Of about 150 cases reported in the literature on pectoralis major ruptures, 108 were selected as presenting enough data to be analyzed for cause, rupture site, injury mechanism, and treatment outcome. We added data on four of our own cases reported here. All patients yet reported have been men. Rupture of the PM occurs most commonly in sports during weight training, weight lifting, or wrestling when the arm is externally rotated and abducted. Most reported ruptures are complete and are located at the insertion to the humerus. Work-related injuries occur more often at the musculo-tendinous junction. The prognosis is related neither to the age of the patient nor to the location of the rupture. Surgical treatment, preferably within the first 8 weeks after the injury, has a significantly better outcome than conservative treatment or delayed repair.
BackgroundThere is emerging evidence that Wnt pathway activity may increase during the progression from colorectal adenoma to carcinoma and that this increase is potentially an important step towards the invasive stage. Here, we investigated whether epigenetic silencing of Wnt antagonists is the biological driver for this increased Wnt activity in human tissues and how these methylation changes correlate with MSI (Microsatelite Instability) and CIMP (CpG Island Methylator Phenotype) statuses as well as known mutations in genes driving colorectal neoplasia.MethodsWe conducted a systematic analysis by pyrosequencing, to determine the promoter methylation of CpG islands associated with 17 Wnt signaling component genes. Methylation levels were correlated with MSI and CIMP statuses and known mutations within the APC, BRAF and KRAS genes in 264 matched samples representing the progression from normal to pre-invasive adenoma to colorectal carcinoma.ResultsWe discovered widespread hypermethylation of the Wnt antagonists SFRP1, SFRP2, SFRP5, DKK2, WIF1 and SOX17 in the transition from normal to adenoma with only the Wnt antagonists SFRP1, SFRP2, DKK2 and WIF1 showing further significant increase in methylation from adenoma to carcinoma. We show this to be accompanied by loss of expression of these Wnt antagonists, and by an increase in nuclear Wnt pathway activity. Mixed effects models revealed that mutations in APC, BRAF and KRAS occur at the transition from normal to adenoma stages whilst the hypermethylation of the Wnt antagonists continued to accumulate during the transitions from adenoma to carcinoma stages.ConclusionOur study provides strong evidence for a correlation between progressive hypermethylation and silencing of several Wnt antagonists with stepping-up in Wnt pathway activity beyond the APC loss associated tumour-initiating Wnt signalling levels.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-891) contains supplementary material, which is available to authorized users.
BackgroundThe incidence of oesophageal adenocarcinoma is increasing rapidly in the developed world. The serine-threonine protein kinase and proto-oncogene Akt has been reported to regulate proliferation and apoptosis in several tissues but there are no data on the involvement of Akt in oesophageal carcinogenesis. Therefore we have examined the activation of Akt in Barrett's oesophagus and oesophageal adenocarcinoma and the functional effects of Akt activation in vitro.MethodsExpression of total and active (phosphorylated) Akt were determined in endoscopic biopsies and surgical resection specimens using immunohistochemistry. The functional effects of Akt were examined using Barrett's adenocarcinoma cells in culture.ResultsIn normal squamous oesophagus, erosive oesophagitis and non-dysplastic Barrett's oesophagus, phospho-Akt was limited to the basal 1/3 of the mucosa. Image analysis confirmed that Akt activation was significantly increased in non-dysplastic Barrett's oesophagus compared to squamous epithelium and further significantly increased in high-grade dysplasia and adenocarcinoma. In all cases of high grade dysplasia and adenocarcinoma Akt was activated in the luminal 1/3 of the epithelium. Transient acid exposure and the obesity hormone leptin activated Akt, stimulated proliferation and inhibited apoptosis: the combination of acid and leptin was synergistic. Inhibition of Akt phosphorylation with LY294002 increased apoptosis and blocked the effects of acid and leptin both alone and in combination. Activation of Akt was associated with downstream phosphorylation and deactivation of the pro-apoptotic protein Bad and phosphorylation of the Forkhead family transcription factor FOXO1.ConclusionAkt is abnormally activated in Barrett's oesophagus, high grade dysplasia and adenocarcinoma. Akt activation promotes proliferation and inhibits apoptosis in Barrett's adenocarcinoma cells and both transient acid exposure and leptin stimulate Akt phosphorylation. Downstream targets of Akt include Bad and Forkhead transcription factors. Activation of Akt in obesity and by reflux of gastric acid may be important in the pathogenesis of Barrett's adenocarcinoma
BACKGROUND: Frailty, history of dementia (HoD), and acute confusional states (ACS) are common in older patients admitted to hospital.
