Clinical Diagnostic Tests Research Articles

Enhancing a low-cost, minimally invasive screening test for dihydropyrimidine dehydrogenase mutations linked to 5-fluorouracil sensitivity by integrating computational mutation predictions.

226 Background: 5-Fluorouracil (5-FU), a common chemotherapy for solid tumors, is metabolized primarily by dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene. With > 200 known variants, individuals with nonfunctional DPYD alleles exhibit impaired 5-FU metabolism and are at risk of severe toxicity. Approximately 35% of the population has partial DPD deficiency, and 0.2% completely lack enzymatic activity. Despite this, DPYD genotyping is not standard practice. This study evaluates the use of non-invasive saliva samples for DPYD genotyping and combines AI-based molecular prediction modeling to search for novel variants within DPYD coding region. Saliva samples were collected from fifty-six healthy individuals and from gastrointestinal (GI) cancer patients including a family cohort of nineteen individuals and three unrelated patients undergoing chemotherapy. Methods: gDNA was sequenced for nine DPYD variants reported to reduced or abrogate DPD activity: c.1905+1G > A, c.1679T > G, c.2846A > T, c.1129-5923C > G, c.1236G > A, c.299_302delTCAT, c.703C > T, c.2983G > T, and c.557A > G. cBioPortal was utilized to search the TCGA database for studies involving colon cancer patients with novel DPYD mutations exhibiting a total FIS score of at least 2 or identified through 3D modeling of DPD using PyMol based on their proximity to or the presence of polar contacts within the active site. Putative pathogenic mutations were analyzed using AlphaMissense and ChimeraX to assign a RSMD score, assessing their potential negative impact on DPD function. Results: Computational studies identified three mutations in DPYD from TCGA colon cancer patients with an unknown impact on DPD and a FIS greater than 4 (c.198G > C/T, c.2161G > A, c.2185G > A), suggesting potential disruption of its function. Four mutations (c.424T > G, c.427T > G, c.2460G > C, c.2909C > A) were identified through protein modeling using PyMol, but only two had a FIS greater than 2. Of these seven identified mutations, four (c.198G > C/T, c.2161G > A, c.2185G > A, c.2909C > A) also scored highly using AlphaMissense and ChimeraX. In silico prediction models from VarSome listed c.2185G > A as Pathogenic Moderate and c.2909C > A as Pathogenic Very Strong. Sequencing of saliva samples indicated mutations c.1129-5923C > G and c.1236G > A were present in four and three volunteers, respectively, and c.1905+1G > A in one case. Mutations identified in GI cancer patients were c.1129-5923C > G and c.1236G > A. Conclusions: By combining computational modeling with the analysis of naturally occurring mutations in colon cancer patients, we have successfully identified potentially pathogenic mutations in the DPYD gene. This information can enhance existing clinical diagnostic tests, providing a more comprehensive assessment of DPYD mutations, including novel variants.

P1216 Mapping the Ulcerative Colitis patient journey in Saudi Arabia from healthcare professionals' perspective: A cross-sectional non-interventional study

