Clinical Care Team's Guide for Awareness on Risk Assessment of Eltrombopag Complicating Acute Kidney Injury in Relapsed Immune Thrombocytopenic Patients: A Case Report.

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder caused by antigen-specific T cells and antiplatelet autoantibodies that inhibit platelet production in the bone marrow or destroy platelets in the spleen. ITP is a form of autoimmunity and is closely associated with inflammation. Corticosteroids are the first-line therapy for ITP, with a total response rate of 53-80%. However, corticosteroid therapy is associated with significant side effects and is often ineffective in patients with corticosteroid-resistant or -intolerant disease. Eltrombopag has been validated as a second-line option in ITP therapy. Despite several studies demonstrating the efficacy and safety of Eltrombopag in immune thrombocytopenia patients, the prevalence of Eltrombopag-induced acute kidney injury has been observed. This case report describes a patient who experienced acute kidney injury during Eltrombopag therapy. A sudden increase in serum creatinine to 6.7 mg/dL and metabolic acidosis occurred after eight weeks of Eltrombopag. The patient's renal failure had worsened, proteinuria was detected, and emergency hemodialysis was initiated. With vigilant kidney function screening and prompt treatment, the patient's renal function improved remarkably following cessation of Eltrombopag and initiation of hemodialysis. This case highlights the importance of comprehensive medication history-taking and vigilant kidney function screening in patients receiving Eltrombopag.

Performance of Multidetector Computed Tomography and Negative Versus Positive Enteric Contrast for Evaluation of Gastrointestinal Neuroendocrine Neoplasms.

BACKGROUND: Routine computed tomography (CT) scans are thought to have poor performance for detection of gastrointestinal (GI) neuroendocrine neoplasms (NENs), which leads to delayed workup. Detection of even 1 bowel tumor can guide diagnostic workup and management. The purposes of this study were to assess the accuracy of multidetector computed tomography (MDCT) and to compare negative versus positive enteric contrast in detecting at least 1 GI tumor per patient with suspected or confirmed diagnosis of a NEN. METHODS: This retrospective study included 107 patients with intravenous and oral contrast (65 positive, 40 negative, and 2 no oral contrast) abdominopelvic MDCT. Two abdominal radiologists independently analyzed the CTs for detection and localization of bowel NENs. Surgical pathology was considered the reference standard. Analyses included κ and summary statistics, McNemar test, Pearson χ2 test, and Fisher exact test. RESULTS: Among the 107 CT scans, there were 30 pathology negative studies and 77 studies with positive pathology for GI NEN. Interreader agreement for CT evaluation was substantial (κ = 0.61). At least 1 GI NEN per patient was detected with 51% to 53% sensitivity, 87% to 93% specificity, 91% to 95% positive predictive value (PPV), 42% negative predictive value, and 63% accuracy for each reader, and 57% accuracy when only the concordant (ie, matching) results of the 2 readers were considered. Computed tomography scans with negative enteric contrast had significantly higher sensitivity for concordant results than CTs with positive enteric contrast (58% vs 30%, P = 0.01). Specificity (100% vs 95%, P = 0.5), PPV (100% vs 93%, P = 0.49), negative predictive value (39% vs 39%, P = 0.99), and accuracy (67% vs 51%, P = 0.10) were not significantly different for negative versus positive enteric contrast for the concordant results. There was no significant difference in GI NEN localization between the readers. CONCLUSIONS: Routine MDCT with either positive or negative enteric contrast can detect at least 1 GI tumor per patient with more than 90% PPV and more than 50% accuracy in patients suspected of GI NEN. Using negative enteric contrast improves sensitivity for GI NEN versus positive enteric contrast. In addition, there is high accuracy in localizing the bowel tumor with positive or negative enteric contrast, which may guide surgery. Radiologists should have heightened awareness that evaluating such scans closely may lead to detection of primary bowel NENs at a higher rate than previously reported.

Assessing the Impact of Structured Reports for Fluoroscopic Double-Contrast Barium Esophagrams.

