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Intestinal failure (IF) is a rare disease that requires ongoing intravenous supplementation to sustain growth and health. Advancements in parenteral nutrition (PN) and central venous access in the 1960s and 1970s transformed a life-limiting disease to a chronic one in which patients are able to administer hydration, electrolytes, micronutrients, and macronutrients in the comfort of their home. However, despite ongoing advancements in the field of home PN (HPN), complications-whether related to central venous catheters or PN itself-remain common and can be associated with significant morbidity and mortality. Central venous access can be associated with thrombosis, central line-associated bloodstream infection, or damage and can result in loss of access over time. PN can be associated with IF-associated liver disease or hyperglycemia. The key to preserving central venous access and quality of life and maintaining health for patients with chronic IF (CIF) is education focused on prevention and prompt management of CIF complications as they arise. This education typically takes place at the time of initiation of HPN, either in the hospital setting or in the patient's home. The present manuscript describes the historical progression of HPN, prevalence and characteristics of CIF, and an in-depth discussion of the most common catheter-related and PN-related complications and their management, along with a discussion of our education and training process.

Coronavirus disease 2019 (COVID-19), after initially being detected in Wuhan, China in late 2019, quickly spread to most regions of the world, meeting World Health Organization criteria for a pandemic. Social distancing along with other measures implemented to control spread had a drastic impact on the provision of healthcare including deferred elective procedures and surgeries as well as delayed care and evaluation for emergent diagnoses such as heart attacks and strokes. In the home nutrition practice, patients began to delay routine laboratory tests and were canceling or deferring annual visits. Our group soon began to rapidly deploy telehealth to meet the needs of the home nutrition patients. Telehealth is not a new concept with descriptions of healthcare being provided at a distance with the use of telephone in the 1870s. However, widespread adoption has been limited because of regulation (licensure, prescriptions, credentialing, and privileges), lack of reimbursement, as well as adoption and availability of technology needed to carry out telehealth visits. As regulations and limits on reimbursements were waived during COVID-19 pandemic, our home nutrition practice began to evaluate core components of the care we provide for our patients and assess which could be successfully transitioned to telehealth. In addition to the history and regulation of telehealth, the current manuscript provides details regarding successful implementation of telehealth visits such as change management, selection of telehealth platform, scheduling and logistics, as well as carrying out the virtual visit including history and physical exam.

Objectives Musculoskeletal disorders often lead to chronic pain in Veterans. Chronic pain puts sufferers at risk for substance misuse, and early intervention is needed for both conditions. This pilot study tested the feasibility and acceptability of a Screening, Brief Intervention, and Referral to Treatment for Pain Management intervention (SBIRT-PM) to help engage Veterans seeking disability compensation for painful musculoskeletal disorders in multimodal pain treatment and to reduce risky substance use, when indicated. Methods This pilot study enrolled 40 Veterans from 8 medical centers across New England in up to 4 sessions of telephone-based counseling using a motivational interviewing framework. Counseling provided education about, and facilitated engagement in, multimodal pain treatments. Study eligibility required Veterans be engaged in no more than 2 Veteran Affairs (VA) pain treatment modalities, and study participation involved a 12-week postassessment and semistructured interview about the counseling process. Results Majorities of enrolled Veterans screened positive for comorbid depression and problematic substance use. Regarding the offered counseling, 80% of participants engaged in at least one session, with a mean of 3 sessions completed. Ninety percent of participants completed the postassessment. Numerically, most measures improved slightly from baseline to week 12. In semistructured interviews, participants described satisfaction with learning about new pain care services, obtaining assistance connecting to services, and receiving support from their counselors. Discussion It was feasible to deliver SBIRT-PM to Veterans across New England to promote engagement in multimodal pain treatment and to track study outcomes over 12 weeks. Preliminary results suggest SBIRT-PM was well-received and has promise for the targeted outcomes.

