Clinical Laboratory Test Results Research Articles

P-05 17Β-HYDROXYSTEROID DEHYDROGENASE 3 DEFICIENCY: TWO CASE REPORTS

Abstract Introduction 17-β-hydroxysteroid dehydrogenase type3 (17β-HSD3) is an enzyme that produces testosterone from androstenedione, encoded by the HSD17B3 gene. Its deficiency causes 46 XY disorder of sex development (DSD) with autosomal recessive inheritance. 46 XY individuals with this enzyme deficiency can exhibit a wide range of phenotypes, ranging from normal female external genitalia to ambiguous genitalia. In early childhood, the diagnosis might be clinically indistinguishable from other causes of 46 XY DSD such as partial androgen insensitivity syndrome (AIS) and 5α-reductase type 2 deficiency. Laboratory diagnosis is based on a low testosterone/androstenedione ratio. The diagnosis is confirmed by molecular genetic testing. If the diagnosis is missed in early infancy, patients present with severe virilization symptoms and amenorrhea during puberty. We present two siblings followed and managed with a presumed diagnosis of AIS until the genetic testing was performed. Clinical Case 1 A 4-month-old patient with female external genitalia was operated on with suspicion of bilateral inguinal hernia, and pathologic investigation revealed immature testicular tissue. No uterus and ovaries could be detected by pelvic ultrasound. The karyotype analysis was consistent with 46 XY, and the patient was followed up with the diagnosis of AIS. The patient’s parents were first cousins. The patient was started on estradiol replacement when she was 13 years old. At the age of 21, she underwent vaginoplasty due to a 2 cm long vaginal canal. A genetic analysis was available when the patient was 21 years old. Next generation sequencing revealed a previously reported homozygous c.277+5g>A mutation in exon 3 of HSD17B3 gene. The diagnosis was established as 17β-HSD3 deficiency. Clinical Case 2 After the index case was diagnosed with AIS karyotype analyses were performed on three other siblings at the time. The patient’s 7 years old sibling, who had a complete female-appearing genitalia, had a karyotype of 46XY. As the presumed diagnosis was AIS, bilateral orchiectomy was performed after counselling. Estradiol replacement was started at the age of 14 and complete breast development was achieved. Vaginal length was reported as 8 cm. Further genetic analysis was performed at the age of 27 and it revealed that the two siblings shared the same genetic mutation. Both preferred to retain the female gender identity during adulthood. Two other female siblings with a karyotype of 46XX and both parents had a heterozygous c.277+5g>A mutation in the HSD17B3 gene. Conclusion Although clinical evaluation and laboratory test results might point out to 17-β-HSD3 deficiency, the definite diagnosis is established with genetic testing. As these patients might develop male gender identity, awareness of the disease and early genetic testing is of importance for the prevention of misdiagnoses, counselling for gender identity, deciding on surgical interventions, and management of these patients.

Unsupervised machine learning model for phenogroup-based stratification in acute type A aortic dissection to identify postoperative acute gastrointestinal injury.

We aimed to explore the application value of unsupervised machine learning in identifying acute gastrointestinal injury (AGI) after extracorporeal circulation for acute type A aortic dissection (ATAAD). Patients who underwent extracorporeal circulation for ATAAD at the First Hospital of Lanzhou University from January 2016 to January 2021 were included. Unsupervised machine learning algorithm was used to stratify patients into different phenogroups according to the similarity of their clinical features and laboratory test results. The differences in the incidence of perioperative AGI and other adverse events among different phenogroups were compared. Logistic regression was used to analyze the high-risk factors for AGI in each phenogroups and random forest (RF) algorithms were used to construct diagnostic models for AGI in different phenogroups. A total of 188 patients were included, with 166 males and 22 females. Unsupervised Machine Learning stratified patients into three phenogroups (phenogroup A, B, and C). Compared with other phenogroups, phenogroup B patients were older (P < 0.01), had higher preoperative lactate and D-dimer levels, and had the highest incidence of AGI (52.5%, P < 0.001) and in-hospital mortality (18.6%, P = 0.002). The random forest model showed that the top four risk factors for AGI in phenogroup B were cardiopulmonary bypass time, operation time, aortic clamping time, and ventilator time, which were significantly different from other phenogroups. The areas under the curve (AUCs) for diagnosing postoperative AGI of phenogroup A, B, and C were 0.943 (0.854-0.992), 0.990 (0.966-1.000), and 0.964 (0.899-0.997) using the RF model, respectively. Phenogroup stratification based on unsupervised learning can accurately identify high-risk populations for postoperative AGI in ATAAD, providing a new approach for implementing individualized preventive and therapeutic measures in clinical practice.

Impact of Biochemical Parameters on Mortality in Critically Ill ICU Patients: The Role of Mechanical Ventilation, Elevated Lactate, Red Blood Cell Distribution Width (RDW-CV) Levels, and Nutrition Risk Screening 2002 (NRS-2002) Score.

