Clinical value of whole body 18F-FDG PET/CT imaging in patients with cutaneous melanoma: A multi-center cohort study.

BACKGROUND: 18F-FDG-PET/CT is a valuable tool in the staging and surveillance of cutaneous melanoma; however, recent studies prompt debate on the clinical significance of imaging patients below the lesser trochanter. This study explored two research questions. In patients with a known primary cutaneous melanoma within the standard field of view (SFOV, between the orbits and lesser trochanter), what is the prevalence of metastasis to sites solely within the lower extremities? and, In patients with a known primary cutaneous melanoma within the SFOV what demographic and clinical factors are associated with sole metastasis to the lower extremities? METHODS: A retrospective, multi-centered, observational study of consecutive case reports was conducted. Subjects included 619 patients who underwent extended field of view (EFOV) 18F-FDG-PET/CT (from vertex to toes) for staging and/or follow-up of cutaneous melanoma. Data was collected at three primary healthcare centers in Canada (Nova Scotia, Alberta, and British Columbia). Inclusion criteria were patients >18 years of age, confirmed primary cutaneous melanoma, and a known location of the primary within the SFOV. Patients with primary cutaneous melanoma lesions in lower extremities and previous other cancers were excluded. To determine the prevalence of lesions located below the lesser trochanter, the proportion of such lesions were computed, and 95% confidence intervals ensured a precise estimation of the proportion. RESULTS: 2512 patient charts were reviewed with 619 meeting the inclusion criteria, 298 of these were females. Six percent had metastases in both the lower extremities and sites within the SFOV. The number of subjects who had no metastasis within their SFOV was 361 (58.3%). The number of subjects who presented with confirmed metastasis in the lower extremities without concurrent metastasis in the SFOV region was one (0.58%). Despite a large initial study sample, the number of patients with metastasis in the lower extremities was insufficient to allow correlation of factors associated with risk of spread to the lower extremities. CONCLUSION: Lower extremity 18F-FDG-PET/CT provided additional, relevant clinical data in a sole patient. This finding supports prior research suggesting the prevalence is rare. Future studies should seek to define demographic and clinical factors that predict such rare occurrences, where follow up would be warranted. This study highlights feasibility challenges associated with such investigation.

Post-Hematopoietic Cell Transplantation Relapsed Acute Lymphoblastic Leukemia: Current Challenges and Future Directions.

Allogeneic hematopoietic cell transplantation (allo-HCT) represents an important and potentially curative treatment option for adult patients with acute lymphoblastic leukemia. Relapse continues to remain the most important factor influencing overall survival post allo-HCT. We discuss early identification, clinical manifestations, and management of relapsed disease. Routine evaluation of measurable residual disease (MRD) and change in donor chimerism play a crucial role in early detection. Pivotal clinical trials have led to FDA approval of multiple novel agents like blinatumomab and inotuzumab. Combining targeted therapy with cellular immunotherapy serves as the backbone for prolonging overall survival in these patients. Donor lymphocyte infusions have traditionally been used in relapsed disease with suboptimal outcomes. This review provides insight into use of cellular therapy in MRD positivity and decreasing donor chimerism. It also discusses various modalities of combining cellular therapy with novel agents and discussing the impact of chimeric antigen receptor T-cell therapy in the setting of post allo-HCT relapse both as consolidative therapy and as a bridge to second transplant.

Investigation into owner-reported differences between dogs born in versus imported into Canada.

