Anaplasma bovis-Like Infections in Humans, United States, 2015-2017.

We detected the DNA of an Anaplasma bovis-like bacterium in blood specimens from 4 patients from the United States with suspected tickborne illnesses. Initial molecular characterization of this novel agent reveals identity to A. bovis-like bacteria detected in Dermacentor variabilis ticks collected from multiple US states.

Sulfur and Azobenzenes, a Profitable Liaison: Straightforward Synthesis of Photoswitchable Thioglycosides with Tunable Properties.

Azobenzene photoswitches are valuable tools for controlling properties of molecular systems with light. We have been investigating azobenzene glycoconjugates to probe carbohydrate-protein interactions and to design glycoazobenzene macrocycles with chiroptical and physicochemical properties modulated by light irradiation. To date, direct conjugation of glycosides to azobenzenes was performed by reactions providing target compounds in limited yields. We therefore sought a more effective and reliable coupling method. In this paper, we report on a straightforward thioarylation of azobenzene derivatives with glycosyl thiols as well as other thiols, thereby increasing the scope of azobenzene conjugation. Even challenging unsymmetrical conjugates can be achieved in good yields via sequential or one-pot procedures. Importantly, red-shifted azoswitches, which are addressed with visible light, were easily functionalized. Additionally, by oxidation of the sulfide bridge to the respective sulfones, both the photochromic and the thermal relaxation properties of the core azobenzene can be tuned. Utilizing this option, we realized orthogonal three-state photoswitching in mixtures containing two distinct azobenzene thioglycosides.

Use of lentiviral vectors to deliver and express bicistronic transgenes in developing chicken embryos.

The abilities of lentiviral vectors to carry large transgenes (∼8kb) and to efficiently infect and integrate these genes into the genomes of both dividing and non-dividing cells make them ideal candidates for transport of genetic material into cells and tissues. Given the properties of these vectors, it is somewhat surprising that they have seen only limited use in studies of developing tissues and in particular of the developing nervous system. Over the past several years, we have taken advantage of the large capacity of these vectors to explore the expression characteristics of several dual promoter and 2A peptide bicistronic transgenes in developing chick neural retina, with the goal of identifying transgene designs that reliably express multiple proteins in infected cells. Here we summarize the activities of several of these transgenes in neural retina and provide detailed methodologies for packaging lentivirus and delivering the virus into the developing neural tubes of chicken embryos in ovo, procedures that have been optimized over the course of several years of use in our laboratory. Conditions to hatch injected embryos are also discussed. The chicken-specific techniques will be of highest interest to investigators using avian embryos, development and packaging of lentiviral vectors that reliably express multiple proteins in infected cells should be of interest to all investigators whose experiments demand manipulation and expression of multiple proteins in developing cells and tissues.

Splanchnic vein thrombosis: management for the thrombosis specialist.

Splanchnic vein thrombosis (SpVT) is an uncommon site of venous thrombosis that is associated with complications including portal hypertension and hepatic dysfunction. The evaluation and management of this patient population has evolved in recent years, but there is limited data from clinical trials to guide management. Given the various acquired and biologic risk factors leading to the development of SpVT and the potential complications that can arise from it, input from a multidisciplinary team can be valuable in managing such patients, including thrombosis specialists or hematologists, gastroenterologists or hepatologists, interventional radiologists, and surgeons. In this manuscript, we present four cases that highlight important issues and considerations in the evaluation of SpVT including: initial diagnostic approach in a patient with a new diagnosis of SpVT, considerations for anticoagulant therapy, management of SpVT in patients with myeloproliferative neoplasms, and the role of interventional vascular procedures in the management of SpVT. By reviewing the current literature, we address clinically relevant questions that are posed to clinicians managing patients with SpVT; we also point out gaps in our current knowledge that merit future investigation.

Impact of thrombocytopenia on bleeding and thrombotic outcomes in adults with cancer-associated splanchnic vein thrombosis.

