Revisiting the sternocleidomastoid flap as a reconstructive option in head and neck surgery.

BACKGROUND: The sternocleidomastoid can be used as a pedicled flap in head and neck reconstruction. It has previously been associated with high complication rates, likely due in part to the variable nature of its blood supply. OBJECTIVE: To provide clinicians with an up-to-date review of clinical outcomes of sternocleidomastoid flap surgery in head and neck reconstruction, integrated with a review of vascular anatomical studies of the sternocleidomastoid. METHODS: A literature search of the Medline and Web of Science databases was conducted. Complications were analysed for each study. The trend in success rates was analysed by date of the study. RESULTS: Reported complication rates have improved over time. The preservation of two vascular pedicles rather than one may have contributed to improved outcomes. CONCLUSION: The sternocleidomastoid flap is a versatile option for patients where prolonged free flap surgery is inappropriate. Modern vascular imaging techniques could optimise pre-operative planning.

Six-month outcomes after restrictive or liberal transfusion for cardiac surgery (TRICS III trial).

CLINICAL QUESTION: Is transfusing red cell components using a restrictive transfusion threshold (Hb < 75 g L-1 ) as safe as a liberal transfusion threshold (Hb < 95 g L-1 in intensive care and < 85 g L-1 outside intensive care) during and after cardiac surgery for adults at moderate to high risk of death? EVIDENCE FROM TRIAL: In adults undergoing cardiac surgery who were at moderate to high risk for death, using a restrictive red-cell transfusion threshold was as safe as a liberal red cell transfusion threshold (composite outcome of death from any cause, myocardial infarction, stroke or new-onset renal failure with dialysis at 6 months after surgery).

Intra-Abdominal Hypertension and Abdominal Compartment Syndrome after Abdominal Wall Reconstruction: Quaternary Syndromes?

BACKGROUND AND AIMS: Reconstruction with reconstitution of the container function of the abdominal compartment is increasingly being performed in patients with massive ventral hernia previously deemed inoperable. This situation places patients at great risk of severe intra-abdominal hypertension and abdominal compartment syndrome if organ failure ensues. Intra-abdominal hypertension and especially abdominal compartment syndrome may be devastating systemic complications with systematic and progressive organ failure and death. We thus reviewed the pathophysiology and reported clinical experiences with abnormalities of intra-abdominal pressure in the context of abdominal wall reconstruction. MATERIAL AND METHODS: Bibliographic databases (1950-2015), websites, textbooks, and the bibliographies of previously recovered articles for reports or data relating to intra-abdominal pressure, intra-abdominal hypertension, and the abdominal compartment syndrome in relation to ventral, incisional, or abdominal hernia repair or abdominal wall reconstruction. RESULTS: Surgeons should thus consider and carefully measure intra-abdominal pressure and its resultant effects on respiratory parameters and function during abdominal wall reconstruction. The intra-abdominal pressure post-operatively will be a result of the new intra-peritoneal volume and the abdominal wall compliance. Strategies surgeons may utilize to ameliorate intra-abdominal pressure rise after abdominal wall reconstruction including temporizing paralysis of the musculature either temporarily or semi-permanently, pre-operative progressive pneumoperitoneum, permanently removing visceral contents, or surgically releasing the musculature to increase the abdominal container volume. In patients without complicating shock and inflammation, and in whom the abdominal wall anatomy has been so functionally adapted to maximize compliance, intra-abdominal hypertension may be transient and tolerable. CONCLUSIONS: Intra-abdominal hypertension/abdominal compartment syndrome in the specific setting of abdominal wall reconstruction without other complication may be considered as a quaternary situation considering the classification nomenclature of the Abdominal Compartment Society. Greater awareness of intra-abdominal pressure in abdominal wall reconstruction is required and ongoing study of these concerns is required.

Interventions to reduce vasovagal reactions in blood donors: a systematic review and meta-analysis.

