Predictors of willingness to receive updated 2023-2024 COVID-19 booster vaccines among a convenience sample in Minnesota.

OBJECTIVES: To determine factors associated with intention to receive recommended COVID-19 booster vaccines in 2023-2024. METHODS: A cross-sectional study of 1,256 individuals at Minnesota State and County fairs was conducted to assess their intention to receive a COVID-19 booster vaccine in the coming year if recommended. The association between booster intention and multiple factors believed to influence willingness to receive the vaccine, including perceived vaccine safety, perceived risk of COVID-19, public health knowledge, fear of future pandemics, and political affiliation, were analyzed using ordinal logistic regression and adjusted odds ratios (aOR). RESULTS: Intention to receive a COVID-19 booster vaccine was high among our participants with 56% reporting they were extremely likely to receive the vaccine this year and another 15% reporting that they were likely to do the same. A strong association with getting a booster vaccine was found between perceived vaccine safety (aOR: 15.3, 95% CI: 10.6-22.2), perceived COVID-19 risk (aOR: 3.5, 95% CI: 2.4-5.1), pandemic fear (aOR: 3.4, 95% CI: 2.4-4.8), public health knowledge (aOR: 1.3, 95% CI: 0.9-1.8), and democrat political affiliation (aOR: 2.8, 95%CI: 1.8-4.4). CONCLUSIONS: Our study emphasizes the importance of perceived vaccine safety as a predictor of intention to accept COVID-19 vaccines and highlights the continued need to effectively communicate with the public about the safety of vaccines.

Open-label, phase II, multicenter study of lasofoxifene plus abemaciclib for treating women with metastatic ER+/HER2- breast cancer and an ESR1 mutation after disease progression on prior therapies: ELAINE 2.

BACKGROUND: Acquired ESR1 mutations in estrogen receptor-positive (ER+) metastatic breast cancer (mBC) drive treatment resistance and tumor progression; new treatment strategies are needed. Lasofoxifene, a next-generation, oral, endocrine therapy and tissue-specific ER antagonist, provided preclinical antitumor activity, alone or combined with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) in ESR1-mutated mBC. PATIENTS AND METHODS: In the open-label, phase II, ELAINE 2 trial (NCT04432454), women with ESR1-mutated, ER+/human epidermal growth factor receptor 2-negative (HER2-) mBC who progressed on prior therapies (including CDK4/6i) received lasofoxifene 5 mg/day and abemaciclib 150 mg b.i.d until disease progression/toxicity. The primary endpoint was safety/tolerability. Secondary endpoints included progression-free survival (PFS), clinical benefit rate (CBR), and objective response rate (ORR). RESULTS: Twenty-nine women (median age 60 years) participated; all but one were previously treated with a CDK4/6i (median duration 2 years). The lasofoxifene-abemaciclib combination was well tolerated with primarily grade 1/2 treatment-emergent adverse events (TEAEs), most commonly diarrhea, nausea, fatigue, and vomiting. One patient (with no prior CDK4/6i) discontinued treatment due to grade 2 diarrhea. No deaths occurred during the study. Median PFS was 56.0 weeks [95% confidence interval (CI) 31.9 weeks-not estimable; ∼13 months]; PFS rates at 6, 12, and 18 months were 76.1%, 56.1%, and 38.8%, respectively. CBR at 24 weeks was 65.5% (95% CI 47.3% to 80.1%). In 18 patients with measurable lesions, ORR was 55.6% (95% CI 33.7% to 75.4%). ESR1-mutant circulating tumor DNA (ctDNA) allele fraction decreased from baseline to week 4 in 21/26 (80.8%) patients. CONCLUSIONS: Lasofoxifene plus abemaciclib had an acceptable safety profile, was well tolerated, and exhibited meaningful antitumor activity in women with ESR1-mutated, ER+/HER2- mBC after disease progression on prior CDK4/6i. Observed decreases in ESR1-mutant ctDNA with lasofoxifene concordant with clinical response suggest target engagement. If the ELAINE 2 findings are confirmed in the initiated, phase III, ELAINE 3 trial, these data could be practice-changing and help address a critical unmet need.

Neurophotonic tools for microscopic measurements and manipulation: status report.

