Specific Test Research Articles

Can triglyceride related indices be reliable markers in the assessment of polycystic ovarian syndrome?

Abstract Objectives This study aimed to evaluate the diagnostic utility of the triglyceride glucose (TyG), triglyceride glucose–body mass (TyG-BMI), and lipid accumulation product (LAP) indices for both screening polycystic ovary syndrome (PCOS) and diagnosing insulin resistance (IR) in women diagnosed with PCOS. Methods Retrospective data from medical records of 124 women were analyzed, with 71 in the PCOS group and 53 in the non-PCOS group. The PCOS diagnosis followed the 2003 Rotterdam criteria. Basic clinical and biochemical parameters were compared. The TyG index was computed using the formula ln [triglyceride (TG) (mmol/L) × fasting plasma glukose (FPG) (mg/dL)/2]. TyG-BMI value was derived as TyG × BMI. LAP was calculated as (waist circumference (WC-58) × TG (mmol/L). IR was identified if Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was >2.7. Results TyG-BMI (AUC=0.62) and LAP indices (AUC=0.61) did not demonstrate statistically significant diagnostic performance for PCOS. Regarding IR in PCOS patients, the highest AUC was for TyG-BMI (0.84, 95 % CI: 0.73–0.93, p<0.001) with a cutoff at 116.15, showing 80 % sensitivity and 86 % specificity. LAP had an AUC of 0.86 with a cutoff of 30.21 (sensitivity 80 %, specificity 81 %), while TyG showed an AUC of 0.78 (95 % CI: 0.67–0.89, p<0.001) with a cutoff of 4.47, demonstrating a sensitivity of 70 % and specificity of 72 %. Conclusions Numerous biochemical markers have been explored for PCOS detection, however, many are expensive, not universally available, and necessitate specific test kits. TyG, TyG-BMI, and LAP indices might not serve as reliable markers for PCOS screening but could offer utility in identifying IR in Turkish women diagnosed with PCOS.

Development of handling energy factors for use of dustiness data in exposure assessment modelling.

Several exposure assessment models use dustiness as an input parameter for scaling or estimating exposure during powder handling. Use of different dustiness methods will result in considerable differences in the dustiness values as they are based on different emission generation principles. EN17199:2019 offers 4 different dustiness test methods considering different dust release scenarios (e.g. powder pouring, mixing and gentle agitation, and vibration). Conceptually, the dustiness value by a given method can be multiplied with a scenario-specific modifier, called a handling energy factor (Hi), that allows conversion of a dustiness value to a release constant. Therefore, a Hi, scaling the effective mechanical energy in the process to the energy supplied in the specific dustiness test, needs to be applied. To improve the accuracy in predictive exposure modelling, we derived experimental Hi to be used in exposure algorithms considering both the mass- and number-based dust release fraction determined by the EN17199-3 continuous drop (CD) and the EN17199-4 small rotating drum (SRD) test methods. Three materials were used to evaluate the relationship between dustiness and dust levels during pouring powder from different heights in a controlled environment. The results showed increasing scatter and difference between the Hi derived for the 2 test methods with increasing pouring height. Nearly all the Hi values obtained for both SRD and CD were <1 indicating that the dustiness tests involved more energy input than the simulated pouring activity and consequently de-agglomeration and dust generation were higher. This effect was most pronounced in CD method showing that SRD mechanistically resembles more closely the powder pouring.

Maternal and congenital human cytomegalovirus infection: laboratory testing for detection and diagnosis.

Human cytomegalovirus (CMV) is the leading cause of congenital infection worldwide and the most common cause of non-genetic sensorineural hearing loss. As there is no vaccine or other specific intervention to prevent congenital CMV infection, there is a need to identify maternal and congenital infections with sensitive and specific testing as early as possible. There is no widely accepted practice for screening during pregnancy or in all newborns for identification of possible cases of congenital CMV. Currently, screening during pregnancy is limited to those identified as at risk followed by fetal and/or neonatal testing when congenital infection is suspected. This review focuses primarily on the current status of laboratory testing for diagnosis of maternal and congenital CMV infections. Primary maternal infection is best diagnosed using serologic testing, including CMV IgM, IgG, and avidity testing, while fetal infection should be assessed by nucleic acid amplification testing (NAAT) of amniotic fluid. Urine and saliva NAATs are the mainstay for diagnosis of congenital CMV in the first 3 weeks of life. Testing of dried blood spots can be useful for diagnosis of congenital CMV outside of the newborn period. The gaps in knowledge such as the prognostic value of viral loads in various sample types are addressed.