Vasovagal reactions (VVRs) in blood donors have significant implications for the welfare of donors, donor retention and the management of donor sessions. We present a systematic review of interventions designed to prevent or reduce VVRs in blood donors. Electronic databases were searched for eligible randomised trials to March 2015. Data on study design and outcomes were extracted and pooled using random effects meta-analyses. Sixteen trials met the inclusion criteria: five trials (12 042 participants) of pre-donation water, eight trials (3500 participants) of applied muscle tension (AMT) and one trial each of AMT combined with water, caffeine, audio-visual distraction and/or social support. In donors receiving pre-donation water, the relative risk (RR) compared with controls for VVRs was 0·79 [95% confidence interval (CI) 0·70-0·89, P < 0·0001] and the mean difference (MD) in severity of VVRs measured with the Blood Donation Reactions Inventory (BDRI) score was -0·32 (95% CI -0·51 to -0·12, P < 0·0001). Excluding trials with a high risk of selection bias, the RR for VVRs was 0·70 (95% CI 0·45-1·11, P = 0·13). In donors who received AMT, there was no difference in the risk of chair recline in response to donor distress from controls (RR 0·76, 95% CI 0·53-1·10, P = 0·15), although the MD in BDRI score was -0·07 (95% CI -0·11 to -0·03, P = 0·0005). There was insufficient data to perform meta-analysis for other interventions. Current evidence on interventions to prevent or reduce VVRs in blood donors is indeed limited and does not provide strong support for the administration of pre-donation water or AMT during donation. Further large trials are required to reliably evaluate the effect of these and other interventions in the prevention of VVRs.

A venue-based analysis of the reach of a targeted outreach service to deliver opportunistic community NHS Health Checks to 'hard-to-reach' groups.

OBJECTIVES: Opportunistic outreach services have been commissioned to overcome potential barriers to uptake, by offering health checks in accessible community venues. This study aimed to evaluate the ability of an outreach health check service to reach key target groups: men, people of South Asian ethnicity and people from deprived areas. The comparator was the health check service provided by GP practices. One aim was to investigate whether the addition of an outreach service would result in a higher percentage of health checks being done for people from the target groups compared to a GP-based service alone. The second aim was to assess which types of venues used for outreach health checks were most effective in reaching these groups. STUDY DESIGN: Evaluation of Public Health Programme with retrospective control group comparison. METHODS: The percentages of completed health checks in men, people of South Asian ethnicity, and participants registered at general practices with lowest quintile area-level deprivation status were compared between all opportunistic community checks conducted by the Outreach Service over a ten month period and checks conducted in general practice in a partially-overlapping time period of the same financial year. For the venue-based comparison of Outreach Service checks, the number of checks per visit and percentage of checks in each target group were calculated for each venue. RESULTS: Of 3849 Outreach Service checks, 38% were in men (compared to 50% of checks conducted in Primary Care), and 11% were in people of South Asian ethnicity (compared to 3% in Primary Care). 3558 Outreach check participants were registered with a general practice in the County (92%), and of these, 32% of checks were in people registered with a general practice in the lowest deprivation quintile (compared to 13% of checks in Primary Care). There were 519 visits by the outreach service to 23 different types of venue. Certain venues recorded large numbers of checks e.g. supermarkets and libraries, but they were not always the most efficient places to recruit people for checks. Mosques and bus stations were the venues with the broadest reach to all target groups. Other venues, despite having lower turnover or recruitment rates, were still good settings to reach specific target groups. CONCLUSION: The NHS Health Check can successfully be targeted at people from deprived areas and people of South Asian ethnicity using a targeted opportunistic community outreach approach. Our findings show that the reach to different groups varies substantially by venue, and therefore best results may be achieved by combining venues and strategies specific to the target group.

High proportions of regulatory T cells in PBSC grafts predict improved survival after allogeneic haematopoietic SCT.

Regulatory T cells (Tregs) modulate immune responses and improve survival in murine transplant models. However, whether the Treg content of allogeneic cell grafts influences the outcome in human haematopoietic stem cell (HSC) transplantation is not well established. In a prospective study of 94 adult allogeneic PBSC transplants (60% unrelated; 85% reduced intensity conditioning), the median Treg (CD3(+)CD4(+)CD25(+)FOXP3(+)CD127(dim/-)) dose transplanted was 4.7 × 10(6)/kg, with Tregs accounting for a median of 2.96% of CD4(+) T cells. Patients transplanted with grafts containing a Treg/CD4(+) T-cell ratio above the median had a 3-year overall survival of 75%, compared with 49% in those receiving grafts with a Treg/CD4(+) T-cell ratio below the median (P=0.02), with a 3-year non-relapse mortality of 13% and 35%, respectively (P=0.02). In multivariate analysis, a high graft Treg/CD4(+) T-cell ratio was an independent predictor of lower non-relapse mortality (hazard ratio (HR), 0.30; P=0.02), improved overall survival (HR, 0.45; P=0.03) and improved sustained neutrophil (HR, 0.52; P=0.002), platelet (HR, 0.51; P<0.001) and lymphocyte (HR, 0.54; P=0.009) recovery. These data support the hypothesis that the proportion of Tregs in allogeneic HSC grafts influences clinical outcome and suggest that Treg therapies could improve allogeneic HSC transplantation.