Abstract Background The burden of ulcerative colitis (UC) is increasing in Saudi Arabia (KSA), and patients often suffer from delayed diagnosis and appropriate management 1. This study investigates the current UC patient journey in KSA from healthcare professionals' (HCPs) perspective. It aims to evaluate treatment patterns, identify critical gaps, and provide insights to guide interventions that enhance the quality of life for UC patients in KSA. Methods Quantitative interviews were conducted with 60 HCPs (45 gastroenterologists and 15 internists) from different regions in KSA using a computer-assisted personal interview (CAPI) system. The survey domains included clinical symptoms, diagnostic testing, endoscopic scoring, treatment goals, and medications sequencing. Data integrity was guaranteed using pre-programmed data checks and a pilot phase for tool validation. We used the Dimensions software 6.0.1 to analyse descriptive statistics. The protocol was approved by the Institutional Review Board (IRB) (NSOT-2023-09-4) of King Saud University. Results Data was collected from 60 HCPs with an average of 17 ± 12.5 years of experience. Most HCPs (60%) use the Modified Mayo Score to categorise UC patients clinically. First-ranked treatment goals were clinical remission (53.3%), endoscopic remission (35%), and quality of life improvement (33.3%). Patients’ lack of awareness and fear of long-term side effects are the main barriers against achieving these goals. For outpatient moderate-to-severe UC, the most common first-line treatments are steroids (34%), (5-ASAs) 5-aminosalicylates (26%), and TNF-α inhibitors (21%). While for second-line treatments, TNF-α inhibitors (23%), interleukin 12/23 inhibitors (19%), and JAK inhibitors (14%) are prevailing. On the other hand, for inpatient acute severe UC, steroids remain the top choice (46%); however, TNF-α inhibitors (28%) surpassed 5-ASAs (12%). Top second-line treatments are the same as moderate-to-severe UC. Sphingosine 1-phosphate (S1P) receptor modulators are not well-utilized since they aren’t SFDA-approved yet. HCPs attribute this to lack of availability (88%), unfamiliarity with the treatment (24%), and formulary exclusion (12%). Conclusion This study underscores the complexities of UC management. While HCPs prioritize clinical and endoscopic remission, patient-related barriers such as lack of awareness impede optimal care. First-line treatments for moderate-to-severe UC include steroids, 5-aminosalicylates, and TNF-α inhibitors, while second-line therapies involve TNF-α inhibitors, interleukin 12/23 inhibitors, and JAK inhibitors. However, limited awareness of newer therapies like S1P modulators suggests a need for broader education and improved access to integrate emerging therapies effectively. References Mosli M, Almudaiheem H, Alameel T, et al. Saudi Arabia consensus guidance for the diagnosis and management of adults with inflammatory bowel disease. Saudi Journal of Gastroenterology. 2023;29(7):1-35. doi:10.4103/sjg.sjg_277_22

Multidisciplinary cardiorenal program for heart failure patients: Improving outcomes through comprehensive care.

The Cardiorenal Program (CRP), implemented within a specialized heart failure and kidney disease clinic, encompasses a multidisciplinary approach to the management of patients with heart failure and kidney disease. It focuses on optimizing therapy and improving patient outcomes. The CRP includes a range of services, including clinical evaluation, diagnostic testing, medical treatment, and patient education. The program provides comprehensive care for patients with cardiorenal syndrome, and includes a variety of healthcare professionals, such as cardiologists, nephrologists, pharmacists, and nurses, working together to provide the best possible care. The program also incorporates specific performance indicators to continuously evaluate and improve patient outcomes. The CRP's integrated multidisciplinary care and patient-centered approach is promising for the management of patients with cardiorenal syndrome.

Clinical phenotype of COVID-19 vaccine-associated myocarditis in Victoria, 2021-22: a cross-sectional study.

To describe myocarditis as an adverse event after coronavirus disease 2019 (COVID-19) vaccination, including a detailed description of clinical phenotypes and diagnostic test results and differences by age, sex, and degree of troponin level elevation. Retrospective cross-sectional study. Cases of suspected myocarditis following the administration of a COVID-19 vaccine in Victoria during 22February 2021 - 30 September 2022 reported to Surveillance of Adverse Events Following Vaccination In the Community (SAEFVIC), with symptom onset within 14 days of vaccination, and deemed to be confirmed myocarditis according to the Brighton Collaboration Criteria. Demographic (sex, broad age group), vaccine, and clinical presentation characteristics; cardiac investigation results (troponin levels, electrocardiography, echocardiography, cardiac magnetic resonance imaging [cMRI]). Of 454 SAEFVIC reports of suspected COVID-19 vaccine-associated myocarditis, 206 were deemed confirmed cases. The median age of people with confirmed myocarditis was 21 years (interquartile range [IQR], 16-32 years; range, 10-76 years); 129 were aged 24 years or younger (63%), 155 were male (75%). The median time from vaccination to symptom onset was two days (IQR, 1-4 days); 201 cases (98%) followed the administration of mRNA vaccines; five cases followed vaccination with AZD122. Forty-six cases followed first vaccine doses (22%), 138 second doses (67%), and 22 cases third vaccine doses (11.0%). In 201 cases, people initially presented to emergency departments; 129 people were admitted to hospital (63%; median length of stay, two days; IQR, 1-3 days). Five people were admitted to intensive care. Echocardiographic abnormalities were identified in 26 of 200 patients (13%); electrocardiographic abnormalities were identified in 105 of 206 patients (51%; less frequently in female than male patients: adjusted odds ratio, 0.75; 95% confidence interval, 0.64-0.89). Troponin levels were elevated in 205 of 206 patients; the median increase was greater in male (95.3-fold; IQR, 5.8-273-fold) than female patients (9.9-fold; IQR, 4.7-50-fold). No cMRI abnormalities were found in patients for whom the troponin increase was threefold or less. The clinical severity of COVID-19 vaccine-associated myocarditis in Victoria was generally mild. Markers of a more severe phenotype were more frequently recorded for male patients and people aged 24 years or younger. A threefold troponin increase could be used as a threshold for risk stratification of people with COVID-19 vaccine-associated myocarditis, especially in hospitals with limited access to cMRI facilities.