The mortality risk for critically ill patients in the intensive care unit (ICU) can be predicted through clinical assessments and laboratory test results. The accurate utilization of these parameters is essential for timely intervention and the initiation of appropriate therapeutic strategies. This study aims to retrospectively examine the relationship between patients' clinical status at ICU admission, prognostic risk scoring systems, biochemical and hematological parameters, and mortality outcomes. This descriptive, cross-sectional, retrospective cohort study was conducted in the Internal Medicine Intensive Care Unit of Kütahya Health Sciences University Evliya Çelebi Training and Research Hospital, Turkey, between July 1, 2018, and July 30, 2020, and included a total of 490 patients. The initial admission data, encompassing variables such as gender, age, chronic conditions, reasons for ICU admission, ICU length of stay, total hospital stay, requirement for mechanical ventilation (MV), Nutrition Risk Screening 2002 (NRS-2002) score, hemogram, and biochemical parameters, were recorded. The clinical and demographic characteristics, along with the initial laboratory values of patients who either died or were discharged from the ICU, were subjected to statistical analysis. Of the 490 patients, 258 were male, and 232 were female, with a median age of 72 (63-80). Of the 490 patients, 211 (43.1%) died, while 279 (46.6%) were discharged from the ICU. Logistic regression analysis showed that MV requirement, NRS-2002 score, lactate, and red cell distribution width (RDW-CV) were independent predictors of mortality (p < 0.05). MV requirement had the highest odds ratio. In both multivariate analysis and clinical practice, the independent predictors of mortality in ICU patients were identified as the need for MV, elevated NRS-2002 scores, increased lactate levels, and higher RDW-CV values. Among these, the strongest predictor of mortality was the requirement for MV. We anticipate that the results of our study will aid in the enhancement of mortality prediction models and provide important parameters to inform clinical practice.

Characteristics and eye disease distribution of HIV-infected or AIDS patients: a single-center study

Objective: To explore the characteristics and eye disease distribution of human immunodeficiency virus (HIV)-infected or acquired immune deficiency syndrome (AIDS) patients reported by Beijing Tongren Hospital, Capital Medical University. Methods: A retrospective case series study was conducted. Data of HIV-infected or AIDS patients who were reported for the first time in the Chinese Center for Disease Control and Prevention Information System by Beijing Tongren Hospital, Capital Medical University from January 1, 2012 to December 31, 2021 were collected. Epidemiological data such as the patient's gender and age were recorded, and information such as the patient's clinical diagnosis, department classification, and laboratory test results were retrieved from the hospital's outpatient and emergency system and laboratory information system. Results: A total of 191 HIV-infected or AIDS patients were included, with an average age of (36.71±13.52) years, including 177 males and 14 females. The proportion of male and female patients showed no statistically significant change over the years (P>0.05). Most cases were initially diagnosed in the department of ophthalmology (75 cases, 38.22%), followed by the department of dermatology (49 cases, 25.65%). There were 42 cases (56.00%) reported in the fundus group, 10 cases (13.33%) in the cataract group, 8 cases (10.67%) in the refractive center, and other cases in the glaucoma, cornea, and ocular tumor groups. The ophthalmological diagnoses included uveitis (21 cases, 28.00%), retinopathy (13 cases, 17.33%), cataract (11 cases, 14.67%), refractive error (7 cases, 9.33%), glaucoma (4 cases, 5.33%), retinal detachment (3 cases, 4.00%), vitreous hemorrhage (3 cases, 4.00%), cytomegalovirus retinitis (2 cases, 2.67%), ocular tumor (2 cases, 2.67%), optic neuropathy (2 cases, 2.67%), conjunctivitis (2 cases, 2.67%), keratoconus (1 case, 1.33%), chronic dacryocystitis (1 case, 1.33%), lacrimal duct obstruction (1 case, 1.33%), corneal endothelial decompensation (1 case, 1.33%), and ectropion (1 case, 1.33%). Some patients had co-infections with syphilis, hepatitis B, and hepatitis C. Conclusions: There are undiagnosed HIV-infected or AIDS patients in some departments of non-infectious general hospitals, and the ophthalmological manifestations are mostly uveitis and retinopathy. Ophthalmologists should pay attention to the HIV infection or AIDS infection status of patients with eye diseases such as uveitis and retinopathy to reduce the risk of occupational exposure.