Over 1 million dogs are imported into the United States and roughly 340,000 dogs into the United Kingdom yearly. Although the official number of dogs arriving to Canada is currently unknown, local animal professionals estimate that thousands of dogs are imported into Canada each year. Dog importation may be increasing globally while regulation and surveillance are still limited, resulting in concerns for the health and welfare of imported dogs. To date, few studies have investigated how the source location of dogs influences the owner-dog relationship. The current report presents two independent studies that were conducted to assess whether owners of imported dogs reported a poorer owner-dog relationships compared to owners of Canadian-born dogs. In both studies, an online survey was distributed to dog owners (Study 1: n = 803; Study 2: n = 878) in British Columbia, Canada, containing questions on various aspects of the owner-dog relationship. The first study included questions from the Lexington Attachment to Pets Scale, Canine Behavioral Assessment and Research Questionnaire, Human-Animal Bond questionnaire, Monash Dog Owner Relationship Scale, and constructed questions about training methods, expectations, and health. The second study was comprised of original questions assessing difficult behaviour, training practices, health, attachment, and perceived level of burden of owning a dog. Both studies found no evidence of a poorer owner-dog relationship in non-Canadian-sourced dogs. In fact, owners of Canadian-sourced dogs used harsh training methods more frequently and had higher expectations for their dog. While no signs of poorer owner-dog relationship in non-Canadian-sourced dogs were found, future research should continue the investigation of age, health, and backgrounds of incoming dogs.

MRD in ALL: Optimization and Innovations.

PURPOSE OF REVIEW: Measurable residual disease (MRD) is an important monitoring parameter that can help predict survival outcomes in acute lymphoblastic leukemia (ALL). Identifying patients with MRD has the potential to decrease the risk of relapse with the initiation of early salvage therapy and to help guide decision making regarding allogeneic hematopoietic cell transplantation. In this review, we discuss MRD in ALL, focusing on advantages and limitations between MRD testing techniques and how to monitor MRD in specific patient populations. RECENT FINDINGS: MRD has traditionally been measured through bone marrow samples, but more data for evaluation of MRD via peripheral blood is emerging. Current and developmental testing strategies for MRD include multiparametric flow cytometry (MFC), next-generation sequencing (NGS), quantitative polymerase chain reaction (qPCR), and ClonoSeq. Novel therapies are incorporating MRD as an outcome measure to demonstrate efficacy, including blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor T (CAR-T) cell therapy. Understanding how to incorporate MRD testing into the management of ALL could improve patient outcomes and predict efficacy of new therapy options.

Chronic Cough: Evaluation of Patients' Motivation to Undergo Cough Suppression Therapy.

INTRODUCTION: Chronic cough is a persistent cough lasting greater than eight weeks. The prevalence rate is estimated to be 9% to 33% in the United States. There are several treatment modalities described in current literature including medical, surgical, and behavioral interventions. Behavioral intervention with a speech-language pathologist (SLP) includes education on laryngeal hygiene and the voluntary control of cough as well as respiratory retraining to suppress or reduce the duration of cough. Cough suppression therapy, like other behavioral therapies, requires patient motivation and commitment to participation and completion in therapy. METHODS: This study was a prospective cross-sectional survey at a single academic institution. Adult patients evaluated by a laryngologist for chronic cough regardless of their primary etiology were included. Patients who were tracheostomy dependent, on oxygen therapy, had vocal fold paralysis/immobility, or had undergone previous laryngeal surgery were excluded. Patients were surveyed at the end of the initial clinic visit or at the beginning of the first cough suppression therapy session. Subjects reported their motivational factors for undergoing cough suppression therapy. RESULTS: The majority of patients, 21 (58.33%), identified as female, 15 patients (41.20%) identified as male, and no patients identified as transgender, nonbinary, and/or other gender. The patients in this study had a mean age of 57.75 (12.12) years. 35 patients (97.22%) were interested in cough suppression therapy. The mean presenting cough severity index (CSI) was 19.39 (10.28) with the mean cough duration of 8.69 (12.10) years. CONCLUSIONS: Patients primarily sought cough suppression therapy due to intrinsic factors rather than extrinsic influence. By understanding the relationship between symptomatology and patient motivation, clinicians can better counsel their patients and improve methods to assess candidacy for behavioral treatment.

Effect of Colonic Absorption on the Pharmacokinetic Properties of Delayed-Release and Extended-Release Methylphenidate: In Vivo, In Vitro, and Modeling Evaluations.