The role of β-catenin/TCF transcriptional activity in endometrial cancer (EC) recurrence is not well understood. We assessed the impact of Wnt/β-catenin inhibition in EC models. In an analysis of the Cancer Genome Atlas, we confirmed that CTNNB1 mutations are enriched in recurrent low-risk EC and showed that aberrant Wnt/β-catenin pathway activation is associated with recurrence. We studied CTNNB1-wildtype (HEC1B, Ishikawa) and CTNNB1-mutant (HEC108, HEC265, HEC1B-S33Y, Ishikawa-S33Y) EC cell lines. Dose response curves were determined for 5 Wnt/β-catenin pathway inhibitors (Wnt-C59, XAV-939, PyrPam, PRI-724, SM04690). XAV939, Wnt-C59 and PyrPam inhibited function upstream of β-catenin transcriptional activity and were ineffective at inhibiting cell viability. In contrast, PRI724 and SM04690 indirectly inhibited β-catenin transcriptional activity and significantly reduced cell viability in CTNNB1-mutant cell lines. Treatment with SM04690 reduced cell viability (Licor Cell stain) in all EC cell lines, but viability was significantly lower in CTNNB1-mutant cell lines (p < 0.01). Mechanistically, SM04690 significantly inhibited proliferation measured via 5'-bromo-2'-deoxyuridine incorporation and reduced T cell factor (TCF) transcriptional activity. HEC1B, HEC1B-S33Y and HEC265 tumor-bearing mice were treated with vehicle or SM04690. Tumors treated with SM04690 had smaller mean volumes than those treated with vehicle (p < 0.001, p = 0.014, p = 0.06). In HEC1B-S33Y and HEC265 tumors, SM04690 treatment significantly reduced Ki67 H-scores compared to vehicle (p = 0.035, p = 0.024). Targeting the Wnt/β-catenin pathway in CTNNB1-mutant EC effectively inhibited proliferation and β-catenin/TCF transcriptional activity and blunted tumor progression in in vivo models. These studies suggest β-catenin transcriptional inhibitors are effective in EC and particularly in CTNNB1-mutant EC, highlighting a potential therapeutic vulnerability for treatment of CTNNB1-mutant EC.

Background Urgent assessment of haematuria is critical to exclude malignancy. The utilization of haematuria clinics in Australia remains in its infancy. It is hoped that the streamlined investigative service will achieve earlier diagnosis of urological malignancy and subsequently decrease morbidity and mortality. We report the 10-year prospectively collected outcomes from Australia's first dedicated one-stop haematuria clinic (OSHC). Methods Since its commencement in May 2008 through to July 2018, all consecutive patients assessed in the OSHC were included in the analysis. Data collected included demographics, presentation, wait times, investigation, assessment, initial treatment, referral and histopathology. Results A total of 3008 patients were seen in the OSHC with non-visible haematuria (1024, 34%) and visible haematuria (1984, 66%). Three hundred and twenty-seven (10.9%) patients were diagnosed with urothelial malignancy. In all, 306 (10.2%) patients had lower tract disease and 21 (0.7%) had upper tract disease. Urothelial cases were compiled of 123 (37.6%) Ta LG, 39 (11.9%) Ta HG, 21 (6.4%) Tis, 67 (20.5%) T1 and 77 (23.6%) T2-4. Urothelial malignancy was diagnosed more often in males (odds ratio (OR) 1.74, 95% confidence interval (CI) 1.35-2.25), older patients elder than 60 years (OR 1.97, 95% CI 1.47-2.64) and patients with visible haematuria (OR 5.42, 95% CI 3.73-7.86). In all, 53.4% of patients were discharged after a single visit to the OSHC. Conclusion The OSHC has served as an effective tool for rapid, streamlined assessment of patients presenting with haematuria. This model of care has been subsequently adopted by numerous public centres across Australia. Current funding structures present a barrier to this excellent approach for rapid access diagnostics.