Evaluation of a novel, sensitive thyroid-stimulating hormone assay as a diagnostic test for thyroid disease in cats.

Clinicians commonly use thyroid-stimulating hormone (TSH) concentrations to diagnose thyroid disorders in humans and dogs. In cats, canine TSH chemiluminescent immunoassays (CLIA) assays are commonly used to measure TSH, but these TSH-CLIAs cannot measure low TSH concentrations (< 0.03 ng/mL) and therefore cannot distinguish between low-normal concentrations and truly low TSH concentrations (characteristic of hyperthyroidism). Our aim was to evaluate a novel TSH assay based on bulk acoustic wave (BAW) technology that has lower functional sensitivity (0.008 ng/mL) than TSH-CLIAs. 169 untreated hyperthyroid cats, 53 cats treated with radioiodine (131I), 12 cats with chronic kidney disease (CKD), and 78 clinically healthy cats. Serum concentrations of T4, TSH-CLIA, and TSH-BAW were measured in all cats. Untreated hyperthyroid cats were divided into 4 severity groups (subclinical, mild, moderate, and severe), whereas 131I-treated cats were divided into euthyroid and hypothyroid groups. Test sensitivity, specificity, and positive predictive value for identifying hyperthyroidism were higher for TSH-BAW (90.5%, 98.9%, and 86.9%) than TSH-CLIA (79.9%, 76.7%, and 21.7%; P < .001). Test sensitivity for identifying 131I-induced hypothyroidism was only 45.5% for T4 versus 100.0% for both TSH-CLIA and TSH-BAW (P = .03), whereas TSH-BAW had a higher positive predictive value (100%) than did either TSH-CLIA (81.2%) or T4 (71.9%). Serum TSH-BAW alone or together with T4 is a highly sensitive and specific diagnostic test for evaluating feline hyperthyroidism and iatrogenic hypothyroidism. Finding low serum TSH-BAW concentrations is most useful for diagnosing subclinical and mild hyperthyroidism, in which serum T4 remains within or only slightly above the reference interval.

The value of sonographic microvascular imaging in the diagnosis of lipedema.

Lipedema is a chronic disease marked by symmetric enlargement of painful nodular and fibrotic adipose tissue, predominantly affecting the limbs. Since there is no specific test or biomarker for this condition, years often pass before the diagnosis of lipedema is established for the first time, thereby causing psychosocial distress, including depression, eating disorders, and social isolation. Over the last few years several advanced Doppler-based technologies have been developed to visualize slow flow blood vessels and superficial microvascular architecture undetectable by traditional color Doppler flow imaging (CDFI). The aim of this study was to evaluate the superficial microvascular anatomy in lipedema patients compared to healthy controls and investigate the clinical significance of the Ultra Micro Angiography (UMA) technology in the diagnosis of lipedema. This new technique may contribute to reduce the diagnostic delay and, eventually, establish and guide treatment strategies toward a better therapeutic outcome in lipedema patients. 25 patients with lipedema and ten healthy controls with no history of lipedema were included in this study. All ultrasound examinations were performed on a novel high-performance ultrasound system (Resona R9/Mindray) using CDFI and the UMA technique. In all of the patients, Ultra Micro Angiography achieved the excellent visualization of microvascular structures, revealing that most lipedema patients showed grade 3 (n = 13) or grade 2 (n = 8) flow. UMA was superior to CDFI for depicting the microvascular structures. Here we show that UMA imaging characterizes the subcutaneous microvasculature with an unprecedented accuracy. The method has the advantage of being sensitive to small, slow-flowing vessels. This allows for the assessment of the course of vessels and vascular pathologies in great detail. Thus, UMA as a non-invasive diagnostic method can improve diagnostic accuracy in lipedema.

