Targeting STAT3 signaling pathway by curcumin and its analogues for breast cancer: A narrative review.

BACKGROUND: Breast cancer (BC) continues to be a significant global health issue, with a rising number of cases requiring ongoing research and innovation in treatment strategies. Curcumin (CUR), a natural compound derived from Curcuma longa, and similar compounds have shown potential in targeting the STAT3 signaling pathway, which plays a crucial role in BC progression. AIMS: The aim of this study was to investigate the effects of curcumin and its analogues on BC based on cellular and molecular mechanisms. MATERIALS & METHODS: The literature search conducted for this study involved utilizing the Scopus, ScienceDirect, PubMed, and Google Scholar databases in order to identify pertinent articles. RESULTS: This narrative review explores the potential of CUR and similar compounds in inhibiting STAT3 activation, thereby suppressing the proliferation of cancer cells, inducing apoptosis, and inhibiting metastasis. The review demonstrates that CUR directly inhibits the phosphorylation of STAT3, preventing its movement into the nucleus and its ability to bind to DNA, thereby hindering the survival and proliferation of cancer cells. CUR also enhances the effectiveness of other therapeutic agents and modulates the tumor microenvironment by affecting tumor-associated macrophages (TAMs). CUR analogues, such as hydrazinocurcumin (HC), FLLL11, FLLL12, and GO-Y030, show improved bioavailability and potency in inhibiting STAT3, resulting in reduced cell proliferation and increased apoptosis. CONCLUSION: CUR and its analogues hold promise as effective adjuvant treatments for BC by targeting the STAT3 signaling pathway. These compounds provide new insights into the mechanisms of action of CUR and its potential to enhance the effectiveness of BC therapies.

Management strategies and outcomes of thromboembolism prevention in atrial fibrillation co-existing with immune thrombocytopenia: A review of evidence.

This review aimed to assess bleeding risks and explore management options in atrial fibrillation (AF) patients with immune thrombocytopenia (ITP), aiming to formulate an optimal therapeutic approach for improved patient prognosis. Employing MeSH terms, a comprehensive search strategy identified articles on bleeding risks and management guidelines in AF combined with ITP. Original research papers were included, while animal studies, reviews, and non-English articles were excluded. From four databases, 1891 articles were initially retrieved, resulting in 10 relevant full-text articles. Eight studies investigated the effectiveness of anticoagulants in managing concurrent AF and ITP, demonstrating reduced bleeding risk and promising outcomes. Two papers explored surgical interventions, particularly left atrial appendage closure, suggesting its safety for AF management in patients with primary hemostatic disorders, including thrombocytopenia. While the pathophysiological mechanisms of AF and ITP remain unclear, anticoagulation regimens exhibited promising reductions in bleeding risks. Larger studies are warranted to enhance understanding and investigate optimal treatments for AF and ITP.

Prevalence of iron overload in patients with chronic kidney disease on peritoneal dialysis: A scoping review.

Background and Aims: Chronic kidney disease (CKD) patients undergoing peritoneal dialysis (PD) are susceptible to complications, including iron overload, which can significantly impact their prognosis and overall health. This scoping review aimed to study the prevalence and implications of iron overload in CKD patients undergoing PD. Methods: A comprehensive search was conducted across five databases, leading to the selection of 18 papers for in-depth analysis. These studies collectively involved 381 PD patients, 60.3% were males. Results: No consensus was reached regarding the exact diagnostic cutoff for iron overload. The investigations revealed four main aspects: (1) Seven papers identified various factors contributing to iron overload, emphasizing the role of different iron supplements and magnetic resonance imaging's capability to diagnose iron accumulation in organs; (2) Iron overload in young patients was found to hinder growth; (3) Six studies highlighted the adverse effects of iron overload, with cardiac issues being the most significant; (4) Three studies demonstrated the efficacy of iron-chelating agents, Deferoxamine and Deferasirox, in treating iron overload patients undergoing PD. Overall, the estimated prevalence of liver iron overload in CKD patients on PD ranges from approximately 10% to 28.6%, which is far lower than the prevalence of 75% elegantly shown in HD patients. Conclusion: While iron overload was a significant concern for CKD patients undergoing PD in the past, it is less common in the current era due to advancements in treatments, such as erythropoiesis-stimulating agents. Treatment with specific chelation agents has proven beneficial, but there is also a risk of adverse effects, necessitating meticulous monitoring and timely intervention.

