriate reconstruction technique. We present our experience with reconstruction of chronic distal biceps tendon ruptures with fascia lata autograft, secured to the bicipital tuberosity with suture anchors. A single anterior incision is used for all patients. Tension is set with the elbow in 50 degrees of flexion. Ninety-two percent of our patients reported improvement in elbow flexion and supination and were pleased with the surgery. Range of motion and isokinetic flexion and supination strength after this procedure was comparable with other distal biceps tendon reconstruction options using tendon grafts and suture anchor fixation from a single anterior approach. Furthermore, common complications associated with distal biceps tendon repair and reconstruction can be avoided with this technique. We therefore feel that this technique is a viable surgical treatment alternative with good subjective and objective outcomes.Level of Evidence: Level IV.     

Expression of blood group antigens including HLA markers in human adult liver

The localisation of the principal blood group antigens has been studied in human liver. These blood group antigens included the erythrocyte antigens and the antigen of the major histocompatibility complex. This study was performed by the indirect immunofluorescence technique using polyclonal antibodies of human or animal origin and monoclonal antibodies from hybridomas. This study has shown that the normal hepatocyte is lacking in blood group antigens. On the contrary, the biliary cell was rich in antigenic markers: the main antigens expressed were Lewis, Pr, HLA-A and B antigens. In Kupffer cells, only i and HLA-DR antigens were clearly expressed. The endothelial cells of blood vessels mainly show A, B, H, HLA-A and B antigens; HLA-DR and Pr are slightly expressed. HLA-DR antigens were more strongly expressed on veins than on arteries. Dendritic cells have been identified in the portal space of human liver. They bore i and HLA-DR antigens.     

The central fibroblast growth factor receptor/beta klotho system: Comprehensive mapping in Mus musculus and comparisons to nonhuman primate and human samples using an automated in situ hybridization platform

Central activation of fibroblast growth factor (FGF) receptors regulates peripheral glucose homeostasis and reduces food intake in preclinical models of obesity and diabetes. The current work was undertaken to advance our understanding of the receptor expression, as sites of ligand action by FGF19, FGF21, and FGF1 in the mammalian brain remains unresolved. Recent advances in automated RNAscope in situ hybridization and droplet digital PCR (ddPCR) technology allowed us to interrogate central FGFR/beta klotho (Klb) system at the cellular level in the mouse, with relevant comparisons to nonhuman primate and human brain. FGFR1-3 gene expression was broadly distributed throughout the CNS in Mus musculus, with FGFR1 exhibiting the greatest heterogeneity. FGFR4 expression localized only in the medial habenula and subcommissural organ of mice. Likewise, Klb mRNA was restricted to the suprachiasmatic nucleus (SCh) and select midbrain and hindbrain nuclei. ddPCR in the rodent hypothalamus confirmed that, although expression levels are indeed low for Klb, there is nonetheless a bonafide subpopulation of Klb+ cells in the hypothalamus. In NHP and human midbrain and hindbrain, Klb + cells are quite rare, as is expression of FGFR4. Collectively, these data provide the most robust central map of the FGFR/Klb system to date and highlight central regions that may be of critical importance to assess central ligand effects with pharmacological dosing, such as the putative interactions between the endocrine FGFs and FGFR1/Klb, or FGF19 with FGFR4.     

Long-term feeding of casein or soy protein with or without cholesterol in Mongolian gerbils. I. Morphologic effects