Interdisciplinary pain therapy in the elderly

Chronic pain in the elderly is becoming increasingly important and is associated with serious health impacts. Therefore, international guidelines demand that pain therapy for the elderly preferably be amultimodal therapy based on abio-psycho-social pain model. Specific psychometric tests and interview guidelines are available for the interdisciplinary pain assessment. Evidence for the effectiveness of multimodal pain therapy in the elderly remains limited. However, controlled clinical trials have shown that these patients benefit-especially if the intervention is adapted to their specific needs. The focus of movement therapy is not only muscle strengthening but also coordination exercises. In individual physical therapy and occupational therapy, everyday solutions can be developed for individual physical limitations that are more frequent in old age. In psychological training, pain acceptance, balancing rest and activity, social integration and dealing with aging are particularly important topics. Relaxation and mindfulness techniques can also favorably affect pain and function. Thus, these are popular with patients and are often adopted in everyday pain management. Pain education is considered useful as an adjunctive measure and can also be increasingly supported by digital media in the elderly. Complementary therapy components include confrontational treatment of fear-avoidance beliefs (the German AMIKA scale, Ältere Menschen in körperlicher Aktion, "older people in physical action") and naturopathic applications as an active self-help strategy. Since it is unclear how long the achieved therapeutic effects last, follow-up care is of particular importance in therapy for older patients.

Characterization of Relevant Bovine Dander Allergen Components.

Diagnostic tests in occupational allergic diseases are highly dependent on the quality of available allergen extracts and specific IgE tests. To enhance diagnostic testing in cattle-related occupational rhinitis, asthma, and urticaria, we produced an in- house cow dander extract, assessed its allergen profile and performance in clinical tests, and compared it with commercial bovine dander extracts. One hundred patients with a suspected cattle-related occupational disease underwent skin prick tests (SPTs) with in-house and 1 or 2 commercial bovine dander extracts. Nasal allergen provocation tests were performed on 31 patients with suspected occupational rhinitis. We used Western blot to study the specific IgE-protein reactions from the sera of the patients with positive provocation test results and identified allergens from immunoblot bands using tandem mass spectrometry. The odorant-binding protein Bos d OBP, bovine serum albumin (Bos d 6), and the lipocalin (Bos d 2) were identified as the major allergens. We found a total of 24 bovine dander allergens, of which several were formerly unknown. The sensitivity and specificity of the in-house extract in SPTs were 100% and 94%, respectively, in 87 patients. The SPT results were negative in 20 healthy controls. Nasal allergen provocation tests with in-house extract detected occupational rhinitis with 100% sensitivity in 21 patients. The provocation results remained negative in 5 healthy controls. Three major and several minor allergens in bovine dander caused occupational rhinitis. Diagnosis of bovine allergen-related occupational diseases requires a sufficient concentration and variety of tested allergens.

Using spherical indentation to determine creep behavior with considering empirical friction coefficient

Indentation testing is a common technique for characterizing the mechanical properties of materials. When it comes to assessing the yield behavior of metals, conical indentation is often favored due to its ability to induce significant plastic deformation at relatively shallow indentation depths. On the other hand, spherical indentation is typically chosen for evaluating metal creep behavior, as it helps minimize the influence of plastic deformation on creep measurements. In spherical indentation tests, the friction at the contact interface is particularly crucial, given the larger contact area and more pronounced slip zones. However, accurately determining the friction coefficient at the contact interface is a complex multi-scale challenge, with the exact coefficient varying based on specific testing conditions and surface treatments. Consequently, empirical friction coefficients are frequently employed, often without thorough justification. In this work, we proposed Bayesian inference method for obtaining the creep constitutive behavior of alloys through spherical indentation tests. Our model considers not only the complexity of creep law, but also the indentation friction, which is unable to consider in most spherical indentation tests with traditional treatment. By using experimental data of spherical indentation tests on 310S stainless steel and pure nickel alloy from literature, present study demonstrates the effectiveness of the Bayesian inference approach, with the inferred constitutive models exhibiting well agreement with uniaxial creep behavior. Furthermore, the method considers the friction coefficient as an extra factor in inferring creep constitutive behavior from indentation tests.

