Organ preservation after neoadjuvant long-course chemoradiotherapy versus short-course radiotherapy.

BACKGROUND: Potential differences in organ preservation between total neoadjuvant therapy (TNT) regimens integrating long-course chemoradiotherapy (LCCRT) and short-course radiotherapy (SCRT) in rectal cancer remain undefined. PATIENTS AND METHODS: This natural experiment arose from a policy change in response to the COVID-19 pandemic during which our institution switched from uniformly treating patients with LCCRT to mandating that all patients be treated with SCRT. Our study includes 323 locally advanced rectal adenocarcinoma patients treated with LCCRT-based or SCRT-based TNT from January 2018 to January 2021. Patients who achieved clinical complete response were offered organ preservation with watch-and-wait (WW) management. The primary outcome was 2-year organ preservation. Additional outcomes included local regrowth, distant recurrence, disease-free survival (DFS), and overall survival (OS). RESULTS: Patient and tumor characteristics were similar between LCCRT (n = 247) and SCRT (n = 76) cohorts. Median follow-up was 31 months. Similar clinical complete response rates were observed following LCCRT and SCRT (44.5% versus 43.4%). Two-year organ preservation was 40% [95% confidence interval (CI) 34% to 46%] and 31% (95% CI 22% to 44%) among all patients treated with LCCRT and SCRT, respectively. In patients managed with WW, LCCRT resulted in higher 2-year organ preservation (89% LCCRT, 95% CI 83% to 95% versus 70% SCRT, 95% CI 55% to 90%; P = 0.005) and lower 2-year local regrowth (19% LCCRT, 95% CI 11% to 26% versus 36% SCRT, 95% CI 16% to 52%; P = 0.072) compared with SCRT. The 2-year distant recurrence (10% versus 6%), DFS (90% versus 90%), and OS (99% versus 100%) were similar between WW patients treated with LCCRT and SCRT, respectively. CONCLUSIONS: While WW eligibility was similar between cohorts, WW patients treated with LCCRT had higher 2-year organ preservation and lower local regrowth than those treated with SCRT, yet similar DFS and OS. These data support induction LCCRT followed by consolidation chemotherapy as the preferred TNT regimen for patients with locally advanced rectal cancer pursuing organ preservation.

Imaging and video of late preterm delivery by midline laparotomy due to incarcerated uterus: A case report and literature review of a rare but morbid condition.

Incarcerated gravid uterus (IGU) is a rare and serious obstetric complication. IGU is defined as the entrapment of the gravid uterus between the pubic symphysis and the sacral promontory. The incidence of IGU is 1 in 3000-10 000 cases. IGU is associated with significant obstetric complications, including preterm labor, intrauterine fetal death, growth restriction, renal failure, uterine ischemia/rupture and thrombosis. Here, we present the case of a primigravida with urinary retention at 14 weeks. On transabdominal ultrasound at 19+5/7 weeks the cervix was difficult to visualize, and the anterior uterine wall appeared thickened. The bladder was elongated superior to the uterus and the placenta was low-lying. Initially the patient was managed with intermittent self-catheterization, and subsequently indwelling catheterization was required from 22 weeks. At 30 weeks, the patient was transferred to a tertiary center and magnetic resonance imaging (MRI) was preformed due to challenging visualization of the cervix on ultrasound and the patient's continued symptoms of constipation and recurrent urinary infections. The MRI found a retroflexed gravid uterus, with vagina and endocervix displaced anteriorly and compressed by the gravid uterus. The findings were consistent with an incarcerated uterus. The patient subsequently had positive urinary cultures for Pseudomonas and rising creatinine. Given the obstructive uropathy and associated morbidity and mortality, a plan for elective pre-term delivery at 33+6/7 weeks was made. Delivery was by midline laparotomy, normal anatomy was restored after manual evacuation of the fundus from below the sacral promontory, and an uncomplicated lower segment transverse uterine cesarean section was performed.

Unusual Cause of Hemoptysis in a Woman With Cystic Fibrosis.