Malignancy is a risk factor for splanchnic vein thrombosis (SpVT). Data on the natural history of cancer-associated SpVT are limited. This was a single-center retrospective cohort study of 581 adult patients with cancer and SpVT. We aimed to characterize the impact of thrombocytopenia on major bleeding and progression or recurrence of SpVT within one year of initial cancer-associated SpVT diagnosis. Baseline thrombocytopenia (platelet < 100,000/uL within 15 days of SpVT diagnosis) was present in 39.5% of patients. A total of 39.2% of patients received therapeutic anticoagulation within two weeks of SpVT diagnosis. The cumulative once-year incidence of major bleeding was 10.7% (95% CI: 8.2-13.2), and for SpVT recurrence/progression was 16.2% (95% CI: 13.2-19.2). In multivariable regression analysis, therapeutic anticoagulation was associated with increased major bleeding (aRR: 1.74, 95% CI: 1.08-2.81) and decreased progression/recurrence of SpVT (aRR: 0.55, 95% CI: 0.35-0.86). Baseline thrombocytopenia was not independently associated with either major bleeding (aRR: 0.76, 95% CI: 0.43-1.34) or progression/recurrence of SpVT (aRR: 1.14, 95% CI: 0.73-1.78). A secondary analysis using inverse probability of treatment weighting with propensity scores for baseline thrombocytopenia corroborated that patients with thrombocytopenia did not have increased bleeding risk (aHR: 0.81, 95% CI: 0.48-1.39). Multivariable analysis treating platelets as a time varying covariate also did not reveal an association with major bleeding (aHR: 0.89, 95% CI: 0.55-1.45). Bleeding and thrombosis progression were frequent in patients with cancer-associated SpVT. Anticoagulation was associated with increased major bleeding and decreased thrombotic progression; thrombocytopenia did not impact outcomes.

Spontaneous Tumor Lysis Syndrome Secondary to Metastatic Pancreatic Adenocarcinoma.

Spontaneous tumor lysis syndrome (STLS) secondary to metastatic pancreatic adenocarcinoma is a rare clinical phenomenon. An 86-year-old woman with a history of pancreatic cysts presented to the emergency department with progressive fatigue, transaminitis, elevated lactate dehydrogenase, and acute kidney injury of unclear etiology. Abdominal imaging and celiac lymph node biopsy were consistent with metastatic pancreatic adenocarcinoma. Her clinical status deteriorated requiring intensive care unit transfer, and her laboratory results were found to be consistent with STLS. Despite treatment, she entered multisystem organ failure and died shortly after. This case adds to the literature of STLS in pancreatic adenocarcinomas.

Anticoagulation for splanchnic vein thrombosis in myeloproliferative neoplasms: a systematic review and meta-analysis.

BACKGROUND: Optimal anticoagulation management in patients with myeloproliferative neoplasms (MPN) experiencing splanchnic vein thrombosis (SpVT) requires balancing risks of bleeding and recurrent thrombosis. OBJECTIVES: We conducted a systematic review and meta-analysis to assess the incidence of bleeding and thrombosis recurrence in patients with MPN-SpVT. METHODS: We included retrospective or prospective studies in English with ≥10 adult patients with MPN-SpVT. Outcomes included recurrent venous thrombosis (SpVT and non-SpVT), arterial thrombosis, and major bleeding. Pooled rates per 100 patient years with 95% CIs were calculated by DerSimonian-Laird method using random-effects model. RESULTS: Out of 4624 studies screened, 9 studies with a total of 443 patients were included in the meta-analysis with median follow-up of 3.5 years. In the 364 patients with MPN-SpVT treated with anticoagulation, pooled event rate for major bleeding was 2.8 (95% CI, 1.5-5.1; I2 = 95%), for recurrent venous thrombosis was 1.4 (95% CI, 0.8-2.2; I2 = 72%), and for arterial thrombosis was 1.4 (95% CI, 0.6-3.3; I2 = 92%) per 100 patient years. Among 79 patients (n = 4 studies) who did not receive anticoagulation, pooled event rate for major bleeding was 3.2 (95% CI, 0.7-12.7; I2 = 97%), for recurrent venous thrombosis 3.5 (95% CI, 1.8-6.4; I2 = 88%), and for arterial thrombosis rate 1.6 (95% CI, 0.4-6.6; I2 = 95%) per 100 patient years. CONCLUSION: Patients with MPN-SpVT treated with anticoagulation have significant risks for both major bleeding and thrombosis recurrence. Further studies are necessary to determine the optimal anticoagulation approach in patients with MPN-SpVT.

The bridging conundrum: perioperative management of direct oral anticoagulants for venous thromboembolism.

Most patients diagnosed with venous thromboembolism (VTE) are currently treated with direct oral anticoagulants (DOACs). Before an invasive procedure or surgery, clinicians face the challenging decision of how to best manage DOACs. Should the DOAC be held, for how long, and are there instances where bridging with other anticoagulants should be considered? Although clinical trials indicate that most patients taking DOACs for atrial fibrillation do not require bridging anticoagulation, the optimal strategy for patients with a history of VTE is undefined. In this review, we present a case-based discussion for DOAC interruption perioperatively in patients receiving anticoagulation for management of VTE.