Objective Real‐time quaking‐induced conversion (RT‐QuIC) assays detect prion‐seeding activity in a variety of human biospecimens, including cerebrospinal fluid and olfactory mucosa swabs. The assay has shown high diagnostic accuracy in patients with prion disorders. Recently, advances in these tests have led to markedly improved diagnostic sensitivity and reduced assay times. Accordingly, an algorithm has been proposed that entails the use of RT‐QuIC analysis of both sample types to diagnose sporadic Creutzfeldt‐Jakob disease with nearly 100% accuracy. Here we present a multi‐center evaluation (ring trial) of the reproducibility of these improved “second generation” RT‐QuIC assays as applied to these diagnostic specimens. Methods Cerebrospinal fluid samples were analyzed from subjects with sporadic Creutzfeldt‐Jakob (n = 55) or other neurological diseases (n = 45) at multiple clinical centers. Olfactory mucosa brushings collected by multiple otolaryngologists were obtained from nine sporadic Creutzfeldt‐Jakob disease cases and 19 controls. These sample sets were initially tested blindly by RT‐QuIC by a coordinating laboratory, recoded, and then sent to five additional testing laboratories for blinded ring trial testing. Results Unblinding of the results by a third party indicated 98‐100% concordance between the results obtained by the testing of these cerebrospinal fluid and nasal brushings at the six laboratories. Interpretation This second‐generation RT‐QuIC assay is highly transferrable, reproducible, and therefore robust for the diagnosis of sporadic Creutzfeldt‐Jakob disease in clinical practice.

Objective The detection of prion seeding activity in CSF and olfactory mucosal brushings using real‐time quaking‐induced conversion assays allows highly accurate clinical diagnosis of sporadic Creutzfeldt–Jakob disease. To gauge transmission risks associated with these biospecimens and their testing, we have bioassayed prion infectivity levels in patients’ brain tissue, nasal brushings, and CSF, and assessed the pathogenicity of amplified products of real‐time quaking‐induced conversion assays seeded with Creutzfeldt–Jakob disease prions. Methods We obtained olfactory mucosal brushings and CSF from patients with a final diagnosis of sporadic Creutzfeldt–Jakob disease subtype MM1 (n = 3). Samples were inoculated intracerebrally into Tg66 transgenic mice that overexpress the homologous human 129M prion protein. The mice were evaluated for clinical, neuropathological, and biochemical evidence of prion infection. Results Patients’ brain tissue at 102 to 105 fold dilutions affected 47/48 Tg66 mice. In contrast, maximum acutely tolerable doses of insoluble pellets from their olfactory mucosa brushings caused evidence of prion disease in only 4/28 inoculated mice, and no effects were seen with 10‐fold dilutions. No clinical prion disease was observed in mice inoculated with antemortem CSF samples or prion‐seeded real‐time quaking‐induced conversion assay products. Interpretation Pellets from patients’ olfactory mucosa brushings had ≥10,000‐fold lower infectivity per unit volume than brain tissue, while CSF lacked detectable infectivity. Nonetheless, the results suggest that appropriate precautions may be warranted in surgical interventions involving the olfactory areas. The lack of pathogenic infectivity in the real‐time quaking‐induced conversion assay products provides evidence that the assay does not replicate biohazardous prions in vitro.

We first theoretically identify the factors that may impact individuals’ routing decisions before empirically examining a large operational dataset in a casual restaurant setting. Analytical models have identified various routing algorithms for service operations management. Although each model may offer advantages over others, they all make a key assumption ‐ decision makers will actually follow the algorithms, if implemented. However, in many settings routing is not done by a computer that is programmed, but instead by a human. People make routing decisions at their own discretion which may hurt or help system performance. We analyze granular transaction data to examine how hosts revise a given routing rule when seating customers. Thereafter, we empirically analyze the effect of the dispersion of table assignments on restaurant performance, and estimate the counterfactual sales impact of adopting an alternative routing priority. Our setting instructs its hosts to follow a round‐robin rule to assign tasks because it ensures fairness and smooths work flow. We find that hosts assign more incoming parties than the round‐robin rule suggests to those waiters who have low contemporaneous workload or high speed skills. The prioritization of high speed skill waiters increases with higher levels of demand. In addition, we show an inverted‐U‐shaped relationship between the inequality of table assignments (measured in terms of the Gini Coefficient of the numbers of tables assigned to each waiter during the same hour) and total sales. Our results suggest that properly adjusting the round‐robin rule is productive; however, too much deviation lowers performance. Our paper empirically highlights the value of routing decisions and front‐line personnel, such as the hosts in our context.