Storage of washed or irradiated red cells in AS-7 improves their in vitro characteristics.

BACKGROUND: AS-7 is a new alkaline hypotonic red cell additive solution (AS) shown to improve red cell quality during storage compared with AS-1. We sought to compare red cells stored in AS-7 with those stored in SAGM using RCC that were either untreated, or washed or irradiated on day 14 of storage. STUDY DESIGN AND METHODS: A pooled and split study design was used to produce seven identical RCC (four in SAGM and three in AS-7). At day 14 following donation, two RCC (one in SAGM and one in AS-7) were gamma irradiated and three RCC (two in SAGM and one in AS-7) were washed and resuspended in either SAGM or AS-7. RCC were sampled for analysis throughout storage and at end of shelf life: day 28 for washed or irradiated and day 35 for untreated RCC. RESULTS: For untreated, washed or irradiated RCC, those stored in AS-7 had lower haemolysis, red cell microvesicles and supernatant potassium content than RCC in SAGM. In addition, ATP levels and pH were better maintained in AS-7 RCC than in SAGM RCC. CONCLUSION: These data suggest that the quality of these components may be improved by storage in AS-7 compared with SAGM.

Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy.

Accumulating evidence reveals that metabolic and cell survival pathways are closely related, sharing common signaling molecules. Hexokinase catalyzes the phosphorylation of glucose, the rate-limiting first step of glycolysis. Hexokinase II (HK-II) is a predominant isoform in insulin-sensitive tissues such as heart, skeletal muscle, and adipose tissues. It is also upregulated in many types of tumors associated with enhanced aerobic glycolysis in tumor cells, the Warburg effect. In addition to the fundamental role in glycolysis, HK-II is increasingly recognized as a component of a survival signaling nexus. This review summarizes recent advances in understanding the protective role of HK-II, controlling cellular growth, preventing mitochondrial death pathway and enhancing autophagy, with a particular focus on the interaction between HK-II and Akt/mTOR pathway to integrate metabolic status with the control of cell survival.

Blood transfusion at the time of the First World War--practice and promise at the birth of transfusion medicine.

The centenary of the start of the First World War has stirred considerable interest in the political, social, military and human factors of the time and how they interacted to produce and sustain the material and human destruction in the 4 years of the war and beyond. Medical practice may appear distant and static and perhaps seems to have been somewhat ineffectual in the face of so much trauma and in the light of the enormous advances in medicine and surgery over the last century. However, this is an illusion of time and of course medical, surgical and psychiatric knowledge and procedures were developing rapidly at the time and the war years accelerated implementation of many important advances. Transfusion practice lay at the heart of resuscitation, and although direct transfusion from donor to recipient was still used, Geoffrey Keynes from Britain, Oswald Robertson from America and his namesake Lawrence Bruce Robertson from Canada, developed methods for indirect transfusion from donor to recipient by storing blood in bottles and also blood-banking that laid the foundation of modern transfusion medicine. This review explores the historical setting behind the development of blood transfusion up to the start of the First World War and on how they progressed during the war and afterwards. A fresh look may renew interest in how a novel medical speciality responded to the needs of war and of post-war society.

Oral deferiprone for iron chelation in people with thalassaemia.

