Creation of a protective space between the rectum and prostate prior to prostate radiotherapy using a hydrogel spacer.

The placement of a polyethylene glycol (PEG) hydrogel spacer is a recently developed technique employed to reduce the radiation dose administered to the rectum during prostate radiotherapy. This procedure has been adopted by urologists and radiation oncologists involved in transperineal prostate biopsy and brachytherapy, and more recently by radiologists with experience in transperineal prostate procedures. Radiologists should be familiar with the product, which may be encountered on computed tomography (CT) or magnetic resonance imaging (MRI). Radiologists may wish to become involved in the delivery of this increasingly utilised procedure. This review familiarises radiologists with the technique and risks and benefits of the use of transperineal delivery of hydrogel spacers with imaging examples.

The Effect of COVID-19 on 30-Day Mortality Rates Amongst Fragility Hip Fracture Patients.

Aim Fragility hip fracture patients have always been vulnerable to high rates of short term mortality, an issue that may have been exacerbated by the ongoing COVID-19 pandemic. To date, published data regarding Irish hip fracture patients in the era of COVID-19 is limited. This study aims to assess the effect of COVID-19 on 30-day mortality rates amongst a group of Irish hip fracture patients. Additionally, patient demographics, length of stay, admission haematological parameters, fracture type and surgical procedure will be assessed. Methods A multicentre, observational, retrospective study of hip fracture patients (n = 1,017) admitted to six Dublin teaching hospitals during the COVID-19 pandemic (4th February to 9th July 2020) was performed. For comparative purposes, equivalent data was retrospectively collected relating to hip fracture patients admitted to the same six teaching hospitals during the same time period in 2019. Results 481 patients were admitted during the specified timeframe in 2020, compared with 536 in 2019. The mean patient age was 77.6 years and 65.9% of patients were female. There was no statistically significant overall difference in 30-day mortality rates between the study and control groups, at 5.4% in 2020 and 4.3% in 2019 (p=0.338). There was an insignificant decrease in mean length of stay (17.85 days in 2020 vs. 18.82 days in 2019; p=0.106). Advancing age (p=0.021), male gender (p=0.019), low admission haemoglobin (p=0.024) and high admission white cell count (p=0.019) were all associated with increased 30-day mortality. Conclusion We found no significant difference in 30-day mortality rates amongst our cohort of hip fracture patients at the height of the COVID-19 pandemic in Ireland. Advancing age, male gender, anaemia at admission and leucocytosis at admission were associated with increased 30-day mortality. The continuation of COVID-19 related safety protocols in the treatment of hip fracture patients is essential in maintaining a safe hip fracture service.

New hints towards a precision medicine strategy for IDH wild-type glioblastoma.

Glioblastoma represents the most common primary malignancy of the central nervous system in adults and remains a largely incurable disease. The elucidation of disease subtypes based on mutational profiling, gene expression and DNA methylation has so far failed to translate into improved clinical outcomes. However, new knowledge emerging from the subtyping effort in the IDH-wild-type setting may provide directions for future precision therapies. Here, we review recent learnings in the field, and further consider how tumour microenvironment differences across subtypes may reveal novel contexts of vulnerability. We discuss recent treatment approaches and ongoing trials in the IDH-wild-type glioblastoma setting, and propose an integrated discovery stratagem incorporating multi-omics, single-cell technologies and computational approaches.

Clinicopathological features and oncological outcomes of patients with young-onset rectal cancer.

BACKGROUND: The incidence of rectal cancer among adults aged less than 50 years is rising. Survival data are limited and conflicting, and the oncological benefit of standard neoadjuvant and adjuvant therapies is unclear. METHODS: Disease-specific outcomes of patients diagnosed with rectal cancer undergoing surgical resection with curative intent between 2006 and 2016 were analysed. RESULTS: A total of 797 patients with rectal cancer were identified, of whom 685 had surgery with curative intent. Seventy patients were younger than 50 years and 615 were aged 50 years or more. Clinical stage did not differ between the two age groups. Patients aged less than 50 years were more likely to have microsatellite instability (9 versus 1·6 per cent; P = 0·003) and Lynch syndrome (7 versus 0 per cent; P < 0·001). Younger patients were also more likely to receive neoadjuvant chemoradiotherapy (67 versus 53·3 per cent; P = 0·003) and adjuvant chemotherapy (41 versus 24·2 per cent; P = 0·006). Five-year overall survival was better in those under 50 years old (80 versus 72 per cent; P = 0·013). The 5-year disease-free survival rate was 81 per cent in both age groups (P = 0·711). There were no significant differences in the development of locoregional recurrence or distant metastases. CONCLUSION: Despite accessing more treatment, young patients have disease-specific outcomes comparable to those of their older counterparts.