Fluoroscopic barium swallow examinations are a commonly performed radiologic study in the evaluation of dysphagia. These studies remain essential in the diagnostic work-up despite the increasing utilization of endoscopy, but current residents are often less experienced with fluoroscopy. Structured reporting has been demonstrated to improve comprehensiveness of reports in multiple settings, but has not been evaluated for barium swallow examinations. A retrospective review identified patients who underwent barium swallow examinations pre-structured reporting in 2017 and followed a multidisciplinary proposal for and adoption of an optional structured report in 2020. Reports were assessed for comprehensiveness by evaluating presence/absence each element (total of 10 elements). Differences in report elements between groups and multiple subgroups was performed utilizing a Mann-Whitney U test. χ2 tests were also utilized to evaluate inclusion of each individual element of the report. A total of 487 reports from 2020 and 757 reports from 2017 were analyzed. Certain elements showed substantial differences in reporting, with greater than 90% of structured reports including them, but much lower numbers including them in non-structured reports from 2017 and 2020. Reports generated in 2020 had a statistically significant increase in report elements included when compared to 2017 (p < 0.01). This statistically significant increase was also observed in comparison of structured reports and non-structured reports from either period (p < 0.01). Adoption of structured reporting for fluoroscopic barium swallow examinations led to significant increase in report comprehensiveness and should be considered after a multidisciplinary approach to development.

Assessment of Renal Cell Carcinoma by Texture Analysis in Clinical Practice: A Six-Site, Six-Platform Analysis of Reliability.

BACKGROUND. Multiple commercial and open-source software applications are available for texture analysis. Nonstandard techniques can cause undesirable variability that impedes result reproducibility and limits clinical utility. OBJECTIVE. The purpose of this study is to measure agreement of texture metrics extracted by six software packages. METHODS. This retrospective study included 40 renal cell carcinomas with contrast-enhanced CT from The Cancer Genome Atlas and Imaging Archive. Images were analyzed by seven readers at six sites. Each reader used one of six software packages to extract commonly studied texture features. Inter- and intrareader agreement for segmentation was assessed with intraclass correlation coefficients (ICCs). First-order (available in six packages) and second-order (available in three packages) texture features were compared between software pairs using Pearson correlation. RESULTS. Inter- and intrareader agreement was excellent (ICC, 0.93-1). First-order feature correlations were strong (r ≥ 0.8, p < .001) between 75% (21/28) of software pairs for mean intensity and SD, 48% (10/21) for entropy, 29% (8/28) for skewness, and 25% (7/28) for kurtosis. Of 15 second-order features, only cooccurrence matrix correlation, gray-level nonuniformity, and run-length nonuniformity showed strong correlation between software packages (r = 0.90-1, p < .001). CONCLUSION. Variability in first- and second-order texture features was common across software configurations and produced inconsistent results. Standardized algorithms and reporting methods are needed before texture data can be reliably used for clinical applications. CLINICAL IMPACT. It is important to be aware of variability related to texture software processing and configuration when reporting and comparing outputs.

GSK3ß-SCFFBXW7α mediated phosphorylation and ubiquitination of IRF1 are required for its transcription-dependent turnover.

IRF1 (Interferon Regulatory Factor-1) is the prototype of the IRF family of DNA binding transcription factors. IRF1 protein expression is regulated by transient up-regulation in response to external stimuli followed by rapid degradation via the ubiquitin-proteasome system. Here we report that DNA bound IRF1 turnover is promoted by GSK3ß (Glycogen Synthase Kinase 3ß) via phosphorylation of the T181 residue which generates a phosphodegron for the SCF (Skp-Cul-Fbox) ubiquitin E3-ligase receptor protein Fbxw7α (F-box/WD40 7). This regulated turnover is essential for IRF1 activity, as mutation of T181 results in an improperly stabilized protein that accumulates at target promoters but fails to induce RNA-Pol-II elongation and subsequent transcription of target genes. Consequently, the anti-proliferative activity of IRF1 is lost in cell lines expressing T181A mutant. Further, cell lines with dysfunctional Fbxw7 are less sensitive to IRF1 overexpression, suggesting an important co-activator function for this ligase complex. As T181 phosphorylation requires both DNA binding and RNA-Pol-II elongation, we propose that this event acts to clear 'spent' molecules of IRF1 from transcriptionally engaged target promoters.