Designs and appropriate choices for diagnostic test accuracy study

Diagnostic tests are indispensable tools in clinical practice and are rigorously evaluated through scientifically designed accuracy studies before the clinical practice. The accuracy of these tests directly affects the correctness of the diagnosis and the rationality of treatment decisions. This article introduces the types of designs and their characteristics used in diagnostic test accuracy studies, including single-group studies, diagnostic case-control studies, single-group paired studies, and parallel-group studies. It recommends appropriate design types based on the research question stage, the diagnostic test's role in the clinical diagnostic pathway, and the actual clinical application scenario to provide suggestions for further standardizing the design of current clinical diagnostic test accuracy research. This article may help clinical researchers better understand and choose the appropriate type of diagnostic test accuracy study design to improve diagnostic test accuracy research quality.

Cerebral Death: Unraveling the Mystery of the Silent Mind

The permanent loss of all brain stem functions, such as breathing, awareness, and cranial nerve reflexes, is known as brain stem death (BSD), and it presents a significant medical and ethical issue. While other bodily functions, such as heart activity and circulation, can be maintained with medical intervention, BSD is defined by the cessation of brain stem activity. The key characteristic that distinguishes BSD from other conditions, such as coma or a persistent vegetative state, is the complete and irreversible loss of brain stem function—a critical control centre for basic physiological processes. Diagnosing BSD requires strict clinical criteria and diagnostic testing to confirm the full and permanent nature of the condition. This typically involves a comprehensive neurological examination, assessment of cranial nerve reflexes, and confirmation through additional tests, such as cerebral blood flow studies or electroencephalography (EEG). A diagnosis of BSD carries significant ethical and legal implications, particularly in relation to organ donation, as it often plays a role in identifying potential donors. The ethical considerations surrounding BSD include its impact on families, the distinction between death and end-of-life care, and the challenges posed by varying legal and cultural perspectives. It highlights the importance of a clear diagnosis, obtaining informed consent, and adhering to established medical protocols to uphold human dignity and ethical standards. As medical technology advances and societal views evolve, the discussion around brain stem death continues to be a critical issue in both bioethics and modern medical practice.

Bayesian Decision Curve Analysis With Bayesdca.

Clinical decisions are often guided by clinical prediction models or diagnostic tests. Decision curve analysis (DCA) combines classical assessment of predictive performance with the consequences of using these strategies for clinical decision-making. In DCA, the best decision strategy is the one that maximizes the net benefit: the net number of true positives (or negatives) provided by a given strategy. Here, we employ Bayesian approaches to DCA, addressing four fundamental concerns when evaluating clinical decision strategies: (i) which strategies are clinically useful, (ii) what is the best available decision strategy, (iii) which of two competing strategies is better, and (iv) what is the expected net benefit loss associated with the current level of uncertainty. While often consistent with frequentist point estimates, fully Bayesian DCA allows for an intuitive probabilistic interpretation framework and the incorporation of prior evidence. We evaluate the methods using simulation and provide a comprehensive case study. Software implementation is available in the bayesDCA R package. Ultimately, the Bayesian DCA workflow may help clinicians and health policymakers adopt better-informed decisions.

TCNQ and Its Derivatives as Electrode Materials in Electrochemical Investigations-Achievement and Prospects: A Review.