A case report of human infection with avian influenza H10N3 with a complex respiratory disease history

BackgroundOn March 16th 2024, the first case of Human infection with avian influenza H10N3 since the end of the global COVID-19 Pandemic was reported in Kunming, China. To enhance comprehension of the source of infection and risk factors of the H10N3 virus infection, this case report summarizes the clinical features, epidemiological investigation, and laboratory test results. Provides recommendations for the prevention and control of Human infection with avian influenza H10N3.Case presentationA 51-year-old male with a history of COVID-19 infection and a smoking habit of 30 years, worked in livestock breeding and was exposed to sick and dead poultry before falling ill with fever and chills on 28th February 2024. A week later, he was diagnosed with severe pneumonia, influenza, and respiratory failure by the Third People's Hospital of Kunming(KM-TPH). He was discharged on 17th April and none of his 6 close contacts showed any symptoms of illness. Environmental samples taken from the epidemic spot revealed that peacock feces tested positive for avian influenza sub-type H9 and waterfowl specimens showed positive results for avian influenza sub-type H5. Gene sequencing conducted on positive specimens from the patient's respiratory tract by the Chinese Centre for Disease Control and Prevention (CCDC) showed a high degree of similarity (98.6–99.5%) with the strain responsible for the second global case of human infected with H10N3 (reported from Zhejiang, China 2022).ConclusionsAccording to the available epidemiological information, there is limited evidence to suggest that H10N3 viruses are excessively lethal. However, adaptive site mutations have been observed in the H10N3 isoform of mammals. While it is unlikely that the H10N3 virus will spread among humans, the possibility of additional cases cannot be entirely ruled out. Symptoms of human infection with H10N3 avian influenza are similar to those of common respiratory infections, which may result in them being overlooked during initial clinical consultations. Therefore, it is essential to improve surveillance of the H10 sub-type of avian influenza and to increase the awareness of hospital-related workers of cases of pneumonia of unknown origin.

Assessment of right ventricular sequelae by speckle tracking echocardiography in recovered COVID-19 patients

Background TTE is the main modality used to assess RV function, but conventional TTE parameters have limited diagnostic value because they may fail to detect early abnormalities in RV systolic function. Due to its ability to detect subclinical impairment of cardiac function, 2D STE has been widely used to investigate RV function. In this study, we aimed to investigate whether there are sequelae of RV function in recovered COVID-19 patients with pulmonary involvement. Methods This is a prospective observational cohort study of 57 healthy volunteers and 54 patients. Participants had no history of chronic illness and no evidence of respiratory or cardiac symptoms. The patients had been hospitalised with COVID-19 with pulmonary involvement but did not require intensive care unit follow-up or non-invasive mechanical ventilation support. TTE was performed. Demographic and clinical characteristics and laboratory test results were collected. Results LVEF, TAPSE, St and FAC were significantly lower in the patient group. LV-LS 3-chamber, LV-GLS, RV-FWS, RV-GLS were significantly lower in the patient group. Conclusions RV-LS and LV-GLS were shown to decrease in the patient group. Although no obvious pathological values were observed in RV parameters on conventional echocardiography, TAPSE, St and FAC values were lower in the patient group.

Development and validation of machine learning-based prediction model for severe pneumonia: A multicenter cohort study

Severe pneumonia (SP) is a prevalent respiratory ailment characterized by high mortality and poor prognosis. Current scoring systems for pneumonia are not only time-consuming but also exhibit limitations in early SP prediction. To address this gap, this study aimed to develop a machine-learning model using inflammatory markers from peripheral blood for early prediction of SP. A total of 204 pneumonia patients from seven medical centers were studied, with 143 (68 SP cases) in the training cohort and 61 (32 SP cases) in the test cohort. Clinical characteristics and laboratory test results were collected at diagnosis. Various models including Logistic Regression, Random Forest, Naïve Bayes, XGBoost, Support Vector Machine, and Decision Tree were built and evaluated. Seven predictors—age, sex, WBC count, T-lymphocyte count, NLR, CRP, TNF-α, IL-4/IFN-γ ratio, IL-6/IL-10 ratio—were selected through LASSO regression and clinical insight. The XGBoost model, exhibiting best performance, achieved an AUC of 0.901 (95 % CI: 0.827 to 0.985) in the test cohort, with an accuracy of 0.803, sensitivity of 0.844, specificity of 0.759, and F1_score of 0.818. Indeed, SHAP analysis emphasized the significance of elevated WBC counts, older age, and elevated CRP as the top predictors. The use of inflammatory biomarkers in this concise predictive model shows significant potential for the rapid assessment of SP risk, thereby facilitating timely preventive interventions.

May Recovered COVID-19 Patients Have Impaired Myocardial Work?