Purpose: The purpose of this study is to improve upon a recently introduced bi-objective treatment planning method for prostate high-dose-rate (HDR) brachytherapy (BT), both in terms of resulting plan quality and runtime requirements, to the extent that its execution time is clinically acceptable. Methods: Bi-objective treatment planning is done using a state-of-the-art multiobjective evolutionary algorithm, which produces a large number of potential treatment plans with different trade-offs between coverage of the target volumes and sparing organs at risk. A graphics processing unit (GPU) is used for large-scale parallelization of dose calculations and the calculation of the dose-volume (DV) indices of potential treatment plans. Moreover, the objectives of the previously used bi-objective optimization model are modified to produce better results. Results: We applied the GPU-accelerated bi-objective treatment planning method to a set of 18 patients, resulting in a set containing a few hundred potential treatment plans with different trade-offs for each of these patients. Due to accelerations introduced in this article, results previously achieved after 1 hour are now achieved within 30 seconds of optimization. We found plans satisfying the clinical protocol for 15 of 18 patients, whereas this was the case for only 4 of 18 clinical plans. Higher quality treatment plans are obtained when the accuracy of DV index calculation is increased using more dose calculation points, requiring still no more than 3 minutes of optimization for 100 000 points. Conclusions: Large sets of high-quality treatment plans that trade-off coverage and sparing are now achievable within 30 seconds, due to the GPU-acceleration of a previously introduced bi-objective treatment planning method for prostate HDR brachytherapy. Higher quality plans can be achieved when optimizing for 3 minutes, which we still consider to be clinically acceptable. This allows for more insightful treatment plan selection in a clinical setting.

Background Patients with chronic intestinal failure who require long-term parenteral nutrition rely on central venous catheters (CVCs) for access to nutrition and hydration. With prolonged use, complications such as central line-associated bloodstream infection (CLABSI), damage to CVC, and central venous thrombosis (CVT) can threaten the availability of life-preserving access. Because of this, all efforts should be made to preserve CVCs with techniques such as catheter salvage in case of CLABSI and catheter repair when damaged. The present study was conducted to evaluate the effectiveness and safety of catheter repair in our patient population. Methods Retrospective review in 1253 adult patients who received home parenteral nutrition at the Mayo Clinic between September 1, 1997, and April 30, 2018, was conducted to determine the incidence of CLABSI and CVT in patients who underwent CVC repair. Results Fifty-five CVC repairs were performed in 36 patients (n = 23 female) with mean age of 57.05 ± 16.96 years. A total of 14 catheters (25.45%) were complicated with 24 episodes of CLABSI. CLABSI rate before and after repair was 0.23/1000 catheter days and 0.21/1000 catheter days, respectively. Most common indications for eventual catheter replacement were mechanical damage (32%), infection (32%), and switching to alternate mode of nutrition (24%). We had a 100% success rate of catheter repair procedure, and no post-procedural complications were present. Conclusion Catheter repair can increase the catheter survival without increasing the risk of CLABSI, providing not only socioeconomic benefit but also decreasing risk of compromising future vascular access.

Cophylogeny is the congruence of phylogenetic relationships between two different groups of organisms due to their long‐term interaction. We investigated the use of tree shape distance measures to quantify the degree of cophylogeny. We implemented a reverse‐time simulation model of pathogen phylogenies within a fixed host tree, given cospeciation probability, host switching, and pathogen speciation rates. We used this model to evaluate 18 distance measures between host and pathogen trees including two kernel distances that we developed for labeled and unlabeled trees, which use branch lengths and accommodate different size trees. Finally, we used these measures to revisit published cophylogenetic studies, where authors described the observed associations as representing a high or low degree of cophylogeny. Our simulations demonstrated that some measures are more informative than others with respect to specific coevolution parameters especially when these did not assume extreme values. For real datasets, trees’ associations projection revealed clustering of high concordance studies suggesting that investigators are describing it in a consistent way. Our results support the hypothesis that measures can be useful for quantifying cophylogeny. This motivates their usage in the field of coevolution and supports the development of simulation‐based methods, i.e., approximate Bayesian computation, to estimate the underlying coevolutionary parameters.