This study was designed to determine whether male Mongolian gerbils (Meriones unguiculatus) develop atherosclerosis (AS) during long-term feeding of diets similar to those consumed by humans. Gerbils were fed diets containing 16% casein (C) or soy (S) protein +/- 0.1% cholesterol (CH) for 15 months. The energy contribution from protein, fat and carbohydrate was similar to the energy distribution reported for the average North American (NA) diet and the level of added dietary CH resembled the average NA intake. At mo 0, 3, 6, 9, 12 and 15, animals were killed and tissue sections were prepared for histologic examination. Microscopic observations of cardiovascular tissues did not reveal any evidence of AS in any of the diet groups. Liver fatty infiltration (FI) was evident in the C+CH and C groups at mo 3 and 9, respectively, and continued to occur at all subsequent sampling times. Livers from gerbils fed S+CH also began to exhibit FI at mo 9, while livers from S-fed gerbils did not show any significant morphologic changes. Biochemical liver total lipid results supported the histological liver findings. Other tissues examined did not reveal any morphological changes related to diet. The gerbil may be a useful animal model to study mechanisms which inhibit AS development.     

Capillary transit time heterogeneity and flow-metabolism coupling after traumatic brain injury

Most patients who die after traumatic brain injury (TBI) show evidence of ischemic brain damage. Nevertheless, it has proven difficult to demonstrate cerebral ischemia in TBI patients. After TBI, both global and localized changes in cerebral blood flow (CBF) are observed, depending on the extent of diffuse brain swelling and the size and location of contusions and hematoma. These changes vary considerably over time, with most TBI patients showing reduced CBF during the first 12 hours after injury, then hyperperfusion, and in some patients vasospasms before CBF eventually normalizes. This apparent neurovascular uncoupling has been ascribed to mitochondrial dysfunction, hindered oxygen diffusion into tissue, or microthrombosis. Capillary compression by astrocytic endfeet swelling is observed in biopsies acquired from TBI patients. In animal models, elevated intracranial pressure compresses capillaries, causing redistribution of capillary flows into patterns argued to cause functional shunting of oxygenated blood through the capillary bed. We used a biophysical model of oxygen transport in tissue to examine how capillary flow disturbances may contribute to the profound changes in CBF after TBI. The analysis suggests that elevated capillary transit time heterogeneity can cause critical reductions in oxygen availability in the absence of ‘classic'' ischemia. We discuss diagnostic and therapeutic consequences of these predictions.     

Reed's Syndrome: A Case of Multiple Cutaneous and Uterine Leiomyomas

Multiple cutaneous and uterine leiomyomatosis, also known as Reed's syndrome, is an autosomal dominant genetic condition. Affected individuals have an increased predisposition to develop benign smooth muscle tumors (leiomyomas) in the skin and uterus. Affected females frequently develop uterine leiomyomas (fibroids) that are larger and more numerous and emerge earlier than those in the general population. Subsets of these patients are at risk for renal cell cancer and have been determined to have mutations in the fumarate hydratase gene. In individuals or families without renal cell cancer, the syndrome may be referred to as multiple cutaneous leiomyomatosis or multiple cutaneous and uterine leiomyomatosis. The term hereditary leiomyomatosis and renal cell cancer refers to families with an increased prevalence of smooth muscle tumors and renal cell cancer as a result of the fumarate hydratase genetic defect. In this article, the authors introduce a case of a young woman who presented with multiple, intermittently painful, cutaneous leiomyomas and a history of large uterine fibroids previously causing anemia and requiring surgical intervention. Further investigation revealed a family history of mutations in the fumarate hydratase gene. The patient is currently being monitored by the National Institutes of Health.     

