A Systematic Review of the Impact of Benzimidazole-based Anthelmintics on Lung Cancer in Animal Models.

BACKGROUND: Emerging studies have reported the potential anticancer activity of FDA-approved benzimidazole-based anthelmintics against lung cancer. Therefore, the current systematic review aimed to explore the anticancer activity of benzimidazole-based anthelmintics in lung cancer animal models. METHOD: The databases including Pubmed, ScienceDirect, and Google Scholar were searched till April 2024 for the animal studies evaluating the anticancer activity of benzimidazole-based anthelmintics against lung cancer. The relevant data was extracted in the prepared format in Microsoft Excel. Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) risk of bias (RoB) was used to assess the quality of included studies. The protocol for this study has been registered in PROSPERO (Registration number: CRD42022352141). RESULTS: Initially, we obtained 4150 articles, and finally eight articles were included in the current study. The information in the included studies was a bit diversified including different benzimidazole-based anthelmintics, dosage, route of administration, and duration of experiments. However, all studies reported that exposure to benzimidazole-based anthelmintics decreased tumor size and tumor volume in animal models of lung cancer. CONCLUSION: In conclusion, benzimidazole-based anthelmintics have the potential to treat lung cancer. However, more controlled and thorough preclinical studies are required to evaluate its efficacy, safety, and mechanism of anticancer activities.

Attenuated adiponectin, omentin, increased interleukin-6 and tumor necrosis factor-alpha levels with altered cognition and depression in non-Hodgkin lymphoma patients: A case-control study.

BACKGROUND AND PURPOSE: Immune dysfunction is one of the risk factors which plays an important role in the development of non-Hodgkin lymphoma (NHL), and inflammation may be involved in its etiology. Minimal data is available on the effect of cytokine levels on neurobehavioral function in lymphoma before the initiation of chemotherapy. Therefore, we aimed to explore the risk of NHL by assessment of cytokine and adipokine levels and their correlation with neurobehavioral changes. METHODS: This case-control study enrolled 62 subjects (age-sex matched: 31 cases and 31 controls). Neurobehavioral assessment was done using Montreal Cognitive Assessment questionnaire (MoCA) and Patient Health Questionnaire (PHQ-9). EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) was used to assess quality of life. Questionnaire assessment and sample collection were done after the patient enrolment and before first cycle of chemotherapy. RESULTS: Mean age of NHL patients and healthy controls was 51.9 ± 11.8 and 50 ± 10.9 years, respectively. NHL patients showed significantly higher levels of IL-6 (0.77 ± 0.11) and TNF- α (1.47 ± 1.31) than controls (0.55 ± 0.4 and 0.66 ± 0.89, respectively) with p-value<0.005. Also, NHL patients showed significantly lower levels of adiponectin (0.31 ± 0.24) and omentin (0.46 ± 0.1) than controls (0.42 ± 0.13 and 0.53 ± 0.11, respectively) with p-value<0.005. Lower MoCA and EORTC QLQ C-30 scores and higher PHQ-9 scores were observed in NHL patients in comparison to healthy control. CONCLUSION: Our results showed that adiponectin, omentin IL-6 and TNF-α may be used as pre-diagnostic markers of NHL risk. Neurobehavioral changes observed in NHL patients may alter the quality of life.

The prevalence of multidrug resistance in uropathogens of patients admitted in the intensive care unit of a tertiary care hospital.