Terminalia bellirica and Andrographis paniculata dietary supplementation in mitigating heat stress-induced behavioral, metabolic and genetic alterations in broiler chickens.

BACKGROUND: Heat stress (HS) is one of the most significant environmental stressors on poultry production and welfare worldwide. Identification of innovative and effective solutions is necessary. This study evaluated the effects of phytogenic feed additives (PHY) containing Terminalia bellirica and Andrographis paniculata on behavioral patterns, hematological and biochemical parameters, Oxidative stress biomarkers, and HSP70, I-FABP2, IL10, TLR4, and mTOR genes expression in different organs of broiler chickens under chronic HS conditions. A total of 208 one-day-old Avian-480 broiler chicks were randomly allocated into four treatments (4 replicate/treatment, 52 birds/treatment): Thermoneutral control treatment (TN, fed basal diet); Thermoneutral treatment (TN, fed basal diet + 1 kg/ton feed PHY); Heat stress treatment (HS, fed basal diet); Heat stress treatment (HS, fed basal diet + 1 kg/ton feed PHY). RESULTS: The findings of the study indicate that HS led to a decrease in feeding, foraging, walking, and comfort behavior while increasing drinking and resting behavior, also HS increased red, and white blood cells (RBCs and WBCs) counts, and the heterophile/ lymphocyte (H/L) ratio (P < 0.05); while both mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) were decreased (P < 0.05). In addition, HS negatively impacted lipid, protein, and glucose levels, liver and kidney function tests, and oxidative biomarkers by increasing malondialdehyde (MDA) levels and decreasing reduced glutathion (GSH) activity (P < 0.05). Heat stress (HS) caused the upregulation in HSP70, duodenal TLR4 gene expression, and the downregulation of I-FABP2, IL10, mTOR in all investigated tissues, and hepatic TLR4 (P < 0.05) compared with the TN treatment. Phytogenic feed additives (PHY) effectively mitigated heat stress's negative impacts on broilers via an improvement of broilers' behavior, hematological, biochemical, and oxidative stress biomarkers with a marked decrease in HSP70 expression levels while all tissues showed increased I-FABP2, IL10, TLR4, and mTOR (except liver) levels (P < 0.05). CONCLUSION: Phytogenic feed additives (PHY) containing Terminalia bellirica and Andrographis paniculata have ameliorated the HS-induced oxidative stress and improved the immunity as well as the gut health and welfare of broiler chickens.

An Uncommon Presentation of Eagle Syndrome in a Primary Care Patient with Chronic Neck Pain: A Case Report and Literature Review.

BACKGROUND Eagle syndrome is an uncommon medical illness that can manifest as neck pain in primary care. It results from an abnormally unilateral or bilateral long styloid process that may compress and affect adjacent structures, which leads to the symptoms. Classical Eagle syndrome has been commonly reported, but this case highlights the uncommon involvement of autonomic nerve dysfunction. CASE REPORT This case report details a 43-year-old woman with chronic neck pain for 5 years who saw numerous medical professionals and underwent 8 physiotherapy sessions. Marginal improvement of her neck pain and recent development of imbalance and a floating sensation prompted escalation of radiological imaging that eventually led to the diagnosis of Eagle syndrome. She was subsequently subjected to tonsillectomy and styloidectomy to address the sources of her neck pain. CONCLUSIONS Neck pain is a common complaint in primary care, but Eagle syndrome is often overlooked due to its complex symptoms, which mimic other conditions resulting in missed diagnoses and prolonged diagnostic evaluations. To improve patient care and outcomes, primary care physicians should consider Eagle syndrome when evaluating neck pain. This involves taking a detailed clinical history, conducting a thorough physical examination, using appropriate imaging techniques, and knowing the treatment options. By considering this potential diagnosis, primary care physicians, other healthcare professionals, and physical therapists play an important role in referring these patients to an otorhinolaryngologist or a maxillofacial surgeon for a comprehensive evaluation and management.

