Neutrophil-mediated lung injury is a cause of significant morbidity and mortality in patients with multiple injuries. We have shown previously that fracture hematoma can activate neutrophils and is thus a putative mediator of the systemic inflammatory response syndrome (SIRS), acute respiratory distress syndrome (ARDS) and multiple organ failure (MOF) in those patients with severe skeletal trauma. Our aim was to establish a rodent model of fracture which caused lung injury and subsequently to administer a drug following fracture to attenuate the lung injury. The drug we chose was N-acetylcysteine, a potent antioxidant.Adult Sprague-Dawley rats were assigned to 4 groups: (1) general anesthetic only, (2) general anesthetic with bilateral femur fractures and nailing, (3) general anesthetic and N-acetylcysteine, (4) general anesthetic with bilateral femur fractures and nailing and N-acetylcysteine after the injury (n = 6 in each group). The dose of N-acetylcysteine was 0.5 mg/kg which was given intraperitoneally after injury to the treated groups. The rats were killed 24 hours after injury and some parameters of lung injury were evaluated--i.e., bronchoalveolar lavage (BAL), lung tissue myeloperoxidase levels (MPO) and wet/dry ratios of lung tissue. The results were analyzed, using one-way analysis of variance.Bilateral femur fracture produced a significant lung injury, measured by increases in MPO (25-43 microg/g tissue) and BAL protein (460-605 microg/mL). This effect was attenuated by treatment with N-acetylcysteine (MPO 43-9 microg/mL, BAL protein 605-198 microg/mL).N-acetyl cysteine, if given after skeletal trauma, is of potential therapeutic benefit, in preventing SIRS, ARDS and MOF.
Subhepatic appendicitis is an unusual presentation of acute appendicitis (AA). Similarly, another uncommon condition that resembles AA is appendiceal diverticulitis (AD), which is a rare form of vermiform appendix pathology. It is exceedingly uncommon for the two to occur simultaneously. We present the case of a 41-year-old male presented with a one-day history of sudden onset of right iliac fossa (RIF) pain associated with a two-day history of nausea and fevers. The only notable lab finding was elevated C-reactive protein (CRP). Clinical examination revealed right abdominal and renal angle tenderness, with RIF rebound and guarding. Computed tomography (CT) concluded acute uncomplicated appendicitis with a subhepatic appendix and he was planned for an emergent laparoscopic appendicectomy. Exposure of the retrocaecal appendix with the caecum in the right loin posed a challenging laparoscopy. The appendix was found to be adherent to the duodenum, right kidney, and transverse colon, and the decision was made to convert to laparotomy to establish safe mobilisation from the duodenum. The appendix was resected in two parts and the histopathology revealed an appendiceal diverticulum with subserosal abscess formation. The subhepatic position of the cecum and appendix is a result of foetal gut malrotation. There is no standard approach for the best course of treatment. The laparotomy conversion gave us better tactile input and direct access to the appendix. Our goal is to educate readers on how to manage an unusual presentation of AA.
Background: The weekend effect is an ongoing concern in healthcare and the exact cause is not fully understood. Recent reports show around 90,000 wasted hospital bed hours due to delayed discharges. We hypothesised that lack of routine ultrasound availability over weekends can lead to delayed discharges. It would be prudent to investigate the possible causes of the “weekend effect” in order to attempt to reverse them.
Background: Over 3,000 new cases of breast cancer are diagnosed annually in Ireland, an increase of 3.5 percent over the last 10 years. In 1999, breast screening was introduced nationally for women aged between 50 and 64 and is currently being extended. With the advent of Breastcheck, we decided to review the age profile of cancers presenting to our symptomatic breast clinic over this time period with the expectation that the percentage of breast cancers diagnosed in this age group would decline. Methods: A retrospective review was carried out on a prospectively maintained database of all breast cancer patients diagnosed in Beaumont Hospital over the last 13 years. This cohort of patients was stratified based on age, focusing on patients aged 51–65, excluding those presenting with recurrent disease. We recorded their cancer subtype, nodal involvement and evidence of metastatic disease at presentation. Results: Over the last 13 years there has been a steady increase in new breast cancers diagnosed via our symptomatic clinic from 133 [2006] to 393 [2018]. During this time period there has been an almost constant percentage of these patients within the 51–65-year-old age group (range, 15–24.5%). Overall, 11.64% of breast cancers diagnosed were DCIS, and 7.8% presented with metastatic disease in 2018 alone. Conclusions: Despite the introduction of a national breast screening service and increased awareness around health promotion, there is a persistent percentage of our new breast cancers diagnosed within the age-group of patients eligible for breast cancer screening. The reasons for this remain unclear.
Abstract HER2-positive (HER2+) breast cancer accounts for 20–25% of all breast cancers. Predictive biomarkers of neoadjuvant therapy response are needed to better identify patients with early stage disease who may benefit from tailored treatments in the adjuvant setting. As part of the TCHL phase-II clinical trial (ICORG10–05/NCT01485926) whole exome DNA sequencing was carried out on normal-tumour pairs collected from 22 patients. Here we report predictive modelling of neoadjuvant therapy response using clinicopathological and genomic features of pre-treatment tumour biopsies identified age, estrogen receptor (ER) status and level of immune cell infiltration may together be important for predicting response. Clonal evolution analysis of longitudinally collected tumour samples show subclonal diversity and dynamics are evident with potential therapy resistant subclones detected. The sources of greater pre-treatment immunogenicity associated with a pathological complete response is largely unexplored in HER2+ tumours. However, here we point to the possibility of APOBEC associated mutagenesis, specifically in the ER-neg/HER2+ subtype as a potential mediator of this immunogenic phenotype.
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