Patient awareness, perceptions, and attitudes towards pharmacists prescribing tobacco cessation medications.

BACKGROUND: Recent legislative advances now permit pharmacists to prescribe tobacco cessation medications in 17 states. While national initiatives are underway to prepare the pharmacy profession for this expanded role, patient perceptions of this role have not been explored. OBJECTIVE: The objective of this study was to characterize patient perceptions, attitudes, and awareness of pharmacists prescribing for tobacco cessation medications. METHODS: A cross-sectional survey of English and Spanish-speaking patients was conducted at 12 locations of a federally-qualified health center in Northwest Indiana. Survey measures assessed sociodemographics, tobacco use history and interest in quitting, prior interactions with pharmacists and awareness of pharmacists' ability to prescribe tobacco cessation medications, and perceptions of pharmacists assisting with cessation. The Theory of Planned Behavior (TPB) served as a framework for item development. Multivariable logistic regression was used for modeling. RESULTS: A total of 2082 individuals (1878 English, 204 Spanish) completed the survey (42.4%). Among current users (n = 592; 28.4%), 46.2% had made a quit attempt in the past year, and 41.0% reported having used a tobacco cessation medication in the past. Over half (60.5%) of current users would be comfortable talking with a pharmacist about quitting, 31.9% intended to talk with a pharmacist about quitting, and 31.7% intended to ask a pharmacist to prescribe a medicine to help with quitting. In multivariable modeling, intention to (a) talk with a pharmacist about quitting and (b) ask a pharmacist to prescribe a medication were significantly associated with TPB constructs. Current tobacco users were receptive to pharmacist-facilitated assistance with quitting, including prescribing of tobacco cessation medications. CONCLUSIONS: Patients' attitudes, subjective norms, and perceived behavioral control, from the Theory of Planned Behavior, were important predictors of intention to engage with pharmacists for quitting and intention to ask a pharmacist to prescribe a cessation medication.

Consensus recommendations on peripheral blood smear review: defining curricular standards and fellow competency.

Graduate medical education training in hematology in North America is accredited by the Accreditation Council for Graduate Medical Education (ACGME). Trainees routinely review peripheral blood smears (PBS) in providing clinical care. Competency in PBS review at graduation is required by the ACGME. However, there are no consensus guidelines on best practices surrounding PBS review, education, or competency. We describe the generation of proposed theory and the consensus recommendations developed through a multi-institutional focus group, developed using constructivist grounded theory and a modified nominal group technique. Eight academic hematologists, spanning classical and malignant hematology, enrolled and participated in 2 one-hour focus groups. All routinely worked with fellows and half had formally instructed trainees on PBS interpretation. Focus group data were analyzed using mixed-methods techniques. Tenets of emerging theory were identified through inductive coding. Consensus recommendations (CR) were generated. Participants reviewed CR in an iterative fashion until consensus was reached. Strong consensus was reached on multiple aspects of PBS education. All agreed that trainees should learn PBS review through a systematic approach. Group discussion focused on disorders of red and white blood cells. The diagnoses of acute leukemia and thrombotic microangiopathies were most commonly discussed, with specific emphasis on disorders in which prompt recognition was required to avert significant patient morbidity. These CR offer external validity to future research and curricular development for both PBS review and other visuospatial tasks in medical education.

Implementing Electronic Patient-Reported Outcomes for Patients With New Oral Chemotherapy Prescriptions at an Academic Site and a Community Site.

PURPOSE: Oral chemotherapy challenges providers' abilities to safely monitor patients' symptoms, adherence, and financial toxicity. COVID-19 has increased the urgency of caring for patients remotely. Collection of electronic patient-reported outcomes (ePROs) has demonstrated efficacy for patients on intravenous chemotherapy, but limited data support their use in oral chemotherapy. We undertook a pilot project to assess the feasibility of implementing an ePRO system for patients starting oral chemotherapy at our cancer center, which includes both an academic site and a community site. METHODS: Patients initiating oral chemotherapy were asked to participate. A five-question tool was built in REDCap. Concerning responses triggered outreach within one business day. The primary outcome was time to first symptom assessment. For comparison, we used a historical cohort of patients who had been prescribed oral chemotherapies by providers in the same disease groups at the cancer center. RESULTS: Twenty-five of 62 (40%) patients completed ePRO assessments. Fifty historical charts were reviewed. Time to first symptom assessment was 7 days (IQR, 4-14 days) in the historical group compared with 3 days (IQR, 2-4 days) in the ePRO group. Time to clinical action was 14 days (7-35 days) in the historical group compared with 8 days (4-19 days) in the ePRO group. No statistically significant differences were detected in 30-day emergency department visit or hospitalization (12% for both groups) or 90-day emergency department visit or hospitalization rates (historical 28% and ePRO 20%). CONCLUSION: An ePRO tool monitoring patient concerns about adherence, cost, and toxicities for patients with new oral chemotherapy regimens is feasible and improves time to symptom assessment. Further investigation is needed to improve patient engagement with ePROs and evaluate the long-term impacts for patients on oral chemotherapy.

