A rare case of necrotizing soft tissue infection following circumcision of buried penis.

Circumcision is generally a safe procedure with rare serious adverse events. We report the case of a 7-month-old male who developed necrotizing soft tissue infection following circumcision of his buried penis. A high index of suspicion must be present to diagnose necrotizing fasciitis, and treatment involves early, aggressive debridement, and broad spectrum antibiotics.

Passive Dynamic Ankle Foot Orthoses Use in Civilian Patients with Arthritic Conditions of the Foot and Ankle.

Background: Nonsurgical interventions such as bracing with ankle foot orthoses (AFOs) aim to assist, restore, and redirect weightbearing forces to address difficulty with mobilization. We identified a custom carbon fiber passive dynamic ankle foot orthosis (PDAFO) that was designed to meet the needs of military combat veterans. We sought to evaluate the off-loading properties of one model of PDAFO (ExoSym) in a civilian population. Methods: Civilian patients 18 years or older were prescribed a PDAFO by a single surgeon. Pedobarographic data were obtained using the Tekscan F-Scan system. With the insole, participants were instructed to walk at a self-selected pace along a 20 m walkway under 3 conditions: (1) insole placed in between the brace and foot (over); (2) insole placed between the brace and insole of the shoe (under); (3) without the brace, the insole was placed in between the foot and insole of the shoe in both limbs (without).For assessment, forefoot and heel areas were evaluated with respect to maximal force, force*time integral (FTI), maximal contact area, maximal contact pressure, pressure*time integral (PTI), center of force (COF) excursion. Results: Six patients with arthritic foot and ankle conditions completed pedobarographic assessment for analysis. The brace reduced forefoot maximal force and contact pressures by 66% and 49%, respectively (538 ± 236 to 185 ± 130 N [P < .001], and 99 ± 38 to 50 ± 24 P < .002). Additionally, participants were observed to load the forefoot portion of the brace with double the maximum contact pressures compared to the unbraced foot (204 ± 57 to 99 ± 38 kPa, P < .001). Conclusion: The results of this study showed that the PDAFO unloaded substantial force and pressure experienced by the forefoot. Participants loaded the brace to a greater extent than when going unbraced. ADAFO can provide measurable pressure relief for patients with arthritic conditions. Level of Evidence: Level IV, case series.

A Portrait of Cord Blood Units Distributed for Transplantation from Canadian Blood Services' Cord Blood Bank: First Analysis.

BACKGROUND: The Canadian Blood Services Cord Blood Bank (CBS CBB) was created to improve access to stem cell products for transplantation for patients across ethnic groups. An analysis of distributed units is needed to assess the effectiveness of the bank to meet the needs of patients from different ethnic groups. METHODS: A descriptive analysis was performed on all cord blood units distributed from the CBS' CBB as of 30 June 2022. RESULTS: Distribution of the first 60 units based on CBS' CBB inventory has been linear over time. A similar proportion of cord blood unit (CBU) recipients were pediatric or adult. More than half of the cord blood units (56.7%) were distributed to recipients outside of Canada, and CBUs were used to treat a broad range of hematologic and immune disorders. 43.3% of distributed CBUs were of non-Caucasian ethnicity and 18% were from donors self-reporting as multi-ethnic. The mean total nucleated cell counts and total CD34+ cell counts were 1.9 ± 0.1 × 109 cells and 5.3 ± 0.5 × 106 CD34+ cells, respectively. CD34+ cells per kg (recipient weight) varied significantly between pediatric (age 0-4), adolescent (age 5-17) and adult recipients (age 18 and older) (3.1 ± 0.5, 1.4 ± 0.5 and 0.9 ± 0.07 × 105 CD34+ cells/kg, respectively). HLA matching was 6/6 (15%), 5/6 (47%) or 4/6 (38%). CONCLUSIONS: The CBS' CBB has facilitated the utilization of banked units for patients across a broad range of ages, geographic distribution, ethnicity, and diseases. Distributed units were well matched for HLA alleles and contained robust cell counts, reflecting a high-quality inventory with significant utility.

