Assessment of drug therapy satisfaction amongst the elderly: A patient reported outcomes measures approach.

BACKGROUND: Understanding elderly experiences enhance healthcare outcomes and patient satisfaction. Recognizing caregivers' role and implementing supportive measures enhance care. OBJECTIVES: Quantify drug satisfaction using patient-reported outcomes measures approach. Assess caregiver burden using short version of Burden Scale for Family Caregivers. METHODS: Six-month cross-sectional study in Department of Geriatrics. Elderly (≥60), minimum one comorbidity, admitted for >48 h, and consenting to participate were enrolled. Patient satisfaction assessed using Treatment Satisfaction with Medicines Questionnaire (SATMED-Q). SPSS version 27 used to calculate odds ratio. RESULTS: 282 participants enrolled. SATMED-Q score 47.41 ± 10.34, indicating overall satisfaction. Treatment satisfaction range 47.07 % to 100 %. Age [OR 0.964, 95 % CI 0.932-0.996 (p = 0.029)] and education [OR 1.500, 95 % CI 1.129-1.992 (p = 0.005)] influenced satisfaction. 268 [95.03 %] had caregivers, 14 [4.96 %] did not. Caregiver burden score 9.25 ± 9.11. CONCLUSION: Insights obtained from assessing satisfaction and caregiver burden enables physicians to improve welfare of elderly and caregivers.

Efficacy of Pharmacotherapies for Bulimia Nervosa: A Systematic Review and Meta-Analysis.

Objective: The main purpose was to evaluate the efficacy and tolerability of different medications used to treat bulimia nervosa (BN). Methods: Randomized controlled trials (RCTs) were identified from published sources through searches in PubMed, Cochrane Library, Web of Science, and Embase from inception to November 2022. Primary outcomes were changes in the frequency of binge eating episodes and vomiting episodes from baseline to endpoint. Secondary outcomes were differences in the improvement of scores in depressive symptoms, tolerability (dropout due to adverse events) and weight change. Results: The literature search ultimately included 11 drugs, 33 studies and 6 types of drugs, 8 trials with TCAs (imipra-mine, desipramine), 14 with SSRIs (fluoxetine, citalopram and fluvoxamine), 6 with MAOIs (phenelzine, moclobemide and brofaromine), 3 with antiepileptic drugs (topiramate), 1 with mood stabilizers (lithium), and 1 with amphetamine-type appetite suppressant (fenfluramine). The reduction in binge eating episodes was more likely due to these drugs than the placebo, and the SMD was -0.4 (95% CI -0.61 ∼ -0.19); the changes in the frequency of vomiting episodes (SMD = -0.16, 95% CI -0.3 ∼ -0.03); weight (WMD = -3.05, 95% CI -5.97 ∼ -0.13); and depressive symptoms (SMD =-0.32, 95% CI -0.51 ∼ -0.13). However, no significant difference was found in dropout due to adverse events (RR = 1.66, 95% CI 1.14 ∼ 2.41). Conclusions: This meta-analysis indicates that most pharmacotherapies decreased the frequency of binge-eating and vomiting episodes, body weight, and depressive symptoms in BN patients, but the efficacy was not significant. In each drug the efficacy is different, treating different aspects, different symptoms to improve the clinical performance of bulimia nervosa.Appeared originally in BMC Pharmacol Toxicol 2023; 24:72.

Palliative Pharmacotherapy for Cardiovascular Disease: A Scientific Statement From the American Heart Association.

Cardiovascular disease exacts a heavy toll on health and quality of life and is the leading cause of death among people ≥65 years of age. Although medical, surgical, and device therapies can certainly prolong a life span, disease progression from chronic to advanced to end stage is temporally unpredictable, uncertain, and marked by worsening symptoms that result in recurrent hospitalizations and excessive health care use. Compared with other serious illnesses, medication management that incorporates a palliative approach is underused among individuals with cardiovascular disease. This scientific statement describes palliative pharmacotherapy inclusive of cardiovascular drugs and essential palliative medicines that work synergistically to control symptoms and enhance quality of life. We also summarize and clarify available evidence on the utility of guideline-directed and evidence-based medical therapies in individuals with end-stage heart failure, pulmonary arterial hypertension, coronary heart disease, and other cardiomyopathies while providing clinical considerations for de-escalating or deprescribing. Shared decision-making and goal-oriented care are emphasized and considered quintessential to the iterative process of patient-centered medication management across the spectrum of cardiovascular disease.