Naomi: a new modelling tool for estimating HIV epidemic indicators at the district level in sub-Saharan Africa.

INTRODUCTION: HIV planning requires granular estimates for the number of people living with HIV (PLHIV), antiretroviral treatment (ART) coverage and unmet need, and new HIV infections by district, or equivalent subnational administrative level. We developed a Bayesian small-area estimation model, called Naomi, to estimate these quantities stratified by subnational administrative units, sex, and five-year age groups. METHODS: Small-area regressions for HIV prevalence, ART coverage and HIV incidence were jointly calibrated using subnational household survey data on all three indicators, routine antenatal service delivery data on HIV prevalence and ART coverage among pregnant women, and service delivery data on the number of PLHIV receiving ART. Incidence was modelled by district-level HIV prevalence and ART coverage. Model outputs of counts and rates for each indicator were aggregated to multiple geographic and demographic stratifications of interest. The model was estimated in an empirical Bayes framework, furnishing probabilistic uncertainty ranges for all output indicators. Example results were presented using data from Malawi during 2016-2018. RESULTS: Adult HIV prevalence in September 2018 ranged from 3.2% to 17.1% across Malawi's districts and was higher in southern districts and in metropolitan areas. ART coverage was more homogenous, ranging from 75% to 82%. The largest number of PLHIV was among ages 35 to 39 for both women and men, while the most untreated PLHIV were among ages 25 to 29 for women and 30 to 34 for men. Relative uncertainty was larger for the untreated PLHIV than the number on ART or total PLHIV. Among clients receiving ART at facilities in Lilongwe city, an estimated 71% (95% CI, 61% to 79%) resided in Lilongwe city, 20% (14% to 27%) in Lilongwe district outside the metropolis, and 9% (6% to 12%) in neighbouring Dowa district. Thirty-eight percent (26% to 50%) of Lilongwe rural residents and 39% (27% to 50%) of Dowa residents received treatment at facilities in Lilongwe city. CONCLUSIONS: The Naomi model synthesizes multiple subnational data sources to furnish estimates of key indicators for HIV programme planning, resource allocation, and target setting. Further model development to meet evolving HIV policy priorities and programme need should be accompanied by continued strengthening and understanding of routine health system data.

A compatibility study on the glycosylation of 4,4'-dihydroxyazobenzene.

Photoresponsive glycoconjugates based on the azobenzene photoswitch are valuable molecules which can be used as tools for the investigation of carbohydrate-protein interactions or as precursors of shape-switchable molecular architectures, for example. To access such compounds, glycosylation of 4,4'-dihydroxyazobenzene (DHAB) is a critical step, frequently giving heterogeneous results because DHAB is a challenging glycosyl acceptor. Therefore, DHAB glucosylation was studied using nine different glycosyl donors, and reaction conditions were systematically varied in order to find a reliable procedure, especially towards the preparation of azobenzene bis-glucosides. Particular emphasis was put on glucosyl donors which were differentiated at the primary 6-position (N3, OAc) for further functionalisation. The present study allowed us to identify suitable glycosyl donors and reaction conditions matching with DHAB, affording the bis-glycosylated products in fair yields and good stereocontrol.

Why focus on patient-reported outcome measures in older colorectal cancer patients?

Colorectal cancer is the most common cancer among older persons, with surgery the recommended treatment for many. With a growing emphasis on value-based care, there is an increasing desire to implement patient-reported outcome measures. Patient-reported outcome measures (PROMs) are the tools and instruments used to collect patient-reported symptoms, functional status, and quality of life. Monitoring and addressing PROMs has been shown to improve patient-centered care in surgical oncology populations and survival in patients with advanced cancer. For older patients, functional status and quality of life are valuable outcomes of cancer treatment. However, experience with PROMs for older patients, and specifically older colorectal cancer patients, is limited and heterogenous. The International Consortium for Health Outcomes Measurement has recommended a set of outcome measures for colorectal cancer patients and a set of outcome measures for older patients, which have considerable overlap, providing a starting point for future investigations of PROMs for older colorectal cancer patients. While many questions remain, it is imperative that PROMs for older colorectal cancer patients be considered for their potential to improve cancer outcomes in this population.