7,7',8,8'-tetracyanoquinodimethane (TCNQ) is one of the most widely used effective surface electron acceptors in organic electronics and sensors, which opens up a very interesting field in electrochemical applications. In this review article, we outline the historical context of electrochemically stable selective electrode materials based on TCNQ and its derivatives and their development, their electrochemical characteristics, and the experimental aspects of their electrochemical applications. TCNQ-modified electrodes are characterized by long-term stability, reproducibility, and a low detection limit compared to other sensors; thus, their use can increase determination speed and flexibility and reduce investigation costs. TCNQ and its derivatives can also be successfully combined with other detector materials for cancer-related clinical diagnostic testing. Examples of simple, rapid, and sensitive detection procedures for various analytes are provided. Applications of new electrochemically stable TCNQ-based metal/covalent-organic hybrid frameworks, with exceptionally large surface areas, tunable pore sizes, diverse functionality, and high electrical conductivity, are also presented. As a result, they also offer enormous potential as revolutionary catalysts, drug carrier systems, and smart materials, as well as for use in gas storage. The use of TCNQ compounds as promising active electrode materials in high-power organic batteries/energy storage devices is discussed. We hope that the information featured in this review will provide readers with a good understanding of the chemistry of TCNQ and, more importantly, help to find good ways to prepare new micro-/nanoelectrode materials for rational sensor design.

Prognostic significance of serum interleukin-6 in severe/critical COVID-19 patients treated with tocilizumab: a detailed observational study analysis

Baseline IL-6 levels have been found to be non-predictive of subsequent outcomes following tocilizumab treatment, highlighting the need for more reliable predictive markers. To address this, a retrospective analysis was conducted on the clinical profiles, diagnostic tests, and follow-up prognoses of 60 patients with severe or critical COVID-19, all of whom were identified as experiencing a cytokine storm and subsequently received tocilizumab treatment. Among the patients, the overall survival rate during follow-up was 80%, with further analysis revealing that advanced age was an independent risk factor for adverse outcomes. Following tocilizumab administration, a statistically significant increase in IL-6 and D-dimer levels was observed, while markers such as C-reactive protein (CRP), procalcitonin (PCT), and fibrinogen demonstrated reductions compared to pre-treatment values. Specifically, IL-6 levels initially surged briefly after tocilizumab intervention before gradually diminishing. To assess the prognostic utility of IL-6, the Receiver Operating Characteristic (ROC) curve was employed, which yielded an area under the curve (AUC) of 0.812, indicating strong predictive capability, with a sensitivity of 100% and a specificity of 53.49%. The optimal cut-off value for IL-6 was identified at 147.79 pg/mL. In conclusion, IL-6 levels tend to rise transiently following tocilizumab therapy, before gradually declining. These post-treatment IL-6 measurements may serve as a valuable biomarker for assessing prognosis in patients undergoing this treatment.

Diagnostic and Therapeutic Value of Endoscopic Retrograde Cholangiopancreatography in Acute Cholangitis: A Study From Kashmir Valley, India.

Background Cholangitis, or bile duct infection, can present in two primary forms, namely, acute ascending cholangitis (the milder form) and acute fulminant cholangitis (the more severe variety). In all types of cholangitis, bile duct obstruction occurs, with choledocholithiasis (the presence of gallstones in the bile duct) being the leading cause of this blockage. Escherichia coli is the most commonly isolated pathogen in these infections. If the biliary duct infection becomes suppurative, sepsis is a common complication. Cholangitis can lead to significant morbidity and mortality, which may persist even with prompt treatment or drainage. Endoscopic retrograde cholangiopancreatography (ERCP) remains a crucial diagnostic and therapeutic tool for managing acute cholangitis. Despite its importance in managing cholangitis, there is limited research on the characteristics and outcomes of ERCP in patients with acute cholangitis from Kashmir in northern India. This study was conducted to explore the role and effectiveness of ERCP in the diagnosis and treatment of acute cholangitis. Methodology This observational study was conducted in the Department of Gastroenterology at a tertiary care hospital in North India over a period of two years, from January 1, 2018, to December 31, 2019. The study included 48 consecutive patients diagnosed with acute cholangitis who underwent ERCP for both diagnostic and therapeutic purposes. Results The median age of the patients included in the study was 55 years and the male-to-female ratio in the study cohort was 1.6:1, with 30 (62.5%) males and 18 (37.5%) females. Among the patients with comorbid conditions, hypertension was the most common, present in 12.5% of cases. Choledocholithiasis was the most frequent diagnosis, identified in 70.83% of patients. Ultrasonography of the abdomen revealed choledocholithiasis in 34 (70.83%) cases, the most common radiological finding. A comparison of clinical symptoms and diagnostic test results before and after 72 hours of ERCP demonstrated a statistically significant improvement in patient outcomes following the procedure. Conclusions In contrast to other diagnostic approaches for evaluating biliary duct obstruction, timely ERCP remains a reliable and effective option for both diagnosis and therapeutic intervention in acute cholangitis. It is associated with improved diagnostic accuracy, enhanced therapeutic outcomes, and reduced morbidity and mortality rates, making it a critical tool in managing this potentially life-threatening condition.