Effective and appropriate use of weight loss medication in pediatric obesity: a narrative review.

Over the past few decades, there has been a notable increase in the incidence of pediatric obesity, which is a significant public health concern. Children who are obese have a greater risk of type 2 diabetes, hypertension, dyslipidemia, polycystic ovary syndrome, obstructive sleep apnea, and adult obesity. Lifestyle modification therapy is typically the initial approach to treat pediatric obesity. For patients who do not achieve success with lifestyle modification therapy alone, pharmacotherapy is the next logical treatment option. When selecting an anti-obesity medication (AOM), it is essential to first ascertain the medical background of the patient, including current medications and obesity-associated comorbidities. Evaluation of obesity phenotypes in patients may also be beneficial. AOMs for pediatric obesity include metformin, orlistat, glucagon-like peptide 1 agonists, phentermine, and the phentermine/topiramate combination. Sufficient lifestyle modification therapy should be administered before considering pharmacotherapy and continued after the initiation of AOM. To ensure healthy development, monitoring growth and puberty development during anti-obesity treatments is essential.

Safety of outpatient commencement of sotalol.

Background: Inpatient monitoring is recommended for sotalol initiation. Objective: The purpose of this study was to assess the safety of outpatient sotalol commencement. Methods: This is a multicenter, retrospective, observational study of patients initiated on sotalol in an outpatient setting. Serial electrocardiogram monitoring at day 3, day 7, 1 month, and subsequently as clinically indicated was performed. Corrected QT (QTc) interval and clinical events were evaluated. Results: Between 2008 and 2023, 880 consecutive patients who were commenced on sotalol were evaluated. Indications were atrial fibrillation/flutter in 87.3% (n = 768), ventricular arrhythmias in 9.9% (n = 87), and other arrhythmias in 2.8% (n = 25). The daily dosage at initiation was 131.0 ± 53.2 mg/d. The QTc interval increased from baseline (431 ± 32 ms) to 444 ± 37 ms (day 3) and 440 ± 33 ms (day 7) after sotalol initiation (P < .001). Within the first week, QTc prolongation led to the discontinuation of sotalol in 4 and dose reduction in 1. No ventricular arrhythmia, syncope, or death was observed during the first week. Dose reduction due to asymptomatic bradycardia occurred in 3 and discontinuation due to dyspnea in 3 within the first week. Overall, 1.1% developed QTc prolongation (>500 ms/>25% from baseline); 4 within 3 days, 1 within 1 week, 4 within 60 days, and 1 after >3 years. Discontinuation of sotalol due to other adverse effects occurred in 41 patients within the first month of therapy. Conclusion: Sotalol initiation in an outpatient setting with protocolized follow-up is safe, with no recorded sotalol-related mortality, ventricular arrhythmias, or syncope. There was a low incidence of significant QTc prolongation necessitating discontinuation within the first month of treatment. Importantly, we observed a small incidence of late QT prolongation, highlighting the need for vigilant outpatient surveillance of individuals on sotalol.

The application of dexamethasone implants in uveitis treatment.

Uveitis refers to a group of ocular inflammatory diseases that can significantly impair vision. Although systemic corticosteroid therapy has shown substantial efficacy in treating uveitis, extensive use of corticosteroids is associated with significant adverse effects. Recently, a biodegradable, sustained-release implant, namely dexamethasone intravitreal implant (Ozurdex), has been reported for treating non-infectious and infectious uveitis. This review aims to summarize the experiences with Ozurdex treatment across various forms of uveitis and to assist readers in understanding the appropriate timing and potential side effects of Ozurdex in uveitis treatment, thereby maximizing patient benefits in uveitis management.