Demand and usage of unrelated donor products for allogeneic haematopoietic cell transplantation during the COVID-19 pandemic: A Canadian Blood Services Stem Cell Registry analysis.

BACKGROUND AND OBJECTIVES: Understanding changes in the demand and usage of unrelated allogeneic haematopoietic cell transplantation (HCT) donors during the COVID-19 pandemic is needed to optimize pandemic preparedness of registry and donor collection services. The aim of this study was to understand the extent to which the pandemic has impacted the demand and usage of unrelated donors and cord blood units (CBUs) at Canadian Blood Services (CBS). MATERIALS AND METHODS: Data regarding stem cell donor interest and product usage for unrelated allogeneic HCT were retrieved from the database at CBS using de-identified anonymous information. RESULTS: Unrelated donor searches for Canadian patients remained unchanged by the pandemic, reflecting stable demand. The number of unrelated allogeneic transplants performed within Canada also remained stable, while the number of cord blood transplants increased, chiefly for paediatric patients. Requests for donor verification typing, a first signal of potential interest, increased from domestic centres during the first 6 months of the pandemic and decreased from international centres, before returning to baseline levels. The proportion of transplants for Canadian patients who used stem cell products procured from Canadian donors increased between 3 and 6 months after the start of the pandemic before returning to baseline and appears to be increasing again more than 1 year after the start of the pandemic. Use of CBUs for Canadian paediatric patients increased and remains elevated. CONCLUSION: Demand for unrelated adult HCT donors has remained stable despite the evolving pandemic with a transient and recurring increased interest and usage of domestic adult donors. Use of CBUs for paediatric patients has increased and remains elevated. Registries and donor collection centres should maintain the capacity to expand services for domestic donor collection during pandemics to offset threats to international donor usage.

Development and evaluation of checklists to support the recruitment of committed hematopoietic stem cell donors.

BACKGROUND: Checklists are memory recall tools used across healthcare to improve outcomes. Here, we describe the development and evaluation of checklists to support recruitment of committed allogeneic hematopoietic stem cell donors. STUDY DESIGN AND METHODS: Checklists were developed with the following objectives: (1) improve best-practice adherence; (2) reduce errors; and (3) support standardization at stem cell drives. Topics included: recruiting needed donors; securing informed consent; maintaining good-documentation practices; and supervising registration and tissue sample collection. Checklists were iteratively revised with input from stakeholders. We evaluated the checklists by examining recruitment outcomes and errors (i.e., preventing registrants from being listed as donors) pre- (11/2011-8/2016) and post- (9/2016-11/2019) implementation by the Canadian donor recruitment organization Stem Cell Club. Quantitative and qualitative methods were employed to analyze recruiters' perspectives on the checklists. RESULTS: The checklists supported recruitment of donors from needed demographic groups as Stem Cell Club expanded its recruitment effort from 4118 registrants (60% male, 58% non-European) pre-implementation to 10,621 (52% male, 56% non-European) post-implementation. Checklist implementation was associated with a marked reduction in errors (from 13.2% to 1.9%) and a three-fold increase in the match rate of recruited donors (from 0.024% to 0.075%). Qualitative and quantitative analysis of recruiter feedback supported that the checklists' objectives were realized from the recruiter perspective. DISCUSSION: We developed checklists to support donor recruitment and showed that their implementation was valued by recruiters and associated with both reduced errors and improved donor recruitment outcomes. The checklists are relevant to donor recruitment organizations worldwide.

Post-Surgical Complications After Bladder Outlet Reducing Surgery: An Analysis of The FDA Manufacturer and User Facility Device Experience (MAUDE) Database.