Diagnosis and typing of leukemia using a single peripheral blood cell through deep learning

AbstractLeukemia is highly heterogeneous, meaning that different types of leukemia require different treatments and have different prognoses. Current clinical diagnostic and typing tests are complex and time‐consuming. In particular, all of these tests rely on bone marrow aspiration, which is invasive and leads to poor patient compliance, exacerbating treatment delays. Morphological analysis of peripheral blood cells (PBC) is still primarily used to distinguish between benign and malignant hematologic disorders, but it remains a challenge to diagnose and type these diseases solely by direct observation of peripheral blood(PB) smears by human experts. In this study, we apply a segmentation‐based enhanced residual network that uses progressive multigranularity training with jigsaw patches. It is trained on a self‐built annotated dataset of 21,208 images from 237 patients, including five types of benign white blood cells(WBCs) and eight types of leukemic cells. The network is not only able to discriminate between benign and malignant cells, but also to typify leukemia using a single peripheral blood cell. The network effectively differentiated acute promyelocytic leukemia (APL) from other types of acute myeloid leukemia (non‐APL), achieving a precision rate of 89.34%, a recall rate of 97.37%, and an F1 score of 93.18% for APL. In contrast, for non‐APL cases, the model achieved a precision rate of 92.86%, but a recall rate of 74.63% and an F1 score of 82.75%. In addition, the model discriminates acute lymphoblastic leukemia(ALL) with the Ph chromosome from those without. This approach could improve patient compliance and enable faster and more accurate typing of leukemias for early diagnosis and treatment to improve survival.

Treatment of equine keratomycosis, part 1: selection of appropriate therapy based on clinical presentation and diagnostic testing improves clinical outcomes.

To determine clinical outcome, treatment costs, and hospitalization duration in horses treated for keratomycosis and identify ophthalmic examination and diagnostic results associated with these outcomes. This was a retrospective study of 126 equine keratomycosis cases between 2004 and 2020 with fungal infection confirmed on cytology, culture, and/or histopathology and a minimum of 1-month follow-up. Details of the ophthalmic examination, diagnostic test results, and treatment and cost outcomes were recorded. Outcomes of interest were analyzed by treatment type. The relationship of patient and diagnostic test variables to the outcomes of interest was determined via logistic and linear regression models. Globe retention and positive visual outcome occurred in 82.5% and 78.9% of medically and 88.4% and 85.5% of surgically treated cases, respectively. While not statistically significant, there were more positive clinical outcomes with surgery; in recent years, the globe and vision were preserved in 94.7% of cases following penetrating keratoplasty. The choice to pursue surgery was related to lesion depth. Medical treatment was associated with statistically shorter hospitalization times and lower total and hospitalization invoices compared to all surgical treatments. Diagnosis of stromal abscess was associated with higher total invoice and longer hospitalization times compared to ulcerative keratomycosis, although clinical outcomes were similar. Overall positive clinical outcomes were achieved despite the severity of the disease in many cases, highlighting the need for appropriate treatment selection based on clinical presentation. Expanding knowledge of clinical decision-making, treatment options, and associated clinical and financial outcomes may further improve outcomes for equine keratomycosis patients.

How, why and when are delayed (back-up) antibiotic prescriptions used in primary care? A realist review integrating concepts of uncertainty in healthcare