Repurposing of some anti-infective drugs for COVID-19 treatment: A surveillance study supported by an in silico investigation.

OBJECTIVE: The repurposing of nitazoxanide, doxycycline and azithromycin may be effective to improve the symptoms in mild and moderate COVID-19 subjects. This study aimed to detect and explain the efficacy of reusing of these drugs in treating COVID-19. METHODS: The study was divided into two parts: clinical and computational parts. In the clinical part, 80 (30 females) subjects with reverse transcription-polymerase chain reaction-confirmed COVID-19 with mild and moderate symptoms were enrolled in the study. Subjects were treated with azithromycin or doxycycline, and nitazoxanide was added to the treatment if the subject had diarrhoea. Subjects were divided into four groups: Group 1: subjects treated with azithromycin (20 subjects); Group 2: subjects treated with doxycycline (20 subjects); Group 3: subjects treated with a combination of nitazoxanide and doxycycline (20 subjects); and Group 4: subjects treated with a combination of nitazoxanide and azithromycin (20 subjects). In the computational part, we docked the three drugs against all currently available COVID-19-related protein targets (viral and non-viral). Subsequently, top hits were subjected to molecular dynamic simulations (MDSs) (50 ns) and binding free energy calculations to further validate the docking experiments and to investigate the binding modes of the potential inhibitors. RESULTS: The symptomatic improvement of mild to moderate subjects was seen on the fifth day after starting treatment in Group 3 and Group 4 and on the seventh day in Group 2. However, for Group 1, the symptomatic improvement of mild to moderate subjects was not seen on the fifth day and required replacement by doxycycline to get the symptomatic improvement. None of the subjects needed intensive care admission and no deaths were reported. In silico, results were in good accordance with the clinical outcomes, where both nitazoxanide and doxycycline achieved the best docking scores against the viral ADP-ribose phosphatase (ADPRP) and the human Adaptor-Associated Kinase 1 (AAK1). MDSs revealed that both drugs were stable in their bindings indicating that they can be considered as lead molecules for targeting ADPRP and AAK1. CONCLUSION: The clinical and computational studies applied on three FDA-approved antimicrobials together with their recent clinical findings revealed that both nitazoxanide and doxycycline have great therapeutic potential against COVID-19. The future in vitro mechanistic investigation may confirm our primary computational outcomes, and in turn, these classes of compounds provide a promising starting point for further anti-COVID-19 therapeutics.

Preresection Radiologic Assessment and Imaging Features of 156 Pathologically Proven Adrenal Adenomas.

PURPOSE: The aims of the study were to assess the typical and atypical radiologic features of pathologically proven adrenal adenomas and to determine the relationship between the radiologic and histopathologic classification. METHODS: We retrospectively studied 156 pathologically proven adrenal adenomas in 154 patients from our institutional databases who have computed tomography (CT) and/or magnetic resonance imaging (MRI) examinations before intervention. We determined the histopathologic diagnosis (typical or atypical) using Weiss scoring and classified the adenomas radiologically into typical, atypical, or indeterminate based on lesion size, precontrast CT attenuation, absolute percentage washout, calcification, and necrosis. The κ statistic was used to assess the agreement between radiologists. The Fisher exact test was used to compare the radiologic and pathological classifications. RESULTS: In consensus, there were 83 typical, 42 atypical, and 31 indeterminate adrenal lesions. Logistic regression model showed that radiologically atypical adenoma was significantly associated with larger size, lobulated shape, higher unenhanced CT attenuation, heterogeneous appearance, nonfunctioning status, absolute percentage washout of less than 60%, and a signal intensity index of less than 16.5%.Pathologically, 147 adenomas were pathologically typical (Weiss 0), and 9 adenomas were pathologically atypical (Weiss 1-2). Radiologically, there was substantial agreement between both readers, with Cohen κ at 0.71. Approximately 98% of radiologically typical adenomas were pathologically typical. Only 17% of radiologically atypical adenomas were pathologically atypical. All radiologically indeterminate adenomas were pathologically typical. However, some of the radiologically indeterminate and typical adenomas still had an atypical component on pathologic analysis, such as necrosis, nuclear atypia, or oncocytic features. CONCLUSIONS: Radiologically atypical lesion was significantly associated with larger size and higher unenhanced CT attenuation. Approximately 27% of the cases demonstrated atypical features on imaging. Most radiologically atypical adrenal adenomas are pathologically typical.