CASE PRESENTATION: A 20-year-old patient with cystic fibrosis (CF) complicated by pansinusitis, pancreatic insufficiency, and diabetes presented to the local ED after an episode of large-volume hemoptysis at home. At baseline, she had advanced lung disease (FEV1, 0.97 L; 31% predicted) and upper lobe-predominant fibrocavitary changes. She was intermittently followed at a regional lung transplant center. She was previously evaluated for transplant but was not listed at the time of this presentation because of nontuberculous mycobacteria infection. She had never used tobacco, without reports of recreational inhaled drug use. Her mother had CF, and one of her brothers died in 2018 at age 24 of respiratory failure resulting from the disease.

Mitigation of gaseous emissions from dairy livestock: A farm-level method to examine the financial implications.

Feeding the world's population while minimising the contribution of agriculture to climate change is one of the greatest challenges facing modern society. This challenge is particularly pronounced for dairy production where the carbon footprint of products and the mitigation costs are high, relative to other food stuffs. This paper reviews a number of mitigation measures that may be adopted by dairy farmers to reduce greenhouse gas emissions from their farms. A simulation model is developed to assess the cost-benefit of a range of mitigation measures. The model is applied to data from Ireland, a country with a large export-oriented dairy industry, for a range of farms including top, middle and bottom performing farms from a profitability perspective. The mitigation measures modelled included animal productivity, grass production and utilisation, better reproductive performance, early compact calving, reduced crude protein, decreased fertiliser N, protected urea, white clover, slurry tank cover and low emission slurry spreading (LESS). The results show that over half of the greenhouse gas abatement potential and most of the ammonia abatement potential were realised with cost-beneficial measures. Animal and feed-related measures that increased efficiency drove the abatement of GHG emissions. Low-emission slurry spreading was beneficial for the bottom and middle one-third of farms, while protected urea and reducing nitrogen use accounted for most of the ammonia abatement potential for the most profitable farms. Results showed that combining mitigation measures resulted in a decrease of 23%, 19%, and 12% in GHG emissions below 2020 levels for the bottom, middle, and top performing dairy farms, respectively. The findings imply that top dairy farms, that are already managed efficiently and optimally, may struggle to achieve the national and international GHG reduction targets with existing technologies and practices.

Tau filaments are tethered within brain extracellular vesicles in Alzheimer's disease.

The abnormal assembly of tau protein in neurons is the pathological hallmark of multiple neurodegenerative diseases, including Alzheimer's disease (AD). In addition, assembled tau associates with extracellular vesicles (EVs) in the central nervous system of patients with AD, which is linked to its clearance and prion-like propagation between neurons. However, the identities of the assembled tau species and the EVs, as well as how they associate, are not known. Here, we combined quantitative mass spectrometry, cryo-electron tomography and single-particle cryo-electron microscopy to study brain EVs from AD patients. We found filaments of truncated tau enclosed within EVs enriched in endo-lysosomal proteins. We observed multiple filament interactions, including with molecules that tethered filaments to the EV limiting membrane, suggesting selective packaging. Our findings will guide studies into the molecular mechanisms of EV-mediated secretion of assembled tau and inform the targeting of EV-associated tau as potential therapeutic and biomarker strategies for AD.

Bone flap infections after craniotomy: a review of 63 cases and the implications for definitions, classification and surveillance methodologies.

BACKGROUND: Bone flap infections (BFIs) occur following neurosurgical procedures such as craniotomies. However, they are poorly defined and often not clearly differentiated from other surgical site infection in neurosurgery. AIM: To review data from a national adult neurosurgical centre to explore some clinical aspects to better inform definitions, classification and surveillance methodologies. METHODS: We retrospectively reviewed data on clinical samples sent for culture from patients with suspected BFI. We also accessed information recorded prospectively from national and local databases for evidence of BFI or related conditions based on terms used in surgical operative notes or discharge summaries and documented monomicrobial and polymicrobial infections related to craniotomy sites. FINDINGS: Between January 2016 and December 2020, we documented 63 patients with a mean age of 45 years (16-80). Craniectomy for infection of the skull was the most common terminology used to describe BFI in the coding used in a national database, 40/63 (63%), but other terms were used. A malignant neoplasm was the most common underlying condition necessitating craniectomy in 28/63 (44%) cases. Specimens submitted for microbiological investigation included 48/63 (76%) bone flaps, 38/63 (60%) fluid/pus, and 29/63 (46%) tissue. Fifty-eight (92%) patients had at least one culture-positive specimen; 32 (55%) were monomicrobial and 26 (45%) were polymicrobial. Gram-positive bacteria predominated and Staphylococcus aureus was the most common. CONCLUSION: Greater clarity on how to define BFI is required to enable better classification and the carrying out of appropriate surveillance. This will inform preventative strategies and more effective patient management.