BackgroundAntimicrobial resistance is a global patient safety priority and inappropriate antimicrobial use is a key contributing factor. Evidence have shown that delayed (back-up) antibiotic prescriptions (DP) are an effective and safe strategy for reducing unnecessary antibiotic consumption but its use is controversial.MethodsWe conducted a realist review to ask why, how, and in what contexts general practitioners (GPs) use DP. We searched five electronic databases for relevant articles and included DP-related data from interviews with healthcare professionals in a related study. Data were analysed using a realist theory-driven approach – theorising which context(s) influenced (mechanisms) resultant outcome(s) (context-mechanism-outcome-configurations: CMOCs).ResultsData were included from 76 articles and 41 interviews to develop a program theory comprising nine key and 56 related CMOCs. These explain the reasons for GPs’ tolerance of risk to different uncertainties and how these may interact with GPs’ work environment, self-efficacy and perceived patient concordance to make using DP as a safety-net or social tool more or less likely, at a given time-point. For example, when a GP uses clinical scores or diagnostic tests: a clearly high or low score/test result may mitigate scientific uncertainty and lead to an immediate or no antibiotic decision; an intermediary result may provoke hermeneutic (interpretation-related) uncertainty and lead to DP becoming preferred and used as a safety net. Our program theory explains how DP can be used to mitigate some uncertainties but also provoke or exacerbate others.ConclusionThis review explains how, why and in what contexts GPs are more or less likely to use DP, as well as various uncertainties GPs face which DP may mitigate or provoke. We recommend that efforts to plan and implement interventions to optimise antibiotic prescribing in primary care consider these uncertainties and the contexts when DP may be (dis)preferred over other interventions to reduce antibiotic prescribing. We also recommend the following and have included example activities for: (i) reducing demand for immediate antibiotics; (ii) framing DP as an ‘active’ prescribing option; (iii) documenting the decision-making process around DP; and (iv) facilitating social and system support.

6793 The Potential Of Melatonin As A Treatment Option For Cushing’s Syndrome In Humans Based On Observations In Cushingoid Dogs

Abstract Disclosure: K. Fecteau: None. It is known that the secretion of cortisol and melatonin is circadian, with the former increasing during morning hours and the latter increasing during the dark hours of night. Studies investigating melatonin concentrations in patients with Cushing’s syndrome have reported differing results, with some having low melatonin concentrations, and others normal or high concentrations. Interestingly, adrenal glands have been shown to express melatonin receptors, and in vitro studies with human adrenal cells have shown a decrease in cortisol, as well as other adrenocortical steroids, when treated with melatonin. In human adrenal gland explants, melatonin reportedly inhibited ACTH stimulated circadian clock genes, as well as cortisol and progesterone production. Melatonin is often used as a first-line of treatment in dogs with atypical Cushing’s, where cortisol is normal, other adrenocortical steroids are elevated, and typical clinical signs of Cushing’s are present. Retrospective data collected in our diagnostic laboratory from dogs that had at least two submissions (before & during treatment), showed 34 percent of dogs on melatonin improved clinically. Of the 34 percent, 26.4 percent experienced either similar or more aberrant steroid concentrations, and 7.6 percent experienced lower steroid concentrations. Approximately 40 percent of dogs had significantly lower androstenedione when retested on melatonin. In humans, Cushing’s disease is a rare cause of androgen excess, with one study reporting occurrence of less than 4 percent in women. Adrenocortical carcinoma is also rare, however, women with this type of tumor may exhibit clinical signs of androgen excess due to adrenal androgen hypersecretion, and up to 25 percent of women with clinical signs had normal testosterone and elevated androstenedione. Therefore, based on the effectiveness of melatonin on lowering androstenedione concentrations and improving clinical signs associated with increased androgens and glucocorticoids in dogs, it may be an inexpensive and conservative option, especially for patients presenting with clinical signs but diagnostic testing is either negative of equivocal for Cushing’s. Presentation: 6/2/2024

B-242 Improved Patient Satisfaction With Novel Capillary Blood Collection Devices as an Alternative to Venipuncture for Applications in Clinical Proteomic Assays