Ovarian Insufficiency in Adolescent Females with Transfusion Dependent -thalassemia; Pituitary Versus Ovarian Iron Overload.

INTRODUCTION: Females with transfusion-dependent -thalassemia (TDT) display menstrual irregularities and subfertility at certain points in their lives, even if well chelated, representing a significant physical and psychological burden. Little is known about the effects of pituitary and ovarian iron contents on ovarian reserve and function. Hence, this study aimed to assess ovarian reserve and pituitary-gonadal axis function in adolescent females with TDT and correlate them with pituitary and ovarian volume, pituitary iron load, and serum ferritin. METHODS: Fifty adolescent females with TDTs were compared with 50 age-matched healthy females. Age at diagnosis of TDT, transfusion index, type of chelation therapy, age at menarche, and Tanner breast stage were assessed. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), and ferritin levels were measured. Magnetic resonance imaging (MRI) was used to measure the pituitary iron content R2* and T2*, and 3-D transabdominal ovarian ultrasound was performed. RESULTS: The mean age of the studied females with TDT was 14.54 ± 2.24 years. Ovarian insufficiency was found in 20 patients (40%). Compared with controls, adolescent females with TDT had a significantly delayed age of menarche, AMH, FSH, LH, antral follicle count (AFC), and ovarian volume. In a comparison of those with and without ovarian insufficiency, adolescents with TDT with ovarian insufficiency had significantly higher serum ferritin and pituitary MRI-R2* values than did those without insufficiency. Multivariate logistic regression revealed that pituitary MRI-R2* was the most significant independent variable associated with ovarian insufficiency among adolescent females with TDT. CONCLUSION: Adolescent females with TDT have decreased ovarian reserves, AFCs and gonadotropins, which are correlated with the serum ferritin level, pituitary iron load and ovarian volume. Hence, regular ovarian reserve assessment should be implemented as a part of the endocrinological follow-up of females with TDT-advising procedures to preserve fertility to those who are likely to have ovarian insufficiency.

Hb SKMC and an unprecedented γδß-thalassemia: first report from Iraq.

BACKGROUND: Thalassemias are genetic disorders of globin chain synthesis. In Iraq, ß-thalassemia is more prevalent than α-thalassemia. This study identifies two unpredicted globin gene mutations, a rare α-globin gene mutation (Hb SKMC) and a novel γδß-thalassemia deletion. METHODS: Over 2 years, the Genetics unit at PAR hospital in Erbil, northern Iraq processed 137 ß-thalassemia and 97 α-thalassemia genetic testing requests. Three symptomatic thalassemia cases with unreported genotypes were identified. Proband-1α and proband-2α had Hb H disease, while proband-1ß had severe transfusion-dependent ß-thalassemia (TDT). Molecular studies included multiplex PCR, reverse hybridization, multiplex ligation-dependent probe amplification (MLPA), and globin gene sequencing. RESULTS: The α-thalassemia probands exhibited moderate microcytic hypochromic anemia with irregular transfusions and splenomegaly. Hb H disease was confirmed by positive Hb H tests and high-performance liquid chromatography (HPLC). Molecular analysis revealed heterozygous -MED deletion in proband-1α and α2Poly-A2 mutation in proband-2α. Sequencing identified the Hb SKMC (HBA1:c.283_300+3dup) mutation in both probands. The ß-thalassemia proband showed anemia and regular transfusions. Molecular studies detected the IVS1.110 G>A mutation and a novel γδß-thalassemia deletion in compound heterozygous form. The maternal sample showed the IVS1.110 G>A mutation, and MLPA confirmed the γδß-thalassemia deletion in the paternal sample. CONCLUSION: These findings highlight the genetic diversity of thalassemias in the region and emphasize the importance of advanced molecular diagnostics in detecting rare mutations.

P-doped carbon dot nano-probe for inner filter effect-based determination of sarecycline in pharmaceutical dosage form and human plasma.