Urinary tract infections (UTIs) are among the most common bacterial infections, posing significant public health challenges due to increasing antimicrobial resistance (AMR). This study aims to assess the prevalence, demographic characteristics, microbial profile, and antimicrobial resistance patterns in Indian patients with UTIs admitted to intensive care unit. A total of 154 patients with positive UTIs were included in this cross-sectional study. The prevalence data including demographics, microbial isolates, and antimicrobial susceptibility patterns were collected. Additionally, risk factors for multidrug resistance uropathogens were assessed using multivariate analyses. The patient cohort had diverse demographic, with a slight male predominance of 52.6% (n = 81). The most common comorbidities were hypertension 59.1% (n = 91) and diabetes mellitus 54.5% (n = 84). The microbial profile was dominated by gram-negative bacteria, particularly Escherichia coli 26.62% (n = 41) and Klebsiella pneumoniae 17.53% (n = 27). The predominant gram-positive and fungal isolate was Enterococcus faecium 7.14% (n = 11) and Candida spp. 18.83% (n = 29), respectively. Substantial resistance was noted against common antimicrobials, with variations across different pathogens. Gram-negative bacteria, particularly Escherichia coli and Klebsiella pneumoniae, exhibited high MDR rates, emphasizing the challenge of antimicrobial resistance. Multivariate logistic regression identified age groups 50-65 and over 65, and prolonged catheterization as significant risk factors for MDR infections. A significantly high resistance rate among pathogens emphasizes the need for judicious antimicrobial use. Our findings emphasize the necessity of ongoing surveillance and tailored interventions based on local pathogen prevalence and antibiogram data to effectively address the threat of AMR threat for better management of UTI management in ICU settings.

Short-Term Impact of Hematopoietic Stem Cell Transplantation on Depressive Behavior, Cognition and Quality of Life in Leukemia Patients.

Hematopoietic stem cell transplantation (HSCT) or Bone Marrow Transplantation (BMT) has significantly improved the survival rates of patients suffering from hematological malignancies. However, the cure can only be achieved at the price of morbidity and long-term complications. Thus, this study aimed to evaluate the short-term effect of HSCT on depressive behavior, cognition, and quality of life (QoL) in leukemia patients. Sixty patients were included in this prospective observational study. The current study assessed depression using Patient Health Questionnaire (PHQ-9) scale, cognition using Montreal Cognitive Assessment (MOCA) scale and QoL using European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30) before 7 days of the therapy i.e., preconditioning/baseline (TP1) and after 30 days of the treatment (TP2) in leukemia patients undergoing HSCT. At TP2, there was a significant improvement in PHQ-9 (p = 0.001), MOCA (p < 0.0001), functional scale (p < 0.0001) and global health & QoL scale (p = 0.001) of EORTC QLQ C30 scores whereas there was a significant decrease in symptom scale of EORTC QLQ C30 score (p = 0.005). Furthermore, at TP2 a statistically significant (p < 0.05) negative correlation was observed between MOCA and symptom scale of EORTC QLQ C30 after Pearson correlation analysis. In conclusion, post-30 days of HSCT there was alleviation in depressive behavior, cognition, and QoL in leukemia patients compared to before therapy.

Spectrum of infections in different regimens of post-induction chemotherapy in acute myeloid leukemia (de-novo): A comparative retrospective study.

Background: Patients diagnosed with acute myeloid leukemia (AML) face a heightened susceptibility to infections, which significantly elevates their risk of mortality and disability. The intensity of the chemotherapy treatment and its specific focus on inhibiting myeloid cell divisions render patients especially vulnerable, particularly during the early stages of chemotherapy. This vulnerability is compounded by the occurrence of repeated episodes of prolonged neutropenia, leaving patients highly susceptible to infections. The compromised immune systems of these individuals make them more susceptible to infections, which adversely affect their physical health and overall well-being. Consequently, our study aimed to investigate the range of infections experienced by patients with newly diagnosed AML undergoing different induction chemotherapy. Methods: This was a comparative retrospective study, conducted at a tertiary hospital providing comprehensive cancer care in North India. All newly diagnosed patients with AML, who received induction chemotherapy from January 1, 2012 to November 1, 2022, were identified from the hospital database and included in this study. Results: Four hundred and twenty AML patients treated with either high-intensity or low-intensity induction chemotherapy was observed in this study. It was found that patients who received high-intensity treatment had a higher rate of clinically and microbiologically documented infections, fever without a known cause, and more cases of febrile neutropenia than those who got low-intensity treatment. These differences between the two groups were particularly evident on day 14 (p = 0.0002) and persisted through day 28 (p = 0.005). Conclusions: These findings underscore the effectiveness and downside of high-intensity induction chemotherapy regimens, as evidenced by the higher incidence of infections observed. Further investigation through prospective clinical studies is warranted to better evaluate and validate the efficacy of this approach.

Neurocognitive outcomes in pediatric hematological cancer survivors post-HSCT: A systematic review.