Qualitative Slow Blood Flow in Lower Extremity Deep Veins on Doppler Sonography: Quantitative Assessment and Preliminary Evaluation of Correlation With Subsequent Deep Venous Thrombosis Development in a Tertiary Care Oncology Center.

OBJECTIVES: To determine whether the qualitative sonographic appearance of slow deep venous flow in the lower extremities correlates with quantitative slow flow and an increased risk of deep venous thrombosis (DVT) in oncology patients. METHODS: In this Institutional Review Board-approved retrospective study, we reviewed lower extremity venous Doppler sonographic examinations of 975 consecutive patients: 482 with slow flow and 493 with normal flow. The subjective slow venous flow and absence of initial DVT were confirmed by 2 radiologists. Peak velocities were recorded at 3 levels. Each patient was followed for DVT development. The associations between DVT and the presence of slow venous flow were examined by the Fisher exact test; a 2-sample t test was used for peak velocity and DVT group comparisons. The optimal cutoff peak velocity for correlation with the radiologists' perceived slow flow was determined by the Youden index. RESULTS: Deep venous thrombosis development in the slow-flow group (21 of 482 [4.36%]) was almost doubled compared with patients who had normal flow (11 of 493 [2.23%]; P = .0456). Measured peak venous velocities were lower in the slow-venous flow group (P < .001). Patients with subsequent DVT did not have a significant difference in venous velocities compared with their respective patient groups. The sum of 3 venous level velocities resulted in the best cutoff for dichotomizing groups into normal versus slow venous flow. CONCLUSIONS: Qualitative slow venous flow in the lower extremities on Doppler sonography accurately correlates with quantitatively slower flow, and this preliminary evaluation suggests an associated mildly increased rate of subsequent DVT development in oncology patients.

Laparoendoscopic Single-Site Surgery (LESS) for Right Donor Nephrectomy in a Patient With Situs Inverses Totalis: A Novel Approach for Such a Case.

Situs inversus totalis (SIT) is a rare congenital condition where the organs of the thorax and abdomen are arranged in a mirror image reversal of their normal position. Patients with SIT present unique challenges in surgical procedures, particularly in laparoscopic surgeries, due to the need to reverse the operator's perspective, technical difficulty in handling the instruments, anatomical variations, and an increased risk of intraoperative complications. In this case report, we present the first case in the English literature of a 49-year-old Arabic male patient with SIT who underwent a successful right laparoendoscopic single-site surgery donor nephrectomy. We described the surgical technique used and highlighted the key challenges faced and overcome during the procedure.

Molecular Diversity and Combining Ability in Newly Developed Maize Inbred Lines under Low-Nitrogen Conditions.