Over a 3-year period, medical staff at this institution have routinely used this risk stratification, which identifies groups of patients at high and low risk of mortality, re-bleeding and need for urgent treatment intervention following acute upper-gastrointestinal haemorrhage. Use of this risk stratification should allow targeting of more intensive treatment where it might be of most benefit. Those patients at lowest risk from outpatient management are also identified.
Helicobacter pylori infection causes a number of gastrointestinal diseases and its current treatment is based on multidrug regimes including acid suppression and antimicrobials. The success of these regimes is determined by a number of factors including antibiotic resistance, which varies widely but is an increasing problem. Local data are important in establishing the most cost-effective eradication regime. Data have been collected prospectively on antibiotic resistance at Ipswich Hospital (Suffolk, UK) in all consecutive isolates of H. pylori from 1991 to 2001. The success of regimes consisting of a proton pump inhibitor, amoxycillin and metronidazole (PPI/A/M) has also been evaluated in patients found positive on serological testing in primary care using urea breath testing. Overall, metronidazole resistance was found in 31. 7 % of isolates and clarithromycin resistance in 5. 3 %. A significant increase in metronidazole resistance from 29. 1 to 37. 0 % (P ¼ 0. 022) and a decrease in clarithromycin resistance from 10. 3 to 3. 8 % (P ¼ 0. 014) was seen over the study period. Metronidazole resistance was significantly more common in women (P , 0. 001) and young patients (P , 0. 001). Eradication with PPI/A/M was successful in 89. 9 % of patients and did not change significantly over the study period. Eradication rates were lower in young patients (P , 0. 001). Whilst metronidazole resistance is increasing in Suffolk, this does not seem to have a significant effect on eradication rates. Metronidazole-based regimes are still effective first-line treatments in most patients. †Present address:
COVID-19 has disrupted healthcare operations and resulted in large-scale cancellations of elective surgery. Hospitals throughout the world made life-altering resource allocation decisions and prioritised the care of COVID-19 patients. Without effective models to evaluate resource allocation strategies encompassing COVID-19 and non-COVID-19 care, hospitals face the risk of making sub-optimal local resource allocation decisions. A discrete-event-simulation model is proposed in this paper to describe COVID-19, elective surgery, and emergency surgery patient flows. COVID-19-specific patient flows and a surgical patient flow network were constructed based on data of 475 COVID-19 patients and 28,831 non-COVID-19 patients in Addenbrooke’s hospital in the UK. The model enabled the evaluation of three resource allocation strategies, for two COVID-19 wave scenarios: proactive cancellation of elective surgery, reactive cancellation of elective surgery, and ring-fencing operating theatre capacity. The results suggest that a ring-fencing strategy outperforms the other strategies, regardless of the COVID-19 scenario, in terms of total direct deaths and the number of surgeries performed. However, this does come at the cost of 50% more critical care rejections. In terms of aggregate hospital performance, a reactive cancellation strategy prioritising COVID-19 is no longer favourable if more than 7.3% of elective surgeries can be considered life-saving. Additionally, the model demonstrates the impact of timely hospital preparation and staff availability, on the ability to treat patients during a pandemic. The model can aid hospitals worldwide during pandemics and disasters, to evaluate their resource allocation strategies and identify the effect of redefining the prioritisation of patients.
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