ANTECEDENTES: La incidencia de cáncer de recto entre adultos menores de 50 años está aumentando. Los datos de supervivencia son limitados y contradictorios, y el beneficio oncológico de los tratamientos neoadyuvantes y adyuvantes estándares no está claro. MÉTODOS: Se analizaron los resultados específicos relacionados con la enfermedad en pacientes diagnosticados de cáncer de recto operados con intención curativa entre 2006 y 2016. RESULTADOS: Se identificaron un total de 797 pacientes con cáncer de recto, de los cuales 685 fueron intervenidos quirúrgicamente con intención curativa. Setenta tenían menos de 50 años y 615 tenían 50 años o más. No hubo diferencias en el estadio clínico entre los dos grupos de edad. Los pacientes menores de 50 años tenían más probabilidades de tener inestabilidad de microsatélites (9% versus 2%, P = 0,003) y síndrome de Lynch (7% versus 0%, P ≤ 0,001). La supervivencia global a los 5 años fue mayor en los pacientes de menos de 50 años (80% y 72%; P = 0,013). La supervivencia libre de enfermedad a los 5 años fue del 81% en ambos grupos de edad (P = 0,711). No hubo diferencias significativas en el desarrollo de recidiva locorregional o metástasis a distancia. Los pacientes más jóvenes tenían más probabilidades de recibir quimiorradioterapia neoadyuvante (67% versus 53%, P = 0,003) y quimioterapia adyuvante (41% versus 24%, P = 0,006). CONCLUSIÓN: A pesar de tener acceso a más tratamientos, los pacientes jóvenes han presentado resultados específicos relacionados con la enfermedad comparables a sus homólogos de mayor edad.

Open and Endovascular Management of Acute Mesenteric Ischaemia: A Systematic Review.

BACKGROUND: Acute mesenteric ischaemia (AMI) is a life-threatening surgical emergency resulting from thromboembolic occlusion of the mesenteric vasculature. Traditional management of AMI has been open revascularisation with or without bowel resection-a procedure which carries considerable morbidity and mortality in an already unwell, compromised patient. Endovascular and more minimally invasive management approaches to AMI have been reported. Proponents of endovascular management suggest this approach may be associated with reduced morbidity and mortality compared with open surgery. OBJECTIVES: To assess the impact of endovascular approach for AMI on mortality and need for subsequent laparotomy and/or bowel resection. DATA SOURCES: The search bodies PubMed and Medline were interrogated. ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: All studies in English with greater than 10 patients examining outcomes for patients undergoing endovascular intervention for acute mesenteric ischaemia were included. All patients over 18 years presenting with a diagnosis of acute mesenteric ischaemia secondary to an arterial thromboembolic source were included. Studies examining endovascular intervention alone or endovascular and open intervention were selected. RESULTS: The 30-day mortality for endovascular approach from all 13 studies was 16-42%. Of the 7 comparative studies including results of open revascularisation, the 30-day mortality for patient treated with an endovascular approach was 15-39% versus 33-50% for open revascularisation. Laparotomy rates post-initial endovascular intervention ranged from 13 to 73%. Bowel resection post-endovascular therapy ranged from 14 to 40% among studies. Concerning 7 comparative studies for open versus endovascular revascularisation, the rate of bowel resection in the endovascular group ranged 14-28% and 33-63% in the open cohort. Endovascular intervention also demonstrated lower median length (s) of bowel resected. LIMITATIONS: Heterogeneity of studies and patient populations studied including selection bias. CONCLUSIONS AND IMPLICATIONS OF FINDINGS: Endovascular management may be associated with reduced mortality and need for/length of bowel resection compared with the traditional open approach, but there remains a paucity of robust data to support this. The available literature illustrates that a subgroup of patients without haemodynamic compromise and more insidious onset may garner benefit from endovascular intervention.