Mix desing method lightweight concrete

There are several methodologies for Portland cement concrete dosage, among these, the method recommended by the Technological Research Institute of the State of São Paulo - IPTUSP, which is widespread in Brazil. Although it does not present dosage factors for lightweight concrete, this paper proposes a dosage method based on the IPT method for lightweight concrete with EPS. The concrete was dosed with CPV ARI cement, sand and EPS, and two volumes of aggregates (m) were made, thus making a rich and a poor trace, for this, two aggregate contents (m) were executed, thus making a rich and a poor mix, being them: 1:1, 1:2 (aggregates mix in real volume (L) per kg of cement), respectively. Then, each mix (1:m) was dosed with three different levels of EPS (25, 50 and 75%, to each "m"). The properties of the concretes were evaluated in the fresh state, through the slump test [1] and specific mass through the known volume method, and, in the hardened state, by the specific mass test [2] and compressive strength [3]. With the results obtained from this study, it was possible to elaborate a dosage diagram for each "m" analyzed, obtaining the values of the EPS content, projection of compressive and slump resistance, indicated in a dosage abacus made from the test results, these parameters are essential for the determination of the concrete mix.

Experimental study of ammonia nucleation boiling onset in dead-end tube segments at different boundary conditions

The nucleation boiling onset of liquid ammonia in stainless steel, aluminium, and titanium tube segments of ID 4 mm, 6 mm, and 8 mm without flow conditions has been experimentally studied at saturation pressures of 12.5–19.8 bar. It has been shown that heterogeneous nucleation is the determining mechanism for the considered cases. Maximal achievable liquid superheating at 19 K has been observed in the tests at low saturation pressure (12.5 bar), decreasing to 6 K at 19.8 bar. The heating rate in the range of 0.2–60 K min−1 (average heat fluxes of ≈0–4 kW m−2) does not impact much on boiling onset. Internal diameter (4, 6 and 8 mm), roughness (1 and 10 μm) and wettability (10°–50°) do not drastically change the level of maximum achievable superheating before boiling onset. However, quantitatively, the titanium surface with the poorest wettability (≈50°) among considered samples leads to higher overshooting of ammonia bulk temperature by several K. A stainless steel surface with artificial scratches shows a bit higher superheating than a smooth surface. The specific tests showed that ammonia boiling could start at nearly saturation level in the case of a strongly overheated wall. In particular, for ammonia at saturation pressure above 12.5 bar, the required overheating of the wall of 19 K ensures the boiling of ammonia without superheating in the bulk of the liquid.

Transduction Efficiency of Zika Virus E Protein Pseudotyped HIV-1gfp and Its Oncolytic Activity Tested in Primary Glioblastoma Cell Cultures.

The development of new tools against glioblastoma multiforme (GBM), the most aggressive and common cancer originating in the brain, remains of utmost importance. Lentiviral vectors (LVs) are among the tools of future concepts, and pseudotyping offers the possibility of tailoring LVs to efficiently transduce and inactivate GBM tumor cells. Zika virus (ZIKV) has a specificity for GBM cells, leaving healthy brain cells unharmed, which makes it a prime candidate for the development of LVs with a ZIKV coat. Here, primary GBM cell cultures were transduced with different LVs encased with ZIKV envelope variants. LVs were generated by using the pNLgfpAM plasmid, which produces the lentiviral, HIV-1-based, core particle with GFP (green fluorescent protein) as a reporter (HIVgfp). Using five different GBM primary cell cultures and three laboratory-adapted GBM cell lines, we showed that ZIKV/HIVgfp achieved a 4-6 times higher transduction efficiency compared to the commonly used VSV/HIVgfp. Transduced GBM cell cultures were monitored over a period of 9 days to identify GFP+ cells to study the oncolytic effect due to ZIKV/HIVgfp entry. Tests of GBM tumor specificity by transduction of GBM tumor and normal brain cells showed a high specificity for GBM cells.

Evaluation of Clinical Subacromial Impingement Test Positive Patients with Ultrasonographic Subacromial Impingement Test

Objective: Knowing which of the special clinical tests used in subacromial impingement syndrome is more successful in making the diagnosis is important for patient evaluation, determining if further examination is necessary, and arranging treatment. Utilizing sonographic impingement as a reference diagnostic technique, the study sought to evaluate how well clinical test results performed in diagnosing patients with subacromial impingement syndrome. Material and method: The study involved 42 patients with shoulder pain and at least one positive subacromial impingement test, including Neer, Hawkins, or Yocum tests. Dynamic sonographic compression of the tendon in the coracoacromial area was examined by abducting the shoulder. Dynamic sonographic compression findings were compared with clinical examination tests. Results: In 40.5% of the patients, the ultrasonographic impingement test was positive. Hawkins test was positive in 81% of patients, Neer test was positive in 69% of patients, and Yocum test was positive in 78.6% of patients. A significant relationship was found between the ultrasonographically evaluated subacromial impingement test and the Neer test, but no significant relationship was found with other special tests (Hawkins and Yocum test) (p = 0.02, p = 0.4, p = 0.12, respectively). Conclusion: We have demonstrated a significant relationship between the ultrasonographic finding of dynamic subacromial impingement and the Neer test, which is a non-invasive and device-independent physical examination test.