OBJECTIVE: To examine voluntary reports in the Food & Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database, categorize complications and assign device-related causality with transurethral resection of the prostate (TURP), prostatic urethral lift (PUL), and transurethral water vapor therapy (TWVT). METHODS: A review was performed using the terms "Urolift," "Rezum," and "transurethral resection of the prostate" between 01/01/2015 and 12/31/2019. Duplicate and incomplete reports were excluded. The Gupta system was used to report complications and device related causality.1 Pearson's Chi-square analysis was performed to compare minor (Level 1) versus major (Levels 2-4) complications. RESULTS: A total of 548 events were examined. After removal of duplicates (n = 60), irrelevant reports (n=65), and incomplete information (n = 14), we included 409 events (74.6%). Of the 409 events, 214 were for TURP, 112 for TWVT, and 83 for PUL. In aggregate, 39.4% of events were minor/Level 1 (n=161/409). The proportion of subjects with Level 2-4 complications versus Level 1 complications was significantly higher for PUL than TURP or TWVT [X2 (2, N = 408) = 41.4023, P < .00001]. Device causality was attributable to device malfunction in 60.4% of cases (n=247/409). CONCLUSION: Device malfunction was noted in all groups and 39.4% of these were minor (Level 1). However, the majority of PUL reports noted a Level 3 or 4 complication (50.6%, 42/83), primarily bleeding related. Previous studies have not revealed significant risk of bleeding and suggests a discrepancy between study data and real-world experience that may alter patient counseling practices.

Factors associated with registrant availability for unrelated adult donor hematopoietic stem cell donation: Analysis of the stem cell registry at Canadian Blood Services.

BACKGROUND: Greater use of unrelated donors to support hematopoietic cell transplantation can be hampered by unavailability of registrants when identified as potential candidates for donation. METHODS: Multivariate analysis was performed to identify donor factors associated with availability for verification of human leukocyte antigen typing (VT) needed before donor activation. All VT requests for registrants on the Canadian Blood Services Stem Cell Registry between 1 January and 31 December 2018 were reviewed (n = 1358). RESULTS: Potential donors identified by transplant centers were categorized as available at the time of VT but ineligible for medical or other reasons (n = 130 and excluded from further analysis), available (n = 622) or unavailable (n = 566) due to scheduling, loss of interest, and/or inability to contact. With multivariate analysis, registrants who previously donated blood, those recruited online or from blood donation clinics, and a shorter interval between registration and VT request were significantly correlated with increased donor availability. Donor sex and geographic location, however, displayed no correlation. CONCLUSION: Online registration and recruitment at whole blood donation centers should be enhanced to increase the availability of registrants at VT. More insight is needed to maintain registrant availability following community in-person recruitment events, especially if the interval between registration and activation is prolonged. Recruitment of male registrants who are well informed should not negatively impact availability.

Development and evaluation of stem cell collection procedure diagrams to support the education and recruitment of committed stem cell donors.

BACKGROUND: Diagrams which allow potential unrelated stem cell donors to visualize the stem cell collection process were hypothesized to support the recruitment and education of committed stem cell donors. STUDY DESIGN AND METHODS: A series of bone marrow and peripheral blood stem cell collection procedure diagrams were developed, featuring young adult male donors of varied ethnic backgrounds. Post-implementation, surveys were conducted to evaluate stakeholder perspective on the diagrams' utility. A quality improvement project was conducted at five stem cell drives from 2017 to 2018 at which recruiters did or did not show the diagrams to potential donors. Following the drives, registrants were invited to complete a survey exploring their experience, knowledge and attitude towards donation. RESULTS: The diagrams were implemented in Canada in 07/2016. Of 293 participating registrants (24·7% non-Caucasian males) recruited at five drives between 2017 and 2018, 76% (n = 197) were shown the diagrams. Participants who were shown the diagrams were significantly more likely to report that the recruiters appeared very knowledgeable (89% vs. 76%, P = 0·019) and to report improved self-reported knowledge of stem cell donation (P = 0·010) compared to participants not shown the diagram. Data are also shown demonstrating that stakeholders in donor recruitment used and valued the diagrams and that use of the diagrams was associated with improved donor recruitment outcomes in Canada. CONCLUSION: This report is the first evaluation of stem cell collection diagrams in the literature. The diagrams are relevant to donor registries, recruitment organizations and transplant centres worldwide, and their use may support efforts to educate and recruit committed, ethnically diverse donors.

Treating chronic pain and opioid misuse disorder among underserved populations in Colorado.