Review of external referrals to a regional stroke centre: it is not just about thrombectomy.

AIMS: To determine the experience of a regional stroke referral centre of external referrals for endovascular thrombectomy (EVT) in patients with symptoms of acute ischaemic stroke (AIS) and large vessel occlusion (LVO). MATERIALS AND METHODS: Data were collected prospectively over two 4-month periods (2017-2018) on consecutive external referrals for EVT. Baseline demographics, imaging findings, and key time parameters were recorded. Reasons for not transferring patients and for not performing EVT were recorded. Key time intervals were calculated and compared between the transferred and non-transferred group with and without intracranial occlusion and between the transferred patients who underwent thrombectomy and those who did not. RESULTS: Two hundred and sixty-two patients were referred. Sixty-one percent (n=159) were accepted and transferred for treatment. Of those transferred, 86% (n=136) had EVT. Fourteen percent (n=23) were unsuitable for EVT on arrival due to no vessel occlusion (48% n=11), poor Alberta Stroke Program Early CT Score (ASPECTS)/established infarct (30%, n=7) haemorrhage (9%, n=2), and clinical recovery (13% n=3). One hundred and three patients (39%) were ineligible for EVT following phone discussion due to absence of intracranial occlusion (59%, n=61), low ASPECTS (22%, n=23), distal occlusion (4%, n=4), low/improving National Institutes of Health Stroke Scale (NIHSS; 10.7%, n=11), and poor modified Rankin Scale (mRS) at baseline (3%, n=3). Patients with LVO but not transferred had longer onset to hospital arrival time compared with those transferred 151.5 versus 91 minutes (p<0.005), with a trend also toward a longer door to CT/CTA 40 minutes versus 30 minutes (p=0.142). CONCLUSION: These data provide valuable insights into the service provision of a comprehensive stroke network. The present rates of EVT and futile transfers are modest compared to published data. Access to neuroradiology and specialised stroke assessment is crucial to optimise time to treatment.

High-flow Nasal Cannulae, Bronchopulmonary Dysplasia and Retinopathy of Prematurity

Aims To determine if HFNC use was associated with changes in incidence of BPD and ROP. Methods This retrospective study examined premature infants (<30 weeks GA or <1500g) in a tertiary neonatal unit from 2010- 2016. Patients were compared before and after introduction of HFNC. Further analysis of high-risk infants (<28 weeks GA or <750g or ventilated) compared those who received HFNC to those who did not across the whole period. Primary outcomes were incidence of BPD and ROP requiring surgery. Results Incidence of BPD rose following the introduction of HFNC (82/232 (35.3%) after vs 33/251 (13.1%) before, p<0.001). On multivariate analysis, the chance of developing BPD after HFNC introduction remained higher (OR 4.353, 95% CI 2.546-7.443). More infants received surgery for ROP following HFNC introduction (0/214 vs 11/205 (5.4%), p=<0.001). In the second analysis, the rate of BPD was higher in those who received HFNC (90/132 (68.1%) vs 33/153 (21.6%), p<0.001). Receiving HFNC demonstrated higher chance of BPD in multivariate analysis (OR 7.802, 95% CI 4.223-14.423). Rate of ROP surgery was higher in those who received HFNC (0/153 vs 13/134 (9.7%), p<0.001). Conclusions In this study, use of HFNC was associated with significantly increased risk of adverse outcomes.

Multifocal discrete osteolysis in a horse with silicate associated osteoporosis.