Nitrogen is an essential element for maize growth, but excessive application can lead to various environmental and ecological issues, including water pollution, air pollution, greenhouse gas emissions, and biodiversity loss. Hence, developing maize hybrids resilient to low-N conditions is vital for sustainable agriculture, particularly in nitrogen-deficient soils. Combining ability and genetic relationships among parental lines is crucial for breeding superior hybrids under diverse nitrogen levels. This study aimed to assess the genetic diversity of maize inbred lines using simple sequence repeat (SSR) markers and evaluate their combining ability to identify superior hybrids under low-N and recommended conditions. Local and exotic inbred lines were genotyped using SSR markers, revealing substantial genetic variation with high gene diversity (He = 0.60), moderate polymorphism information content (PIC = 0.54), and an average of 3.64 alleles per locus. Twenty-one F1 hybrids were generated through a diallel mating design using these diverse lines. These hybrids and a high yielding commercial check (SC-131) were field-tested under low-N and recommended N conditions. Significant variations (p < 0.01) were observed among nitrogen levels, hybrids, and their interaction for all recorded traits. Additive genetic variances predominated over non-additive genetic variances for grain yield and most traits. Inbred IL3 emerged as an effective combiner for developing early maturing genotypes with lower ear placement. Additionally, inbreds IL1, IL2, and IL3 showed promise as superior combiners for enhancing grain yield and related traits under both low-N and recommended conditions. Notably, hybrids IL1×IL4, IL2×IL5, IL2×IL6, and IL5×IL7 exhibited specific combining abilities for increasing grain yield and associated traits under low-N stress conditions. Furthermore, strong positive associations were identified between grain yield and specific traits like plant height, ear length, number of rows per ear, and number of kernels per row. Due to their straightforward measurability, these relationships underscore the potential of using these traits as proxies for indirect selection in early breeding generations, particularly under low-N stress. This research contributes to breeding nitrogen-efficient maize hybrids and advances our understanding of the genetic foundations for tolerance to nitrogen limitations.

Nutrient-sensitizing drug repurposing screen identifies lomerizine as a mitochondrial metabolism inhibitor of chronic myeloid leukemia.

In chronic myeloid leukemia (CML), the persistence of leukemic stem cells (LSCs) after treatment with tyrosine kinase inhibitors (TKIs), such as imatinib, can lead to disease relapse. It is known that therapy-resistant LSCs rely on oxidative phosphorylation (OXPHOS) for their survival and that targeting mitochondrial respiration sensitizes CML LSCs to imatinib treatment. However, current OXPHOS inhibitors have demonstrated limited efficacy or have shown adverse effects in clinical trials, highlighting that identification of clinically safe oxidative pathway inhibitors is warranted. We performed a high-throughput drug repurposing screen designed to identify mitochondrial metabolism inhibitors in myeloid leukemia cells. This identified lomerizine, a US Food and Drug Administration (FDA)-approved voltage-gated Ca2+ channel blocker now used for the treatment of migraines, as one of the top hits. Transcriptome analysis revealed increased expression of voltage-gated CACNA1D and receptor-activated TRPC6 Ca2+ channels in CML LSCs (CD34+CD38-) compared with normal counterparts. This correlated with increased endoplasmic reticulum (ER) mass and increased ER and mitochondrial Ca2+ content in CML stem/progenitor cells. We demonstrate that lomerizine-mediated inhibition of Ca2+ uptake leads to ER and mitochondrial Ca2+ depletion, with similar effects seen after CACNA1D and TRPC6 knockdown. Through stable isotope-assisted metabolomics and functional assays, we observe that lomerizine treatment inhibits mitochondrial isocitrate dehydrogenase activity and mitochondrial oxidative metabolism and selectively sensitizes CML LSCs to imatinib treatment. In addition, combination treatment with imatinib and lomerizine reduced CML tumor burden, targeted CML LSCs, and extended survival in xenotransplantation model of human CML, suggesting this as a potential therapeutic strategy to prevent disease relapse in patients.

Agenesis of flexor pollicis longus without thenar hypoplasia: a case report and literature review.

We present a case of congenital of flexor pollicis longus agenesis without thenar hypoplasia in a 12-year-old girl with no history of trauma. Two-staged corrective surgery was planned. In the first stage, the flexor pulley was reconstructed using silicone followed by the second stage 3 months later when flexor pollicis longus reconstruction was performed using tendon transfer of the flexor digitorum superficialis. The patient completed post-operative physiotherapy and the result of the surgical treatment in both functional and cosmetic aspects was, in the authors' opinion, excellent.