Based on novel phosphorus-doped carbon dots (PCDs), a simple, quick, and accurate fluorescence probe for sarecycline (SAR) determination has been created. The PCDs were prepared in just five minutes using green, straightforward one-step microwave pyrolysis. To create the PCD probe, sodium phosphate monobasic was utilized as a phosphorus dopant and citric acid as a carbon supply. The proposed synthesis method was energy efficient and yielded CDs with a narrow particle size distribution. Based on inner-filter effect mechanism, the generated PCDs were used as nano-probe for SAR determination. The fluorescence quenching intensity showed a strong linear relationship with SAR concentration in the 3-90-µM range with a detection limit of 0.88 µM. Because there is no surface alteration of the CDs or creation of a covalent bond between SAR and PCDs, the developed approach is quick, easy, inexpensive, and requires less time. The new probe's enhanced sensitivity, broad linear range, and acceptable selectivity made it suitable for SAR measurement in pharmaceutical formulations and spiked human plasma. Most importantly, the Green Analytical Procedure Index (GAPI) and Analytical GREEnness (AGREE) assessments showed that the suggested method was environmentally friendly.

Outcomes with single-agent gilteritinib for relapsed or refractory FLT3-mutant AML after contemporary induction therapy.

Gilteritinib is the current standard of care for relapsed or refractory FLT3-mutated AML in many countries, however outcomes for patients relapsing after contemporary first-line therapies (intensive chemotherapy with midostaurin, or non-intensive chemotherapy with venetoclax) are uncertain. Moreover, reported data on toxicity and healthcare resource use is limited. Here we describe a large real-world cohort of 152 patients receiving single-agent gilteritinib in 38 UK hospitals. Median age was 61 and 36% had received 2 prior lines of therapy, including a FLT3 inhibitor in 41% and venetoclax in 24%. A median of 4 cycles of gilteritinib were administered, with 56% of patients requiring hospitalisation in the first cycle (median 10 days). Over half of patients required transfusion in each of the first 4 cycles. Complete remission (CR) was achieved in 21% and CR with incomplete recovery in a further 9%. Remission rates were lower for patients with FLT3-TKD or adverse karyotype. Day 30 and day 60 mortality were 1% and 10.6% and median overall survival was 9.5 months. On multivariable analysis, increasing age, KMT2A rearrangement and complex karyotype were associated with worse survival while RUNX1 mutations were associated with improved survival. Twenty patients received gilteritinib as first salvage having progressed following first-line therapy with venetoclax, with CR/CRi achieved in 25% and median survival 4.5 months. Real-world results with gilteritinib mirror those seen in the clinical trials but outcomes remain suboptimal, with more effective strategies needed.

PLLA Membranes Enriched with Chitosan/DCPA: Innovative Approach to Bone Tissue Engineering.

Bone tissue engineering has been very promising. The use of scaffolds of synthetic and natural materials is an alternative to combine the advantages of both types of materials. This study aimed to evaluate electrospun polymeric matrices of pure PLLA or associated with 5% or 10% of chitosan particles loaded or not with DCPA in bone proliferation and differentiation of periodontal ligament stem cells (PDLSC). The particles and matrices were characterized by scanning electron microscopy. PDLSC were isolated from periodontal ligament fragments of human permanent teeth using the explant technique. Cell proliferation assay (Alamar Blue) was performed from 1 to 21 days of culture in clonogenic medium and Alizarin Red assay was performed after 21 days of culture in osteogenic medium. The data were analyzed using Kruskal-Wallis test, and the comparison between media was given by the Student-Newman-Keuls test (α = 0.05). On days 1 and 7 there were no statistical difference between materials regarding cell proliferation (p>0.05). The materials with 5 and 10% chitosan / DCPA showed greater proliferation than PLLA control on days 14 and 21 and the material with 10% pure chitosan was greater than the control in 21 days. Regarding the alizarin red assay, PLLA 5% chitosan, PLLA 5 and 10% chitosan / DCPA showed a greater degree of mineralization than the control and the PLLA 10% chitosan material, and they were similar to each other. We conclude that PLLA 5 and 10% chitosan / DCPA materials were able to increase both, cell proliferation and differentiation of PDLSC in bone cells. Key words:Chitosan, PLLA, polymeric matrix, electrospinning.