Abstract Background Two new clinical diagnostic tests are available that aid in the identification of lung nodules as likely malignant or likely benign. One test is an ELISA that measures the levels of seven autoantibodies to tumor-associated antigens that aids in the identification of patients with likely malignant lung nodules who may benefit from timely intervention. The other is an LC-MS/MS-based (MRM) test that measures the ratio of two proteins (LG3BP and C163A) combined with several clinical and radiological factors to aid in the identification of patients with likely benign lung nodules who may benefit from additional CT surveillance. Since commercialization, we have found that test access may be improved by providing alternatives to traditional venipuncture. Therefore, we conducted evaluation studies with two novel non-fingerstick capillary blood collection devices. These devices puncture the skin by utilizing either microneedles (Device A) or a lancet (Device B) for capillary blood collection. Methods Blood specimens were collected from consented donors using one of the two capillary blood collection devices and by venipuncture into K2EDTA blood collection tubes. Feedback was also solicited from the healthcare professionals and donors via a standard questionnaire. The whole blood specimens were shipped to the testing laboratory where the samples were processed according to the respective clinical assay workflows. Feasibility testing for the ELISA-based assay was conducted with both devices using normal healthy donor specimens (105 donors for Device A and 43 for Device B). Clinical evaluation was executed utilizing only Device B (77 donors with lung cancer and 13 with an indeterminate lung nodule). Feasibility testing for the LC-MS/MS-based assay was conducted with both devices using healthy donor specimens (103 donors for Device A and 41 for Device B), while clinical evaluation utilized only Device B (80 donors with lung cancer and 30 with an indeterminate lung nodule). Results Both capillary blood collection devices revealed good correlations to venous blood draws for the ELISA-based test during feasibility. The two devices also showed good correlations for the LC-MS/MS-based test, with the results from Device A requiring a correction factor. Due to technical and operational challenges throughout feasibility, Device B became the preferred device to be evaluated for the clinical study. Good correlations for both diagnostic tests were observed from the clinical study. During clinical evaluation, healthcare professionals and donors were asked to rate the ease-of-use, pain, and speed of collection when using Device B. Most healthcare professionals (108/126) rated the device as easy to use. Ninety-five percent of the donors reported minimal pain while the remainder reported moderate pain. Ninety-one percent of the donors felt that the time required to collect blood using Device B was acceptable. Sixty percent of the donors preferred the capillary collection device (Device B), 17% preferred venipuncture, while 23% reported no preference for blood collection. Conclusions The novel capillary blood collection devices demonstrated high correlations for two clinical diagnostic tests. Feedback collected from healthcare professionals and donors revealed that the majority preferred the capillary blood collection device as compared to traditional venipuncture for blood collection.

Ocular Complications of Mpox: Evolving Understanding and Future Directions.

Mpox (formerly known as monkeypox), an infectious disease caused by the monkeypox virus (MPXV), has been endemic in regions of Central and Western Africa. In 2022, the global spread of the clade IIb MPXV led to a multinational outbreak, primarily affecting sexual transmission networks among men who have sex with men. Despite interventions, new cases have continued to emerge. In Africa, the spread of a novel strain of clade I MPXV, clade Ib, has prompted a Public Health Emergency of International Concern designation by the World Health Organization in August 2024. This article provides an updated overview of the epidemiology, systemic, and ocular manifestations, highlighting the clinical features, diagnostic testing, and implications relevant to ophthalmologists and eye care providers, including infection prevention and control measures. The ocular manifestations of mpox primarily involve the ocular surface and anterior segment, with presentations ranging from conjunctivitis to severe, vision-threatening keratitis and uveitis. While the 2022 to 2024 Clade IIb outbreak has shown a lower incidence of ocular involvement compared with previous outbreaks, the potential for significant visual morbidity remains. Treatment involves both systemic and topical therapies, with tecovirimat being the primary systemic option, though its efficacy and ophthalmic bioavailability remain under investigation. Ongoing surveillance and research are essential to further understand the epidemiology and ophthalmic features of mpox and, ultimately, to optimize prevention and treatment strategies for patients.

Wong-Type Dermatomyositis: Literature Review of a Rare Variant.

Wong-type dermatomyositis (WTDM) was first formally discussed in the literature in 1969 by Dr. K.O. Wong. This rare variant of dermatomyositis (DM) is characterized by overlapping features of both classic DM and the cutaneous features of pityriasis rubra pilaris. Since 1969, few cases of WTDM have been published in the literature likely due to the rarity of this condition or lack of recognition by clinicians. This narrative review presents the current published English literature on WTDM, analyzing its clinical presentation, diagnostic testing, and treatments along with a comparison to classic DM. Given the overlap of features of both diseases and patients experiencing a better response to classic DM treatments, our results suggest that WTDM is a rare subtype of DM rather than simply an overlap of pityriasis rubra pilaris and DM presenting in 1 patient. We suggest that clinicians evaluate WTDM patients with very thorough histories, physical examinations, histopathology, and appropriate serological studies and monitor closely for systemic symptoms and development of malignancy. WTDM should be treated using conventional treatments for classical DM. Further studies are needed to understand the pathogenesis of WTDM including more specific and distinguishing autoantibody profiles from classical DM, as well as long-term clinical course of WTDM for best management, including recently available biological treatments.

Dominant stop-loss HNRNPA1 variants in juvenile-onset myopathy.