The increased use of prescription opioids has resulted in widespread misuse. As a result, more than 40,000 Americans lost their lives to opiate overdose in 2016 alone. These data have led to a national movement focused on appropriate opioid prescribing practices. The Centers for Disease Control and Prevention (CDC) developed its Guidelines for Prescribing Opioids for Chronic Pain (2017), a template for pain management and substance assessment in primary care. These CDC guidelines aim to prevent misuse/deaths and early identification of substance use disorders. Although the guidelines are appropriate for initiation of opioid therapy, they are not sufficient to manage patients who have already developed misuse disorders. Other modalities such as medication-assisted treatment (MAT) have been described as beneficial for patients with high risk for or who have an opioid misuse disorder. This article builds on the CDC's 2017 advisory document by applying it in praxis: first, non-opioid medication therapy options and nonmedication therapy options are explored; next, a case study is presented of an integrated primary care-managed patient who presented with both chronic pain and established opioid use disorder. Although the CDC guidelines were not followed in the patient's initial prescription opioid treatment regimen, those guidelines were used as a starting point for follow-up treatment, helping both to assess the patient's risk for opioid misuse disorder and to determine that MAT was an appropriate method of treatment.

Identification of infectious species after resection of soft-tissue sarcomas.

BACKGROUND: Pathogenic species in deep tissue infections after soft-tissue sarcoma (STS) resection is largely unstudied, particularly the role of anaerobic bacteria, risks factors for those pathogens, and the time course of infection presentation. METHODS: Retrospective analysis of 64 patients requiring operative debridement for deep tissue infection after STS resection was undertaken to identify infectious species and study risk factors for anaerobic infections. Kaplan-Meier methods examined the time course of infection presentation. RESULTS: STS subtypes were most commonly pleomorphic STS, myxofibrosarcoma, and undifferentiated STS. Staphylococcus aureus was the most common organism isolated (56%). Twenty (31%) infections were positive for ≥1 anaerobic organism. Twelve gram-positive and 10 gram-negative aerobic organisms were isolated. Most (90%) anaerobic-containing infections were polymicrobial, vs 52% of purely aerobic infections. No significant risk factors for anaerobic infections were identified. Median time from tumor resection until debridement was significantly greater for anaerobic infections (54.5 days) than for purely aerobic infections (29.5 days; P = 0.004), a difference so pronounced that using "presentation after 53 days" as a proxy for the presence of anaerobic pathogens had an accuracy of 81%. CONCLUSIONS: Because polymicrobial and anaerobic bacterial infections are common, we strongly support antibiotic use with anaerobic coverage at debridement, particularly for infections presenting later.

Infinicare framework for integrated understanding of health-related activities in clinical and daily-living contexts.

Clinical and consumer health informatics interventions promise to transform health care, yielding higher quality, more accessible care at a lower cost. However, the potential of these interventions cannot be achieved if they are developed and rolled out in a disconnected way: clinic-based systems typically do not interface with home-based systems that capture patient-generated health-related data. The fragmentation between these interventions severely limits the benefits of all interventions; given that health care is a continuum between clinical and daily-living settings. We introduce the Infinicare framework, which posits that clinical health-related activities "shape" daily-living-based health-related activities and, conversely, that daily-living-based health-related activities "inform" activities in clinics. Non-alignment of activities across these diverse contexts yields systemic gaps. Workflow studies that capture health-related activities and characterise gaps between clinical and daily-living contexts can inform the design and implementation of gap-filling, collaborative health information technologies. To inform these technologies, workflow studies should be patient-oriented, include both clinical and daily-living settings and subsume both process and structure variables. Novel methodologies are needed to effectively and efficiently capture health-related activities across both clinical and daily-living settings and their contexts. Guidelines for applying these recommendations in developing collaborative health information technologies are provided.

The Colorado Collaborative for Nursing Research: Providing Trended Nurse-Sensitive Patient Outcome Data Across Entities.

Nurse leaders lack timely access to trended electronic health record (EHR) data to drive decision making. Robust nurse-sensitive patient outcome data are difficult to locate in EHRs and largely absent across entities. The Colorado Collaborative for Nursing Research is currently testing a federated data system to get nurse leaders the information they need, when they need it.