A Novel Cellular Senescence-related lncRNA Signature for Predicting the Prognosis of Breast Cancer Patients.

Background: Long non-coding RNA (lncRNA), a crucial regulator in breast cancer (BC) development, is intricately linked with cellular senescence. However, there is a lack of cellular senescence-related lncRNAs (CSRLs) signature to evaluate the prognosis of BC patients. Methods: Correlation analysis was conducted to identify lncRNAs associated with cellular senescence. Subsequently, a CSRL signature was crafted in the training cohort. The model's accuracy was evaluated through survival analysis and receiver operating characteristic curves. Furthermore, prognostic nomograms amalgamating cellular senescence and clinical characteristics were devised. Tumor microenvironment and checkpoint disparities were compared between low-risk and high-risk groups. The correlation between these signatures and treatment response in BC patients was also investigated. Finally, functional experiments were conducted for validation. Results: A signature comprising nine CSRLs was devised, which demonstrated adept prognostic capability in BC patients. Functional enrichment analysis revealed that tumor and immune-related pathways were predominantly enriched. Compared to the low-risk group, the high-risk group could benefit more from immunotherapy and certain chemotherapeutic agents. The expression of the 9 CSRLs was validated through in vitro experiments in different subtypes of BC cell lines and tissues. AC098484.1 was specifically verified for its association with senescence-associated secretory phenotypes. Conclusion: The CSRLs signature emerges as a promising prognostic biomarker for BC, with implications for immunological studies and treatment strategies. AC098484.1 has potential relevance in the treatment of BC cell senescence, and these findings improve the clinical treatment levels for BC patients.

[Management of Cytomegalovirus Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients]. / Abordagem à Infeção pelo Vírus Citomegálico em Doentes Submetidos a Transplante Alogénico de Progenitores Hematopoiéticos.

Cytomegalovirus (CMV) is a type of double-stranded deoxyribonucleic acid virus belonging to the herpesviridae family. Following a primary infection, the virus becomes latent in various types of white blood cells. Cytomegalovirus infection can remain latent or become active, especially in immunocompromised individuals, such as those undergoing hematopoietic stem cell transplantation (HSCT), where CMV reactivation can occur. In this context, CMV infection is common and associated with high rates of morbidity and mortality. Pneumonia is one of the most serious complications, with mortality rates exceeding 50%. Additionally, even in the absence of organ-specific disease, CMV infection is related to increased mortality unrelated to hematologic neoplasm recurrence. Given the frequency and severity of this infection in HSCT patients, it is crucial to implement effective strategies for monitoring, prevention, and treatment. This guideline was developed to identify patient groups that benefit from a systematic approach to CMV infection and to define the most appropriate strategy for each group. Monitoring CMV viral load in peripheral blood is crucial, especially in patients at moderate to high risk of active infection. Primary prophylaxis with letermovir (an antiviral drug) is recommended to reduce the incidence of active infection, especially in high-risk patients. Secondary prophylaxis with valganciclovir (antiviral drug) is recommended after an episode of active infection, while preemptive and disease treatment is based on monitoring viral load and clinical response. The aim of this guideline is to improve the approach to CMV infection in HSCT patients, ensuring an effective and safe preventive and therapeutic approach.