Silicate associated osteoporosis (SAO) was diagnosed post mortem in an adult horse with the shortest documented exposure to cytotoxic silicates of 2 years. The horse was evaluated for a 6-months history of progressive back tenderness and acute onset of lameness. The horse had a marked (4/5) [American Association of Equine Practitioners scale] left forelimb lameness, moderate (2/5) hindlimb ataxia and weakness, and cervical pain upon palpation. Physical examination did not reveal clinical skeletal deformities or respiratory compromise. Radiographs revealed widespread, discrete, sharply delineated, osteolytic lesions in the skull, vertebral column, ribs, scapulae and middle phalanx (P2) of the left forelimb and a diffuse bronchointerstitial lung pattern. The presumptive clinical diagnosis was widespread, metastatic osteolytic neoplasia. Due to the poor quality of life and grave prognosis, the horse was humanely euthanised. Post mortem examination revealed pulmonary silicosis in the lungs and hilar lymph nodes and osteolytic lesions with numerous, large osteoclasts and disorganised bone remodeling both consistent with SAO. SAO should be included as a differential diagnosis for horses with widespread, multifocal, discrete osteolysis and history of exposure to endemic regions with possible cytotoxic silicate inhalation. Exposure time of 2 years is potentially sufficient to develop SAO.

Oxygen tension modulates the effects of TNFα in compressed chondrocytes.

OBJECTIVE AND DESIGN: Oxygen tension and biomechanical signals are factors that regulate inflammatory mechanisms in chondrocytes. We examined whether low oxygen tension influenced the cells response to TNFα and dynamic compression. MATERIALS AND METHODS: Chondrocyte/agarose constructs were treated with varying concentrations of TNFα (0.1-100 ng/ml) and cultured at 5 and 21 % oxygen tension for 48 h. In separate experiments, constructs were subjected to dynamic compression (15 %) and treated with TNFα (10 ng/ml) and/or L-NIO (1 mM) at 5 and 21 % oxygen tension using an ex vivo bioreactor for 48 h. Markers for catabolic activity (NO, PGE2) and tissue remodelling (GAG, MMPs) were quantified by biochemical assay. ADAMTS-5 and MMP-13 expression were examined by real-time qPCR. 2-way ANOVA and a post hoc Bonferroni-corrected t test were used to analyse data. RESULTS: TNFα dose-dependently increased NO, PGE2 and MMP activity (all p < 0.001) and induced MMP-13 (p < 0.05) and ADAMTS-5 gene expression (pp < 0.01) with values greater at 5 % oxygen tension than 21 %. The induction of catabolic mediators by TNFα was reduced by dynamic compression and/or L-NIO (all p < 0.001), with a greater inhibition observed at 5% than 21 %. The stimulation of GAG synthesis by dynamic compression was greater at 21 % than 5 % oxygen tension and this response was reduced with TNFα or reversed with L-NIO. CONCLUSIONS: The present findings revealed that TNFα increased production of NO, PGE2 and MMP activity at 5 % oxygen tension. The effects induced by TNFα were reduced by dynamic compression and/or the NOS inhibitor, linking both types of stimuli to reparative activities. Future therapeutics should develop oxygen-sensitive antagonists which are directed to interfering with the TNFα-induced pathways.

Nanoclusters and nanolines: the effect of molybdenum oxide substrate stoichiometry on iron self-assembly.

The growth of Fe nanostructures on the stoichiometric MoO2/Mo(110) and oxygen-rich MoO2+x /Mo(110) surfaces has been studied using low-temperature scanning tunnelling microscopy (STM) and density functional theory calculations. STM results indicate that at low coverage Fe nucleates on the MoO2/Mo(110) surface, forming small, well-ordered nanoclusters of uniform size, each consisting of five Fe atoms. These five-atom clusters can agglomerate into larger nanostructures reflecting the substrate geometry, but they retain their individual character within the structure. Linear Fe nanocluster arrays are formed on the MoO2/Mo(110) surface at room temperature when the surface coverage is greater than 0.6 monolayers. These nanocluster arrays follow the direction of the oxide rows of the strained MoO2/Mo(110) surface. Slightly altering the preparation procedure of MoO2/Mo(110) leads to the presence of oxygen adatoms on this surface. Fe deposition onto the oxygen-rich MoO2+x /Mo(110) surface results in elongated nanostructures that reach up to 24 nm in length. These nanolines have a zigzag shape and are likely composed of partially oxidised Fe formed upon reaction with the oxygen-rich surface.