Most stimulants used to treat attention-deficit/hyperactivity disorder are administered in the morning and absorbed in the upper gastrointestinal tract. DR/ER-MPH (formerly HLD200), an evening-dosed delayed-release and extended-release methylphenidate, is predicted to be absorbed in the proximal colon. The pharmacokinetic (PK) profile of DR/ER-MPH is characterized by an 8- to 10-hour delay in initial methylphenidate absorption and a subsequent gradual increase in plasma concentration, followed by a slow decline. To examine the relationship of absorption site to pharmacokinetics, the DR/ER-MPH formulation was altered to release methylphenidate in the small intestine and distal colon. The 3 formulations were administered in an open-label, 3-way, crossover study in healthy adults (N = 18). Compared with the small intestine formulation, the PK profile of the proximal colon (DR/ER-MPH) formulation exhibited a longer delay before initial methylphenidate absorption, decreased peak methylphenidate concentration, increased time to peak concentration, and decreased bioavailability; these characteristics were amplified in the distal colon formulation. Safety profiles fell within the expectations for methylphenidate products. Modeled PK profiles were similar between the small intestine formulation and a morning-dosed extended-release methylphenidate (both predicted to release methylphenidate in the upper gastrointestinal tract), providing additional evidence that the PK profile of DR/ER-MPH is shaped by colonic absorption.

Cardiac point-of-care ultrasound publication trends.

INTRODUCTION: Cardiac point-of-care ultrasound (c-POCUS) is an increasingly implemented diagnostic tool with the potential to guide clinical management. We sought to characterize and analyze the existing c-POCUS literature with a focus on the temporal trends and differences across specialties. METHODS: A literature search for c-POCUS and related terms was conducted using Ovid (MEDLINE and Embase) and Web of Science databases through 2020. Eligible publications were classified by publication type and topic, author specialty, geographical region of senior author, and journal specialty. RESULTS: The initial search produced 1761 potential publications. A strict definition of c-POCUS yielded a final total of 574 cardiac POCUS manuscripts. A yearly increase in c-POCUS publications was observed. Nearly half of publications were original research (48.8%) followed by case report or series (22.8%). Most publications had an emergency medicine senior author (38.5%), followed by cardiology (20.8%), anesthesiology (12.5%), and critical care (12.5%). The proportion authored by emergency medicine and cardiologists has decreased over time while those by anesthesiology and critical care has generally increased, particularly over the last decade. First authorship demonstrated a similar trend. Articles were published in emergency medicine (24.4%) and cardiology journals (20.5%) with comparable frequency. CONCLUSION: The annual number of c-POCUS publications has steadily increased over time, reflecting the increased recognition and utilization of c-POCUS. This study can help inform clinicians of the current state of c-POCUS and augment the discussion surrounding barriers to continued adoption across all specialties.

Airborne Isolation Cardiac Arrest: A Simulation Program for Interdisciplinary Code Blue Team Training.

Introduction: In-hospital cardiac arrest in patients with COVID-19 presents significant challenges to health care teams. Airborne precautions can delay patient care, place providers at high risk of virus exposure, and exacerbate an already stressful environment. Within the constraints of an ongoing pandemic, an efficient educational program is required to prepare health care teams for airborne isolation code blue. Methods: This simulation was conducted in a room on the target unit using a CPR manikin to represent the patient. A "talk-through walk-through" scripted simulation directed learners (internal medicine residents, unit nurses, and other code blue responders) through a resuscitation using an airborne isolation code blue protocol. Key scripted events prompted role identification, communication, and item transfer. Learners self-assessed their airborne isolation code blue knowledge and skills and their confidence in providing quality care while maintaining safety using a pre-/posttraining 5-point Likert-scale survey. Results: We trained 100 participants over a 5-month period, with 65 participants surveyed (43 respondents; 16 residents, 22 nurses). Following training, participants had a statistically significant (p < .001) increase in percentage selecting agree/strongly agree for all statements related to knowledge and skills specific to airborne isolation code blue protocol, as well as confidence in providing care while keeping themselves and their colleagues safe. Discussion: Our simulation program allowed a small number of educators to feasibly train a large number of learners, let learners practice required skills, and improved learners' self-assessed knowledge, skills, and confidence regarding quality and safety of care.

Variant Acute Promyelocytic Leukemia Presenting Without Auer Rods Highlights the Need for Correlation with Cytogenetic Data in Leukemia Diagnosis.