Association of Isolated Gastrocnemius Tightness in Patients with Heel Pain

Background: Heel pain is a common musculoskeletal complaint among adults, significantly impacting quality of life. Recent studies suggest a strong association between isolated gastrocnemius tightness and heel pain, although comprehensive research in diverse populations remains scarce. Understanding the relationship between gastrocnemius tightness and heel pain is crucial for developing effective treatment strategies. Objective: This study aimed to investigate the association of isolated gastrocnemius tightness with heel pain in a Pakistani adult population, focusing on the prevalence of gastrocnemius tightness among individuals presenting with heel pain and the effectiveness of specific diagnostic tests in identifying this condition. Methods: A prospective cross-sectional study was conducted involving 223 participants from various hospitals in Lahore, Pakistan. The study population comprised adults aged 30 to 60 years experiencing heel pain. Diagnostic assessments included the Windlass and Silfverskiöld tests to evaluate plantar fasciitis and gastrocnemius tightness, respectively. Data on age, gender, and test outcomes were collected and analyzed using SPSS version 25.0, employing descriptive statistics, Pearson's correlation, and significance testing to explore the association between heel pain and gastrocnemius tightness. Results: The average age of participants was 42.24 ± 4.973 years, with a gender distribution of 59.6% females and 40.4% males. The Windlass test was positive in 89.2% (199) of participants, while the Silfverskiöld test showed a positive outcome for gastrocnemius tightness in 79.8% (178) of cases. A significant correlation was found between the results of the Windlass and Silfverskiöld tests (Pearson correlation = .691, p &lt; .000), indicating a strong association between isolated gastrocnemius tightness and heel pain. Conclusion: This study confirms a significant association between isolated gastrocnemius tightness and heel pain among adults in Lahore, Pakistan. The findings underscore the importance of assessing gastrocnemius tightness in patients presenting with heel pain and suggest that targeted interventions addressing this condition could enhance treatment outcomes.

Fatigue life reinforcement of carbon black filled natural rubber under non‐relaxing torsion loadings and comparison with non‐relaxing tension loadings

AbstractIn this paper, the effect of non‐relaxing torsion loadings on the fatigue lifetime reinforcement of carbon black filled natural rubber is fully addressed. Torsion fatigue tests with different loading ratios have been performed with highly notched axisymmetric‐shaped specimens. Finite element analysis is used to predict the mechanical state at any point in the specimens. The prediction is significantly improved by taking into account the heterogeneous accommodation. The first Haigh diagram under fatigue torsion is built and analyzed by calculating the minimum loading in terms of the Cauchy stress as the normal stress to the crack for the minimum angle prescribed during the cycle. A strong lifetime reinforcement has been observed, which is found to be of the same amplitude to the one obtained under uniaxial tension with the same material. This has been confirmed by specific tests that combined non‐relaxing torsion and non‐relaxing tension loadings. Post‐mortem analysis carried out at the macroscopic and the microscopic scales enabled us to identify damage mechanisms, especially in the cases where the lifetime reinforcement was observed.

Internal Equity Annual Changes and Security Returns of Companies Listed in The Nairobi Securities Exchange.