Primary facial nerve paraganglioma: report and review of the literature.

This report describes the diagnosis and treatment of a patient with a rare primary facial nerve paraganglioma as well as a review of the current literature. A 60-year-old male patient presented to our clinic with a 4-month history of left-sided progressive facial paralysis House-Brackmann V. Biopsy taken during facial nerve (FN) decompression confirmed the diagnosis of paraganglioma. The left FN was sacrificed during resection of the mass and a 12-7 jump graft, using the left greater auricular nerve, was performed with acceptable outcomes. The rarity of these tumours does not discount their clinical importance or the necessity to include them in the differential when presented with unilateral FN paralysis. Investigation should begin with CT and MRI imaging to identify and localise the potential mass. Histologic confirmation requires tissue. While surveillance imaging is occasionally an option, often complete surgical resection of the mass and sacrifice of the nerve is necessary.

Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders.

Small intestinal bacterial overgrowth (SIBO) has been implicated in symptoms associated with functional gastrointestinal disorders (FGIDs), though mechanisms remain poorly defined and treatment involves non-specific antibiotics. Here we show that SIBO based on duodenal aspirate culture reflects an overgrowth of anaerobes, does not correspond with patient symptoms, and may be a result of dietary preferences. Small intestinal microbial composition, on the other hand, is significantly altered in symptomatic patients and does not correspond with aspirate culture results. In a pilot interventional study we found that switching from a high fiber diet to a low fiber, high simple sugar diet triggered FGID-related symptoms and decreased small intestinal microbial diversity while increasing small intestinal permeability. Our findings demonstrate that characterizing small intestinal microbiomes in patients with gastrointestinal symptoms may allow a more targeted antibacterial or a diet-based approach to treatment.

Pediatric Emergency Medicine Simulation Curriculum: Electrical Injury.

Introduction: Electrical injuries are rare but potentially life-threatening medical emergencies that require providers to manage a critically ill patient while recognizing and treating the unique sequelae associated with the diagnosis. This simulation case is designed to give pediatric and emergency medicine residents, fellows, attendings, and nurses the opportunity to practice these skills in a realistic setting. Methods: This simulation-based curriculum was designed for a high-fidelity mannequin in an emergency department resuscitation room but can be adapted to fit a variety of learning environments. The case featured a 16-year-old boy presenting to the emergency department after arresting in the field after sustaining an electrical injury. He developed ventricular tachycardia during the simulation and had significant hyperkalemia, requiring emergent management. The included debriefing tools assisted instructors in providing formative feedback to learners. Results: A total of 40 residents, medical students, and fellows participated in this scenario and provided overwhelmingly positive feedback about the learning experience. Mean Likert scores for participant confidence related to learning objectives after the simulation were 4 or greater on a 5-point scale. Discussion: This case was developed to help learners at various levels of training recognize and manage a low-frequency, high-acuity scenario in a standardized environment. Participants specifically had the opportunity to perform airway management, cardiopulmonary resuscitation, defibrillation, and management of hyperkalemia, which may present in real life from a multitude of etiologies. The included materials helped prepare and assist facilitators with debriefing, supplemental education, and bidirectional feedback.

Early commitment facilitates optimal choice by pigeons.

Prior commitment has been found to facilitate choice of a larger later reward (e.g., healthy living) and avoid the impulsive choice of the smaller immediate reward (e.g., smoking, drug taking). In this research with pigeons, we investigated the ephemeral choice task in which pigeons are given a choice between two alternatives, A and B, with similar reinforcement provided for each; however, if they choose A, they can also choose B, whereas if they choose B, A is removed. Thus, choosing A gives them two rewards, whereas choosing B gives them only one. Paradoxically, pigeons actually show a preference for B, the suboptimal alternative. We tested the hypothesis that pigeons made suboptimal choices because they were impulsive. To reduce impulsivity, we required the pigeons to make their initial choice 20 s before receiving the first reward. We found that requiring the pigeons to make a prior commitment encouraged them to choose optimally. The control group, for which the reward was provided immediately following initial choice, continued to choose suboptimally. The results confirm that requiring animals to make a prior commitment can facilitate the development of optimal choice. Furthermore, they may help explain why, without prior commitment, impulsive species, such as primates and pigeons have difficulty with this task, whereas presumably less impulsive species, such as wrasse fish and under some conditions parrots, are able to choose optimally even without prior commitment.