BACKGROUND: Pediatric hematological cancer survivors who undergo hematopoietic stem cell transplantation (HSCT) may experience long-term neurocognitive impairments. This systematic review aims to assess the neurocognitive outcomes in pediatric hematological cancer survivors at least 5 years post-HSCT. METHODOLOGY: A comprehensive search was conducted in multiple databases, including PubMed, ScienceDirect, Cochrane Library, and ClinicalTrials.gov, until October 2022. Relevant studies assessing the neurocognitive affect after 5 years of HSCT were identified and included in the review. The quality of included studies was assessed using the ROBINS-I tool to evaluate the risk of bias. RESULTS: A total of five studies met the inclusion criteria and were included in the review. The studies consistently demonstrated adverse effects of HSCT on neurocognitive outcomes in pediatric hematological cancer survivors after 5 years of the treatment. The most prominent impact was observed on global cognitive outcomes, including intelligence, attention, memory, and executive functioning. Specific cognitive domains, such as processing speed and academic achievement, were also significantly affected. Several studies reported a relationship between HSCT-related factors (e.g., age at transplantation, radiation therapy, graft-versus-host disease) and neurocognitive impairments. CONCLUSION: This systematic review provides evidence of the adverse impact of HSCT on neurocognitive outcomes in pediatric hematological cancer survivors at least 5 years post-transplantation. The findings highlight the importance of long-term monitoring and intervention strategies to mitigate these neurocognitive sequelae. Future research should focus on identifying risk factors and developing targeted interventions to optimize the neurocognitive functioning of this vulnerable population. Healthcare professionals involved in the care of pediatric hematological cancer survivors should be aware of these potential long-term neurocognitive effects and incorporate appropriate assessments and interventions into survivorship care plans.

Role of Polyphenols, Their Nano-formulations, and Biomaterials in Diabetic Wound Healing.

A diabetic wound is one of the major complications arising from hyperglycemia, neuropathy, and oxidative stress in diabetic patients. Finding effective treatments for diabetic wounds has been difficult owing to the complex pathophysiology of diabetic wound environments. Chronic wounds are notoriously difficult to treat with conventional wound care methods. In recent years, polyphenols found in plants have received much interest as a potential treatment for diabetic wounds. Their key benefits are their safety and the fact that they act through many molecular routes to treat diabetic wounds. However, problems with their formulation development, including lipophilicity, light sensitivity, limited membrane permeability, rapid systemic elimination, and enzymatic degradation, prevented them from gaining clinical attention. This article highlights and discusses the mechanism of polyphenols and various polyphenol-based drug delivery systems used till now to treat diabetic wounds. The consideration that should be taken in polyphenols-based nano-formulations and their prospect for diabetic wounds are also discussed briefly.

Network pharmacology and molecular docking study-based approach to explore mechanism of benzimidazole-based anthelmintics for the treatment of lung cancer.

Emerging studies have reported the potential anticancer activity of benzimidazole-based anthelmintics (BBA) against lung cancer (LC). However, mechanism underlying the anticancer activity of BBA is unclear. Therefore, in the current study, network pharmacology and molecular docking-based approach were used to explore the potential molecular mechanism for the treatment of LC. The potential targets for BBA were obtained from multiple databases including SwissTargetPrediction, Drug Bank, Therapeutic Target Database, and Comparative Toxicogenomics Database while LC targets were collected from DisGeNet gene discovery platform, Integrated Genomic Database of NSCLC, Catalogue of Somatic Mutations in Cancer and Online Mendelian Inheritance in Man database. Protein-protein interaction (PPI) diagram of common targets was constructed using STRING online platform. Topological analysis was performed using Cytoscape and gene enrichment analysis was conducted using FunRich software. Highest degree targets were then confirmed using molecular docking and molecular dynamics simulations. The BBA were prioritized according to their S scores, with ricobendazole ranking highest followed by flubendazole, fenbendazole, mebendazole, triclabendazole, albendazole, oxibendazole, parbendazole, thiabendazole and oxfendazole. The potential targets of BBA identified using topological analysis and molecular docking were found to be CCND1 (cyclin D1), EGFR (Epidermal Growth Factor Receptor), ERBB2 (Erb-B2 Receptor Tyrosine Kinase 2/CD340), PTGS2 (Prostaglandin-endoperoxide synthase 2), and SRC (Proto-oncogene tyrosine-protein kinase). Furthermore, molecular dynamics confirmed that CCND1 and EGFR are the potential targets of ricobendazole for the treatment of LC. BBA can be further explored as a therapeutic strategy for the treatment of lung cancer under in vitro and in vivo studies.Communicated by Ramaswamy H. Sarma.