Neurophotonics was launched in 2014 coinciding with the launch of the BRAIN Initiative focused on development of technologies for advancement of neuroscience. For the last seven years, Neurophotonics' agenda has been well aligned with this focus on neurotechnologies featuring new optical methods and tools applicable to brain studies. While the BRAIN Initiative 2.0 is pivoting towards applications of these novel tools in the quest to understand the brain, this status report reviews an extensive and diverse toolkit of novel methods to explore brain function that have emerged from the BRAIN Initiative and related large-scale efforts for measurement and manipulation of brain structure and function. Here, we focus on neurophotonic tools mostly applicable to animal studies. A companion report, scheduled to appear later this year, will cover diffuse optical imaging methods applicable to noninvasive human studies. For each domain, we outline the current state-of-the-art of the respective technologies, identify the areas where innovation is needed, and provide an outlook for the future directions.

Pneumorrhachis following cervical spine surgery.

A 66-year-old man experienced symptomatic pneumorrhachis (air within the spinal canal) following a cervical laminoplasty for the excision of meningioma. Following an uneventful intraoperative course, he suffered a fluctuating hemiparesis of varying severity. Urgent imaging demonstrated extradural and intradural air in the spinal canal. Treatment with supplemental oxygen and dexamethasone was commenced, and the patient's symptoms improved over a period of three days with full resolution at six weeks. Pneumorrhachis can be avoided by allowing air to escape from the spinal canal through positioning, and displacement with irrigation fluid at the time of wound closure. However, if pneumorrhachis does occur, oxygen therapy, positioning of the patient to mitigate the gravitational effect of the air bubbles and supportive treatment are the central elements of management. Other possible causes of neurological deficit should be ruled out. This is particularly important as treatment options for some differential diagnoses can potentially cause harm if started based on clinical impression alone, for example, re-exploration for suspected haematoma. Only a small number of previous reports have described symptomatic pneumorrhachis as a complication of spinal surgery. This patient was successfully managed with conservative measures following the exclusion of other spinal cord pathologies.

Modelling dielectric elastomer circuit networks for soft biomimetics.

In order to obtain entirely soft bio-inspired robots, fully soft electronic circuits are needed. Dielectric elastomers (DEs) are electroactive polymers that have demonstrated multifunctionality. The same material can achieve different tasks like actuation, sensing, or energy harvesting. It has been shown that basic logic and memory functions can be realized with similar soft structures by combining multiple DE actuators and DE switches. Thus it would be possible to build, with the same materials and processes, a soft structure that mimics a biological being with all these capabilities. This contribution is focused on the modelling of the aforementioned soft electro-mechanical circuit networks. It is here reported the building process of a comprehensive SIMULINK model including the electro-mechanical behaviour of DE logic units and their interconnections. Conventional models deal with a single aspect of DEs, generating complex finite-element simulations. This contribution, based on a former model for an inverter-based DEO, shows how to integrate these various mathematical models and, with the help of direct measurements, create a software representation of DE circuit networks. This work is intended to demonstrate the validity of a recently introduced model and apply it to more complex circuit networks that have a higher number of components. Since, at the present state, the building processes are by hand, adding components generates more variability due to sample-to-sample variation and human error. Despite this, the model still shows a qualitatively good prediction of the devices' behaviour. Furthermore, the introduction of new materials and automatic processes will help to reduce this variability, allowing the model to reach even better performance.

Failure to rescue patients after emergency laparotomy for large bowel perforation: analysis of the National Emergency Laparotomy Audit (NELA).