Background: The aim of this study was to investigate whether there are sequelae in left ventricular (LV) systolic function by comparing LV function in fully recovered COVID-19 patients with pulmonary involvement and healthy controls without COVID-19 by conventional echocardiography and myocardial work. Materials and Methods: 55 healthy volunteers and 61 patients hospitalized with COVID-19 with pulmonary in-volvement were included. Patients did not need non-invasive or invasive mechanical ventilation support during hospitalization. Patients were included in the study if they were asymptomatic for at least six months after recov-ery from COVID-19. Transthoracic echocardiography (TTE) was performed. Demographic and clinical characteris-tics and laboratory test results were collected. Clinical characteristics, blood tests, TTE, speckle-tracking echocar-diography (STE) and myocardial work results were compared. Results: No statistically significant differences were found in the longitudinal strain parameters of the LV among the study groups. The patient group exhibited notably reduced levels of global work index (GWI), global con-structed work (GCW), and global work efficiency (GWE). The patient group exhibited a notably elevated global wasted work (GWW). Conclusions: The group of fully recovered asymptomatic COVID-19 patients with pulmonary involvement showed significantly lower values for GWI, GCW, and GWE, while GWW showed a significantly higher value. Myocardial work parameters may be useful in determining myocardial sequelae.

Clinical features and prognostic factors of cryptococcal infections in HIV-infected patients: a 10-year study from an infectious disease specialist hospital.

Cryptococcosis is an invasive infection that commonly affects immunosuppressed individuals, especially patients with HIV infection. Cryptococcal infection in HIV-infected patients should be considered a major health concern because it is associated with high morbidity and mortality rates. In this study, we aimed to evaluate the clinical characteristics and prognostic factors of cryptococcal infections in human immunodeficiency virus (HIV)-infected patients to facilitate effective clinical management and improve patient outcomes. We reviewed and analyzed the clinical data and relevant laboratory test results of HIV-infected patients with positive cryptococcal cultures and reserved strains between 2013 and 2023 from Beijing Youan Hospital affiliated to Capital Medical University. The clinical characteristics and laboratory test results of the patients were compared, and the correlation between parameters and the prognoses of the patients at different observation timepoints (3, 6, 9, and 12 months) was analyzed. A total of 76 patients (70 males and six females; median age, 37 years) were included in this study. The results indicated that the later the initiation of antiretroviral therapy (ART) after the diagnosis of HIV infection (> 6 months), the higher the probability of death. Analysis of the correlation between the time of ART initiation and the timing of treatment for cryptococcal infections showed that the time of ART initiation was strongly related to survival at different timepoints. Initiation of ART time within 0-4 weeks, 4-6 weeks and more than 6weeks of starting treatment for Cryptococcus infection was associated with a lower mortality rate at 12-month, the 3-month, 6- and 9-month follow-up timepoint separately. Although cryptococcal infection in HIV-infected patients continues to be a challenging and intricate issue, ART is a key factor that affects its prognosis. The later ART is started, the worse the prognosis of the infection. The time of ART initiation and the timing of treatment for cryptococcal infections should be further refined and balanced based on different clinical courses. Thus, clinicians should pay closer attention to cryptococcal infections in patients with HIV infection and initiate ART based on the patient's clinical condition.

Drug resistance in drug-resistant tuberculosis patients with and without diabetes mellitus: a comparative analysis

BackgroundThis dual burden of tuberculosis (TB) and diabetes mellitus (DM) has become a global public health concern. This study aims to compare drug resistance in drug-resistant tuberculosis (DR-TB) patients with and without DM and analyse the risk factors of multidrug-resistant tuberculosis (MDR-TB).MethodsA total of 893 DR-TB patients were admitted to Wenzhou Central Hospital between January 2018 and December 2022. After excluding 178 cases with incomplete clinical and laboratory data, 715 patients were included in the study. These patients were then categorized into two groups based on the presence of type 2 DM: the DM group (160 cases) and the non-DM group (555 cases). Demographic information, baseline clinical characteristics, laboratory and imaging test results, clinical diagnoses, and other relevant data were collected for analysis. Statistical analysis was conducted on demographic information, clinical parameters, drug resistance spectrum, and risk factors for multidrug resistance.ResultsIn both the DM and non-DM groups, the order of resistance to first-line anti-tuberculosis drugs is isoniazid, streptomycin, rifampicin, and ethambutol. There is no significant difference in the proportion of mono-resistant tuberculosis, polydrug-resistant tuberculosis, and multidrug-resistant tuberculosis between the two groups (P > 0.05). The prevalence of MDR-TB in both groups shows a downward trend between 2018 and 2022, but the trend is not statistically significant (P > 0.05). Among patients without DM, residence in rural areas, retreatment of tuberculosis, pulmonary cavity, and uric acid ≥ 346 µmol/L are identified as independent risk factors for MDR-TB. Among patients with DM, residence in rural areas, retreatment of tuberculosis, pulmonary cavity, and HbA1c ≥ 9.8% were identified as independent risk factors for MDR-TB.ConclusionIsoniazid is the most resistant drug among DR-TB patients with and without DM. There is no statistically significant difference in drug resistance patterns between the two groups. Some progress has been made in the prevention and control of DR-TB in this area, but the effect is not very significant. There are differences in the risk factors of MDR-TB between patients with and without DM.