Comparison of Knotless Versus Knot-Tying Suture Anchors for Arthroscopic Repair of Hip Labral Tears.

Background: Both knotless and knot-tying anchors are commonly employed in the arthroscopic repair of hip labral tears. Purpose: To compare the midterm clinical results of arthroscopic hip labral repair using knot-tying versus knotless suture anchors. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent arthroscopic hip labral repair between January 2017 and January 2021 and who had at least 2 years of follow-up were included. The patients were divided into 2 groups based on the suture anchor type: a 2.9-mm knotless suture anchor (knotless group) or a 1.8-mm knot-tying suture anchor (knot-tying group). All patients underwent femoroplasty for cam lesions and acetabular rim trimming for pincer lesions. The modified Harris Hip Score (mHHS), Hip Outcome Score-Sport-Specific Subscale (HOS-SSS), Hip Outcome Score-Activities of Daily Living (HOS-ADL), 12-item International Hip Outcome Tool (iHOT-12), and visual analog scale (VAS) for pain were administered both preoperatively and postoperatively. The consistency of the outcome scores was assessed using the minimal clinically important difference and Patient Acceptable Symptom State. The statistical significance between groups was evaluated using the Mann-Whitney test and quantile-based analysis of variance. Results: A total of 413 patients were included: 256 patients in the knotless group (median age, 35 years [interquartile range, 31-38 years]; median follow-up, 34 months) and 157 patients in the knot-tying group (median age, 34 years [interquartile range, 30-38 years]; median follow-up, 25 months). There were no significant differences in postoperative mHHS, HOS-ADL, or iHOT-12 scores between the 2 groups. However, there were significant differences, favoring the knotless group over the knot-tying group, in postoperative HOS-SSS (87 ± 2 vs 86 ± 1, respectively) and VAS pain (1 vs 2, respectively) scores (P < .0001 for both). Postoperative synovitis was found in significantly more patients in the knot-tying group than in the knotless group (17 vs 5, respectively; P = .01). Conclusion: In this study, patients who underwent arthroscopic hip labral repair with knotless suture anchors had slightly better postoperative HOS-SSS and VAS pain scores and a lower incidence of postoperative synovitis compared with patients who underwent repair with knot-tying suture anchors.

Prison healthcare service use and associated factors: a cross sectional study in Northwestern Ethiopia.

Introduction: Studies on inmates' Health Care Service (HCS) utilization are scarce globally, infrequent in Ethiopia while findings about the factors associated with HCS utilization are inconsistent. The present study, therefore, examined inmates' HCS utilization and associated socio-demographic and imprisonment related factors in Northwestern Ethiopia. Methods: The study employed institution-based cross sectional research design and data was collected using questionnaire from 422 inmates in three prisons. The questionnaire collected data about prisoners' demographic characters, imprisonment related information and HCS utilization. Descriptive statistical techniques as well as bi-variate and multiple logistic regressions were used to analyse the data. Results and discussions: The study found that 72.5%, 66.1% and 13.3% of the inmates, respectively, used medical services, guidance and counseling services, and psychiatric services. Inmates with primary education, with secondary education, and who know the availability of the services were more likely to use medical services. Inmates with accused status were less likely to use medical services than inmates with convict status. Divorced marital status and knowledge of the service availability were associated with high guidance and counseling service use. An increase in the length of stay in the prison was associated with a decrease in psychiatry service use while knowledge of service availability was associated with higher odds of psychiatry service use. There are high medical care service utilization while low mental health care service utilization among inmates in Northwestern Ethiopia. Results of the study implied that there is a critical need for immediate health care service promotion and education measures. Besides, there are also needs for large scale, longitudinal and potentially cross-cultural studies to better understand additional factors that influence inmates' HCS utilization.

Revolutionizing treatment for topical fungal infections: evaluating penetration-enhancer-containing vesicles as a fluconazole delivery system: Ex-vivo and in-vivo dermal testing.