BACKGROUND: Past studies have highlighted variation in in-hospital mortality rates among hospitals performing emergency laparotomy for large bowel perforation. The aim of this study was to investigate whether failure to rescue (FTR) contributes to this variability. METHODS: Patients aged 18 years or over requiring surgery for large bowel perforation between 2013 and 2016 were extracted from the National Emergency Laparotomy Audit (NELA) database. Information on complications were identified using linked Hospital Episode Statistics data and in-hospital deaths from the Office for National Statistics. The FTR rate was defined as the proportion of patients dying in hospital with a recorded complication, and was examined in hospitals grouped as having low, medium or high overall postoperative mortality. RESULTS: Overall, 6413 patients were included with 1029 (16.0 per cent) in-hospital deaths. Some 3533 patients (55.1 per cent) had at least one complication: 1023 surgical (16.0 per cent) and 3332 medical (52.0 per cent) complications. There were 22 in-hospital deaths following a surgical complication alone, 685 deaths following a medical complication alone, 150 deaths following both a surgical and medical complication, and 172 deaths with no recorded complication. The risk of in-hospital death was high among patients who suffered either type of complication (857 deaths in 3533 patients; FTR rate 24.3 per cent): 172 deaths followed a surgical complication (FTR-surgical rate 16.8 per cent) and 835 deaths followed a medical complication (FTR-medical rate of 25.1 per cent). After adjustment for patient characteristics and hospital factors, hospitals grouped as having low, medium or high overall postoperative mortality did not have different FTR rates (P = 0.770). CONCLUSION: Among patients having emergency laparotomy for large bowel perforation, efforts to reduce the risk of in-hospital death should focus on reducing avoidable complications. There was no evidence of variation in FTR rates across National Health Service hospitals in England.

Pharyngeal reconstruction with a modified free alt flap with parastomal fascial wings.

AIM: Previous reports have demonstrated good outcomes with the use of the Anterolateral Thigh Flap (ALT) in pharyngeal reconstruction. We report a new modification of free ALT flap pharyngeal reconstruction utilizing vascularised fascial wings or extensions placed in the parastomal gutters to cover the major neck vessels. PATIENTS AND METHODS: This was a single-center retrospective case review. Between November 2017 and January 2019, 8 patients (6 male, 2 female mean age 61, range 35 to 74) underwent near circumferential pharyngeal reconstruction by the modified technique. 3 patients had laryngopharyngectomy for radiorecurrent larynx SCC, 2 for primary, advanced laryngeal SCC, and 3 for primary hypopharyngeal SCC. RESULTS: All eight patients regained adequate swallow to maintain nutrition without tube-feeding. Two of the patients have been assessed as appropriate for tracheo-esophageal puncture and are awaiting placement. One patient uses an electrolarynx for speech and 5 patients aphonic only. One patient died 2 months after the procedure from chest infection. There were no flap failures, no fistulas and no strictures at one year. One patient who underwent a salvage laryngopharyngectomy experienced parastomal wound dehiscence, but critically there was no return to theater for exposed major vessels and the wound healed within 6 weeks requiring dressings only. CONCLUSION: Here we report outcomes of pharyngeal reconstruction with a modified single perforator free ALT flap using fascial extensions to line the parastomal gutters. In the event of parastomal dehiscence, the placement of vascularized tissue parastomally may facilitate spontaneous healing and prevent major vessel exposure.

Modelling of the electrocardiographic signal during an angioplasty procedure in the right coronary artery.

Dynamical models are useful tools to generate sets of varied morphological signals by synthesizing human electrocardiograms (ECGs). These signals are used for testing and improving algorithms of ECG delineation, patient monitoring and heart disease detection. This work presents a procedure based on the ECGSYN model to synthesize ECG morphological changes induced by a percutaneous transluminal coronary angioplasty (PTCA) procedure in the right coronary artery. We provide a set of parameters to be used in ECGSYN and generate heartbeats with altered ST-T complexes. These characteristic model parameters were obtained through a non-linear fitting algorithm applied to every available heartbeat. To extend these parameters, normal distributions were generated with their means and standard deviations obtained from the STAFF III database. Parameters were presented for P, QRS and T-waves at leads II, III and aVF. The synthesis procedure shows an average correlation and positive predictive value of 92.2% and 88.2%, respectively. In conclusion, we provide a technique capable of synthesizing electrocardiographic ischemic morphology with physiological plausibility. Then, the generation of data sets for algorithm testing can benefit from this system of ECG signal synthesis.

Recurrent intestinal fistulation after porcine acellular dermal matrix reinforcement in enteric fistula takedown and simultaneous abdominal wall reconstruction.