TG/HDL-C Ratio for Predicting Insulin Resistance in Obese Children from Beijing, China.

International studies have found that the blood triglycerides to highdensity lipoproteins (TG/HDL-C) ratio predicted insulin resistance in children with overweight and obesity. However, there is a lack of such reports on children from China. The objective of this study is to explore the ability of the TG/HDL-C ratio as a blood biomarker for insulin resistance (IR) in obese children in Beijing. We evaluated 262 children with obesity from our paediatric outpatient clinic in a cross-sectional study. Detailed medical histories of all children were ascertained, as were clinical examination and laboratory test results, including blood lipids, fasting glucose, insulin, and glycated haemoglobin. We divided them into age groups of 6-9 and 10-13.5 years and then into IR and non-IR groups based on the homeostatic model assessment for IR (HOMA-IR). Analysis was accomplished with SPSS software (version 22.0). The TG/HDL-C ratio was higher in children with IR in the 6-9 and 10-13.5-year age groups (p < 0.001). Univariate and multivariate analyses displayed that the TG/HDL-C ratio and HOMA-IR were correlated in the 6-9 and 10-13.5-year-old groups (p < 0.05). In the 6-9-yearold group, IR identified by a TG/HDL-C ratio ≥ 0.645 had a sensitivity, specificity, and an area under the curve (AUC) of 79.1%, 60.9%, and 0.734, respectively. In the 10-13.5-year-old group, IR identified by a TG/HDL-C ratio ≥ 0.725 had a sensitivity, specificity, and an AUC of 79.4%, 62.9%, and 0.724, respectively. We showed the application of the TG/HDL-C ratio to predict insulin resistance in obese children in Beijing with different diagnostic thresholds based on age (6-9-year-old group with TG/HDL-C ≥ 0.645; 10-13.5-year-old group with TG/HDL-C ≥ 0.725), which were lower compared with the diagnostic threshold for insulin resistance in children reported in other countries.

Cerebral edema in an adolescent patient with diabetic ketoacidosis: a case report with a review of literature

The objective was to describe a case of cerebral edema (CE) in an adolescent patient with type 1 diabetes mellitus (DM) complicated with diabetic ketoacidosis (DKA), and to perform an analysis and review of publications devoted to this topic.Materials and methods. We describe the rare clinical case of CE complicated with DKA in the 14-year-old adolescent patient, including the dynamics of the patient’s clinical condition and laboratory test results. The topic of interest was researched through analysis of publications found in the Cochrane Library, PubMed, eLibrary.ru and Medscape databases using the following search terms: diabetic ketoacidosis, children and adolescents, cerebral edema, intensive therapy. A total of 38 publications in Russian and English were selected for being fully compliant with the purpose of this work. The features of the reported clinical case were analyzed and compared with information obtained from the current scientific literature.Results: This case demonstrates specific features presenting in the course of CE and describes aspects of the intensive treatment provided to the patient. Manifestations of severe hypokalemia and hypernatremia have been recorded as rare electrolyte disturbances in CE in the adolescent with DKA. The report demonstrates that the steps and specific parameters of the provided intensive treatment are unlikely to have triggered the development of CE in the clinic in this particular clinical case. It cannot be ruled out that the development of this complication was triggered by the delayed initiation of treatment (caused by the patient) at the prehospital stage, including the patient’s rude noncompliance with the prescribed insulin treatment scheme.Conclusions. CE is the rare but severe (with a high fatality rate) complication of DKA in patients with type 1 DM. Timely initiation of emergency care for CE may reduce risks associated with this complication and improve treatment outcomes and patient prognosis.

The prevalence of polypharmacy and hyper-polypharmacy among middle-aged vs. older patients in Saudi Arabia: a cross-sectional study.

Polypharmacy, the use of multiple medications, is a growing concern among middle-aged and older patients, posing potential risks and challenges in healthcare management. This study aimed to identify the prevalence of polypharmacy and hyper-polypharmacy among populations of middle-aged vs. older patients and identify its associated common comorbidities and prescribed medications in Qatif Central Hospital (QCH), Saudi Arabia. Patients aged 40 years or older who presented to an outpatient medical care clinic at QCH, Saudi Arabia, between 1 January and 31 December 2021 were included, and their comorbidities, prescribed medications, and recent clinical laboratory test results were collected. The Charlson comorbidity index (CCI) score was calculated to predict the risk of mortality. Logistic regression was used to compute the association between the prevalence of polypharmacy and patient characteristics. The results were presented as odds ratios (ORs) and 95% confidence intervals (95% CIs). A total of 14,081 patients were included; 31% of the cohort comprised older patients, and 66% of the cohort was identified with polypharmacy. The majority of the polymedicated patients were presented to an internal medicine care unit (34%). The prevalence of polypharmacy was positively associated with CCI (OR = 3.4, 95% CI 3.3-3.6), having a disease related to the musculoskeletal system (MSD) (OR = 4.2, 95% CI 3.8-4.7), and alimentary tract and metabolism (ATM) (OR = 3.8, 95% CI 3.4-4.2). Conversely, the prevalence of polypharmacy was negatively associated with age (OR = 0.9, 95% CI 0.89-0.91) and patients with cardiovascular diseases (OR = 0.6, 95% CI 0.5-0.7). Polypharmacy is still an ongoing concern. Patients, particularly those with diseases related to MSD or ATM, should be considered for reviewing prescriptions by pharmacists to reduce the risk of adverse drug reactions and future consequences of polypharmacy.