Fungal infections pose a significant challenge in numerous developing nations and worldwide, necessitating urgent solutions. Oral administration of antifungal medications often leads to severe adverse reactions. Hence, employing topical delivery systems is preferred to ensure efficient dermal delivery of antifungal agents while minimizing side effects. Furthermore, the incorporation of penetration enhancers into nanocarriers loaded with antifungal agents has demonstrated enhanced efficacy in combating mycotic infections. Consequently, ultra-deformable penetration enhancer-containing vesicles (PEVs) were developed to explore this promising approach. In this study, Labrasol® and Transcutol® were used as penetration enhancers in formulating ultra-deformable PEVs containing the antifungal agent Fluconazole (FCZ). The PEVs underwent comprehensive characterization, including measurements of particle size (PS), charge, and entrapment efficiency (EE%). The results revealed that the size of tested PEVs ranged from 100 to 762 nm. All particles exhibited a negative charge, with a minimum zeta potential (ZP) of -38.26 mV, and an intermediate entrapment efficiency (EE%) that reached approximately 40%w/w. Ex-vivo studies demonstrated the ability of PEVs to deliver FCZ to the dermis while minimizing transdermal delivery. The selected formula was tested in-vivo using candidiasis-induced rat model and showed a superiority in its antifungal effect against Candida Albicans compared to the drug control. Stability studies were executed for the selected formula, and revealed good stability shown by the insignificant change in the PS, ZP& EE% over a six-month period.

[Fatal outcome of complete resection of undifferentiated pleomorphic cardiac sarcoma : About a case]. / Évolution fatale d'une résection complète d'un sarcome cardiaque pléomorphe indifférencié : à propos d'un cas.

INTRODUCTION: Undifferentiated pleomorphic sarcoma (UPS) is a very rare malignant primary cardiac tumor with a poor prognosis. OBSERVATION: A 34-year-old woman complained of dyspnea evolving in a febrile context with altered general condition: Transthoracic echocardiography (TTE) revealed a left intra-atrial mass measuring 51/26 mm in diameter. A thoracic computed tomography (CT) revealed a mass occupying the left atrium measuring 42/28/34 mm, associated with two pulmonary metastases. The cardiac mass was resected and the postoperative suites were fatal. Histological diagnosis was UPS. CONCLUSION: We present an atypical case of invasive UPS, which was surgically resected and scheduled for radio-chemotherapy with a fatal outcome.

Facile synthesis, release mechanism, and life cycle assessment of amine-modified lignin for bifunctional slow-release fertilizer.

Biomass-based slow-release fertilizers (SRFs) are a sustainable solution for addressing food scarcity, improving fertilizer efficiency, and reducing pollution, whereas they still face complex preparation, high costs, and low release characteristics. This study introduces a simple and innovative approach to producing bifunctional green SRFs with controlled release and conditioning properties for saline soils and harsh environments. The method involves a one-pot preparation of microsphere-structured amine-modified lignin slow-release fertilizer (L-UX) using biomass lignin as the starting material. The L-UX demonstrates an exceptional fertilizer loading rate (66.2 %) and extended slow-release performance (288 h), effectively enhancing the fertilizer's release ability. Compared to traditional fertilizers, the bifunctional L-UX significantly improves soil water retention capacity (824.3 %), plant growth, and germination percentage in challenging soil conditions (133 %). These findings highlight the potential of L-UX as a large-scale controlled-release fertilizer in harsh environments. A life cycle assessment (LCA) was also conducted to evaluate the environmental impact of L-UX from its production to disposal. This revealed that L-UX has a minimal environmental footprint compared to conventional inorganic fertilizers. This study further supports the widespread application of L-UX as an environmentally friendly alternative.

Early Detection of Renal Complication in Children With Sickle Cell Disease: A Single Center Prospective Study.