O vírus citomegálico (CMV) é um tipo de vírus de ácido desoxirribonucleico de dupla cadeia que pertence à família herpesviridae. Após uma infeção primária, o vírus torna-se latente em vários tipos de glóbulos brancos. A infeção por CMV pode permanecer latente ou tornar-se ativa, especialmente em indivíduos imunodeprimidos, como aqueles submetidos a transplantes de células progenitoras hematopoiéticas (TPH), onde a reativação do CMV pode ocorrer. Neste contexto, a infeção por CMV é comum e associada a elevadas taxas de morbilidade e mortalidade. A pneumonite é uma das complicações mais graves, com taxas de mortalidade superiores a 50%. Além disso, mesmo na ausência de doença específica do órgão, a infeção por CMV está relacionada com um aumento da mortalidade não relacionada com a recidiva da neoplasia hematológica. Dada a frequência e gravidade desta infeção em doentes submetidos a TPH, é crucial implementar estratégias eficazes de monitorização, prevenção e tratamento. Este protocolo foi desenvolvido para identificar os grupos de doentes que se beneficiam de uma abordagem sistematizada para a infeção por CMV e definir a estratégia mais adequada para cada grupo. A monitorização da carga viral de CMV no sangue periférico é fundamental, especialmente em doentes com risco moderado a elevado de infeção ativa. A profilaxia primária com letermovir (fármaco antiviral) é recomendada para reduzir a incidência de infeção ativa, especialmente em doentes com alto risco. A profilaxia secundária com valganciclovir (fármaco antiviral) é recomendada após um episódio de infeção ativa, enquanto o tratamento de antecipação e de doença é baseado na monitorização da carga viral e na resposta clínica. Este protocolo visa melhorar a abordagem da infeção por CMV em doentes submetidos a TPH, garantindo uma abordagem preventiva e terapêutica eficaz e segura.

Key steps and barriers in the journey of patients with epilepsy through the National Healthcare System in Spain: The EPIPASS qualitative study.

OBJECTIVE: Epilepsy requires continuous medical attention from multiple healthcare specialists, specialized facilities, and community-based care. In Spain, there is no standardized approach to epilepsy care. The aim of this study was to identify the factors impacting on the delivery of high-quality care by exploring key steps and barriers along the patient journey through the Spanish National Healthcare System (NHS). METHODS: A qualitative study was conducted using opinions and experiences of neurologists, nurses, patients, and caregivers shared in discussion meetings. Using thematic content analyses, relevant aim-focused statements were coded according to prespecified issues in a discussion map (i.e., key steps and barriers), and sub-coded according to emerging issues. Thematic saturation and co-occurrence of key steps/barriers were evaluated to identify the most relevant factors impacting on the delivery of high-quality care. RESULTS: Sixty-five stakeholders took part in discussion meetings (36 neurologists, 10 nurses, 10 patients, and nine caregivers). Six key steps on the patient journey were identified: emergency care, diagnosis, drug therapy, follow-up, referral, and interventional treatment. Of these, follow-up was the most relevant step impacting on the delivery of high-quality patient care, followed by drug therapy and diagnosis. Emergency care was considered a hot-spot step with impact throughout the patient journey. Communication (among HCPs and between HCPs and patients) was a barrier to the delivery of high-quality care at several stages of the patient journey, including drug therapy, follow-up, referral, and interventional treatment. Resource availability was a barrier for diagnosis (especially for confirmation), drug therapy (drug availability), and referral (lack of professionals and specialized centers, and long waiting lists). SIGNIFICANCE: This is the first study capturing perspectives of four key stakeholders involved in epilepsy care in Spain. We provide an overview of the patient journey through the Spanish NHS and highlight opportunities to improve the delivery of patient-centered care with a chronicity perspective. PLAIN LANGUAGE SUMMARY: Patients with epilepsy may require prolonged medical care. In Spain, care is provided by a range of specialist and non-specialist centers. In this study, a team of Spanish neurologists, nurses, patients and caregivers identified barriers that affect the delivery of high-quality care for patients with epilepsy at each stage of their journey through the Spanish NHS. Specific epilepsy training for healthcare providers, appropriate resources for diagnosing and treating patients, and good communication between healthcare workers and patients were identified as important factors in providing high-quality care for patients with epilepsy.

Chronic kidney disease and pulmonary hypertension: Progress in diagnosis and treatment.

Pulmonary hypertension (PH) is a medical condition characterized by elevated pulmonary vascular resistance and pressure, resulting from different diseases. Due to their high occurrence of PH, intricate hemodynamic classification, and frequently multifactorial cause and mechanism, individuals suffering from chronic kidney disease (CKD) are categorized as the fifth primary group of PH. Based on both domestic and international research, this article provides information on the epidemiology, risk factors, pathogenesis, and targeted drug treatment of PH associated with CKD.