Evaluation of P16 expression in canine appendicular osteosarcoma.

BACKGROUND: Osteosarcoma (OSA) is a common malignant bone tumor of large breed dogs that occurs at predictable anatomic sites. At the time of initial diagnosis, most affected dogs have occult pulmonary metastases. Even with aggressive surgical treatment combined with chemotherapy, the majority of dogs diagnosed with OSA live less than 1 year from the time of diagnosis. The ability to identify canine OSA cases most responsive to treatment is needed. In humans, OSA is also an aggressive tumor that is histologically and molecularly similar to canine OSA. The expression of the tumor suppressor gene product P16 by human OSA tissue has been linked to a favorable response to chemotherapy. RESULTS: We identified an antibody that binds canine P16 and developed a canine OSA tissue microarray in order to test the hypothesis that P16 expression by canine OSA tissue is predictive of clinical outcome following amputation and chemotherapy. Although statistical significance was not reached, a trend was identified between the lack of canine OSA P16 expression and a shorter disease free interval. CONCLUSIONS: The identification of a molecular marker for canine OSA is an important goal and the results reported here justify a larger study.

Clinical and Histopathologic Characterization of Canine Chronic Ulcerative Stomatitis.

Canine chronic ulcerative stomatitis, also known as chronic ulcerative paradental stomatitis, is a painful condition of the oral cavity. The purpose of this study was to determine if there are commonalities in clinical and radiographic features among patients, whether the histopathologic evaluation might inform the pathogenesis, and whether the condition appears similar to human oral mucosal diseases. To do this, we prospectively collected clinical, radiographic, and histopathologic data from 20 dogs diagnosed with the disease. Clinical data were based on a clinical disease activity index, oral and periodontal examination parameters, and full-mouth dental radiographs. The histopathological and immunohistochemical data were based on oral mucosal samples obtained from erosive or ulcerated areas. Our findings revealed that canine chronic stomatitis is clinically characterized by painful oral mucosal ulcers of varying size, pattern, appearance, and distribution, most often associated with teeth with early periodontitis. Histologic examination revealed a subepithelial lichenoid band (interface mucositis) where B cells, T cells, and Forkhead-box protein 3 (FoxP3)- and interleukin-17-expressing cells were present. These cells might play a role in the underlying immune response and an immune-mediated pathogenesis is suspected. The clinical and histopathologic features of this chronic inflammatory mucosal disease in dogs resemble those of oral lichen planus in humans.

Regulation of diapause in carnivores.

Embryonic diapause is an evolutionary strategy to ensure that offspring are born when maternal and environmental conditions are optimal for survival. In many species of carnivores, obligate embryonic diapause occurs in every gestation. In mustelids, the regulation of diapause and reactivation is influenced by photoperiod, which then acts to regulate the secretion of pituitary prolactin. Prolactin in turn regulates ovarian steroid function. Reciprocal embryo transplant studies indicate that this state of embryonic arrest is conferred by uterine conditions and is presumed to be due to a lack of specific factors necessary for continued development. Studies of global gene expression in the mink (Neovison vison) revealed reduced expression of a cluster of genes that regulate the abundance of polyamines in the uterus during diapause, including the rate-limiting enzyme in polyamine production, ornithine decarboxylase (ODC). In addition, in this species, in vivo inhibition of the conversion of ornithine to the polyamine, putrescine, induces a reversible arrest in embryonic development and an arrest in both trophoblast and inner cell mass proliferation in vitro. Putrescine, at 0.5, 2 and 1,000 µM concentrations induced reactivation of mink embryos in culture, indicated by an increase in embryo volume, observed within five days. Further, prolactin induces ODC1 expression in the uterus, thereby regulating uterine polyamine levels. These results indicate that pituitary prolactin acts on ovarian and uterine targets to terminate embryonic diapause. In summary, our findings suggest that the polyamines, with synthesis under the control of pituitary prolactin, are the uterine factor whose absence is responsible for embryonic diapause in mustelid carnivores.