Network pharmacology and molecular docking analysis on potential molecular targets and mechanism of action of BRAF inhibitors for application in wound healing.

Topical application of BRAF inhibitors has been shown to accelerate wound healing in murine models, which can be extrapolated into clinical applications. The aim of the study was to identify suitable pharmacological targets of BRAF inhibitors and elucidate their mechanisms of action for therapeutic applicability in wound healing, by employing bioinformatics tools including network pharmacology and molecular docking. The potential targets for BRAF inhibitors were obtained from SwissTargetPrediction, DrugBank, CTD, Therapeutic Target Database, and Binding Database. Targets of wound healing were obtained using online databases DisGeNET and OMIM (Online Mendelian Inheritance in Man). Common targets were found by using the online GeneVenn tool. Common targets were then imported to STRING to construct interaction networks. Topological parameters were assessed using Cytoscape and core targets were identified. FunRich was employed to uncover the signaling pathways, cellular components, molecular functions, and biological processes in which the core targets participate. Finally, molecular docking was performed using MOE software. Key targets for the therapeutic application of BRAF inhibitors for wound healing are peroxisome proliferator-activated receptor γ, matrix metalloproteinase 9, AKT serine/threonine kinase 1, mammalian target of rapamycin, and Ki-ras2 Kirsten rat sarcoma viral oncogene homolog. The most potent BRAF inhibitors that can be exploited for their paradoxical activity for wound healing applications are Encorafenib and Dabrafenib. By using network pharmacology and molecular docking, it can be predicted that the paradoxical activity of BRAF inhibitors can be used for their potential application in wound healing.

Recent drug development and treatments for fungal infections.

Fungal infections are now becoming a hazard to individuals which has paved the way for research to expand the therapeutic options available. Recent advances in drug design and compound screening have also increased the pace of the development of antifungal drugs. Although several novel potential molecules are reported, those discoveries have yet to be translated from bench to bedside. Polyenes, azoles, echinocandins, and flucytosine are among the few antifungal agents that are available for the treatment of fungal infections, but such conventional therapies show certain limitations like toxicity, drug interactions, and the development of resistance which limits the utility of existing antifungals, contributing to significant mortality and morbidity. This review article focuses on the existing therapies, the challenges associated with them, and the development of new therapies, including the ongoing and recent clinical trials, for the treatment of fungal infections. Advancements in antifungal treatment: a graphical overview of drug development, adverse effects, and future prospects.

A Systematic Review on Interferon Alpha-Induced Cognitive Impairment in Hepatitis C Patients.

OBJECTIVE: Interferon-alpha (IFN-α) is an important treatment modality for the hepatitis C virus (HCV). However, treatment with IFN-α is often associated with cognitive difficulties in HCV patients. Thus, this systematic review was performed to assess the effects of IFN-α on cognitive functioning in patients suffering from HCV. METHODS: Relevant literature was identified by performing a comprehensive literature search in major databases including PubMed, clinicaltrials.gov, and Cochrane Central using a combination of suitable keywords. We retrieved studies that were published from the start of each database until August 2021. RESULTS: Out of 210 articles, 73 studies were selected after removing the duplicates. In the first pass, 60 articles were excluded. Out of 13 full-text articles, only 5 articles qualified for qualitative analyses in the second pass. We observed conflicting results concerned with the use of IFN-α and the risk of neurocognitive impairment in HCV patients. CONCLUSION: In conclusion, we have observed conflicting results regarding the impact of INF-α treatment on the cognitive functioning of patients suffering from HCV. Thus, there is an urgent need for an extensive study to evaluate the exact association between INF-αtherapy and cognitive functioning in HCV patients.

Risk of Mortality in Bone Marrow Transplant Patients During SARS-CoV-2 Infection: A Systematic Review.