PURPOSE: Porcine acellular dermal matrix (PADM) has been promoted as a suitable material for the reinforcement of the abdominal wall in Ventral Hernia Working Group (VHWG) Grade 3/4 wounds by Ventral Hernia Working Group et al. (Surgery 148(3):544-548). We describe our experience of, and assess the mechanisms for the failure of PADM (PermacolTM) in intestinal and abdominal wall reconstruction (AWR) for enterocutaneous fistulation (ECF). METHODS: All patients referred to our unit who had PADM used for AWR and ECF were studied from a prospectively maintained database. Follow-up data until 31/12/2018 were analysed. PADM was explanted at further surgery and examined histologically. RESULTS: 13 patients, (median age-58.5 years) underwent AWR with PADM reinforcement. Twelve of these (92%) patients had developed abdominal wall defects (AWD) and ECF following complications of previous surgery. Six patients underwent fistula takedown and AWR with PADM, of which 5(83%) refistulated. Seven patients referred to us had already undergone similar procedures in their referring hospitals and had also refistulated. Median (range) time to fistulation after AWR with PADM was 17 (7-240) days. In all cases, PADM had been used to bridge the defect and placed in direct contact with bowel. At reconstructive surgery for refistulation, PADM was inseparable from multiple segments of small intestine, necessitating extensive bowel resection. Histological examination confirmed that the PADM almost completely integrated with the seromuscular layer of the small intestine. CONCLUSION: PADM may become inseparable from serosa of the human small intestinal serosa when it is left in the abdomen during reconstructive surgery. This technique is associated with recurrent intestinal fistulation and intestinal failure and should be avoided if at all possible.

Delay in Source Control in Perforated Peptic Ulcer Leads to 6% Increased Risk of Death Per Hour: A Nationwide Cohort Study.

BACKGROUND: Delay to theatre for patients with intra-abdominal sepsis is cited as a particular risk factor for death. Our aim was to evaluate the potential relationship between hourly delay from admission to surgery and post-operative mortality in patients with perforated peptic ulcer (PPU). METHODS: All patients entered in the National Emergency Laparotomy Audit who had an emergency laparotomy for PPU within 24 h of admission from December 2013 to November 2017 were included. Time to theatre from admission was modelled as a continuous variable in hours. Outcome was 90-day mortality. Logistic regression adjusting for confounding factors was performed. RESULTS: 3809 patients were included, and 90-day mortality rate was 10.61%. Median time to theatre was 7.5 h (IQR 5-11.6 h). The odds of death increased with time to operation once adjustment for confounding variables was performed (per hour after admission adjusted OR 1.04 95% CI 1.02-1.07). In patients who were physiologically shocked (N = 334), there was an increase of 6% in risk-adjusted odds of mortality for every hour Em Lap was delayed after admission (OR 1.06 95% CI 1.01-1.11). CONCLUSION: Hourly delay to theatre in patients with PPU is independently associated with risk of death by 90 days. Therefore, we suggest that surgical source control should occur as soon as possible after admission regardless of time of day.

National prospective cohort study of the burden of acute small bowel obstruction.

Background: Small bowel obstruction is a common surgical emergency, and is associated with high levels of morbidity and mortality across the world. The literature provides little information on the conservatively managed group. The aim of this study was to describe the burden of small bowel obstruction in the UK. Methods: This prospective cohort study was conducted in 131 acute hospitals in the UK between January and April 2017, delivered by trainee research collaboratives. Adult patients with a diagnosis of mechanical small bowel obstruction were included. The primary outcome was in-hospital mortality. Secondary outcomes included complications, unplanned intensive care admission and readmission within 30 days of discharge. Practice measures, including use of radiological investigations, water soluble contrast, operative and nutritional interventions, were collected. Results: Of 2341 patients identified, 693 (29·6 per cent) underwent immediate surgery (within 24 h of admission), 500 (21·4 per cent) had delayed surgery after initial conservative management, and 1148 (49·0 per cent) were managed non-operatively. The mortality rate was 6·6 per cent (6·4 per cent for non-operative management, 6·8 per cent for immediate surgery, 6·8 per cent for delayed surgery; P = 0·911). The major complication rate was 14·4 per cent overall, affecting 19·0 per cent in the immediate surgery, 23·6 per cent in the delayed surgery and 7·7 per cent in the non-operative management groups (P < 0·001). Cox regression found hernia or malignant aetiology and malnutrition to be associated with higher rates of death. Malignant aetiology, operative intervention, acute kidney injury and malnutrition were associated with increased risk of major complication. Conclusion: Small bowel obstruction represents a significant healthcare burden. Patient-level factors such as timing of surgery, acute kidney injury and nutritional status are factors that might be modified to improve outcomes.

