Current State of Dermatology Mobile Applications With Artificial Intelligence Features.

Importance: With advancements in mobile technology and artificial intelligence (AI) methods, there has been a substantial surge in the availability of direct-to-consumer mobile applications (apps) claiming to aid in the assessment and management of diverse skin conditions. Despite widespread patient downloads, these apps exhibit limited evidence supporting their efficacy. Objective: To identify and characterize current English-language AI dermatology mobile apps available for download, focusing on aspects such as purpose, supporting evidence, regulatory status, clinician input, data privacy measures, and use of image data. Evidence Review: In this cross-sectional study, both Apple and Android mobile app stores were systematically searched for dermatology-related apps that use AI algorithms. Each app's purpose, target audience, evidence-based claims, algorithm details, data availability, clinician input during development, and data usage privacy policies were evaluated. Findings: A total of 909 apps were initially identified. Following the removal of 518 duplicates, 391 apps remained. Subsequent review excluded 350 apps due to nonmedical nature, non-English languages, absence of AI features, or unavailability, ultimately leaving 41 apps for detailed analysis. The findings revealed several concerning aspects of the current landscape of AI apps in dermatology. Notably, none of the apps were approved by the US Food and Drug Administration, and only 2 of the apps included disclaimers for the lack of regulatory approval. Overall, the study found that these apps lack supporting evidence, input from clinicians and/or dermatologists, and transparency in algorithm development, data usage, and user privacy. Conclusions and Relevance: This cross-sectional study determined that although AI dermatology mobile apps hold promise for improving access to care and patient outcomes, in their current state, they may pose harm due to potential risks, lack of consistent validation, and misleading user communication. Addressing challenges in efficacy, safety, and transparency through effective regulation, validation, and standardized evaluation criteria is essential to harness the benefits of these apps while minimizing risks.

How do we achieve blinding in modern electronic and paper medical records during the conduct of transfusion trials?

BACKGROUND: Regulatory aspects of transfusion medicine add complexity in blinded transfusion trials when considering various electronic record keeping software and blood administration processes. The aim of this study is to explore strategies when blinding transfusion components and products in paper and electronic medical records. METHODS: Surveys were collected and interviews were conducted for 18 sites across various jurisdictions in North America to determine solutions applied in previous transfusion randomized control trials. RESULTS: Sixteen responses were collected of which 11 had previously participated in a transfusion randomized control trial. Various solutions were reported which were specific to the laboratory information system (LIS) and electronic medical record (EMR) combinations although solutions could be grouped into four categories which included the creation of a study product code in the LIS, preventing the transmission of data from the LIS to the EMR, utilizing specialized stickers and labels to conceal product containers and documents in the paper records, and modified bedside procedures and documentation. DISCUSSION: LIS and EMR combinations varied across sites, so it was not possible to determine combination-specific solutions. The study was able to highlight solutions that may be emphasized in future iterations of LIS and EMR software as well as procedural changes that may minimize the risk of unblinding.

Femoral neck stress fracture return to activity and the effect of metabolic dysfunction on recovery: A systematic review.

Background: Femoral neck stress fractures are rare fractures traditionally found in athletes and military personnel. There is limited literature on return to activity. Objectives: To report return to activity rates and times, and long-term outcomes for femoral neck stress fractures reported in the literature. To examine the effects of bone metabolic dysfunction and surgical management on return to activity following FNSF. Research design & methods: A systematic literature review of case reports and case series on adults with femoral neck stress fracture that were diagnosed by gross fracture line on X-ray or gold-standard diagnosis with MRI was conducted. Initial search was limited to articles published from January 1997 to Jan 2023 listed in Medline, Embase, and Scopus. Additional articles were manually added via search of retained paper sources. Patient demographics, fracture type, return to activity time, and surgical vs non-surgical treatment modality were collected. In addition, long-term outcomes and metabolic effects, if reported, were abstracted. Results: A total of 40 case reports or case series were retained. 123 stress fractures of the femoral neck from 103 patients were compiled. Of the 103 patients, data on return to activity at least one year following treatment was available for 53 patients. 71% (37/53) of those with long-term follow-up information returned to full pre-injury activity. 24% (13/53) at long-term follow-up had functional recovery but did not return to pre-injury activity due to residual pain. 4% (3/53) had disabling pain. Metabolic workup information was available for 36 patients. Conclusion: Long-term follow-up and return to activity information following FNSF treatment are not commonly reported. Based on the available data, outcomes appear benign with most returning to full activity. There is a clear need for standardization of follow-up periods and hip function measure after FNSF treatment. Additionally, a sizable proportion of FNSF occurred in a new population of low-activity individuals with abnormal bone metabolism, which warrants further exploration.