OBJECTIVES: Recipients of bone marrow transplant with COVID-19 are at high risk of mortality and morbidity from their underlying immunocompromised state. Graft-versus-host disease and other comorbidities lead to poor COVID-19 outcomes in these patients. Understanding the outcomes and clinical characteristics of bone marrow transplant recipients with COVID-19 is needed to devise potential life-saving therapies for patients with hematologic malignancies. Reviewing large data sets from different ethnic groups and regions can lead to better understanding. We conducted a systematic review ofreal-world data from prospective and retrospective observational cohort studies that reported the clinical outcomes of COVID- 19 in bone marrow transplant patients. MATERIALS AND METHODS: We used electronic databases (PubMed, ScienceDirect, Google Scholar), with a cut off date of May 31, 2022, to conduct our search. After screening 349 articles, we selected 33 original reports for screening. After screening these articles for eligibility criteria, we selected 12 studies for final data extraction. We extracted data per the preferred reporting items followed for systematic reviews. Quality evaluation was done with a Cochrane risk-of bias tool for nonrandomized studies (ROBINS-1). RESULTS: Bone marrow transplant recipients with COVID-19 experienced poor disease outcomes and high mortality rates. Patient age, immunosuppressant intensity, and presence of graft-versus-host disease or other underlying comorbidities directly affected mortality rates of bone marrow transplant recipients with COVID-19. Other factors, like type of malignancy, type of transplant, and time between transplant and COVID-19 diagnosis, did not affect mortality or poor outcomes of COVID-19. CONCLUSIONS: Bone marrow transplant recipients have a higher risk of mortality and poor disease outcomes from COVID-19. Because curative therapies for COVID- 19 are not available, the only option available is its prevention. Transplant centers worldwide, as pertheir capacities, should develop and adhere to strict standard operating procedures based on international or national guidelines related to transplant recipients with COVID-19.

Role of Cytokines in Chemotherapy-related Cognitive Impairment of Breast Cancer Patients: A Systematic Review.

BACKGROUND: Cognitive impairment is one of the most common problems experienced by patients receiving chemotherapy, and evidence suggests that cytokines might play an important role. Various studies were conducted to evaluate the role of cytokines in chemotherapy-related cognitive impairment (CRCI). However, the association between CRCI due to cytokines is not well-established. Thus, this systematic review aims to assess the role of cytokines in CRCI in breast cancer patients. METHODS: This systematic review was conducted according to the Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA) guidelines. An intense literature search was carried out for inclusion criteria in major databases, including PubMed and Clinicaltrials.gov, in August 2021. Studies assessing cognitive parameters through objective and subjective assessment in breast cancer patients receiving chemotherapy were included. RESULTS: A total of 4052 studies were identified, and 15 studies were included in this systematic review. We found that IL-6, IL-1ß, and TNF-α were associated with varying degrees of cognitive impairment in breast cancer patients receiving chemotherapy. CONCLUSION: This systematic review showed a correlation between various cytokines and chemotherapy- associated cognitive decline in breast cancer patients.

Metformin alone and in combination with sitagliptin induces depression and impairs quality of life in type 2 diabetes mellitus patients: An observational study.

BACKGROUND: Various studies have reported the association of cognition and depression with diabetes. Literature suggests that metformin and sitagliptin used to control hyperglycemia in type 2 diabetes mellitus (T2DM) possess a beneficial effect on neurological symptoms associated with diabetes. However, there are scarce data in the clinical setting. Thus, this study aims to compare depression, cognitive impairment, and quality of life (QoL) of newly diagnosed T2DM patients with those of healthy individuals. Further, the impact of metformin alone or in combination with dipeptidyl peptidase-4 inhibitors on cognition, depression, and QoL of T2DM patients was also compared with newly diagnosed T2DM patients. MATERIALS AND METHODS: This was a prospective observational study in 120 subjects. The subjects were equally divided into four groups: healthy controls, newly diagnosed T2DM patients, and T2DM patients taking either metformin alone or in combination with sitagliptin. We assessed cognition using Mini-Mental State Examinations (MMSE), depression using Hamilton Depression Rating Scale (HAM-D), and health status using Short-Form Health Survey-36 (SF-36). RESULTS: No significant change in MMSE score was observed among the groups. However, a significant increase in the HAM-D score of newly diagnosed patients (p < 0.001), T2DM patients receiving metformin alone (p < 0.05), and in combination with sitagliptin (p < 0.001) was observed as compared to healthy controls (p < 0.001). Also, a statistically significant increase in HAM-D score was observed in patients receiving sitagliptin in combination with metformin as compared to metformin alone (p < 0.01). A decrease in SF-36 scores was observed in all groups as compared to healthy controls. CONCLUSION: To conclude, this preliminary study indicates that T2DM patients are most likely to suffer from depression and impaired QoL. Moreover, both the conventional and recent antidiabetic agents might lead to neurobehavioral complications and adverse impact on the QoL of these patients. Thus, we warrant the assessment of cognitive functions, depression, and QoL in patients receiving metformin and sitagliptin.