A rare variant of mirror hand deformity.

Congenital hand and forearm anomalies pose a unique challenge in plastic and pediatric surgery. We present a case report of an 8-months-old girl with a congenital left sided hand and forearm anomaly, provisionally diagnosed as atypical left mirror hand anomaly. Classically there is absence of radius and duplication of ulna; however, our case had normal radius and ulna and a hand with seven digits arranged in two groups. We did a surgery which involved a ray amputation of the finger ulnar to the most radial digit, aiming to preserve an adequate first web space to reconstruct the thumb. The result of the surgical treatment in both functional and cosmetic aspects was, in authors' opinion, good.

The Impact of Social Media on the Mental Health of Adolescents and Young Adults: A Systematic Review.

Adolescents increasingly find it difficult to picture their lives without social media. Practitioners need to be able to assess risk, and social media may be a new component to consider. Although there is limited empirical evidence to support the claim, the perception of the link between social media and mental health is heavily influenced by teenage and professional perspectives. Privacy concerns, cyberbullying, and bad effects on schooling and mental health are all risks associated with this population's usage of social media. However, ethical social media use can expand opportunities for connection and conversation, as well as boost self-esteem, promote health, and gain access to critical medical information. Despite mounting evidence of social media's negative effects on adolescent mental health, there is still a scarcity of empirical research on how teens comprehend social media, particularly as a body of wisdom, or how they might employ wider modern media discourses to express themselves. Youth use cell phones and other forms of media in large numbers, resulting in chronic sleep loss, which has a negative influence on cognitive ability, school performance, and socio-emotional functioning. According to data from several cross-sectional, longitudinal, and empirical research, smartphone and social media use among teenagers relates to an increase in mental distress, self-harming behaviors, and suicidality. Clinicians can work with young people and their families to reduce the hazards of social media and smartphone usage by using open, nonjudgmental, and developmentally appropriate tactics, including education and practical problem-solving.

Patient Characteristics and Predictors of Pulmonary Embolism in Patients Infected with COVID - 19 in Upper Egypt.

Background: A little is known about the risk factors and predictors of pulmonary embolism (PE) in Coronavirus disease 2019 (Covid-19) infected patients. Therefore, we directed this study to investigate the predictors of PE in patients infected with Covid - 19 in Upper Egypt. Methods: We conducted a retrospective cohort study on 297 patients infected with COVID-19, aged ≥ 18 years old. Suspicion of COVID-19 infection was based on the World Health Organization (WHO) criteria and confirmed by nasal and pharyngeal swab for real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. The patient was also determined to have COVID-19 when CT results that were thought to be typical for COVID-19 and clinical data that were compatible were present. Results: PE was diagnosed in 18.2% of patients. We found that the incidence of PE was significantly higher in older patients, females, those with higher BMI, hypertensive patients, diabetics, and patients with co-morbidities. Also, PE was significantly higher in patients presented with dyspnea, chest pain, longer duration of symptoms at hospital admission, and lower oxygen concentration. The mean serum Hb level, platelet count, TLC and absolute lymphocytic count were markedly reduced in those who had PE. All the patients who developed PE had a CO-RADS scale five on their CT chest scan. Age > 65, BMI > 25, DM, and associated co-morbidities were the independent patients' characteristics associated with the development of PE after the multivariate regression analysis. Conclusion: PE is a common complication of Covid 19 infection. PE is associated with a variety of clinical and laboratory parameters in univariate analysis, but age > 65, BMI > 25, DM, and associated co-morbidities were the independent patients' characteristics associated with the development of PE in those infected with Covid-19.

Increasing Awareness of Hypertensive Patients About Their Blood Pressure Readings During Clinic Visits in a Tertiary Hospital in Riyadh.