Transfusion of ABO-group identical red blood cells following uncrossmatched transfusion does not lead to higher mortality in civilian trauma patients.

BACKGROUND: Questions persist about the safety of switching non-group O recipients of group O uncrossmatched red blood cells (RBC) or low titer group O whole blood (LTOWB) to ABO-identical RBCs during their resuscitation. METHODS: The database of an earlier nine-center study of transfusing incompatible plasma to trauma patients was reanalyzed. The patients were divided into three groups based on 24-h RBC transfusion: (1) group O patients who received group O RBC/LTOWB units (control group, n = 1203), (2) non-group O recipients who received only group O units (n = 646), (3) non-group O recipients who received at least one unit of group O and non-group O units (n = 562). Fixed marginal effect of receipt of non-O RBC units on 6- and 24-h and 30-day mortality was calculated. RESULTS: The non-O patients who received only group O RBCs received fewer RBC/LTOWB units and had slightly but significantly lower injury severity score compared to control group; non-group O patients who received both group O and non-O units received significantly more RBC/LTOWB units and had a slightly but significantly higher injury severity score compared to control group. In the multivariate analysis, the non-O patients who received only group O RBCs had significantly higher mortality at 6-h compared to the controls; the non-group O recipients of O and non-O RBCs did not demonstrate higher mortality. At 24-h and 30-days, there were no differences in survival between the groups. CONCLUSION: Providing non-group O RBCs to non-group O trauma patients who also received group O RBC units is not associated with higher mortality.

Severe fetal anemia caused by anti-Jra : Burst forming unit-erythroid colony formation inhibition assay suggesting possible erythroid suppression mechanism.

BACKGROUND: The Jr blood group system includes a single, high-prevalence antigen, Jra , encoded by the ABCG2 gene. The impact of anti-Jra in pregnancy is variable, ranging from no clinical effect to severe anemia including some fetal deaths. Case reports have postulated that anti-Jra mediated fetal anemia is poorly hemolytic, suggesting other mechanisms of anemia may be involved. STUDY DESIGN AND METHODS: We describe the case of severe anti-Jra mediated fetal anemia. At Canadian Blood Services laboratories, maternal anti-Jra was tested for phagocytic activity via a monocyte monolayer assay (MMA) and erythroid suppression via inhibition of burst forming unit-erythroid (BFU-E) colony formation assays. The New York Blood Center sequenced exons 4 and 7 of the ABCG2 gene. RESULTS AND DISCUSSION: Sequencing of exons 4 and 7 of the ABCG2 gene revealed maternal compound heterozygosity for two nonsense mutations at exon 7 (c.706 C > T and c.784G > T). Fetal sequencing revealed the c.706C > T polymorphism. The MMA showed a borderline phagocytic index (around the cutoff of five for both donor segments tested [5 ± 1 and 7 ± 3]). The BFU-E colony formation inhibition assay suggested a dose-dependent inhibition of BFU-E colony formation with inhibition percentages of 4%, 11%, and 43% at maternal serum concentrations of 2%, 5%, and 10%, respectively. Our findings support the hypothesis that anti-Jra may impair erythropoiesis leading to clinically significant fetal/neonatal anemia. A referral to maternal fetal medicine is recommended if anti-Jra is detected in pregnancy, regardless of the titer.

Serologic reactivity of unidentified specificity in antenatal testing and hemolytic disease of the fetus and newborn: The BEST collaborative study.