INTRODUCTION: This observational cross-sectional study aimed to identify predictors of renal complications in pediatric patients with sickle cell disease (SCD) at King Salman Armed Forces Hospital, Tabuk, Saudi Arabia, over six months from February 2023 to July 2023. The study evaluated microalbuminuria as an early indicator of renal injury and explored its correlations with clinical and laboratory parameters and abdominal ultrasound (US) findings. METHODS: Included were pediatric patients aged 1 to 14 years with confirmed SCD, excluding those with acute infections or pre-existing renal diseases. Data from 100 patients' electronic medical records were analyzed using IBM SPSS Statistics for Windows, Version 26 (Released 2019; IBM Corp., Armonk, New York, United States), with a significance set at p ≤ 0.05. RESULTS: The mean age was 7.6 ± 3.3 years, with 51 males and 49 females; 11 were diagnosed with Hb-S-beta thalassemia. Hydroxyurea (HU) compliance was high, with only four non-compliant patients, though all took folic acid. Among 42 tested for albuminuria, all had negative results (<30 mg/g creatinine). A significant association was found between SCD diagnosis and kidney, ureter, and bladder (KUB) US results (p=0.008), with abnormal KUB findings more prevalent in the Hb-S-beta thalassemia group. Patients with abnormal KUB results had significantly lower mean weight (p=0.024). Additionally, Hb-S-beta thalassemia patients had lower mean weight than hemoglobin SS (HGSS) patients (p=0.04). Though not statistically significant, Hb-S-beta thalassemia patients had higher mean systolic blood pressure (p=0.053). CONCLUSION: Significant associations were identified between SCD diagnosis type and renal US results, with lower body weight emerging as a potential predictor of renal complications. High HU compliance and its impact on renal outcomes warrant further investigation. Routine monitoring of microalbuminuria and KUB US may aid early detection of renal complications in pediatric SCD patients. Further studies with larger sample sizes are recommended to validate these findings and develop comprehensive renal protective strategies.

The Effectiveness of Measuring Thiopurine Metabolites in the Treatment of Autoimmune Hepatitis Patients.

The thiopurine drugs-azathioprine and mercaptopurine-are purine antimetabolites used for the treatment of autoimmune hepatitis. These drugs undergo metabolism through genetically determined pathways, which influences their effectiveness and toxicity. There is scarce information regarding the clinical effects of measuring drug metabolites in these patients. The goal of the study is to test the clinical significance of measuring thiopurine metabolites in patients unsuccessfully treated with thiopurines. Clinical and laboratory data collected for patients who were treated for autoimmune hepatitis between 2015 and 2018, and did not achieve full remission under thiopurine therapy and had thiopurine metabolite levels measured due to lack of response and suspicious side effects were chosen. We compared clinical and laboratory data before and after the therapy change. The study included 25 tests of thiopurine metabolites in 21 patients. Six tests had therapeutic levels. Three tests showed high levels leading to lowering the drug dose. In 11 cases, levels of 6-thioguanine nucleotide were low; the dose was not changed in 3 of these, and the dose was increased in the remaining 8. Shunting was observed in 5 cases, 2 of which were mild and the dose was not changed. In the remaining 3, the dose was decreased, and allopurinol was added. Significant improvements in liver enzymes were observed following dose adjustments. We showed that, in cases of suboptimal response to thiopurine treatment, measuring thiopurine metabolites had an important role in optimizing therapy. In most patients, changing the dose led to a significant improvement with no need to switch to secondline therapies.

Metastatic Non-Small-Cell Lung Cancer Presenting as Renal Failure From IgA Nephropathy.

Studies have highlighted a potential link between malignancies and immunoglobulin A nephropathy (IgAN). In such studies, the treatment of malignancy improved the symptoms of IgAN. Here, we report a patient case involving a history of hypertension, tobacco use disorder, and chronic kidney disease (CKD) presenting with hematuria with acute renal failure secondary to IgAN per renal biopsy. Prompted by this association, a malignancy workup was performed including computed tomography (CT) body imaging and biopsies of mediastinal and cervical lymph nodes which revealed a metastatic adenocarcinoma. Current knowledge includes a general mechanism behind the development of IgAN that points toward glomerular deposition of tumor-specific immunoglobulin A (IgA) immunoglobulins. However, the association of IgAN and malignancy has no definitive management guidelines. This clinical case serves as an important contribution in the hopes of future development of guidelines regarding the surveillance and management of IgAN in the setting of malignancy.