BACKGROUND: Thalassaemia major is a genetic disease characterised by a reduced ability to produce haemoglobin. Management of the resulting anaemia is through transfusions of red blood cells. Repeated transfusions result in excessive accumulation of iron in the body (iron overload), removal of which is achieved through iron chelation therapy. A commonly used iron chelator, deferiprone, has been found to be pharmacologically efficacious. However, important questions exist about the efficacy and safety of deferiprone compared to another iron chelator, desferrioxamine. OBJECTIVES: To summarise data from trials on the clinical efficacy and safety of deferiprone and to compare the clinical efficacy and safety of deferiprone for thalassaemia with desferrioxamine. SEARCH STRATEGY: We searched the Group's Haemoglobinopathies Trials Register, MEDLINE, EMBASE, Biological Abstracts, ZETOC, Current Controlled Trials and bibliographies of relevant publications. We contacted the manufacturers of deferiprone and desferrioxamine. Most recent searches: June 2006. SELECTION CRITERIA: Randomised controlled trials comparing deferiprone with another iron chelator; or comparing two schedules of deferiprone, in people with transfusion-dependent thalassaemia. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. Missing data were requested from the original investigators. MAIN RESULTS: Ten trials involving 398 people (range 10 to 144 people) were included. Nine trials compared deferiprone with desferrioxamine or a combination of deferiprone and desferrioxamine and one compared different schedules of deferiprone. There was little consistency between outcomes and little information to fully assess the methodological quality of most of the included trials. No trial reported long-term outcomes (mortality and end organ damage). There was no consistent effect on reduction of iron overload between all treatment comparisons, with the exception of urinary iron excretion in comparisons of deferiprone with desferrioxamine. An increase in iron excretion levels favoured deferiprone in one trial and desferrioxamine in three trials, even though measurement of urinary iron excretion underestimates total iron excretion by desferrioxamine.Adverse events were recorded in trials comparing deferiprone with desferrioxamine. There was evidence of adverse events in all treatment groups. Adverse events in one trial were significantly more likely with deferiprone than desferrioxamine, relative risk 2.24 (95% confidence interval 1.19 to 4.23). AUTHORS' CONCLUSIONS: We found no reason to change current treatment recommendations, namely deferiprone is indicated for treating iron overload in people with thalassaemia major when desferrioxamine is contraindicated or inadequate. However, there is an urgent need for adequately-powered, high quality trials comparing the overall clinical efficacy and long-term outcome of deferiprone with desferrioxamine.

Desferrioxamine mesylate for managing transfusional iron overload in people with transfusion-dependent thalassaemia.

BACKGROUND: Thalassaemia major is a genetic disease characterised by a reduced ability to produce haemoglobin. Management of the resulting anaemia is through transfusions of red blood cells. Repeated transfusions results in excessive accumulation of iron in the body (iron overload), removal of which is achieved through iron chelation therapy. Desferrioxamine is the most widely used iron chelator. Substantial data have shown the beneficial effects of desferrioxamine. However, important questions exist about whether desferrioxamine is the best schedule for iron chelation therapy. OBJECTIVES: To determine the effectiveness (dose and method of administration) of desferrioxamine in people with transfusion-dependent thalassaemia. SEARCH STRATEGY: We searched the Cochrane Haemoglobinopathies Trials Register, MEDLINE, EMBASE, ZETOC, Current Controlled Trials and bibliographies of relevant publications. We also contacted the manufacturers of desferrioxamine and other iron chelators. Date of last searches: April 2004. SELECTION CRITERIA: Randomised controlled trials comparing desferrioxamine with placebo; with another iron chelator; or comparing two schedules of desferrioxamine, in people with transfusion-dependent thalassaemia. DATA COLLECTION AND ANALYSIS: Four authors working independently, were involved in trial quality assessment and data extraction. Missing data were requested from the original investigators. MAIN RESULTS: Eight trials involving 334 people (range 20 to 144 people) were included. One trial compared desferrioxamine with placebo, five compared desferrioxamine with another iron chelator (deferiprone) and two compared different schedules of desferrioxamine. Overall, few trials measured the same outcomes.Compared to placebo, desferrioxamine significantly reduced iron overload. The number of deaths at 12 years follow up and evidence of reduced end-organ damage was less for desferrioxamine than placebo. When desferrioxamine was compared to deferiprone or a different desferrioxamine schedule there were no statistically significant differences in measures of iron overload. Compliance was recorded by two trials. Compliance was less for desferrioxamine than deferiprone in one trial and of no difference in comparison with desferrioxamine and deferiprone combined with a second trial. Adverse events were recorded in trials comparing desferrioxamine with other iron chelators. There was evidence of adverse events in all treatment groups. In one trial, adverse events were significantly less likely with desferrioxamine than deferiprone, relative risk 0.45 (95% confidence interval 0.24 to 0.84). Assessment of the methodological quality of included trials was not possible, given the general absence of these data in the trials. AUTHORS' CONCLUSIONS: We found no reason to change current treatment recommendations. However, considerable uncertainty continues to exist about the optimal schedule for desferrioxamine in people with transfusion-dependent thalassaemia.