BACKGROUND: The clinical significance of serologic reactivity of unidentified specificity (SRUS) in pregnancy is not clear based on available literature. The aim of this study is to determine if SRUS is associated with hemolytic disease of the fetus and newborn (HDFN). STUDY DESIGN AND METHODS: Retrospective data were collected from eight institutions over an 11-year study period (2010-2020), when available (5/8 sites). The outcome of the pregnancies with SRUS-no, mild, moderate, or severe HDFN-was determined. RESULTS: SRUS was demonstrated in 589 pregnancies. After excluding those with incomplete data, a total of 284 pregnancies were included in the primary HDFN outcome analysis. SRUS was detected in 124 (44%) pregnancies in isolation, and none were affected by HDFN. Of 41 pregnancies with SRUS and ABO incompatibility, 37 (90%) were unaffected, and 4 (10%) were associated with mild HDFN. Of 98 pregnancies with SRUS and concurrent identifiable antibody reactivity(s), 80 (81%) were unaffected, and 19 (19%) were associated with mild to severe HDFN. There was 1 case of mild HDFN and 1 case of severe HDFN in the 21 pregnancies with SRUS, ABO incompatibility, and concurrent identifiable antibody reactivity(s), and 19 (90%) were unaffected by HDFN. Among all patients with repeat testing, newly identified alloantibodies or other antibodies were identified in 63 of 212 (30%) patients. Although most were not clinically significant, on occasion SRUS preceded clinically significant antibody(s) associated with HDFN (3%, 5/188). CONCLUSION: The antenatal serologic finding of SRUS in isolation is not associated with HDFN but may precede clinically significant antibodies.

An online immunohematology educational resource for post-graduate hematology trainees: LearnSerology.ca.

BACKGROUND: Canadian hematology residents are required to demonstrate competencies in transfusion medicine by the end of their 2-year training. Prior evaluation of final year trainees revealed significant variation in knowledge. To address the lack of standardization in serology teaching, an online educational immunohematology resource was created and evaluated. STUDY DESIGN AND METHODS: All Canadian post-graduate trainees completing a residency program in adult hematology during the 2018/2019 academic year were invited to participate. Only trainees from one university were exposed to the program curriculum. A validated exam was administered to trainees at both exposed and unexposed sites at the start of the academic year as a pre-test and in the following year as a post-test. The effectiveness of the program was assessed by both comparing the degree of improvement from pre- to post-test, and by comparing performance on the post-test. RESULTS: 57 trainees from 13 universities completed the pre-test, and 45 trainees from 14 universities completed the post-test. A strong trend towards better performance in the exposed vs non-exposed trainees on the post-test was observed, and the difference was more pronounced, and statistically significant, when analysis was limited to two questions relating to interpretation of an antibody investigation panel. DISCUSSION: LearnSerology.ca is effective and may be potentially superior to traditional immunohematology teaching. The interactive capability of the platform can improve skills related to the resolution of red cell antibody panels.

How do I provide rare red cells to patients?

BACKGROUND: The demand for rare blood is expected to increase in Canada as its population continues to expand through immigration from diverse regions of the world. MATERIAL AND METHODS: This paper outlines a national approach to providing rare red cells for patients through the Rare Blood Program of Canadian Blood Services (CBS). Data detailing the rare red cell requests and inventory managed by CBS' Rare Blood Program is provided. RESULTS: The provision of rare red cells involves multiple considerations such as multidisciplinary communication, serologic/molecular confirmation, donor recruitment, inventory optimization and logistical factors. CONCLUSION: The description of CBS' Rare Blood Program will inform others that seek to create, optimize, or expand programs that facilitate the provision of rare blood. New technologies such as next-generation sequencing may also affect how rare donors are identified and recruited in the future.

Prediction of massive transfusion with the Revised Assessment of Bleeding and Transfusion (RABT) score at Canadian level I trauma centers.