Numerical Simulation of the Freeze-Thaw Behavior of Mortar Containing Deicing Salt Solution.

This paper presents a one-dimensional finite difference model that is developed to describe the freeze-thaw behavior of an air-entrained mortar containing deicing salt solution. A phenomenological model is used to predict the temperature and the heat flow for mortar specimens during cooling and heating. Phase transformations associated with the freezing/melting of water/ice or transition of the eutectic solution from liquid to solid are included in this phenomenological model. The lever rule is used to calculate the quantity of solution that undergoes the phase transformation, thereby simulating the energy released/absorbed during phase transformation. Undercooling and pore size effects are considered in the numerical model. To investigate the effect of pore size distribution, this distribution is considered using the Gibbs-Thomson equation in a saturated mortar specimen. For an air-entrained mortar, the impact of considering pore size (and curvature) on freezing was relatively insignificant; however the impact of pore size is much more significant during melting. The fluid inside pores smaller than 5 nm (i.e., gel pores) has a relatively small contribution in the macroscopic freeze-thaw behavior of mortar specimens within the temperature range used in this study (i.e., +24 °C to -35 °C), and can therefore be neglected for the macroscopic freeze-thaw simulations. A heat sink term is utilized to simulate the heat dissipation during phase transformations. Data from experiments performed using a low-temperature longitudinal guarded comparative calorimeter (LGCC) on mortar specimens fully saturated with various concentration NaCl solutions or partially saturated with water is compared to the numerical results and a promising agreement is generally obtained.

The Influence of Cellulose Nanocrystals on the Hydration and Flexural Strength of Portland Cement Pastes.

Recent research has shown that cellulose nanocrystals (CNCs) can be used at low dosage levels (approximately 0.2% by volume of cement) to increase the extent of hydration and to improve the flexural strength of cement pastes. However, the previous work was based on using a CNC made from a single source material and processing technique and was performed using only Type V cement. This work examines the influence of various raw material sources and processing techniques used to make the CNCs. In total, nine different CNCs were investigated with pastes made using Type I/II and Type V cements. Isothermal calorimetry (IC), thermogravimetric analysis (TGA) and ball-on-three-ball (B3B) flexural strength testing were used to quantify the performance of CNC-cement composites. IC and TGA results showed that CNCs increased the degree of hydration in all systems. IC results showed that the increase in total heat release was greater in the Type V than in the Type I/II cement paste systems. B3B flexural testing indicated an increase in flexural strength of up to 20% with both Type I/II and Type V systems. These results also showed that the performance of CNC-cement composites can be affected by the source and manufacturing process used to make the CNC.

Efficient Palladium-Triggered Release of Vorinostat from a Bioorthogonal Precursor.

Bioorthogonal uncaging strategies have recently emerged as an experimental therapeutic approach to control drug release. Herein we report a novel masking strategy that enables to modulate the metal chelating properties of hydroxamic acid groups by bioorthogonal chemistry using Pd-functionalized resins. This novel approach allowed to devise an inactive precursor of the histone deacetylase inhibitor vorinostat that was efficiently uncaged by heterogeneous Pd catalysis in cell culture models of glioma and lung cancer.

A Workflow Framework for Health Management in Daily Living Settings.

Daily-living settings are increasingly becoming care delivery settings, particularly for chronic conditions. Workflow studies can help understand care delivery in daily-living settings, but traditional frameworks originally developed for institutional settings may not be appropriate to study health management in daily-living settings. Based on a qualitative study of health management patterns among eight patients at an academic hospital anticoagulation clinic, we have developed a model for examining daily living setting-based workflow. This model can inform consumer informatics interventions.

Rapid Discovery and Structure-Activity Relationships of Pyrazolopyrimidines That Potently Suppress Breast Cancer Cell Growth via SRC Kinase Inhibition with Exceptional Selectivity over ABL Kinase.