Cognitive subtypes in youth at clinical high risk for psychosis.

Introduction: Schizophrenia is a mental health condition that severely impacts well-being. Cognitive impairment is among its core features, often presenting well before the onset of overt psychosis, underscoring a critical need to study it in the psychosis proneness (clinical high risk; CHR) stage, to maximize the benefits of interventions and to improve clinical outcomes. However, given the heterogeneity of cognitive impairment in this population, a one-size-fits-all approach to therapeutic interventions would likely be insufficient. Thus, identifying cognitive subtypes in this population is crucial for tailored and successful therapeutic interventions. Here we identify, validate, and characterize cognitive subtypes in large CHR samples and delineate their baseline and longitudinal cognitive and functional trajectories. Methods: Using machine learning, we performed cluster analysis on cognitive measures in a large sample of CHR youth (n = 764), and demographically comparable controls (HC; n = 280) from the North American Prodrome Longitudinal Study (NAPLS) 2, and independently validated our findings with an equally large sample (NAPLS 3; n = 628 CHR, 84 HC). By utilizing several statistical approaches, we compared the clusters on cognition and functioning at baseline, and over 24 months of followup. We further delineate the conversion status within those clusters. Results: Two main cognitive clusters were identified, "impaired" and "intact" across all cognitive domains in CHR compared to HC. Baseline differences between the cognitively intact cluster and HC were found in the verbal abilities and attention and working memory domains. Longitudinally, those in the cognitively impaired cluster group demonstrated an overall floor effect and did not deteriorate further over time. However, a "catch up" trajectory was observed in the attention and working memory domain. This group had higher instances of conversion overall, with these converters having significantly more non-affective psychotic disorder diagnosis versus bipolar disorder, than those with intact cognition. In the cognitively intact group, we observed differences in trajectory based on conversion status, where those who start with intact cognition and later convert demonstrate a sharp decline in attention and functioning. Functioning was significantly better in the cognitively intact than in the impaired group at baseline. Most of the cognitive trajectories demonstrate a positive relationship with functional ones. Conclusion: Our findings provide evidence for intact and impaired cognitive subtypes in youth at CHR, independent of conversion status. They further indicate that attention and working memory are important to distinguish between the CHR with intact cognition and controls. The cognitively intact CHR group becomes less attentive after conversion, while the cognitively impaired one demonstrates a catch up trajectory on both attention and working memory. Overall, early evaluation, covering several cognitive domains, is crucial for identifying trajectories of improvement and deterioration for the purpose of tailoring intervention for improving outcomes in individuals at CHR for psychosis.

Mitral Transcatheter Edge-to-Edge Repair and Clinical Value of Novel Echocardiographic Biomarkers: A Hypothesis-Generating Study.

BACKGROUND: Longitudinal data on reverse cardiac remodeling and outcomes after transcatheter edge-to-edge repair (TEER) are limited. METHODS: A total of 78 patients with severe mitral regurgitation (MR) were included retrospectively. All patients had echocardiography at baseline and again six months after TEER. They were monitored for a primary composite endpoint, consisting of heart failure hospitalization and cardiovascular death, over 13 months. RESULTS: Significant decreases in the left ventricular ejection fraction (LVEF), all myocardial work indices (except global wasted work), and the left atrial reservoir were observed after TEER. Additionally, there was a decrease in the pulmonary artery systolic pressure and an increase in the tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio. A post-TEER TAPSE/PASP ratio of <0.47 (HR: 4.76, p-value = 0.039), and a post-TEER left atrial reservoir of <9.0% (HR: 2.77, p-value = 0.047) were associated with the primary endpoint. CONCLUSIONS: Echocardiography post-TEER reflects impairment in ventricular performance due to preload reduction and right ventricle and pulmonary artery coupling improvement. Short-term echocardiography after TEER identifies high-risk patients who could benefit from a close clinical follow-up. The prognostic significance of LA strain and the TAPSE/PASP ratio should be validated in subsequent large-scale prospective studies.