This study examined the effect of annual changes in internal equity on ordinary equity security returns in Kenyan public limited firms. Internal equity is the portion of a company's equity generated through retained earnings and the issuance of new shares to existing shareholders. The study was guided by the research philosophy of positivism, given that it relied on quantitative data and espoused the scientific approach to research. It adopted a causal or explanatory research design to check how the annual changes in public firms' internal equity impacted a firm's stock market value. A census study of 67 public companies was employed, of which 49 met data requirements. The study used secondary data from the company's financial statements for eleven years, from January 2012 to December 2022. The data collected was analyzed using descriptive and inferential statistics. The hypothesis that annual changes in internal debts had no significant effect on security returns was tested at a 95% confidence interval using the t-statistic and p-value. The study adopted panel data to carry out the research analysis. Panel regression analysis using the random effects model was undertaken after appropriate normality, model specification, homoscedasticity, linearity and autocorrelation diagnostic tests. Findings reveal significant variability in internal equity changes across sectors. Correlation analysis establishes a positive and significant association between internal equity changes and security returns. Panel regression analysis further confirms a strong and positive relationship, indicating that an increase in internal equity corresponds to higher returns on equity securities. The results emphasize the importance of internal equity in signalling a company's financial health and stability, impacting investor confidence and potentially leading to higher equity security returns. Investors are urged to conduct sector-specific analyses, considering variability in financial structures. The study contributes valuable insights to understanding internal equity's role in influencing financial well-being and security returns in the Kenyan business landscape.&#x0D;

Multiplex Serology for Sensitive and Specific Flavivirus IgG Detection: Addition of Envelope Protein Domain III to NS1 Increases Sensitivity for Tick-Borne Encephalitis Virus IgG Detection.

Tick-borne encephalitis is a vaccine-preventable disease of concern for public health in large parts of Europe, with EU notification rates increasing since 2018. It is caused by the orthoflavivirus tick-borne encephalitis virus (TBEV) and a diagnosis of infection is mainly based on serology due to its short viremic phase, often before symptom onset. The interpretation of TBEV serology is hampered by a history of orthoflavivirus vaccination and by previous infections with related orthoflaviviruses. Here, we sought to improve TBEV sero-diagnostics using an antigen combination of in-house expressed NS1 and EDIII in a multiplex, low-specimen-volume set-up for the detection of immune responses to TBEV and other clinically important orthoflaviviruses (i.e., West Nile virus, dengue virus, Japanese encephalitis virus, Usutu virus and Zika virus). We show that the combined use of NS1 and EDIII results in both a specific and sensitive test for the detection of TBEV IgG for patient diagnostics, vaccination responses and in seroprevalence studies. This novel approach potentially allows for a low volume-based, simultaneous analysis of IgG responses to a range of orthoflaviviruses with overlapping geographic circulations and clinical manifestations.

Machine learning-based prediction model for battery levels in IoT devices using meteorological variables

Efficient energy management is vital for the sustainability of IoT devices employing solar harvesting systems, particularly to circumvent battery depletion during periods of diminished solar incidence. Embracing the structured methodology of CRISP-DM, this study introduces machine learning (ML) models that utilise meteorological data to predict battery charge levels in solar-powered IoT devices. These models enable proactive adjustments to the devices’ data sampling frequencies, ensuring effective energy utilisation. The proposed ML models were evaluated using authentic battery charge data and weather forecast records. The empirical results of this study corroborate the predictive prowess of the models, with an average accuracy reaching as high as 94.09% in specific test cases. This substantiates the potential of the developed methodology to significantly enhance the energy autonomy of IoT devices through predictive analytics.

Exploration of the Advanced VIVOTM Joint Simulator: An In-Depth Analysis of Opportunities and Limitations Demonstrated by the Artificial Knee Joint.

In biomechanical research, advanced joint simulators such as VIVOTM offer the ability to test artificial joints under realistic kinematics and load conditions. Furthermore, it promises to simplify testing with advanced control approaches and the ability to include virtual ligaments. However, the overall functionality concerning specific test setup conditions, such as the joint lubrication or control algorithm, has not been investigated in-depth so far. Therefore, the aim of this study was to analyse the basic functionality of the VIVOTM joint simulator with six degrees of freedom in order to highlight its capabilities and limitations when testing a total knee endoprostheses using a passive flexion-extension movement. For this, different test setup conditions were investigated, e.g., the control method, repeatability and kinematic reproducibility, waveform frequency, lubrication, and implant embedding. The features offered by the VIVOTM joint simulator are useful for testing joint endoprostheses under realistic loading scenarios. It was found that the results were highly influenced by the varying test setup conditions, although the same mechanical load case was analysed. This study highlights the difficulties encountered when using six degrees of freedom joint simulators, contributes to their understanding, and supports users of advanced joint simulators through functional and tribological analysis of joint endoprostheses.