Novel pyrazolopyrimidines displaying high potency and selectivity toward SRC family kinases have been developed by combining ligand-based design and phenotypic screening in an iterative manner. Compounds were derived from the promiscuous kinase inhibitor PP1 to search for analogs that could potentially target a broad spectrum of kinases involved in cancer. Phenotypic screening against MCF7 mammary adenocarcinoma cells generated target-agnostic structure-activity relationships that biased subsequent designs toward breast cancer treatment rather than to a particular target. This strategy led to the discovery of two potent antiproliferative leads with phenotypically distinct anticancer mode of actions. Kinase profiling and further optimization resulted in eCF506, the first small molecule with subnanomolar IC50 for SRC that requires 3 orders of magnitude greater concentration to inhibit ABL. eCF506 exhibits excellent water solubility, an optimal DMPK profile and oral bioavailability, halts SRC-associated neuromast migration in zebrafish embryos without inducing life-threatening heart defects, and inhibits SRC phosphorylation in tumor xenografts in mice.

Normalization to Maximal Voluntary Contraction is Influenced by Subacromial Pain.

In this study, we aimed to determine if electromyography (EMG) normalization to maximal voluntary isometric contractions (MVIC) was influenced by subacromial pain in patients with subacromial impingement syndrome. Patients performed MVICs in unique testing positions for each shoulder muscle tested before and after subacromial injection of local anesthetic. In addition to collection of MVIC data, EMG data during an arm elevation task were recorded before and after injection. From a visual analog pain scale, patients had a 64% decrease in pain following the injection. Significant increases in MVICs were noted in 4 of the 7 shoulder muscles tested: anterior, middle and posterior deltoid, and lower trapezius. No significant differences were noticed for the upper trapezius, latissimus dorsi, or serratus anterior. MVIC condition (pre and post injection) had a significant influence on EMG normalization for the anterior deltoid and lower trapezius muscle. Results indicate that subacromial pain can influence shoulder muscle activity, especially for the deltoid muscles and lower trapezius. In addition, normalization to MVIC in the presence of pain can have unpredictable results. Caution should be taken when normalizing EMG data to MVIC in the presence of pain.

The Influence of Calcium Chloride Deicing Salt on Phase Changes and Damage Development in Cementitious Materials.

The conventional CaCl2-H2O phase diagram is often used to describe how calcium chloride behaves when it is used on a concrete pavement undergoing freeze-thaw damage. However, the chemistry of the concrete can alter the appropriateness of using the CaCl2-H2O phase diagram. This study shows that the Ca(OH)2 present in a hydrated portland cement can interact with CaCl2 solution creating a behavior that is similar to that observed in isoplethal sections of a ternary phase diagram for a Ca(OH)2-CaCl2-H2O system. As such, it is suggested that such isoplethal sections provide a reasonable model that can be used to describe the behavior of concrete exposed to CaCl2 solution as the temperature changes. Specifically, the Ca(OH)2 can react with CaCl2 and H2O resulting in the formation of calcium oxychloride. The formation of the calcium oxychloride is expansive and can produce damage in concrete at temperatures above freezing. Its formation can also cause a significant decrease in fluid ingress into concrete. For solutions with CaCl2 concentrations greater than about 11.3 % (by mass), it is found that calcium oxychloride forms rapidly and is stable at room temperature (23 °C).

Palladium-mediated dealkylation of N-propargyl-floxuridine as a bioorthogonal oxygen-independent prodrug strategy.

Herein we report the development and biological screening of a bioorthogonal palladium-labile prodrug of the nucleoside analogue floxuridine, a potent antineoplastic drug used in the clinic to treat advanced cancers. N-propargylation of the N3 position of its uracil ring resulted in a vast reduction of its biological activity (~6,250-fold). Cytotoxic properties were bioorthogonally rescued in cancer cell culture by heterogeneous palladium chemistry both in normoxia and hypoxia. Within the same environment, the reported chemo-reversible prodrug exhibited up to 1,450-fold difference of cytotoxicity whether it was in the absence or presence of the extracellular palladium source, underlining the precise modulation of bioactivity enabled by this bioorthogonally-activated prodrug strategy.