Biological evidence analysis from contact traces is adversely affected by low quantity and quality of DNA. Proteins in these samples contain potentially individualizing information and may be particularly important for difficult surfaces such as brass, where DNA may yield incomplete profiles. In this study, touched unfired brass cartridges were sampled using dry tape or wet swabs and analyzed by separating DNA and protein from the same collected material, thus producing both genomic and proteomic information. DNA recovery was similar for both collection methods, with tape yielding an average of 1.36 ± 1.87 ng and swabs, 1.34 ± 3.04 ng. Analysis by mass spectrometry identified 95 proteins, with the two collection methods showing no significant difference (p = 0.76) in the average number of collected proteins: 44.5 ± 10.9, (tape) versus 47.9 ± 20.4 (swabs). Proteins can be collected from fingerprints at levels necessary to provide identifying information, thus expanding information obtained from challenging evidence.

Although home parenteral nutrition (HPN) is lifesaving for patients with chronic intestinal failure (IF), long-term use can be associated with complications such as infections, metabolic abnormalities, and IF-associated liver disease (IFALD). The key to treatment of many of these complications is prevention. Guidelines recommend avoidance of overfeeding, use of oral/enteral nutrition if possible, cyclic PN, and maintaining dose of soybean oil (SO) intravenous lipid emulsion (ILE)1 g/kg/day as preventive strategies for IFALD. Additionally, with development of IFALD, ω-6/ω-3 polyunsaturated fatty acid ratio should be decreased in ILE. The newly available mixed-oil (MO) ILE offers such an opportunity; however, there is a paucity of long-term data available.The current study reports our long-term experience with MO ILE use in HPN patients.Seventeen patients (8 female and 9 male) with an average age of 47 ± 12 years and median HPN duration of 4.6 years (1.1-32.1 years) have utilized MO ILE for12 months after being transitioned from SO ILE because of intolerance. Use of MO ILE allowed an increase in ILE energy from 8% ± 8% to 22% ± 8% while reducing dextrose energy from 66% ± 8% to 54% ± 5%, maintaining stability in alkaline phosphatase and triglyceride levels, and achieving improvement in aspartate aminotransferase, alanine aminotransferase, total bilirubin, and α-tocopherol levels.In this HPN cohort with SO ILE intolerance, MO ILE was well tolerated and allowed an improvement in macronutrient composition while improving some liver parameters over a 12-month period.

PURPOSE The increased prevalence of home enteral nutrition (HEN), reemergence of blenderized tube feeding (BTF), and conversion of enteral connectors to the ISO 80369-3 standard are creating a significant need to better understand the practices of the HEN population. A cross-sectional survey of current HEN consumers was conducted to evaluate the demographics of HEN consumers, including formulas and feeding tubes being used. METHODS In order to disseminate the survey to a wide range of HEN consumers, we partnered with private infusion companies (Coram and Pediatric Home Services) along with the Oley and Tube Feeding Awareness Foundations. A validated survey focusing on patient demographics, tube types, formula used, and tube clogging complications was placed online from September 1, 2016, to October 15, 2016. RESULTS During the study period, 1519 surveys were completed, with 1062 respondents in the pediatric group (

To quantify how frequently intraoperative parathyroid hormone levels increase during thyroid surgery and to explore a possible relationship between secondary hyperparathyroidism due to vitamin D deficiency and elevation in intraoperative parathyroid hormone.Case series with chart review.Tertiary academic center.A total of 428 consecutive patients undergoing completion and total thyroidectomy by the senior author over a 7-year period were included for analysis. All patients had baseline and postexcision intraoperative parathyroid hormone levels as well as vitamin D levels from the same laboratory. Institute of Medicine criteria were employed for vitamin D stratification (30, normal; 20-29.9, insufficient;20, deficient) . Other data analyzed include sex, age, neck dissection status, and parathyroid autotransplantation.A total of 118 patients (27.6%) had an intraoperative parathyroid hormone elevation above baseline. Patients with vitamin D deficiency were significantly more likely to experience hormone elevation ( P = .04). When parathyroid hormone rose, it did so by a mean 32.1 pg/mL. Patients with vitamin D deficiency demonstrated significantly larger hormone increases ( P = .03).Elevation in intraoperative parathyroid hormone levels above baseline after completion and total thyroidectomy occurs in over one-fourth of cases and is significantly associated with vitamin D deficiency. This study is the first to report this observation. We hypothesize that vitamin D deficiency in these patients may create a subclinical secondary hyperparathyroidism that leads to intraoperative parathyroid hormone elevation when the glands are manipulated. Additional studies will be needed to explore this physiologic mechanism and its clinical significance.