Management of vagus nerve stimulation therapy in the peri-operative period: Guidelines from the Association of Anaesthetists: Guidelines from the Association of Anaesthetists.

Vagus nerve stimulation is a well-established treatment option for patients with drug-resistant epilepsy and has an expanding range of other clinical indications. Side effects of vagus nerve stimulation therapy include: cough; voice changes; vocal cord adduction; rarely, obstructive sleep apnoea; and arrhythmia. Patients with implanted vagus nerve stimulation devices may present for unrelated surgery and critical care to clinicians who are unfamiliar with their function and safe management. These guidelines have been formulated by multidisciplinary consensus based on case reports, case series and expert opinion to support clinicians in the management of patients with these devices. The aim is to provide specific guidance on the management of vagus nerve stimulation devices in the following scenarios: the peri-operative period; peripartum period; during critical illness; and in the MRI suite. Patients should be aware of the importance of carrying their personal vagus nerve stimulation device magnet with them at all times to facilitate urgent device deactivation if necessary. We advise that it is generally safer to formally deactivate vagus nerve stimulation devices before general and spinal anaesthesia. During periods of critical illness associated with haemodynamic instability, we also advise cessation of vagus nerve stimulation and early consultation with neurology services.

Confirmation of the passive transfer of maternal antibodies to calves following vaccination of pregnant cows with an inactivated Mannheimia haemolytica and Bovine herpes virus type 1 vaccine.

The objective of this study was to evaluate the passive transfer of maternal antibodies to calves following vaccination of pregnant cows with an inactivated Mannheimia haemolytica (MH) and Bovine herpes virus type 1 (IBR) vaccine (Bovilis® MH + IBR). Sixty-two pregnant cows were allocated at random to two groups; one group was retained as a negative control group (T01), while the other group (T02) was vaccinated with Bovilis® MH + IBR on two occasions during their third trimester of pregnancy. Following calving, blood samples were collected from calves for the measurement of serum antibody titres to IBR and MH, with samples collected prior to suckling (Day 0) and on days 5 (±2), 14 (±3), 28, 56, 84, 112, 140, 168, 196, 224, 252 and 280. The group mean IBR blocking percentage remained low for T01 calves (calves born to T01 cows) between days 0 and 224 (range 4.5%-15.4%), while the group mean IBR blocking percentage increased for T02 calves (calves born to T02 cows) from 14.3% on Day 0 to 94.9% on Day 5 and remained significantly higher than T01 calves up until Day 252. The group mean MH titre (Log2) for T01 calves increased after suckling to 8.9 on Day 5, before declining and remaining stable (range 5.0-6.5). The group mean MH titre for T02 calves increased after suckling to 13.6 on Day 5 and then gradually declined; however, it remained significantly higher than T01 calves between days 5 and 140. Outcomes from this study have confirmed that colostral transfer of IBR and MH antibodies to newborn calves was successful and a high level of passive immunity was acquired by calves.

Vancomycin-Resistant Enterococci in Patients Attending for Colonoscopy: An Estimate of Community Prevalence.

Aims Ireland has the highest vancomycin-resistant Enterococcus faecium (VRE) bloodstream infection prevalence in Europe. Two patterns of VRE carriage are recognised. European, with widespread community prevalence and North American, where carriage is predominantly nosocomial. It is unclear which pattern is dominant in Ireland. This uncertainty limits infection control measures. This study sought to explore this issue via a cross sectional point prevalence study. Methods Asymptomatic community volunteers, represented by patients undergoing elective outpatient colonoscopy testing, were opportunistically screened for VRE. Demographic and risk factor data were collected via a patient survey. Rectal swabs were collected before colonoscopy and VRE was identified using the VITEK MS system. Results 102 patients were cultured. A single patient tested positive, representing a prevalence rate of 0.98% (95% CI <0.01-5.8%). This patient demonstrated traditional risk factors, suggesting nosocomial rather than community acquisition. 94% (N=94) of patients had no knowledge of VRE, while 83% (N=83) had low levels of concern regarding hospital acquired infections. Conclusion There is a low incidence of VRE in the Irish community setting, in contrast to other European Countries, suggesting asymptomatic community colonization is not responsible for the high rates of VRE seen in Ireland. Wider screening or atypical infection control measures would not be supported by this data.