Variant acute promyelocytic leukemia (vAPL) is a rare leukemia characterized by rearrangement between RARα and a non-PML partner gene. This type of leukemia can be difficult to recognize by histomorphologic evaluation, particularly in patients with few or no Auer rods, and by flow cytometry, but it can be identified by distinct cytogenetic features. Herein, we report on a patient with vAPL with t(11;17)(q23;q21) who presented an initial diagnostic challenge. Detailed flow cytometry findings are presented for this rare entity. Our case study also presents novel treatment (chemotherapy in combination with venetoclax) chosen based on mechanistic data from preclinical studies.

Remembering the Legacy of Judi Tuerck.

Judith "Judi" Tuerck, RN, MS, one of the true pioneers in the development of newborn screening (NBS), passed away on Saturday, 18 June 2022 (Figure 1) [...].

Barriers to Care in Veterinary Services: Lessons Learned From Low-Income Pet Guardians' Experiences at Private Clinics and Hospitals During COVID-19.

This qualitative study aimed to explore the experiences of low-income pet guardians in accessing veterinary care during COVID-19. Participants were recruited through a purposive sampling method: 12 individuals who applied to and met the low-income threshold to access support for veterinary fees from the Vancouver Humane Society (VHS) were invited for semi-structured in-depth telephone interviews. Participants indicated that they experienced pandemic-related barriers related to and compounded by their low-income status. Their experiences fit into three categories: the barriers to accessing veterinary care pre-and peri-COVID-19, the emotional impact of compounding barriers related to accessing veterinary care during COVID-19, and the human-animal bond and resilience in the context of COVID-19. Drawing on the One Health, One Welfare approach, we argue that veterinary and animal services should evaluate and improve their support services, particularly programs developed for low-income pet guardians. Based on the participants' recommendations, we propose that veterinary and animal services prepare for future disaster situations by increasing their financial capacity to support people needing assistance, undergoing training to better work with people experiencing financial and emotional stress, and providing easily accessible resources to better distribute knowledge about animal needs and available financial assistance programming. The suggestions are intended to benefit animals, their guardians, and both veterinary and animal service sector workers.

Affordability, Feasibility, and Accessibility: Companion Animal Guardians with (Dis)Abilities' Access to Veterinary Medical and Behavioral Services during COVID-19.

The research aims to explore COVID-19 health and safety protocol impacts on companion animal guardians living with (dis)abilities relating to veterinary medical and behavioral service access. The COVID-19 global public health crisis has impacted almost all international communities; however, vulnerable and marginalized groups have been disproportionately affected. Within the human-companion animal domain, COVID-19-driven societal impacts (e.g., social, health, and economic) not only boomed with new companion animal guardians, but also negatively influenced guardians' access to veterinary services. Although studies have examined guardian-related COVID-19-specific challenges, there is a paucity of concentration on vulnerable populations, such as persons with disabilities (PWDs). Responding to this research deficit, this study recruited twelve companion animal guardians to participate in semi-structured in-depth interviews, and eight (67%) of the twelve participants self-identified as PWDs. From a PWD perspective, this research reveals three pandemic-triggered primary barriers, preventing PWDs from pursuing veterinary services: (1) service affordability, (2) assistance program feasibility, and (3) veterinary service accessibility. This article argues that PWD-driven approaches could improve existing assistance and support programs to address PWDs' unique requirements, promoting a healthy human-animal bond.

Pegaspargase in Practice: Minimizing Toxicity, Maximizing Benefit.

PURPOSE OF REVIEW: The incorporation of pegaspargase in chemotherapy regimens has significantly improved the prognosis of ALL in adults. However, pegaspargase use poses many challenges due to its unique toxicity profile. Here, we review pegaspargase's most clinically significant toxicities, and provide guidance for their prevention and management in order to avoid unnecessary drug discontinuation and achieve maximum clinical benefit. RECENT FINDINGS: Clinically significant toxicities of pegaspargase include thrombosis, hypersensitivity and inactivation, hepatotoxicity, pancreatitis, and hypertriglyceridemia. The majority of these toxicities are temporary, nonfatal, and can be managed supportively without permanent pegaspargase discontinuation. Special attention should be paid to inactivation, which can lead to treatment failure, as well as pancreatitis, which necessitates complete cessation of asparaginase therapy. The question of how to best proceed in patients who cannot tolerate pegaspargase remains unanswered, and is an important area of future investigation. Pegaspargase is an essential component of the pediatric-inspired regimens that have improved survival in adult ALL. Although pegaspargase's toxicity profile is unique, it is also highly manageable and should not be a barrier to achieving maximum clinical benefit using this drug.