Cognitive impairment and elevated peripheral cytokines in breast cancer patients receiving chemotherapy.

BACKGROUND: Anthracyclines-based regimen (5-fluorouracil, doxorubicin, and cyclophosphamide (FAC); cyclophosphamide, epirubicin, and 5-fluorouracil [CEF]) and non-anthracycline based regimens (cyclophosphamide, methotrexate, and 5-fluorouracil [CMF]) are widely used as neoadjuvant chemotherapy for breast cancer patients. OBJECTIVE: The present study was conducted to observe the effects of FAC, CEF, and CMF regimen on cognition and circulatory proinflammatory cytokines (interleukin 6 [IL-6] and interleukin 1ß [IL-1ß]) for the duration of three cycles of chemotherapy in breast cancer patients. METHODS: Eighty newly diagnosed HER-2 negative breast cancer patients were enrolled and divided into 3 groups as FAC- (n = 27), CEF- (n = 26), and CMF- (n = 27) receiving patients. Serum IL-6 and IL-1ß levels were measured by using enzyme-linked immunosorbent assay (ELISA), and cognition was assessed using the Mini-Mental State examination (MMSE) questionnaire. RESULTS: Anthracycline-based regimen was found to increase the levels of IL-6, IL-1ß, and decreased MMSE scores compared with CMF regimen (p < 0.05). CONCLUSION: Anthracycline-based regimen caused comparatively higher peripheral inflammation, which could be the reason for more decline in cognition in anthracycline-receiving patients than non-anthracycline group.

ANTECEDENTES: Regime baseado em antraciclinas (5-fluorouracil, doxorrubicina e ciclofosfamida [FAC]; ciclofosfamida, epirrubicina e 5-fluorouracil [CEF]) e regimes não baseados em antraciclina (ciclofosfamida, metotrexato e 5-fluorouracil (CMF]) são amplamente utilizados como quimioterapia neoadjuvante para pacientes com câncer de mama. OBJETIVO: O presente estudo foi realizado para observar os efeitos do regime FAC, CEF e CMF na cognição e citocinas pró-inflamatórias circulatórias (interleucina 6 [IL-6] e interleucina 1ß [IL-1ß]) durante três ciclos de quimioterapia em pacientes com câncer de mama. MéTODOS: Oitenta pacientes recém-diagnosticadas com câncer de mama HER-2 negativo foram recrutadas e divididas em 3 grupos de pacientes que receberam FAC (n = 27), CEF (n = 26) ou CMF (n = 27). Os níveis séricos de IL-6 e IL-1ß foram medidos por enzyme-linked immunosorbent assay (ELISA) e a cognição foi avaliada por meio do questionário Mini-Mental State Examination (MMSE). RESULTADOS: O regime baseado em antraciclinas aumentou os níveis de IL-6, IL-1ß e diminuiu os escores do MMSE em comparação com o regime CMF (p < 0,05). CONCLUSãO: O regime baseado em antraciclinas causou inflamação periférica comparativamente mais alta, o que pode ser a razão para maior declínio na cognição em pacientes que receberam antraciclinas do que no grupo que não recebeu antraciclina.