Lhermitte-Duclos disease (dysplastic cerebellar gangliocytoma) in the setting of cowden syndrome: a case report and literature review on COLD syndrome.

Lhermitte-Duclos Disease is a rare clinical entity involving a dysplastic lesion of the cerebellum. The dysplastic cerebellar ganglioblastoma is often seen in association with Cowden Syndrome, an autosomal dominant disorder consisting of a mutation in the phosphatase and homologous tensin (PTEN) gene. Characteristic findings on neuroimaging allow for a pre-operative diagnosis to be made, which guides further management of the condition. This report describes the diagnosis and management of Lhermitte-Duclos Disease in a 51-year-old lady, spanning a period of almost seven years. The characteristic radiological and histological findings are presented, along with the clinical features associated with Cowden Syndrome. This patient ultimately underwent surgical intervention for symptomatic relief, which is described here.

Management strategies for adult patients with dental anxiety in the dental clinic: a systematic review.

Anxiety is an adaptive emotional response to potentially threatening or dangerous situations; moderated by the sympathetic nervous system. Dental anxiety is common and presents before, during or after dental treatment. The physiological response includes an increase in heart rate, blood pressure, respiratory rate, and cardiac output. Consequently, extensive distress leads to avoidance of dental treatment and multiple failed appointments, impacting both oral and general health. Dental anxiety can generate a variety of negative consequences for both the dentist and the patient. Evidence-based strategies are essential for mitigating and relieving anxiety in the dental clinic. Psychotherapeutic behavioural strategies can modify the patient's experience through a minimally invasive approach with nil or negligible side effects, depending on patient characteristics, anxiety level and clinical situations. These therapies involve muscle relaxation, guided imagery, physiological monitoring, utilizing biofeedback, hypnosis, acupuncture, distraction and desensitization. Pharmacological intervention utilizes either relative analgesia (nitrous oxide), conscious intravenous sedation or oral sedation, which can have undesirable side effects, risks and contraindications. These modalities increase the cost and availability of dental treatment.

Antimicrobial use and antimicrobial resistance in Enterobacterales and Enterococcus faecium: a time series analysis.

BACKGROUND: Irish and European antimicrobial resistance (AMR) surveillance data have highlighted increasing AMR in Enterobacterales and vancomycin resistance in Enterococcus faecium (VRE). Antimicrobial consumption (AC) in Irish hospital settings is also increasing. METHODS: A retrospective time series analysis (TSA) was conducted to evaluate the trends and possible relationship between AC of selected antimicrobials and AMR in Enterobacterales and vancomycin resistance in E. faecium, from January 2017 to December 2020. RESULTS: Increased AC was seen with ceftriaxone (P = 0.0006), piperacillin/tazobactam (P = 0.03) and meropenem (P = 0.054), while ciprofloxacin and gentamicin use trended downwards. AMR rates in Escherichia coli, Klebsiella pneumoniae and other Enterobacterales were largely stable or decreasing, an increase in ertapenem resistance in the latter from 0.58% in 2017 to 5.19% in 2020 (P = 0.003) being the main concern. The proportion of E. faecium that was VRE did not changed significantly (64% in 2017; 53% in 2020, P = 0.1). TSA identified a correlation between piperacillin/tazobactam use and the decreasing rate of ceftriaxone resistance in E. coli. CONCLUSION: Our data suggest that the hospital antimicrobial stewardship programme is largely containing, but not reducing AMR in key nosocomial pathogens. An increase in AC following the COVID-19 pandemic appears as yet to have had no impact on AMR rates.