Prediction of Oncotype DX Recurrence Score Based on Systematic Evaluation of Ki-67 Scores in Hormone Receptor-Positive Early Breast Cancer.

PURPOSE: Oncotype DX (ODX) predicts the risk of recurrence and benefits of adding chemotherapy for patients with estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer. We aimed to develop a simplified scoring system using readily available clinicopathological parameters to predict a high-risk ODX recurrence score (RS) while minimizing reproducibility issues regarding Ki-67 index evaluation methods. METHODS: We enrolled 300 patients with ER+/HER2- early breast cancer, for whom ODX RS data were available in the test set. Using the QuPath image analysis platform, we systematically evaluated the average, hotspot, and hottest spot Ki-67 scores in the test set. Logistic regression analyses were conducted to establish a predictive scoring system for high-risk ODX RS. An independent validation set comprising 117 patients over different periods was established. RESULTS: Factors such as age ≤ 50 years, invasive ductal carcinoma tumor type, histologic grade 2 or 3, tumor necrosis, progesterone receptor negativity, and a high Roche-analyzed Ki-67 score (> 20) were associated with high-risk ODX RS. These variables were incorporated into our scoring system. The area under the curve of the scoring system was 0.8057. When applied to both the test and validation sets with a cutoff value of 3, the sensitivity of our scoring system was 92%. CONCLUSION: We successfully developed a scoring system based on the systematic evaluation of Ki-67 scoring methods. We believe that our user-friendly predictive scoring system for high risk ODX RS could help clinicians in identifying patients who may or may require additional ODX testing.

Effects of heavy-load strength training during (neo-)adjuvant chemotherapy on muscle strength, muscle fiber size, myonuclei, and satellite cells in women with breast cancer.

To investigate the effects of heavy-load strength training during (neo-)adjuvant chemotherapy in women with breast cancer on muscle strength, body composition, muscle fiber size, satellite cells, and myonuclei. Women with stage I-III breast cancer were randomly assigned to a strength training group (ST, n = 23) performing supervised heavy-load strength training twice a week during chemotherapy, or a usual care control group (CON, n = 17). Muscle strength and body composition were measured and biopsies from m. vastus lateralis collected before the first cycle of chemotherapy (T0) and after chemotherapy and training (T1). Muscle strength increased significantly more in ST than in CON in chest-press (ST: +10 ± 8%, p < .001, CON: -3 ± 5%, p = .023) and leg-press (ST: +11 ± 8%, p < .001, CON: +3 ± 6%, p = .137). Both groups reduced fat-free mass (ST: -4.9 ± 4.0%, p < .001, CON: -5.2 ± 4.9%, p = .004), and increased fat mass (ST: +15.3 ± 16.5%, p < .001, CON: +16.3 ± 19.8%, p = .015) with no significant differences between groups. No significant changes from T0 to T1 and no significant differences between groups were observed in muscle fiber size. For myonuclei per fiber a non-statistically significant increase in CON and a non-statistically significant decrease in ST in type I fibers tended (p = .053) to be different between groups. Satellite cells tended to decrease in ST (type I: -14 ± 36%, p = .097, type II: -9 ± 55%, p = .084), with no changes in CON and no differences between groups. Strength training during chemotherapy improved muscle strength but did not significantly affect body composition, muscle fiber size, numbers of satellite cells, and myonuclei compared to usual care.

Real-world evidence of systemic treatment practices for biliary tract cancer in Japan: Results of a database study.