A Study To Assess The Prevalence Of Exercise-Induced Bronchoconstriction In Inter-County Hurling.

Exercise-Induced Bronchoconstriction (EIB) is an acute, transient airway narrowing occurring after exercise which may impact athletic performance. Studies report 10% of the general population and up to 90% of asthmatics experience EIB. Ninety-two players from three elite hurling squads underwent a spirometric field-based provocation test with real-time heart rate monitoring and lactate measurements to ensure adequate exertion. Players with a new diagnosis of EIB and those with a negative field-test but with a previous label of EIB or asthma underwent further reversibility testing and if negative, methacholine challenge. Eight (8.7%) of players had EIB, with one further athlete having asthma with a negative field test. Interestingly, only three out of 12 players who had previously been physician-labelled with EIB or asthma had their diagnosis objectively confirmed. Our study highlights the role of objective testing in EIB.

Photoinduced Enhancement of the Charge Density Wave Amplitude.

Symmetry breaking and the emergence of order is one of the most fascinating phenomena in condensed matter physics. It leads to a plethora of intriguing ground states found in antiferromagnets, Mott insulators, superconductors, and density-wave systems. Exploiting states of matter far from equilibrium can provide even more striking routes to symmetry-lowered, ordered states. Here, we demonstrate for the case of elemental chromium that moderate ultrafast photoexcitation can transiently enhance the charge-density-wave (CDW) amplitude by up to 30% above its equilibrium value, while strong excitations lead to an oscillating, large-amplitude CDW state that persists above the equilibrium transition temperature. Both effects result from dynamic electron-phonon interactions, providing an efficient mechanism to selectively transform a broad excitation of the electronic order into a well-defined, long-lived coherent lattice vibration. This mechanism may be exploited to transiently enhance order parameters in other systems with coupled degrees of freedom.

Nasal Cavity Masses Resembling Chondro-osseous Respiratory Epithelial Adenomatoid Hamartomas in 3 Dogs.

Chondro-osseous respiratory epithelial adenomatoid hamartomas (COREAHs) are rare tumors in the nasal cavity of people, which have not been described in other species. COREAHs in people are minimally invasive and rarely recur following excision. Histologically, these tumors are composed of disorganized, mature, nasal turbinate tissue that is organized into polypoid growths. These growths are lined by respiratory epithelium, contain glandular elements, and are organized around central cores of chondro-osseous matrix. This report describes 3 cases of dogs with nasal tumors that have histomorphology similar to that of COREAH in people. The tumors were all identified within the nasal cavity and were associated with regional bony lysis of the turbinates and surrounding skull bones, a feature that has not been reported in COREAH in people. There was no evidence of metastasis or extension beyond the nasal cavity in any of the 3 cases.

Surgical Pulmonary Embolectomy: Experience in a Series of 37 Consecutive Cases.

BACKGROUND: Massive pulmonary embolism is a poorly tolerated condition. Treatment options in this condition include anticoagulation and primary reperfusion therapy - systemic thrombolysis, catheter based treatments or surgical embolectomy. There is little data on the relative efficacy of each treatment. METHODS: The preoperative characteristics and outcomes of patients referred for surgical embolectomy between 2000-2014 was reviewed. Echocardiography was performed in the majority of patients before and after surgery. RESULTS: Thirty-seven patients underwent pulmonary embolectomy between 2000-2014. One patient died within 30 days, another before leaving hospital. All other patients were alive at the time of follow-up (survival 94.6% at median 36 months). Median ventilation time was 24hours. Median hospital length of stay was 10.5 days. There was echocardiographic evidence of severe right ventricular strain (increased size and decreased function) before surgery, which was significantly improved to within the normal range by discharge, and follow-up. CONCLUSIONS: Surgical embolectomy is a safe procedure, with low mortality, improved postoperative right ventricular function and pulmonary pressure, and good long-term outcome. Early relief of a large proportion of the clot burden can be life-saving. There should be consideration for its use as an initial treatment strategy in patients with massive or submassive pulmonary embolus with a large burden of proximal clot. A multidisciplinary approach for the treatment of these patients is required.