The thermal structure of the Tibetan plateau ‐‐ the largest orogenic system on Earth ‐‐ remains largely unknown. Numerous avenues, provide fragmentary pressure/temperature information, both at the present (predominantly informed though geophysical observation), and on the evolution of the thermal structure over the recent past (combining petrological, geochemical, and geophysical observables). However, these individual constraints have proven hard to reconcile with each other. Here, we show that models for the simple underthrusting of India beneath southern Tibet are capable of matching all available constraints on its thermal structure, both at the present day and since the Miocene. Many parameters in such models remain poorly constrained, and we explore the various trade‐offs among the competing influences these parameters may have. However, three consistent features to such models emerge: (i) that present day geophysical observations require the presence of relatively cold underthrust Indian lithosphere beneath southern Tibet; (ii) that geochemical constraints require the removal of Indian mantle from beneath southern Tibet at some point during the early Miocene, although the mechanism of this removal, and whether it includes the removal of any crustal material is not constrained by our models; and (iii) that the combination of the southern extent of Miocene mantle‐derived magmatism and the present‐day geophysical structure and earthquake distribution of southern Tibet require that the time‐averaged rate of underthrusting of India relative to central Tibet since the middle Miocene has been faster than it is at present.

Objectives/hypothesis Intraoperative neural monitoring is a useful adjunct for the laryngeal nerve function assessment during thyroid and parathyroid surgery. Typically, monitoring is performed by measurement of electromyographic responses recorded by endotracheal tube (ETT) surface electrodes. Tube position alterations during surgery can cause displacement of the electrodes relative to the vocal cords, leading to false positive loss of signal. Numerous reports have denoted monitoring equipment-related issues, especially endotracheal tube displacement, as the dominant source of false positive error. The false positive error may result in inappropriate decisions by the surgeon. This study tests the hypothesis that anterior laryngeal electrodes (ALEs) can help reduce this error. Placement of ALEs directly onto the thyroid cartilage represent an adjunctive and possible alternative method to standard ETT surface electrodes. Study design Retrospective review. Methods Fifteen consecutive patients undergoing thyroid and parathyroid surgery with intraoperative neuromonitoring using both ETT electrodes and ALEs were studied. Data collected included site of neural stimulation, laterality, and electromyographic parameters. Results With vagal and recurrent laryngeal nerve stimulation, the ALEs recorded mean vocalis muscle waveform amplitude within 83% of that recorded with standard ETT electrodes. The latency measurements with the anterior laryngeal and endotracheal electrodes were similar, with both electrodes recording significantly longer latency for the left vagus nerve as compared to the right vagus nerve. With superior laryngeal nerve stimulation, the ALEs recorded a 800% greater mean amplitude than the ETT electrodes. The ALEs demonstrated similar sensitivity to stimulation at low current as ETT electrodes and provided stable intraoperative monitoring information. Conclusions Compared to ETT surface electrodes, the ALEs provide similar and stable electromyographic responses with equal sensitivity for recording evoked responses during neural monitoring in thyroid and parathyroid surgery. The ALEs offer significantly more robust monitoring of the external branch of the superior laryngeal nerve. Furthermore, ALEs are contained within the operative field, are totally surgeon controlled, and are unaffected by the potential vicissitudes of ETT position during surgery. Level of evidence 4 Laryngoscope, 128:2910-2915, 2018.