Gamma spectrometry analysis of radioiodine in charcoal from high volume aerosol samples.

Following accidental releases, gamma spectrometry of impregnated charcoal filters is used to measure gaseous 131I contamination, but is subject to sampling inhomogeneity. In this study two germanium detectors are calibrated using a charcoal multi-gamma standard. Activities in samples spiked with a matrix of 131I aliquots are compared based on measurement, spike known activity, and monte-carlo simulation, and used to test a simple mixing method. Measurement efficiency, and removal of 11% inhomogeneity effect by mixing, was successfully reproduced in GESPECOR calculations.

Safety of elective paediatric surgery during the coronavirus disease 2019 pandemic.

INTRODUCTION: Corona-virus Disease 2019 (COVID-19) has had a huge impact on the delivery of healthcare worldwide, particularly elective surgery. There is a lack of data regarding risk of postoperative COVID-19 infection in children undergoing elective surgery, and regarding the utility of pre-operative COVID-19 testing, and preoperative "cocooning" or restriction of movements. The purpose of this present study was to examine the safety of elective paediatric Otolaryngology surgery during the COVID-19 pandemic with respect to incidence of postoperative symptomatic COVID-19 infection or major respiratory complications. MATERIALS AND METHODS: Prospective cohort study of paediatric patients undergoing elective Otolaryngology surgery between September and December 2020. Primary outcome measure was incidence of symptomatic COVID-19 or major respiratory complications within the 14 days after surgery. Parents of prospectively enrolled patients were contacted 14 days after surgery and enquiry made regarding development of postoperative symptoms, COVID-19 testing, or diagnosis of COVID-19. RESULTS: 302 patients were recruited. 125 (41.4%) underwent preoperative COVID-19 RT-PCR testing. 66 (21.8%) restricted movements prior to surgery. The peak 14-day COVID-19 incidence during the study was 302.9 cases per 100,000 population. No COVID-19 infections or major respiratory complications were reported in the 14 day follow-up period. CONCLUSION: The results of our study support the safety of elective paediatric Otolaryngology surgery during the pandemic, in the setting of community incidence not exceeding that observed during the study period.

Surveying the Challenges to Improve Linear Accelerator-based Radiation Therapy in Africa: a Unique Collaborative Platform of All 28 African Countries Offering Such Treatment.

Radiation therapy is a critical component for curative and palliative treatment of cancer and is used in more than half of all patients with cancer. Yet there is a global shortage of access to this treatment, especially in Sub-Saharan Africa, where there is a shortage of technical staff as well as equipment. Linear accelerators (LINACs) offer state-of-the-art treatment, but this technology is expensive to acquire, operate and service, especially for low- and middle-income countries (LMICs), and often their harsh environment negatively affects the performance of LINACs, causing downtime. A global initiative was launched in 2016 to address the technology and system barriers to providing radiation therapy in LMICs through the development of a novel LINAC-based radiation therapy system designed for their challenging environments. As the LINAC prototype design phase progressed, it was recognised that additional information was needed from LMICs on the performance of LINAC components, on variables that may influence machine performance and their association, if any, with equipment downtime. Thus, a survey was developed to collect these data from all countries in Africa that have LINAC-based radiation therapy facilities. In order to understand the extent to which these performance factors are the same or different in high-income countries, facilities in Canada, Switzerland, the UK and the USA were invited to participate in the survey, as was Jordan, a middle-income country. Throughout this process, LMIC representatives have provided input on technology challenges in their respective countries. This report presents the method used to conduct this multilevel study of the macro- and microenvironments, the organisation of departments, the technology, the training and the service models that will provide input into the design of a LINAC prototype for a LINAC-based radiation therapy system that will improve access to radiation therapy and thus improve cancer treatment outcomes. It is important to note that new technology should be introduced in a contextual manner so as not to disrupt existing health systems inadvertently, especially with regards to existing staffing, infrastructure and socioeconomic issues. A detailed analysis of data is underway and will be presented in a follow-up report. Selected preliminary results of the study are the observation that LINAC-based facilities in LMICs experience downtime associated with failures in multileaf collimators and vacuum pumps, as well as power instability. Also, that there is a strong association of gross national product per capita with the number of LINACs per population.