The ability of a host plant to associate with different symbiotic partners affects ectomycorrhizal functioning.

Some plants that associate with ectomycorrhizal (ECM) fungi are also able to simultaneously establish symbiosis with other types of partners. The presence of alternative partners that may provide similar benefits may affect ECM functioning. Here we compared potential leucine-aminopeptidase (LA) and acid phosphatase (AP) enzyme activity (involved in N and P cycling, respectively) in ECM fungi of three hosts planted under the same conditions but differing in the type of partners: Pinus (ECM fungi only), Eucalyptus (ECM and arbuscular mycorrhizal -AM- fungi) and Acacia (ECM, AM fungi and rhizobial bacteria). We found that the ECM community on Acacia and Eucalyptus had higher potential AP activity than the Pinus community. The ECM community in Acacia also showed increased potential LA activity compared to Pinus. Morphotypes present in more than one host showed higher potential AP and LA activity when colonizing Acacia than when colonizing another host. Our results suggest that competition with AM fungi and rhizobial bacteria could promote increased ECM activity in Eucalyptus and Acacia. Alternatively, other host-related differences such as ECM community composition could also play a role. We found evidence for ECM physiological plasticity when colonizing different hosts, which might be key for adaptation to future climate scenarios.

Association between surgeon special interest and mortality after emergency laparotomy.

BACKGROUND: Approximately 30 000 emergency laparotomies are performed each year in England and Wales. Patients with pathology of the gastrointestinal tract requiring emergency laparotomy are managed by general surgeons with an elective special interest focused on either the upper or lower gastrointestinal tract. This study investigated the impact of special interest on mortality after emergency laparotomy. METHODS: Adult patients having emergency laparotomy with either colorectal or gastroduodenal pathology were identified from the National Emergency Laparotomy Audit database and grouped according to operative procedure. Outcomes included all-cause 30-day mortality, length of hospital stay and return to theatre. Logistic and Poisson regression were used to analyse the association between consultant special interest and the three outcomes. RESULTS: A total of 33 819 patients (28 546 colorectal, 5273 upper gastrointestinal (UGI)) were included. Patients who had colorectal procedures performed by a consultant without a special interest in colorectal surgery had an increased adjusted 30-day mortality risk (odds ratio (OR) 1·23, 95 per cent c.i. 1·13 to 1·33). Return to theatre also increased in this group (OR 1·13, 1·05 to 1·20). UGI procedures performed by non-UGI special interest surgeons carried an increased adjusted risk of 30-day mortality (OR 1·24, 1·02 to 1·53). The risk of return to theatre was not increased (OR 0·89, 0·70 to 1·12). CONCLUSION: Emergency laparotomy performed by a surgeon whose special interest is not in the area of the pathology carries an increased risk of death at 30 days. This finding potentially has significant implications for emergency service configuration, training and workforce provision, and should stimulate discussion among all stakeholders.

Status of the northern muriqui (Brachyteles hypoxanthus) in the time of yellow fever.

Understanding the impact of zoonotic diseases on wild primate populations is important for assessing local extinction risks and for evaluating potential mitigating factors. Comparative data on demographic changes in two isolated populations of the northern muriqui (Brachyteles hypoxanthus) during a severe yellow fever outbreak in southeastern Brazil provide unique insights into the potential effects of this disease in this Critically Endangered species. From October 2016 to April 2017, the muriqui population at the Reserva Particular do Patrimônio Natural-Feliciano Miguel Abdala (Caratinga) lost 31 of its 324 members, or nearly 10%, whereas the population at the Reserva Particular do Patrimônio Natural-Mata do Sossego (Sossego) declined from 34 to 25 individuals, or 26%. Greater per-capita risks to muriquis in the Sossego population could be related to ecological and anthropogenic differences, including a wetter climate and an absence of sympatric howler monkeys (Alouatta guariba), which may have directly or indirectly buffered the Caratinga muriquis. Although we lack definitive confirmation that the muriqui population declines were caused by yellow fever, the timing and magnitude of the losses strongly implicate the disease. We highlight the risks of catastrophic population declines in small populations and emphasize the value of long-term demographic monitoring studies.

Organisational factors and mortality after an emergency laparotomy: multilevel analysis of 39 903 National Emergency Laparotomy Audit patients.