Sonic hedgehog expression correlates with fundic gland differentiation in the adult gastrointestinal tract.

BACKGROUND: Sonic hedgehog (Shh) is an important endodermal morphogenetic signal during the development of the vertebrate gut. It controls gastrointestinal patterning in general, and gastric gland formation in particular. We have previously shown that Shh regulates gastric gland proliferation in the adult but detailed analysis of its expression along the adult gastrointestinal tract has never been undertaken. We therefore studied Shh expression along the normal human and rodent adult gastrointestinal tract as well as in intestinal metaplasia of the stomach, gastric and intestinal metaplasia of the oesophagus, and gastric heterotopia in Meckel's diverticulum. METHODS: The studies were performed with in situ hybridisation and by immunohistochemistry using an antibody that recognises the Shh precursor form. RESULTS: We found that in the normal gastrointestinal tract, high levels of Shh were expressed in the fundic glands of the stomach. Shh expression was also found in fundic gland metaplasia and heterotopia. However, Shh expression was lost in intestinal metaplasia of the stomach. CONCLUSION: We found a strong correlation between Shh expression and fundic gland differentiation. Our current study therefore provides evidence that in addition to its role in gastric epithelial development, Shh plays a unique role in gastric epithelial differentiation in adults.

Porphyrin accumulation induced by 5-aminolaevulinic acid esters in tumour cells growing in vitro and in vivo.

The ability of 5-aminolaevulinic acid and some of its esterified derivatives to induce porphyrin accumulation has been examined in CaNT murine mammary carcinoma cells growing in culture and as tumours in vivo. Topical or intravenous administration of 5-aminolaevulinic acid-esters to mice bearing subcutaneous tumours produced lower porphyrin levels in the tumour than an equimolar dose of 5-aminolaevulinic acid. Reducing the dose of intravenous hexyl- or benzyl-ALA and topical hexyl-5-aminolaevulinic acid resulted in a dose-dependent reduction in porphyrin accumulation. A number of normal tissues accumulated higher concentrations of porphyrins than tumour tissue following intravenous administration of 5-aminolaevulinic acid-esters. Esterase activity in these normal tissues was greater than that in tumour tissue. In contrast to the situation in vivo, all of the 5-aminolaevulinic acid-esters examined were at least as effective as 5-aminolaevulinic acid when applied to cloned CaNT cells in vitro, with the drug concentration required for maximum porphyrin accumulation varying with ester chain-length. Tumour cells growing in culture released esterase activity into the medium. These findings suggest that the efficacy of 5-aminolaevulinic esters may vary depending on the esterase activity of the target tissue, and suggest caution when interpreting the findings of in vitro studies using these and similar prodrugs.

A role for CD36 in the regulation of dendritic cell function.

Dendritic cells (DC) are crucial for the induction of immune responses and thus an inviting target for modulation by pathogens. We have previously shown that Plasmodium falciparum-infected erythrocytes inhibit the maturation of DCs. Intact P. falciparum-infected erythrocytes can bind directly to CD36 and indirectly to CD51. It is striking that these receptors, at least in part, also mediate the phagocytosis of apoptotic cells. Here we show that antibodies against CD36 or CD51, as well as exposure to early apoptotic cells, profoundly modulate DC maturation and function in response to inflammatory signals. Although modulated DCs still secrete tumor necrosis factor-alpha, they fail to activate T cells and now secrete IL-10. We therefore propose that intact P. falciparum-infected erythrocytes and apoptotic cells engage similar pathways regulating DC function. These findings may have important consequences for the treatment of malaria and may suggest strategies for modulating pathological immune responses in autoimmune diseases.

Cloning and expression of a novel cysteine-rich secreted protein family member expressed in thyroid and pancreatic mesoderm within the chicken embryo.

We have isolated a new chicken gene that is a member of the cysteine-rich secreted protein family (CRISP). The CRISP family is composed of over 70 members that are found in many phyla of organisms, including: vertebrates, plants, fungi, yeast, and insects. Here we describe the cloning of a novel member of this family, SugarCrisp, and its expression pattern throughout chicken embryogenesis. We also describe its utility as a marker of thyroid and pancreatic mesoderm in the developing chicken embryo and its expression within the human and mouse in glandular tissue.