Introduction Hypertension (HTN) is one of the most important cardiovascular risk factors. It is associated with significant complications, such as coronary artery disease, stroke, and chronic kidney disease. Awareness among hypertensive patients regarding their blood pressure (BP) is low in the Kingdom of Saudi Arabia. Aim This study aimed to evaluate the awareness of patients regarding their BP readings and to identify which aspects of HTN they needed to be informed about. Patients and methods A descriptive cross-sectional study was conducted among hypertensive patients attending outpatient clinics at King Fahad Medical City, Riyadh, Saudi Arabia. An electronic questionnaire was used by a trained physician to collect data from patients during telephone interviews. The information included socio-demographic data (i.e., age, gender, and education), family history, compliance with medications, and BP measurements. Patients were asked to answer questions to assess their awareness of their BP readings. Results Of the 475 hypertensive patients included in this study, 32.7% were aged between 56 and 65 years and 60.4% were female. The proportion of patients who had knowledge of their target BP (systolic: 120-129 mmHg; diastolic: 80-84 mmHg) was 74.4%. The significant independent predictors of increased knowledge about BP were a high level of education, regular measurement of BP, and having received education about a healthy lifestyle. The significant independent predictor of decreased knowledge about BP was having an acceptable or poor understanding of chronic BP. Conclusion Hypertensive patients visiting the outpatient clinic at King Fahad Hospital had a good understanding of their target BP readings. Educated patients who regularly measured their BP and who received education about a healthy lifestyle tended to exhibit a higher motivation to achieve their BP targets. More research is needed to gain more insights into the knowledge of hypertensive patients and into how they manage their BP to determine the factors that influence their knowledge.

The Outcomes and Adverse Drug Patterns of Immunomodulators and Thrombopoietin Receptor Agonists in Primary Immune Thrombocytopenia Egyptian Patients with Hemorrhage Comorbidity.

Immune thrombocytopenia (ITP) treatment has evolved recently. However, none of the treatments have only benefits without drawbacks. This study aimed to compare the clinical outcomes and adverse drug patterns of Eltrombopag, Romiplostim, Prednisolone + Azathioprine, High Dose-dexamethasone (HD-DXM) (control group), and Rituximab in primary ITP Egyptian patients. All patients were initiated with corticosteroids, HD-DXM, as a first-line treatment for the first month immediately following diagnosis. Four hundred sixty-seven ITP patients were randomly assigned to five groups. The outcome measures were judged at baseline, at the end of treatment (6 months), and after an additional 6-month free treatment period. The follow-up period for which relapse is noted was 6 months after the end of treatment. Eltrombopag and Romiplostim resulted in a significantly higher incidence of sustained response than Rituximab, HD-DXM, and Prednisolone + Azathioprine (55.2% and 50.6% vs. 29.2%, 29.1%, and 18%, respectively; p-value < 0.001). More patients on immunomodulators (Prednisolone+ Azathioprine, HD-DXM, and Rituximab) relapsed than those on Romiplostim and Eltrombopag (81.9%, 70.8%, and 70.7% vs. 49.3%, and 44.7%, respectively; p-value < 0.01). We also describe 23 reports of pulmonary hypertension with Prednisolone+ Azathioprine and 13 reports with HD-DXM. The thrombotic events occurred in 16.6% and 13% of patients who received Eltrombopag and Romiplostim treatment, respectively. Most patients had at least one or two risk factors (92.8% of cases). Corticosteroids are effective first-line therapy in primary ITP patients. However, relapse is frequent. Eltrombopag and Romiplostim are safer and more effective than Prednisolone, HD-DXM, and Rituximab. They might be reasonable beneficial options after a one-month HD-DXM regimen.

Therapeutic Outcomes of High Dose-Dexamethasone versus Prednisolone + Azathioprine, Rituximab, Eltrombopag, and Romiplostim Strategies in Persistent, Chronic, Refractory, and Relapsed Immune Thrombocytopenia Patients.