BACKGROUND: Early damage control resuscitation and massive transfusion (MT) protocol activations improve outcomes in trauma patients with hemorrhagic shock, where scores to guide MT prediction are used including: the Assessment of Blood Consumption (ABC), Shock Index (SI), and Revised Assessment of Bleeding and Transfusion (RABT) scores. Our aim was to validate the RABT score in patients from two level I trauma centers in Canada. METHODS: A retrospective review of adult patients meeting trauma team activation criteria receiving >1 unit of red blood cells (RBCs) within 24 h of admission, from 2015 to 2020, was conducted. A RABT score ≥ 2, ABC score ≥ 2, and Shock Index (SI) ≥ 1 was used to predict MT using both research (≥10 RBCs in 24 h) and clinical (≥3 RBCs in 3 h) definitions. Scores were assessed and compared using sensitivity, specificity, and the area under the receiver operating characteristic (AUROC). RESULTS: We analyzed 514 patients with a mean age of 44.4 (19.2) years and a median injury severity score of 29 [18-38]. For both MT definitions, the RABT score trended towards higher sensitivity and lower specificity compared to ABC score and SI. For both research and clinical definitions of MT, the AUROC for the RABT score was not significantly higher (Research - RABT: 0.673 [0.610-0.735], ABC: 0.642 [0.551-0.734], SI 0.691 [0.625-0.757]; Clinical - RABT: 0.653 [0.608-0.698], ABC: 0.646 [0.600-0.691], SI 0.610 [0.559-0.660]). CONCLUSION: The RABT score is a valid tool for predicting the need for MTPs, performing similarly with a trend towards higher sensitivity when compared to the ABC score and SI.

Impacts of COVID-19 and elective surgery cancellations on platelet supply and utilization in the Canadian Province of British Columbia.

BACKGROUND AND OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic raised concerns about the vulnerability of platelet supply and the uncertain impact of the resumption of elective surgery on utilization. We report the impact of COVID-19 on platelet supply and utilization across a large, integrated healthcare system in the Canadian province of British Columbia (BC). MATERIALS AND METHODS: Historical platelet use in BC by indication was compiled for fiscal year 2010/2011-2019/2020. Platelet collections, initial daily inventory and disposition data were assessed pre-COVID-19 (1 April 2018-15 March 2020) and for two COVID-19 time periods in BC: a shutdown phase with elective surgeries halted (16 March-17 May, 2020) and a renewal phase when elective surgeries resumed (18 May-27 September 2020); comparisons were made provincially and for individual health authorities. RESULTS: Historically, elective surgeries accounted for 10% of platelets transfused in BC. Initial daily supplier inventory increased from baseline during both COVID-19 periods (93/90 units vs. 75 units pre-COVID-19). During the shutdown phase, platelet utilization decreased 10.4% (41 units/week; p < 0.0001), and remained significantly decreased during the ensuing renewal period. Decreased platelet utilization was attributed to fewer transfusions during the shutdown phase followed by a decreased discard/expiry rate during the renewal phase compared to pre-COVID-19 (15.2% vs. 18.9% pre-COVID-19; p < 0.0001). Differences in COVID-19 platelet utilization patterns were noted between health authorities. CONCLUSION: Decreased platelet utilization was observed in BC compared to pre-COVID-19, likely due to a transient reduction in elective surgery as well as practice and policy changes triggered by pandemic concerns.

Pharmacokinetics of Orally Administered GS-441524 in Dogs.

Despite being FDA-approved for COVID-19, the clinical efficacy of remdesivir (Veklury®) remains contentious. We previously pointed out pharmacokinetic, pharmacodynamic and toxicology reasons for why its parent nucleoside GS-441524, is better suited for COVID-19 treatment. Here, we assess the oral bioavailability of GS-441524 in beagle dogs and show that plasma concentrations ~24-fold higher than the EC50 against SARS-CoV-2 are easily and safely sustained. These data support translation of GS-441524 as an oral agent for COVID-19.

Transfusion of blood components containing ABO-incompatible plasma does not lead to higher mortality in civilian trauma patients.