Abstract PO3-19-08: A phase 2 randomized pre-operative,window of opportunity trial investigating the effect of elacestrant with/without triptorelin in premenopausal patients with HR+/HER2- breast cancer – SOLTI-2104-PremiÈRe trial

Abstract Background. Premenopausal women diagnosed with HR+/HER2- breast cancer (BC) often have a different biology and worse prognosis. The SOFT and TEXT studies demonstrated an increase diseasefree survival (DFS) with ovarian function suppression (OFS) plus tamoxifen or exemestane compared to tamoxifen alone. Of note, high-risk clinicopathologic features, adjuvant chemotherapy, or aged ≤35 years correlated with greater OFS benefit. However, adding OFS in this context has intrinsic issues as higher toxicity, which led to treatment discontinuation (20% in SOFT trial), and suboptimal OFS was found in around 25% of patients (pts) with exemestane plus monthly triptorelin (SOFT-EST sub-study). Thus, new effective ET options without OFS are needed for premenopausal patients (pts). Elacestrant is the first oral, non-steroidal, selective estrogen receptor degrader (SERD) to demonstrate improved efficacy to SOC treatments and specifically compared to fulvestrant in postmenopausal pts with HR+/HER2- metastatic BC at the phase III EMERALD trial. In menopausal patients with HR+/HER2- early BC, the window of opportunity SOLTI-1905 ELIPSE trial (NCT04797728), showed that elacestrant was associated with a 27.3% rate of Complete Cell Cycle Arrest (CCCA) and a statistically significant suppression of Ki-67. Among Luminal A tumors, the CCCA rate was 45% and the average decrease in Ki-67 was 64.6%, while no CCCA was reported and the suppression of Ki-67 was less pronounced (31.7%) in the Luminal B population. There is still a need for investigating elacestrant without OFS in the premenopausal scenario. We hypothesize that elacestrant as a single agent or in combination with triptorelin is an effective and safe treatment regimen in premenopausal pts with HR+/HER2-negative early BC capable of achieving an equivalent CCCA rate as a subrogate of effectiveness regardless the use of OFS Study design. PREMIERE is a parallel, non-comparative, two-arm, randomized 1:1, open-label, multicenter, exploratory study in premenopausal women with primary operable HR+/HER2-negative BC. The study aims to evaluate the biological effects of elacestrant with or without triptorelin. Participants must have histologically confirmed HR+ (≥ 10%) and HER2- operable early BC stage I to stage IIB &amp;gt;1 cm with a Ki-67 between 10-35%. The primary objective is to assess the ability of each treatment arm to induce CCCA determined by central assessment of Ki-67 (% Ki-67 ≤ 2.7%). No formal comparison between treatment arms is intended. Secondary objectives include evaluating the biological activity of elacestrant with or without OFS, antiproliferative activity, changes in gene expression including PAM50 subtype changes, and the effect of optimal vs suboptimal suppression on CCCA . Serum E2 and FSH levels will also be evaluated. Safety and tolerability will be assessed based on adverse events and clinical laboratory test results. Pts will undergo screening and randomization, with stratification by PAM50 subtype (Luminal A vs Non-luminal A). Treatment will be elacestrant 400 mg once daily or elacestrant 400 mg once daily plus triptorelin 3.75 mg days +1 and +29 for 30 (+7) days. Surgery or biopsy will be performed after treatment completion, and a post-surgery visit will mark the end of the active follow-up period. Patients will receive SOC treatment after surgery. 48 patients will be recruited in 9 sites within SOLTI Spanish network in 9 months period. This study is financially supported by Menarini-Stemline. Citation Format: Meritxell Bellet- Ezquerra, Cristina Hernando, Pablo Tolosa, Maria Vidal, Yolanda Fernández, Santiago González-Santiago, Pilar Sanchez, Susana De La Cruz, Vanesa Ortega, Xavier Gonzalez-Farré, Milana Bergamino, Alejandra Espinosa, Tomás Pascual. A phase 2 randomized pre-operative,window of opportunity trial investigating the effect of elacestrant with/without triptorelin in premenopausal patients with HR+/HER2- breast cancer – SOLTI-2104-PremiÈRe trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-19-08.