Understanding Bone Strength Is Not Enough

Increases in fracture risk beyond what are expected from bone mineral density (BMD) are often attributed to poor “bone quality,” such as impaired bone tissue strength. Recent studies, however, have highlighted the importance of tissue material properties other than strength, such as fracture toughness. Here we review the concepts behind failure properties other than strength and the physical mechanisms through which they cause mechanical failure: strength describes failure from a single overload; fracture toughness describes failure from a modest load combined with a preexisting flaw or damage; and fatigue strength describes failure from thousands to millions of cycles of small loads. In bone, these distinct failure mechanisms appear to be more common in some clinical fractures than others. For example, wrist fractures are usually the result of a single overload, the failure mechanism dominated by bone strength, whereas spinal fractures are rarely the result of a single overload, implicating multiple loading cycles and increased importance of fatigue strength. The combination of tissue material properties and failure mechanisms that lead to fracture represent distinct mechanistic pathways, analogous to molecular pathways used to describe cell signaling. Understanding these distinct mechanistic pathways is necessary because some characteristics of bone tissue can increase fracture risk by impairing fracture toughness or fatigue strength without impairing bone tissue strength. Additionally, mechanistic pathways to failure associated with fracture toughness and fatigue involve multiple loading events over time, raising the possibility that a developing fracture could be detected and interrupted before overt failure of a bone. Over the past two decades there have been substantial advancements in fracture prevention by understanding bone strength and fractures caused by a single load, but if we are to improve fracture risk prevention beyond what is possible now, we must consider material properties other than strength. © 2017 American Society for Bone and Mineral Research.     

Alterations to the Gut Microbiome Impair Bone Strength and Tissue Material Properties

Alterations in the gut microbiome have been associated with changes in bone mass and microstructure, but the effects of the microbiome on bone biomechanical properties are not known. Here we examined bone strength under two conditions of altered microbiota: (1) an inbred mouse strain known to develop an altered gut microbiome due to deficits in the immune system (the Toll‐like receptor 5–deficient mouse [TLR5KO]); and (2) disruption of the gut microbiota (ΔMicrobiota) through chronic treatment with selected antibiotics (ampicillin and neomycin). The bone phenotypes of TLR5KO and WT (C57Bl/6) mice were examined after disruption of the microbiota from 4 weeks to 16 weeks of age as well as without treatment (n = 7 to 16/group, 39 animals total). Femur bending strength was less in ΔMicrobiota mice than in untreated animals and the reduction in strength was not fully explained by differences in bone cross‐sectional geometry, implicating impaired bone tissue material properties. Small differences in whole‐bone bending strength were observed between WT and TLR5KO mice after accounting for differences in bone morphology. No differences in trabecular bone volume fraction were associated with genotype or disruption of gut microbiota. Treatment altered the gut microbiota by depleting organisms from the phyla Bacteroidetes and enriching for Proteobacteria, as determined from sequencing of fecal 16S rRNA genes. Differences in splenic immune cell populations were also observed; B and T cell populations were depleted in TLR5KO mice and in ΔMicrobiota mice (p < 0.001), suggesting an association between alterations in bone tissue material properties and immune cell populations. We conclude that alterations in the gut microbiota for extended periods during growth may lead to impaired whole‐bone mechanical properties in ways that are not explained by bone geometry. © 2017 American Society for Bone and Mineral Research.     

A pilot multi‐centre prospective randomised controlled trial of RECELL for the treatment of venous leg ulcers

Venous leg ulcers (VLUs) have a significant impact on approximately 3% of the adult population worldwide, with a mean NHS wound care cost of £7600 per VLU over 12 months. The standard care for VLUs is compression therapy, with a significant number of ulcers failing to heal with this treatment, especially with wound size being a risk factor for non‐healing. This multicentre, prospective, randomised trial evaluated the safety and effectiveness of autologous skin cell suspension (ASCS) combined with compression therapy compared with standard compression alone (Control) for the treatment of VLUs. Incidence of complete wound closure at 14 weeks, donor site closure, pain, Health‐Related Quality of Life (HRQoL), satisfaction, and safety were assessed in 52 patients. At Week 14, VLUs treated with ASCS + compression had a statistically greater decrease in ulcer area compared with the Control (8.94 cm² versus 1.23 cm², P = .0143). This finding was largely driven by ulcers >10 to 80 cm² in size, as these ulcers had a higher mean percentage of reepithelialization at 14 weeks (ASCS + compression: 69.97% and Control: 11.07%, P = .0480). Additionally, subjects treated with ASCS + compression experienced a decrease in pain and an increase in HRQoL compared with the Control. This study indicates that application of ASCS + compression accelerates healing in large venous ulcers.