Delivering a Novel Medical Education "Escape Room" at a National Scientific Conference: First Live, Then Pivoting to Remote Learning Because of COVID-19.

Escape Rooms are gaining prominence as education modalities; the use of principles of game design have been shown to augment knowledge acquisition in a fun, team-based learning experience ("edutainment"). In this report, we outline some of the medical literature and then provide our step-by-step approach and lessons learned when building what was, to our knowledge, the first continuing medical education Escape Room at a national scientific meeting. We then comment on how this innovative educational offering was reimagined the following year for remote (virtual) learning because of the COVID-19 pandemic.

TAK-101 Nanoparticles Induce Gluten-Specific Tolerance in Celiac Disease: A Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND & AIMS: In celiac disease (CeD), gluten induces immune activation, leading to enteropathy. TAK-101, gluten protein (gliadin) encapsulated in negatively charged poly(dl-lactide-co-glycolic acid) nanoparticles, is designed to induce gluten-specific tolerance. METHODS: TAK-101 was evaluated in phase 1 dose escalation safety and phase 2a double-blind, randomized, placebo-controlled studies. Primary endpoints included pharmacokinetics, safety, and tolerability of TAK-101 (phase 1) and change from baseline in circulating gliadin-specific interferon-γ-producing cells at day 6 of gluten challenge, in patients with CeD (phase 2a). Secondary endpoints in the phase 2a study included changes from baseline in enteropathy (villus height to crypt depth ratio [Vh:Cd]), and frequency of intestinal intraepithelial lymphocytes and peripheral gut-homing T cells. RESULTS: In phase 2a, 33 randomized patients completed the 14-day gluten challenge. TAK-101 induced an 88% reduction in change from baseline in interferon-γ spot-forming units vs placebo (2.01 vs 17.58, P = .006). Vh:Cd deteriorated in the placebo group (-0.63, P = .002), but not in the TAK-101 group (-0.18, P = .110), although the intergroup change from baseline was not significant (P = .08). Intraepithelial lymphocyte numbers remained equal. TAK-101 reduced changes in circulating α4ß7+CD4+ (0.26 vs 1.05, P = .032), αEß7+CD8+ (0.69 vs 3.64, P = .003), and γδ (0.15 vs 1.59, P = .010) effector memory T cells. TAK-101 (up to 8 mg/kg) induced no clinically meaningful changes in vital signs or routine clinical laboratory evaluations. No serious adverse events occurred. CONCLUSIONS: TAK-101 was well tolerated and prevented gluten-induced immune activation in CeD. The findings from the present clinical trial suggest that antigen-specific tolerance was induced and represent a novel approach translatable to other immune-mediated diseases. ClinicalTrials.gov identifiers: NCT03486990 and NCT03738475.

Procedure Training Workshop for Internal Medicine Residents that Emphasizes Procedural Ultrasound: Logistics and Teaching Materials.

Introduction: Early formal instruction in procedural skills may increase the frequency with which residents perform procedures in the clinical setting. This workshop trained internal medicine residents in ultrasound skills and manual skills required to perform procedures common on medicine wards and required for board eligibility. Methods: Since 2016, our internal medicine residency program has executed three annual half-day workshops for interns during orientation, before clinical duties began. Prior to the workshop, we directed interns to relevant educational resources in the form of online modules and videos. At the workshop, trainees rotated in small groups through facilitated stations to learn basics of procedural ultrasound and to practice manual tasks performed during paracentesis, thoracentesis, lumbar puncture, and peripheral intravenous catheter placement. We administered questionnaires before and immediately after the workshop and used Wilcoxon signed rank tests to compare self-assessed independence and confidence. Results: Two hundred four interns with little prior procedural training participated in the workshop. Most participants (85%) indicated that orientation was the best timing for this training experience when compared to later options. Confidence and independence increased for ultrasound-marked thoracentesis, paracentesis, and peripheral intravenous catheters and for lumbar puncture without ultrasound. Discussion: This internal medicine intern orientation workshop on procedures and procedural ultrasound was well received and increased participants' confidence and sense of independence. This publication contains materials needed to reproduce the training experience.