Risk Factors for Early Treatment Discontinuation Due to Toxicity Among Patients With Metastatic Castration-resistant Prostate Cancer Receiving Androgen Receptor-targeted Therapy.

Androgen receptor-targeted therapies (ARTs) improve survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC); however, a significant portion of patients discontinue treatment for various reasons including treatment-related toxicity. We aim to describe reasons for ART treatment discontinuation and identify predictors associated with increased risk of treatment discontinuation due to toxicity. We performed a single-institution retrospective review of patients with mCRPC receiving ART between 2010 and 2021. Our primary aim was to identify risk factors for treatment discontinuation due to toxicity. Our secondary aim was to describe ART discontinuation patterns among patients with mCRPC. One hundred thirty-three patients with mCRPC started and discontinued ARTs. Fourteen patients (10.5%) discontinued treatment due to toxicity. Common reasons for treatment discontinuation include Prostate Specific Antigen test progression, radiographic progression, toxicity, and death. Significant predictors of treatment discontinuation due to toxicity on bivariate analysis and multivariate analysis included patient-reported falls (odds ratio [OR]: 7.67, CI: [1.31-40.42]; P =0.016), rash (OR: 13.4, CI: [1.35-134.81]; P =0.026), and weakness (OR: 4.16, CI: [1.15-15.0]; P =0.019). Our work presents the first description of ART treatment discontinuation and its causes in the real-world setting, as well as patient-reported side effects. Most patients with mCRPC discontinued treatment due to the progression of disease and a minority of patients discontinued secondary to treatment toxicity. Initial multivariable analysis suggests that patient-reported weakness, falls, and rash were associated with a higher likelihood of treatment discontinuation due to toxicity. Early monitoring of this population can prolong the duration of treatment and prevent unnecessary treatment burden.

Feasibility and comparability of different platelet function tests in acute stroke with or without prior antiplatelet therapy.

The clinical course of ischemic and hemorrhagic strokes can be influenced by the coagulation status of individual patients. The prior use of antiplatelet therapy (APT) such as acetylsalicylic acid (ASA) or P2Y12-antagonists has been inconsistently described as possibly increasing the risk of hemorrhagic transformation or expansion. Since clinical studies describing prior use of antiplatelet medication are overwhelmingly lacking specific functional tests, we aimed to implement testing in routine stroke care. We used fluorescence-activated cell sorting (FACS) with antibodies against CD61 for thrombocyte identification and CD62p or platelet activation complex-1 (PAC-1) to determine platelet activation. Aggregometry and automated platelet functioning analyzer (PFA-200) were employed to test thrombocyte reactivity. FACS and aggregometry samples were stimulated in vitro with arachidonic acid (AA) and adenosine diphosphate (ADP) to measure increase in CD62p-/PAC-1-expression or aggregation, respectively. Between February and July 2023, 20 blood samples (n = 11 ischemic strokes; n = 7 hemorrhagic strokes; n = 2 controls) were acquired and analyzed within 24 h of symptom onset. N = 11 patients had taken ASA, n = 8 patients no APT and n = 1 ASA+clopidogrel. ASA intake compared to no APT was associated with lower CD62p expression after stimulation with AA on FACS analysis (median 15.8% [interquartile range {IQR} 12.6-37.2%] vs. 40.1% [IQR 20.3-56.3%]; p = 0.020), lower platelet aggregation (9.0% [IQR 7.0-12.0%] vs. 88.5% [IQR 11.8-92.0%]; p = 0.015) and longer time to plug formation with PFA-200 (248.0 s [IQR 157.0-297] vs. 121.5 s [IQR 99.8-174.3]; p = 0.027). Significant correlations were noted between AA-induced CD62p expression and aggregometry analysis (n = 18; ρ = 0.714; p < 0.001) as well as a negative correlation between CD62p increase and PFA clot formation time (n = 18; ρ = -0.613; p = 0.007). Sensitivity for ASA intake was highest for PFA (81.8% for values ≥155.5 s). The combination of ASA + clopidogrel also affected ADP-induced CD62p and PAC-1 expression. In the clinical setting it is feasible to use differentiated platelet analytics to determine alterations caused by antiplatelet therapy. Among the tests under investigation, PFA-200 showed the highest sensitivity for the intake of ASA in stroke patients. FACS analysis on the other hand might be able to provide a more nuanced approach to altered platelet reactivity.