BACKGROUND: Studies across healthcare systems have demonstrated between-hospital variation in survival after an emergency laparotomy. We postulate that this variation can be explained by differences in perioperative process delivery, underpinning organisational structures, and associated hospital characteristics. METHODS: We performed this nationwide, registry-based, prospective cohort study using data from the National Emergency Laparotomy Audit organisational and patient audit data sets. Outcome measures were all-cause 30- and 90-day postoperative mortality. We estimated adjusted odds ratios (ORs) for perioperative processes and organisational structures and characteristics by fitting multilevel logistic regression models. RESULTS: The cohort comprised 39 903 patients undergoing surgery at 185 hospitals. Controlling for case mix and clustering, a substantial proportion of between-hospital mortality variation was explained by differences in processes, infrastructure, and hospital characteristics. Perioperative care pathways [OR: 0.86; 95% confidence interval (CI): 0.76-0.96; and OR: 0.89; 95% CI: 0.81-0.99] and emergency surgical units (OR: 0.89; 95% CI: 0.80-0.99; and OR: 0.89; 95% CI: 0.81-0.98) were associated with reduced 30- and 90-day mortality, respectively. In contrast, infrequent consultant-delivered intraoperative care was associated with increased 30- and 90-day mortality (OR: 1.61; 95% CI: 1.01-2.56; and OR: 1.61; 95% CI: 1.08-2.39, respectively). Postoperative geriatric medicine review was associated with substantially lower mortality in older (≥70 yr) patients (OR: 0.35; 95% CI: 0.29-0.42; and OR: 0.64; 95% CI: 0.55-0.73, respectively). CONCLUSIONS: This multicentre study identified low-technology, readily implementable structures and processes that are associated with improved survival after an emergency laparotomy. Key components of pathways, perioperative medicine input, and specialist units require further investigation.

Development and internal validation of a novel risk adjustment model for adult patients undergoing emergency laparotomy surgery: the National Emergency Laparotomy Audit risk model.

BACKGROUND: Among patients undergoing emergency laparotomy, 30-day postoperative mortality is around 10-15%. The risk of death among these patients, however, varies greatly because of their clinical characteristics. We developed a risk prediction model for 30-day postoperative mortality to enable better comparison of outcomes between hospitals. METHODS: We analysed data from the National Emergency Laparotomy Audit (NELA) on patients having an emergency laparotomy between December 2013 and November 2015. A prediction model was developed using multivariable logistic regression, with potential risk factors identified from existing prediction models, national guidelines, and clinical experts. Continuous risk factors were transformed if necessary to reflect their non-linear relationship with 30-day mortality. The performance of the model was assessed in terms of its calibration and discrimination. Interval validation was conducted using bootstrap resampling. RESULTS: There were 4458 (11.5%) deaths within 30-days among the 38 830 patients undergoing emergency laparotomy. Variables associated with death included (among others): age, blood pressure, heart rate, physiological variables, malignancy, and ASA physical status classification. The predicted risk of death among patients ranged from 1% to 50%. The model demonstrated excellent calibration and discrimination, with a C-statistic of 0.863 (95% confidence interval, 0.858-0.867). The model retained its high discrimination during internal validation, with a bootstrap derived C-statistic of 0.861. CONCLUSIONS: The NELA risk prediction model for emergency laparotomies discriminates well between low- and high-risk patients and is suitable for producing risk-adjusted provider mortality statistics.

Two step reconstruction of traumatic ear skin avulsion using Integra graft.

Treatment of traumatic ear injuries have always been a challenge. Preservation of the auricular cartilage is key for reconstruction. Many techniques have been reported for the management of exposed ear perichondrium. We present patient who sustained right ear soft tissue avulsion. Initial examination the patient revealed skin avulsion with exposed cartilage from the concha, scapha and antihelix on the right ear. The treatment sequence included debridement and application of Integra graft. This was followed by dressing changes every three days and three weeks. Once adequate vascularization was noted a split thickness skin graft was used for final reconstruction. Integra has been widely used for the management of burns as well as exposed bone and cartilage. However, its use in traumatic ear injuries has not been reported. This technique allowed for the reconstruction of a large skin avulsion from the right ear with minimal donor site morbidity and avoidance of local rotational flaps that could hinder later reconstructions if needed.