Cognitive impairment and elevated peripheral cytokines in breast cancer patients receiving chemotherapy / Comprometimento cognitivo e citocinas periféricas elevadas em pacientes com câncer de mama recebendo quimioterapia

Abstract Background Anthracyclines-based regimen (5-fluorouracil, doxorubicin, and cyclophosphamide (FAC); cyclophosphamide, epirubicin, and 5-fluorouracil [CEF]) and non-anthracycline based regimens (cyclophosphamide, methotrexate, and 5-fluorouracil [CMF]) are widely used as neoadjuvant chemotherapy for breast cancer patients. Objective The present study was conducted to observe the effects of FAC, CEF, and CMF regimen on cognition and circulatory proinflammatory cytokines (interleukin 6 [IL-6] and interleukin 1β [IL-1β]) for the duration of three cycles of chemotherapy in breast cancer patients. Methods Eighty newly diagnosed HER-2 negative breast cancer patients were enrolled and divided into 3 groups as FAC- (n= 27), CEF- (n= 26), and CMF- (n= 27) receiving patients. Serum IL-6 and IL-1β levels were measured by using enzyme-linked immunosorbent assay (ELISA), and cognition was assessed using the Mini-Mental State examination (MMSE) questionnaire. Results Anthracycline-based regimen was found to increase the levels of IL-6, IL-1β, and decreased MMSE scores compared with CMF regimen (p< 0.05). Conclusion Anthracycline-based regimen caused comparatively higher peripheral inflammation, which could be the reason for more decline in cognition in anthracycline-receiving patients than non-anthracycline group.

Resumo Antecedentes Regime baseado em antraciclinas (5-fluorouracil, doxorrubicina e ciclofosfamida [FAC]; ciclofosfamida, epirrubicina e 5-fluorouracil [CEF]) e regimes não baseados em antraciclina (ciclofosfamida, metotrexato e 5-fluorouracil (CMF]) são amplamente utilizados como quimioterapia neoadjuvante para pacientes com câncer de mama. Objetivo O presente estudo foi realizado para observar os efeitos do regime FAC, CEF e CMF na cognição e citocinas pró-inflamatórias circulatórias (interleucina 6 [IL-6] e interleucina 1β [IL-1β]) durante três ciclos de quimioterapia em pacientes com câncer de mama. Métodos Oitenta pacientes recém-diagnosticadas com câncer de mama HER-2 negativo foram recrutadas e divididas em 3 grupos de pacientes que receberam FAC (n= 27), CEF (n= 26) ou CMF (n= 27). Os níveis séricos de IL-6 e IL-1β foram medidos por enzyme-linked immunosorbent assay (ELISA) e a cognição foi avaliada por meio do questionário Mini-Mental State Examination (MMSE). Resultados O regime baseado em antraciclinas aumentou os níveis de IL-6, IL-1β e diminuiu os escores do MMSE em comparação com o regime CMF (p< 0,05). Conclusão O regime baseado em antraciclinas causou inflamação periférica comparativamente mais alta, o que pode ser a razão para maior declínio na cognição em pacientes que receberam antraciclinas do que no grupo que não recebeu antraciclina.

Risk Factors for Hematopoietic Stem Cell Transplantation-Associated Bone Loss.

Hematopoietic stem cell transplantation (HSCT), including bone marrow transplantation, is the treatment of choice for many hematologic diseases, including hematologic malignancies and different types of anemia. The use of HSCT is increasing annually, mainly because advanced research that has been conducted in this area has exponentially expanded the indications for HSCT and significantly improved transplantation techniques and supportive care practices. Collectively, these improvements have led to an increase in the overall survival of HSCT patients. However, as post-HSCT survival is increasing, awareness of the potential late complications of HSCT is also growing. Unpredictable bone loss is one of the major post-HSCT complications that can cause significant morbidity and impair the quality of life of survivors. Although the exact mechanism of post-HSCT bone loss is not yet known, previous studies have suggested that numerous factors, including destructive preparative regimens (eg, high-dose chemotherapy, total body irradiation), treatment-related complications (eg, graft-versus-host disease), endocrine abnormalities (eg, diabetes mellitus, thyroid dysfunction, adrenal insufficiency), lack of physical activity, and the underlying disease itself are responsible for HSCT-associated bone loss. Sufficient data have been collected to suggest that post-HSCT bone loss can be prevented and treated using the same preventive and treatment modalities as used for the general population. Various guidelines have been formulated to help keep a check on HSCT recipients' deteriorating bone health.