BACKGROUND: Primary immune thrombocytopenia (ITP) is an inflammatory autoimmune disease that can be managed with several treatment options. However, there is a lack of comparative data on the efficacy of these options in different phases of the disease. AIM OF THE STUDY: This study aimed to evaluate the efficacy of high-dose Dexamethasone (HD-DXM), Prednisolone + Azathioprine, Rituximab, Eltrombopag, and Romiplostim schedules in persistent, chronic refractory or relapsed Egyptian ITP patients with a platelet count ≤30 × 109/L. The primary outcome measure was a sustained increase in platelet counts over 50 × 109/L for an additional 12 months without additional ITP regimens. The study also aimed to identify a suitable treatment regimen with a long remission duration for each phase of ITP. RESULTS: Prednisolone + Azathioprine was significantly more effective in achieving an overall response in persistent patients than Romiplostim, high-dose Dexamethasone, and Rituximab. (90.9% vs. 66.6, [Odds ratio, OR: 5; confidence interval, CI 95% (0.866-28.86)], 45%, [OR: 0.082, CI 95% (0.015-0.448)] and, 25%, [OR: 30, CI 95% (4.24-211.8)], respectively, p-value < 0.01). Eltrombopag was significantly more effective in achieving a durable response in refractory ITP than HD-DXM, Rituximab, and Prednisolone; (80% compared to 32.2% [OR: 0.119, CI 95% (0.035-0.410)], 22.2% [OR:0.071, CI 95% (0.011-0.455)], and 18.1% [OR: 0.056, CI 95% (0.009-0.342)], respectively, p-value < 0.01). CONCLUSIONS: Finally, Eltrombopag following HD-DXM showed the highest percentage of patients with complete treatment-free survival times of at least 330 days. These findings could help clinicians choose the most appropriate treatment for their patients with ITP based on the phase of the disease. This trial is registered in clinicaltrials.gov with registration number NCT05861297.

Pyruvate anaplerosis is a targetable vulnerability in persistent leukaemic stem cells.

Deregulated oxidative metabolism is a hallmark of leukaemia. While tyrosine kinase inhibitors (TKIs) such as imatinib have increased survival of chronic myeloid leukaemia (CML) patients, they fail to eradicate disease-initiating leukemic stem cells (LSCs). Whether TKI-treated CML LSCs remain metabolically deregulated is unknown. Using clinically and physiologically relevant assays, we generate multi-omics datasets that offer unique insight into metabolic adaptation and nutrient fate in patient-derived CML LSCs. We demonstrate that LSCs have increased pyruvate anaplerosis, mediated by increased mitochondrial pyruvate carrier 1/2 (MPC1/2) levels and pyruvate carboxylase (PC) activity, in comparison to normal counterparts. While imatinib reverses BCR::ABL1-mediated LSC metabolic reprogramming, stable isotope-assisted metabolomics reveals that deregulated pyruvate anaplerosis is not affected by imatinib. Encouragingly, genetic ablation of pyruvate anaplerosis sensitises CML cells to imatinib. Finally, we demonstrate that MSDC-0160, a clinical orally-available MPC1/2 inhibitor, inhibits pyruvate anaplerosis and targets imatinib-resistant CML LSCs in robust pre-clinical CML models. Collectively these results highlight pyruvate anaplerosis as a persistent and therapeutically targetable vulnerability in imatinib-treated CML patient-derived samples.

Multimodality annotated hepatocellular carcinoma data set including pre- and post-TACE with imaging segmentation.

Hepatocellular carcinoma (HCC) is the most common primary liver neoplasm, and its incidence has doubled over the past two decades owing to increasing risk factors. Despite surveillance, most HCC cases are diagnosed at advanced stages and can only be treated using transarterial chemo-embolization (TACE) or systemic therapy. TACE failure may occur with incidence reaching up to 60% of cases, leaving patients with a financial and emotional burden. Radiomics has emerged as a new tool capable of predicting tumor response to TACE from pre-procedural computed tomography (CT) studies. This data report defines the HCC-TACE data collection of confirmed HCC patients who underwent TACE and have pre- and post-procedure CT imaging studies and available treatment outcomes (time-to-progression and overall survival). Clinically curated segmentation of pre-procedural CT studies was done for the purpose of algorithm training for prediction and automatic liver tumor segmentation.