PURPOSE: To describe the real-world treatment patterns of systemic therapies for biliary tract cancer (BTC) and to examine the frequency and management of biliary infection in Japan. METHODS: Patients diagnosed with BTC and prescribed systemic therapy between January 2011 and September 2020 were retrieved from the Japanese Medical Data Vision database. The look-back period was set to 5 years. Patient characteristics, treatment patterns, and biliary infection-induced treatment interruption were analyzed. RESULTS: The full analysis set comprised 22 742 patients with a mean age of 71.0 years and 61.6% were male. The most common BTC type was extrahepatic cholangiocarcinoma (44.6%). The three most common first-line regimens were S-1 monotherapy (33.0%), gemcitabine+cisplatin (32.5%), and gemcitabine monotherapy (18.7%) over the entire observation period (January 2011-September 2021). Patients who received monotherapies tended to be older. Biliary infection-induced treatment interruption occurred in 29.5% of patients, with a median time to onset of 64.0 (interquartile range 29.0-145.0) days. The median duration of intravenous antibiotics was 12.0 (interquartile range 4.0-92.0) days. CONCLUSIONS: These results demonstrated potential challenges of BTC in Japanese clinical practice particularly use of multiple regimens, commonly monotherapies, which are not recommended as first-line treatment, and the management of biliary infections during systemic therapy.

Potentiation of BKCa channels by cystic fibrosis transmembrane conductance regulator (CFTR) correctors VX-445 and VX-121.

Cystic fibrosis (CF) results from mutations in the CFTR anion channel, ultimately leading to diminished transepithelial anion secretion and mucociliary clearance. CFTR correctors are therapeutics that restore the folding/trafficking of mutated CFTR to the plasma membrane. The BKCa potassium channel is also critical for maintaining lung ASL volume. Here, we show the CFTR corrector, VX-445 (Elexacaftor), a component of Trikafta, induces K+ secretion across WT and F508del CFTR primary human bronchial epithelial cells (HBEs), which was entirely inhibited by the BKCa antagonist paxilline. Similar results were observed with VX-121 - a corrector under clinical evaluation. Whole-cell patch-clamp recordings confirmed potentiated channel activity from CFTR correctors on the BKCa α-subunit, and excised patch-clamp recordings demonstrated a significant increase in open probability. In mesenteric artery, VX-445 induced a paxilline-sensitive vasorelaxation of preconstricted arteries. VX-445 also reduced action potential firing frequency in primary hippocampal and cortical neurons. VX-445 effects were observed at low micomolar concentrations (1-10 µM) - within the range reported in plasma and tissues from CF patients. We raise the possibilities that CFTR correctors gain additional clinical benefit by activation of BKCa in the lung, yet may lead to adverse events through BKCa activation, elsewhere.

East meets West: Bringing the ESH 2023 hypertension guidelines into Asia.

Hypertension remains a major problem worldwide, especially across the Asia-Pacific region, which reports high prevalence rates and slow improvements in treatment rate and blood pressure (BP) control rate. Asian patients with hypertension may also vary with regard to phenotype and the epidemiology of the complications of hypertension, especially when compared with Western patients. Given these differences, Western guidelines may not necessarily be applicable to countries in the Asia Pacific. This narrative review aims to provide a critical comparison between the recently published European Society of Hypertension (ESH) 2023 guidelines and existing local guidelines in select Asian countries, offer expert opinion on how to fill gaps in the ESH 2023 guidelines for hypertension in the Asian context, and examine the need for harmonisation of hypertension guidelines worldwide. This review focuses on the definition and diagnosis of hypertension, the treatment thresholds and targets, and recommendations on the use of pharmacotherapy.

Identification of ibuprofen targeting CXCR family members to alleviate metabolic disturbance in lipodystrophy based on bioinformatics and in vivo experimental verification.