BACKGROUND: This study investigated the effect on mortality of transfusing ABO-incompatible plasma from all sources during trauma resuscitation. METHODS: Demographic, transfusion, and survival data were retrospectively extracted on civilian trauma patients. Patients were divided by receipt of any quantity of ABO-incompatible plasma from any blood product (incompatible group) or receipt of solely ABO-compatible plasma (compatible group). The primary outcome was 30-day mortality, while other outcomes included 6- and 24-hour mortality. Mixed-effects logistic regression was used to model the effect of various predictor variables, including receipt of incompatible plasma, on mortality outcomes. RESULTS: Nine hospitals contributed data on a total of 2618 trauma patients. There were 1282 patients in the incompatible group and 1336 patients in the compatible group. In both the unadjusted and adjusted models, the 6-hour, 24-hour, and 30-day mortality rates were not significantly different between these groups. The patients in the incompatible group were then divided into high volume (>342 mL) and low volume (≤342 mL) incompatible plasma recipients. In the adjusted model, the high-volume group had higher 24-hour mortality when the Trauma Injury Severity Score survival prediction was >50%. Mortality at 6 hours and 30 days was not higher in this model. The low-volume group did not have increased mortality at any of the time points in this adjusted model. CONCLUSION: The transfusion of incompatible plasma in civilian trauma resuscitation does not lead to higher 30-day mortality. The finding of higher mortality in a select group of recipients in the secondary analysis warrants further study.

Bioreducible Phosphonoamidate Pro-drug Inhibitor of Enolase: Proof of Concept Study.

Glycolysis inhibition remains aspirational in cancer therapy. We recently described a promising phosphonate inhibitor of enolase for cancers harboring homozygous deletions of ENO1. Here, we describe the application of a nitroheterocycle phosphonoamidate pro-drug pair to capitalize on tumor hypoxia. This bioreducible prodrug exhibits greater-than 2-fold potency under hypoxic conditions compared to normoxia and exhibits robust stability in biological fluids. Our work provides strong in vitro proof-of-concept for using bioreduction as a pro-drug delivery strategy in the context of enolase inhibition.

Why Great Mitotic Inhibitors Make Poor Cancer Drugs.

Chemotherapy is central to oncology, perceived to operate only on prolific cancerous tissue. Yet, many non-neoplastic tissues are more prolific compared with typical tumors. Chemotherapies achieve sufficient therapeutic windows to exert antineoplastic activity because they are prodrugs that are bioactivated in cancer-specific environments. The advent of precision medicine has obscured this concept, favoring the development of high-potency kinase inhibitors. Inhibitors of essential mitotic kinases exemplify this paradigm shift, but intolerable on-target toxicities in more prolific normal tissues have led to repeated failures in the clinic. Proliferation rates alone cannot be used to achieve cancer specificity. Here, we discuss integrating the cancer specificity of prodrugs from classical chemotherapeutics and the potency of mitotic kinase inhibitors to generate a class of high-precision cancer therapeutics.

Utilising red cell antigen genotyping and serological phenotyping in sickle cell disease patients to risk-stratify patients for alloimmunisation risk.

BACKGROUND: Alloimmunisation and haemolytic transfusion reactions (HTRs) can occur in patients with sickle cell disease (SCD) despite providing phenotype-matched red blood cell (RBC) transfusions. Variant RBC antigen gene alleles/polymorphisms can lead to discrepancies in serological phenotyping. We evaluated differences between RBC antigen genotyping and phenotyping methods and retrospectively assessed if partial antigen expression may lead to increased risk of alloimmunisation and HTRs in SCD patients at a tertiary centre in Canada. METHODS: RBC antigen phenotyping and genotyping were performed by a reference laboratory on consenting SCD patients. Patient demographic, clinical and transfusion-related data were obtained from a local transfusion registry and chart review after research ethics board approval. RESULTS: A total of 106 SCD patients were enrolled, and 91% (n = 96) showed additional clinically relevant genotyping information when compared to serological phenotyping alone. FY*02N.01 (FY*B GATA-1) (n = 95; 90%) and RH variant alleles (n = 52, 49%; majority accompanied by FY*02N.01) were common, the latter with putative partial antigen expression in 25 patients. Variability in genotype-phenotype antigen prediction occurred mostly in the Rh system, notably with the e antigen (kappa: 0.17). Fifteen (14.2%) patients had a history of alloimmunisation, with five having HTR documented; no differences in clinical outcomes were found in patients with partial antigen expression. Genotype/extended-phenotype matching strategies may have prevented alloimmunisation events. CONCLUSION: We show a high frequency of variant alleles/polymorphisms in the SCD population, where genotyping may complement serological phenotyping. Genotyping SCD patients before transfusion may prevent alloimmunisation and HTRs, and knowledge of the FY*02N.01 variant allele increases feasibility of finding compatible blood.