Development of a Focused Cardiac Ultrasound Image Acquisition Assessment Tool.

Background: Focused cardiac ultrasound (FCU) is widely used by healthcare providers to answer specific questions about cardiac structure and function at the bedside. Currently, no widely accepted FCU image acquisition checklist exists to assess learners with varying skill levels from different specialties. Objective: The primary objective of this project was to develop a consensus-based FCU image acquisition checklist using a multispecialty group of point-of-care ultrasound (POCUS) experts. Methods: The essential components of an FCU examination were identified on the basis of published recommendations from echocardiography and international ultrasound societies. A checklist of the essential components of an FCU examination was drafted. A panel of POCUS experts from different medical specialties in the United States and Canada was convened to vote on each checklist item by answering two questions: 1) Is this item important to include in a checklist of essential FCU skills applicable to any medical specialty? and 2) Should the learner be required to successfully complete this item to be considered competent? A modified Delphi approach was used to assess the level of agreement for each checklist item during four rounds of voting. Checklist items that achieved an agreement of 80% or greater were included in the final checklist. Results: Thirty-one POCUS experts from seven different medical specialties voted on sixty-five items to be included in the FCU image acquisition assessment tool. The majority of POCUS experts (61%) completed all four rounds of voting. During the first round of voting, 59 items reached consensus, and after revision and revoting, an additional 3 items achieved 80% or greater consensus. A total of 62 items were included in the final checklist, and 57 items reached consensus as a requirement for demonstration of competency. Conclusion: We have developed a multispecialty, consensus-based FCU image acquisition checklist that may be used to assess the skills of learners from different specialties. Future steps include studies to develop additional validity evidence for the use of the FCU assessment tool and to evaluate its utility for the translation of skills into clinical practice.

Auditory-Perceptual Evaluation of Deep Brain Stimulation on Voice and Speech in Patients With Dystonia.

OBJECTIVE: To determine the effects of globus pallidus interna (GPi) deep brain stimulation (DBS) on speech and voice quality of patients with primary, medically refractory dystonia. METHODS: Voices of 14 patients aged ≥18 years (males = 7 and females = 7) with primary dystonia (DYT1 gene mutation dystonia = 4, cervical dystonia = 6, and generalized dystonia = 4) with bilateral GPi DBS were assessed. Five blinded raters (two fellowship-trained laryngologists and three speech/language pathologists) evaluated audio recordings of each patient pre- and post-DBS. Perceptual voice quality was rated using the Grade, Roughness, Breathiness, Asthenia, and Strain scale and changes in speech intelligibility were assessed with the Clinical Global Impression scale of Severity instrument. Inter-rater and intrarater reliability rates for perceptual voice ratings were assessed using the kappa coefficient. RESULTS: Voice quality parameters showed mean improvements in Grade (P < 0.0001), Roughness (P = 0.0043), and Strain (P < 0.0001) 12 months post-DBS. Asthenia increased from baseline to 6 months (P = 0.0022) and declined significantly from 6 to 12 months (P = 0.0170). Breathiness did not change significantly over time. Speech intelligibility also improved from 6 to 12 months (P = 0.0202) and from pre-DBS to 12 months post-DBS (P = 0.0022). Grade and Strain ratings had nearly perfect and substantial inter-rater agreement (0.84 and 0.71, respectively). CONCLUSIONS: Voice and speech intelligibility improved after bilateral GPi DBS for dystonia. GPi DBS may emerge as a potential treatment option for patients with medically refractory laryngeal dystonia.