Background: Lipodystrophy is a rare disease that is poorly diagnosed due to its low prevalence and frequent phenotypic heterogeneity. The main therapeutic measures for patients with clinical lipodystrophy are aimed at improving general metabolic complications such as diabetes mellitus, insulin resistance, and hypertriglyceridemia. Therefore, there is an urgent need to find new biomarkers to aid in the diagnosis and targeted treatment of patients with congenital generalized lipodystrophy (CGL). Methods: Dataset GSE159337 was obtained via the Gene Expression Omnibus database. First, differentially expressed genes (DEGs) between CGL and control samples were yielded via differential expression analysis and were analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment to explore the functional pathways. Next, protein-protein interaction analysis and the MCC algorithm were implemented to yield candidate genes, which were then subjected to receiver operating characteristic (ROC) analysis to identify biomarkers with an area under the curve value exceeding 0.8. Moreover, random forest (RF), logistic regression, and support vector machine (SVM) analyses were carried out to assess the diagnostic ability of biomarkers for CGL. Finally, the small-molecule drugs targeting biomarkers were predicted, and ibuprofen was further validated in lipodystrophy mice. Results: A total of 71 DEGs in GSE159337 were sifted out and were involved in immune receptor activity, immune response-regulating signaling pathway, and secretory granule membrane. Moreover, CXCR2, TNFSF10, NLRC4, CCR2, CEACAM3, TLR10, TNFAIP3, and JUN were considered as biomarkers by performing ROC analysis on 10 candidate genes. Meanwhile, RF, logistic regression, and SVM analyses further described that those biomarkers had an excellent diagnosis capability for CGL. Eventually, the drug-gene network included ibuprofen-CXCR1, ibuprofen-CXCR1, cenicriviroc-CCR2, fenofibrate-JUN, and other relationship pairs. Ibuprofen treatment was also validated to downregulate CXCR1 and CXCR2 in peripheral blood mononuclear cells (PBMCs) and improve glucose tolerance, hypertriglyceridemia, hepatic steatosis, and liver inflammation in lipodystrophy mice. Conclusion: Eight biomarkers, namely, CXCR2, TNFSF10, NLRC4, CCR2, CEACAM3, TLR10, TNFAIP3, and JUN, were identified through bioinformatic analyses, and ibuprofen targeting CXCR1 and CXCR2 in PBMCs was shown to improve metabolic disturbance in lipodystrophy, contributing to studies related to the diagnosis and treatment of lipodystrophy.

CDKL3 is a targetable regulator of cell cycle progression in cancers.

Cell cycle regulation is largely abnormal in cancers. Molecular understanding and therapeutic targeting of the aberrant cell cycle are essentially meaningful. Here, we identified an under-appreciated Serine/Threonine kinase, CDKL3 (Cyclin-dependent kinase like 3), crucially drives the rapid cell cycle progression and cell growth in cancers. Mechanism-wise, CDKL3 localizes in the nucleus and associates with specific cyclin to directly phosphorylate Retinoblastoma (Rb) for quiescence exit. In parallel, CDKL3 prevents the ubiquitin-proteasomal degradation of CDK4 by direct phosphorylation on T172 to sustain G1 phase advancement. The crucial function of CDKL3 in cancers was demonstrated both in vitro and in vivo. We also designed, synthesized and characterized a first-in-class CDKL3-specific inhibitor, HZ1. HZ1 exhibits greater potency than CDK4/6 (Cyclin-dependent kinase 4/6) inhibitor in pan-cancer treatment by causing cell cycle arrest and overcomes the acquired resistance of the latter. In particular, CDKL3 has significant clinical relevance in colon cancer, and the effectiveness of HZ1 was demonstrated by murine and patient-derived cancer models. Collectively, this work presented an integrated paradigm of cancer cell cycle regulation and suggested CDKL3-targeting as a feasible approach in cancer treatment.

Treatment for appendicitis in cancer patients on chemotherapy: a retrospective cohort study.