Early changes in cardiac troponin T and NT-proBNP levels in neonates receiving ECMO support: a single-center experience

ObjectiveThis study aimed to examine the changes in absolute value and decline rate of early serum cardiac troponin T (cTnT) and N-terminal pro b-type natriuretic peptide (NT-proBNP) in neonates who received veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) support therapy within the first week of life.MethodsWe retrospectively collected clinical data and laboratory test results of 18 neonates who underwent V-A ECMO support within one week of birth, from July 2021 to June 2023, using the electronic medical record system. These patients were categorized into survival and death groups. Comparative analyses of the absolute values and decline rates of cTnT and NT-proBNP were made between the groups at baseline, and at 24, 48, and 72 h post-ECMO initiation.ResultsOut of the 18 neonates, 12 survived (survival rate: 66.7%), while 6 succumbed. The survival group exhibited significantly lower absolute values of cTnT and NT-proBNP than the death group, and their decline rates were significantly higher. Notably, all neonates without an early decline in cTnT and NT-proBNP levels were in the death group.ConclusionThe early changes in the absolute value and decline rate of serum cTnT and NT-proBNP in neonates undergoing V-A ECMO may serve as predictors of their prognosis.

Assessment of subclinical left ventricular systolic and diastolic dysfunction in patients with type 2 diabetes mellitus under follow-up at Tikur Anbessa specialized hospital, Ethiopia: a case-control study

BackgroundIndividuals with diabetes mellitus are at increased risk of cardiovascular diseases, which in turn are the most common cause of morbidity and mortality in the diabetic population. A peculiar feature of cardiovascular diseases in this population is that they can have significant cardiac disease while remaining asymptomatic. There is a paucity of data regarding subclinical cardiac imaging features among diabetic adults in Africa, particularly in Ethiopia. This study was conducted to compare the magnitude and spectrum of left ventricular systolic and diastolic dysfunction among asymptomatic type 2 diabetic adults versus a normotensive, non-diabetic control group and to evaluate the determinants of left ventricular diastolic and systolic dysfunction.MethodsThis was a case-control study conducted at Tikur Anbessa specialized hospital, Addis Ababa, Ethiopia. A standard transthoracic echocardiography was done for all study participants with type 2 diabetes mellitus and their normotensive and non-diabetic controls. Structured questionnaires were used to collect demographic and clinical characteristics and laboratory test results. Statistical analysis was done using the SPSS 25.0 software. The data was summarized using descriptive statistics. Bivariate and multivariate analysis was performed to determine the association between variables and echocardiographic parameters. The strength of statistical association was measured by adjusted odds ratios and 95% confidence intervals, with significant differences taken at p < 0.05.ResultsWe analyzed age- and sex-matched 100 participants in the study (diabetic) group and 200 individuals in the control group. Left ventricular systolic and diastolic dysfunction were significantly more prevalent among diabetic adults than their sex and age matched controls. Among diabetic individuals, ages of 60 years and above, dyslipidemia, use of Metformin and Glibenclamide, high serum triglyceride level, presence of neuropathy and use of statins correlated significantly with the presence of left ventricular diastolic dysfunction. Chronic kidney disease and neuropathy were determinants of left ventricular systolic dysfunction.ConclusionLeft ventricular systolic and diastolic dysfunction were significantly more prevalent among diabetic patients than their sex- and age-matched controls in our study. We recommend early screening for subclinical left ventricular dysfunction, especially in the elderly and in those with chronic kidney disease, dyslipidemia, and microvascular complications such as neuropathy.

The utility of electrodiagnostic testing in unprovoked rhabdomyolysis in the era of next-generation sequencing.

Rhabdomyolysis is an etiologically heterogeneous, acute necrosis of myofibers characterized by transient marked creatine kinase (CK) elevation associated with myalgia, muscle edema, and/or weakness. The study aimed to determine the role of electrodiagnostic (EDX) testing relative to genetic testing and muscle biopsy in patients with unprovoked rhabdomyolysis in identifying an underlying myopathy. EDX database was reviewed to identify unprovoked rhabdomyolysis patients who underwent EDX testing between January 2012 and January 2022. Each patient's clinical profile, EDX findings, muscle pathology, laboratory, and genetic testing results were analyzed. Of 66 patients identified, 32 had myopathic electromyography (EMG). Muscle biopsy and genetic testing were performed in 41 and 37 patients, respectively. A definitive diagnosis was achieved in 15 patients (11 myopathic EMG and 4 nonmyopathic EMG; p = .04) based on abnormal muscle biopsy (4/11 patients) or genetic testing (12/12 patients, encompassing 5 patients with normal muscle biopsy and 3 patients with nonmyopathic EMG). These included seven metabolic and eight nonmetabolic myopathies (five muscular dystrophies and three ryanodine receptor 1 [RYR1]-myopathies). Patients were more likely to have baseline weakness (p < .01), elevated baseline CK (p < .01), and nonmetabolic myopathies (p = .03) when myopathic EMG was identified. Myopathic EMG occurred in approximately half of patients with unprovoked rhabdomyolysis, more likely in patients with weakness and elevated CK at baseline. Although patients with myopathic EMG were more likely to have nonmetabolic myopathies, nonmyopathic EMG did not exclude myopathy, and genetic testing was primarily helpful to identify an underlying myopathy. Genetic testing should likely be first-tier diagnostic testing following unprovoked rhabdomyolysis.