Heterogeneous nuclear ribonucleoprotein A1 is involved in nucleic acid homeostatic functions. The encoding gene HNRNPA1 has been associated with several neuromuscular disorders including an amyotrophic lateral sclerosis-like phenotype, distal hereditary motor neuropathy, multisystem proteinopathy, and various myopathies. We report two unrelated individuals with monoallelic stop loss variants affecting the same codon of HNRNPA1. Two individuals with unsolved juvenile-onset myopathy were enrolled under approved institutional protocols. Phenotype data were collected and genetic analyses were performed, including whole-exome sequencing (WES). The two probands (MNOT002-01 and K1440-01) showed a similar onset of slowly progressive extremity and facial weakness in early adolescence. K1440-01 presented with facial weakness, winged scapula, elevated serum creatine kinase (CK) levels, and mild neck weakness. MNOT002-01 also exhibited elevated CK levels along with facial weakness, cardiomyopathy, respiratory dysfunction, pectus excavatum, a mildly rigid spine, and loss of ambulation. On quadriceps muscle biopsy, K1440-01 displayed rounded myofibers, mild variation in fiber diameter, and type 2 fiber hypertrophy, while MNOT002-01 displayed rimmed vacuoles. Monoallelic stop-loss variants in HNRNPA1 were identified for both probands: c.1119A>C p.*373Tyrext*6 (K1440-01) and c.1118A>C p.*373Serext*6 (MNOT002-01) affect the same codon and are both predicted to lead to the addition of six amino acids before termination at an alternative stop codon. Both stop-loss variants in our probands are likely pathogenic. Our findings contribute to the disease characterization of pathogenic variants in HNRNPA1. This gene should be screened in clinical diagnostic testing of unsolved cases of sporadic or dominant juvenile-onset myopathy.

Diagnostic Utility of SARS-CoV-2 Nucleocapsid Antigenemia: A Meta-analysis.

Studies of the diagnostic performance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid antigen in blood (antigenemia) have reached variable conclusions. The potential utility of antigenemia measurements as a clinical diagnostic test needs clarification. We performed a systematic review of Pubmed, Embase, and Scopus through July 15, 2023, and requested source data from corresponding authors. Summary sensitivity from 16 studies (4543 cases) sampled at ≤14 days of symptoms was 0.83 (0.75-0.89), and specificity was 0.98 (0.87-1.00) from 6 studies (792 reverse transcription polymerase chain reaction-negative controls). Summary sensitivity and specificity for paired respiratory specimens with cycle threshold values ≤33 were 0.91 (0.85-0.95) and 0.56 (0.39-0.73) from 10 studies (612 individuals). Source data from 1779 cases reveal that >70% have antigenemia 2 weeks following symptom onset, which persists in <10% at 28 days. The available studies suffer from heterogeneity, and Omicron-era data are scarce. Nucleocapsid antigenemia currently has limited utility due to limitations of existing studies and lack of Omicron-era data. Improved study designs targeting potential clinical uses in screening, surveillance, and complex clinical decision-making-especially in immunocompromised patients-are needed.

Clinical characteristics and diagnostic test for spherophakia: A retrospective analysis

BackgroundThis study aimed to analyze ocular characteristics in patients diagnosed with spherophakia, establish effective diagnostic criteria, and aid clinicians in prompt identification and management. MethodsA retrospective case series identified spherophakia cases through medical records and literature searches. The case group included spherophakia patients, and the control group comprised individuals with similar eye conditions. Intraocular lens calculations used the SRK-T formula, and statistical analyses were performed using SPSS. Diagnostic efficacy was assessed through receiver operating characteristic (ROC) curve analysis. ResultsThe study included 12 cases (23 eyes) from medical records and 86 patients (142 eyes) from literature sources. Characteristics of spherophakia included bilateral involvement, younger age, shallow anterior chamber depth, lens dislocation, and secondary glaucoma. A diagnostic criterion based on lens power demonstrated high sensitivity (94.3 %) and specificity (91.9 %). ROC analysis yielded area under the ROC curve (AUROC) values of 0.974 for lens power, outperforming refractive error (0.119), corneal curvature (0.465) and axial length (0.496). The lens power cutoff for diagnosing spherophakia was 31.25D. ConclusionThe study offers crucial insights into spherophakia's clinical characteristics and presents a practical diagnostic criterion using lens power, enhancing early detection and management. Further research is needed to validate and refine these findings, establishing standardized diagnostic criteria for spherophakia.