Purpose: Whether to perform surgery or conservatively manage appendicitis in immunosuppressed patients is a concern for clinicians. This study aimed to compare the outcomes of these 2 treatment options for appendicitis in patients with cancer undergoing chemotherapy. Methods: This retrospective study included 206 patients with cancer who were diagnosed with acute appendicitis between August 2001 and December 2021. Among them, patients who received chemotherapy within 1 month were divided into surgical and conservative groups. We evaluated the outcomes, including treatment success within 1 year, 1-year recurrence, and the number of days from the diagnosis of appendicitis to chemotherapy restart, between the 2 groups. Results: Among the 206 patients with cancer who were diagnosed with acute appendicitis, 78 received chemotherapy within 1 month. The patients were divided into surgery (n = 63) and conservative (n = 15) groups. In the surgery group, the duration of antibiotic therapy (7.0 days vs. 16.0 days, P < 0.001) and length of hospital stay (8.0 days vs. 27.5 days, P = 0.002) were significantly shorter than conservative groups. The duration from the diagnosis of appendicitis to the restart of chemotherapy was shorter in the surgery group (20.8 ± 15.1 days vs. 35.2 ± 28.2 days, P = 0.028). The treatment success rate within 1 year was higher in the surgery group (100% vs. 33.3%, P < 0.001). Conclusion: Surgical treatment showed a significantly higher success rate than conservative treatment for appendicitis in patients less than 1 month after chemotherapy. Further prospective studies will be needed to clinically determine treatment options.

Follow-Up of Patients Diagnosed With Germinal Testicular Tumors (Seminomas and Non-seminomatous) Treated With a Bone Marrow Transplant and a High Dose of Chemotherapy.

INTRODUCTION: Germinal testicular tumors are the most common malignant neoplasm in men around 20 to 34 years. Even though they are unusual, they have increased incidence in the last decade; they have an excellent prognosis and overall survival at five years, approximately 95%. Divergent data exists regarding treatment options in patients with first, second, and third relapses with conventional therapy. Some studies describe the possible benefit of using high-dose chemotherapy associated with a bone marrow transplant with variable results. METHODS:  The present study describes clinical outcomes, clinical response, mortality, overall survival, and progression-free survival to two years in a group of patients with germinal malignant tumors, seminoma versus non-seminomatous with evidence of progression of the disease at first, second, or third conventional chemotherapy regimens, and who received high dose chemotherapy and bone marrow transplantation at the National Cancer Institute between 2010 and 2021. RESULTS: A retrospective observational study of case series showed that 57% of patients in third-line therapy received high-dose chemotherapy and bone marrow transplantation, with progression disease median time from diagnosis more than two years. Patients in the post-graft period presented infectious complications (71%). The most common were febrile neutropenia (29%) with a mortality rate of 71% (n=5), progression-free survival of 2.3 months, and overall survival of 7.4 months. CONCLUSIONS:  These results show that in this group of patients, regimens with high-dose chemotherapy associated with bone marrow transplants, have a worse prognosis compared to other cohorts of patients, and may not be the best candidates for this rescue therapy.

Shifting Views on Cancer Pain Management: A Systematic Review and Network Meta-Analysis.

CONTEXT: Strong opioids are the cornerstone in the treatment of cancer-related pain. OBJECTIVES: This study aims to compare analgesic effectiveness of different strong opioids for the treatment of cancer-related pain. METHODS: PubMed and Embase were searched for RCTs that compared strong opioids for treatment of cancer-related pain against one another. A network meta-analysis was conducted and the related Surface Under the Cumulative RAnking (SUCRA)-based treatment ranks were calculated. Primary outcome was pain intensity (numerical rating scale (NRS)) and/or the percentage of patients with ≥50% pain reduction, after 1 and 2-4 weeks. RESULTS: Sixteen RCTs (1813 patients) were included. Methadone showed, with a high certainty of evidence, increased ORs for treatment success at 1 week, compared with morphine, buprenorphine, fentanyl, and oxycodone, range 3.230-36.833. Methadone had the highest likelihood to be the treatment of preference (ToP) (SUCRA 0.9720). For fentanyl, ORs were lower, however significant and with high certainty. After 2-4 weeks, methadone again showed the highest likelihood for ToP, however, with moderate certainty and nonsignificant ORs. The combination of morphine/methadone, compared with morphine, buprenorphine, fentanyl, hydromorphone, methadone, and oxycodone achieved a treatment effect of mean NRS difference after 2-4 weeks between -1.100 and -1.528 and had the highest likelihood for ToP. CONCLUSION: The results suggest that methadone possibly deserves further promotion as first-line treatment for the treatment of cancer-related pain.