Modern management of leukemoid reactions

ABSTRACT. Leukemoid reaction (LR) is a transient hematological syndrome of reactive nature characterized by persistent leukocytosis of more than 50,000 cells/µL. LR can be caused by a variety of factors, including infections, intoxications, malignant neoplasms, severe hemorrhages, or acute hemolysis.&#x0D; The most common form of LR is neutrophilic myeloid reaction, which occurs in 80-90 % of cases. The diagnosis of LR is based on clinical examination and laboratory test results, including complete blood count with differential leukocyte formula, determination of leukocyte alkaline phosphatase level, aspiration and biopsy of bone marrow.&#x0D; Differential diagnosis of LR from other forms of leukemia is a challenging task. For this, it is necessary to conduct a thorough examination, including cytogenetic and molecular analysis of peripheral blood and bone marrow granulocytes. Despite certain advances in the differential diagnosis of LR, the mortality rate of patients in the world remains high, which requires the attention of doctors of various profiles.&#x0D; Treatment of LR depends on the underlying cause that caused it. The article proposes a diagnostic and treatment algorithm for LR in the case of its toxico-infectious origin.

Machine learning reveals serum myristic acid, palmitic acid and heptanoylcarnitine as biomarkers of coronary artery disease risk in patients with type 2 diabetes mellitus

BackgroundCoronary heart disease (CHD) is the most important complication of type 2 diabetes mellitus (T2DM) and the leading cause of death. Identifying the risk of CHD in T2DM patients is important for early clinical intervention. MethodsA total of 213 participants, including 81 healthy controls (HCs), 69 T2DM patients and 63 T2DM patients complicated with CHD were recruited in this study. Serum metabolomics were conducted by using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Demographic information and clinical laboratory test results were also collected. ResultsMetabolic phenotypes were significantly altered among HC, T2DM and T2DM-CHD. Acylcarnitines were the most disturbed metabolites between T2DM patients and HCs. Lower levels of bile acids and higher levels of fatty acids in serum were closely associated with CHD risk in T2DM patients. Artificial neural network model was constructed for the discrimination of T2DM and T2DM complicated with CHD based on myristic acid, palmitic acid and heptanoylcarnitine, with accuracy larger than 0.95 in both training set and testing set. ConclusionAltogether, these findings suggest that myristic acid, palmitic acid and heptanoylcarnitine have a good prospect for the warning of CHD complications in T2DM patients, and are superior to traditional lipid, blood glucose and blood pressure indicators.

Coagulation Function Testing Clinical Demand and Current Status in China

Diseases or symptoms related to coagulation function are widely present in clinical daily work, as coagulation function plays a central role in maintaining homeostasis in the internal environment. Therefore, coagulation dysfunction often leads to serious harm to patients. At the same time, coagulation related treatments such as the use of anticoagulants or transfusion therapy have potential serious side effects, even leading to patient death. For many years, balancing the bleeding or embolism caused by anticoagulants has been a challenge that clinical workers have to face, which poses great challenges to clinical work. Therefore, monitoring coagulation function is very important for clinical diagnosis and treatment. The rapid and accurate completion of coagulation function diagnosis conclusions and early transmission to clinical workers are important guarantees for patient life. However, at present, due to technical limitations and the complexity of the detection process, this demand cannot be met. At present, in China, coagulation function testing is mostly concentrated in laboratory departments, and the limitation of distance may affect the timeliness of coagulation function testing. Therefore, many clinical departments of institutions tend to conduct coagulation function testing themselves, which has led to many new demands for coagulation function testing, such as fast and convenient POCT coagulation function testing and coagulation function testing of cell models that are more in line with clinical needs, More joint detection of coagulation markers and so on, of course, these needs must be established on the premise that clinical testing equipment and laboratory testing results are consistent. However, in order to meet the needs of miniaturization and rapid testing, the coagulation function testing equipment used in clinical departments often has significant methodological differences from laboratory testing equipment, which further leads to differences in testing results. Based on this situation, many new technologies, including microfluidic technology, as well as more detection techniques, have been widely and deeply applied to clinical coagulation function testing, which has brought a lot of good news to clinical coagulation function diagnosis to a large extent.