Life cycle assessment of pasture-based suckler steer weanling-to-beef production systems: Effect of breed and slaughter age.

Demand for beef produced from pasture-based diets is rising as it is perceived to be healthier, animal friendly and good for the environment. Animals reared on a solely grass forage diet, however, have a lower growth rate than cereal-fed animals and consequently are slaughtered at an older age. This study focused on the former by conducting life cycle assessments of beef production systems offering only fresh or conserved grass, and comparing them to a conventional pasture-based beef production system offering concentrate feeding during housing. The four suckler weanling-to-beef production systems simulated were: (i) Steers produced to slaughter entirely on a grass forage diet at 20 months (GO-20); (ii) Steers produced to slaughter entirely on a grass forage diet at 24 months (GO-24); (iii) Steers produced to slaughter on a grass forage diet with concentrate supplementation during housing (GC-24), and (iv) Steers produced to slaughter entirely on a grass forage diet at 28 months (GO-28). Two breed types were evaluated: early-maturing and late-maturing (LM). The environmental impacts assessed were global warming potential (GWP), non-renewable energy (NRE), acidification potential (AP), eutrophication potential (marine (MEP) and freshwater) were expressed per animal, per kg live weight gain (LWG), kg carcass weight gain, and kg meat weight gain (MWG). The GO-20 production system had the lowest environmental impact across all categories and functional units for both breeds. Extending age at slaughter increased environmental impact across all categories per animal. The LWG response of EM steers to concentrate feed supplementation in GC-24 was greater than the increase in total environmental impact resulting in GC-24 having a lower environmental impact across categories per kg product than GO-24. Concentrate feed supplementation had a similar effect on LM steers with the exception of NRE and AP. The increase in daily LWG in the third grazing season in comparison to the second grazing and housing resulted in GO-28 having lower GWP, NRE, AP, and MEP per kg product than GO-24. Early-maturing steers had lower environmental impact than LM when expressed per kg LWG. However the opposite occurred when impacts were expressed per kg MWG, despite LM steers producing the least LWG. The LM steers compensated for poor LWG performance by having superior carcass traits, which caused the breed to have the lowest environmental impact per kg MWG. The results reaffirms the importance of functional unit and suggests reducing the environmental impact of LWG does not always translate into improvements in the environmental performance of meat.

Greenhouse gas emissions and nitrogen efficiency of dairy cows of divergent economic breeding index under seasonal pasture-based management.

Greenhouse gas (GHG) emissions and nitrogen (N) efficiencies were modeled for 2 genetic groups (GG) of Holstein-Friesian cows across 3 contrasting feeding treatments (FT). The 2 GG were (1) high economic breeding index (EBI) animals representative of the top 5% of cows nationally (elite) and (2) EBI representative of the national average (NA). The FT represented (1) generous feeding of pasture, (2) a slight restriction in pasture allowance, and (3) a high-concentrate feeding system with adequate pasture allowance. Greenhouse gas and N balance models were parameterized using outputs generated from the Moorepark Dairy Systems model, a stochastic budgetary simulation model, having integrated biological data pertaining to the 6 scenarios (2 GG × 3 FT) obtained from a 4-yr experiment conducted between 2013 and 2016. On a per hectare basis, total system GHG emissions were similar for both elite and NA across the 3 FT. Per unit of product, however, the elite group had 10% and 11% lower GHG emissions per kilogram of fat- and protein-corrected milk and per kilogram of milk solids (MSO; fat + protein kg), respectively, compared with the NA across the 3 FT. The FT incorporating high concentrate supplementation had greater absolute GHG emissions per hectare as well as GHG per kilogram of fat- and protein-corrected milk and MSO. The elite group had a slightly superior N use efficiency (N output/N input) and lower N surplus (N input - N output) compared with the NA group. The high concentrate FT had an inferior N use efficiency and a higher N surplus. The results of the current study demonstrate that breeding for increased EBI will lead to a general improvement in GHG emissions per unit of product as well as improved N efficiency. The results also illustrate that reducing concentrate supplementation will reduce GHG emissions, GHG emissions intensity, while improving N efficiency in the context of pasture-based dairy production.