Increased serum interleukin-9 and interleukin-1ß are associated with depression in type 2 diabetes patients.

BACKGROUND: Co-morbid diabetes and depression are prevalent chronic conditions negatively affecting quality of life (QoL). Inflammation has been considered as an integral mechanism in patients with both diabetes and depression. OBJECTIVE: The aim of the present study was to investigate depression and its association with interleukins (IL)-1ß and IL-9 in type 2 diabetic patients (T2DM) and controls. The QoL in diabetic patient was also assessed. METHODS: Eighty subjects were included, distributed among three groups: Group 1 - Healthy controls; Group 2 - T2DM patients without depression; Group 3 - T2DM patients with depression. Depression and QoL were assessed using Patient Health Questionnaire (PHQ-9) and The Audit of Diabetes-Dependent QoL (ADDQoL), respectively. IL-1ß and IL-9 were measured in serum samples of all the patients using ELISA kit. RESULTS: The PHQ score in the Group 3 was significantly higher as compared to Group 1. The ADDQoL scores in the Group 3 were significantly higher as compared to Group 2. Levels of IL-9 and IL-1ß were elevated in Group 3, as compared to the other groups. CONCLUSION: This study showed positive association between depression and IL-1ß, IL-9 in T2DM patients. Additionally, the diabetic patients have poorer quality of life, which is further worsened by the presence of depression. Thus, routine assessment for the presence of depression is suggested in T2DM patients.

Increased serum interleukin-9 and interleukin-1β are associated with depression in type 2 diabetes patients / Interleucina-9 e interleucina-1β séricas aumentadas estão associadas à depressão em pacientes com diabetes tipo 2

ABSTRACT Background: Co-morbid diabetes and depression are prevalent chronic conditions negatively affecting quality of life (QoL). Inflammation has been considered as an integral mechanism in patients with both diabetes and depression. Objective: The aim of the present study was to investigate depression and its association with interleukins (IL)-1β and IL-9 in type 2 diabetic patients (T2DM) and controls. The QoL in diabetic patient was also assessed. Methods: Eighty subjects were included, distributed among three groups: Group 1 - Healthy controls; Group 2 - T2DM patients without depression; Group 3 - T2DM patients with depression. Depression and QoL were assessed using Patient Health Questionnaire (PHQ-9) and The Audit of Diabetes-Dependent QoL (ADDQoL), respectively. IL-1β and IL-9 were measured in serum samples of all the patients using ELISA kit. Results: The PHQ score in the Group 3 was significantly higher as compared to Group 1. The ADDQoL scores in the Group 3 were significantly higher as compared to Group 2. Levels of IL-9 and IL-1β were elevated in Group 3, as compared to the other groups. Conclusion: This study showed positive association between depression and IL-1β, IL-9 in T2DM patients. Additionally, the diabetic patients have poorer quality of life, which is further worsened by the presence of depression. Thus, routine assessment for the presence of depression is suggested in T2DM patients.

RESUMO Introdução: O diabetes e a depressão comórbidas são condições crônicas prevalentes que afetam negativamente a qualidade de vida (QdV). A inflamação tem sido considerada como um mecanismo integral em pacientes com diabetes e depressão. Objetivo: Investigar a depressão e sua associação com interleucinas (IL)-1β e IL-9 em pacientes diabéticos tipo 2 (DM2) e controles. A QdV em diabéticos também foi avaliada. Métodos: Foram incluídos 80 indivíduos, divididos em três grupos: Grupo 1 - controles saudáveis; Grupo 2 - pacientes com DM2 sem depressão; Grupo 3 - pacientes com DM2 com depressão. A depressão e a QdV foram avaliadas usando o Questionário de Saúde do Paciente (Patient Health Questionnaire - PHQ-9) e a auditoria de QdV dependente de diabetes (Audit of Diabetes-Dependent Quality of Life - ADDQoL), respectivamente. IL-1β e IL-9 foram medidas em amostras de soro de todos os pacientes utilizando kit de ELISA. Resultados: O escore do PHQ no grupo 3 foi significativamente maior em comparação ao grupo 1. Os escores de ADDQoL no grupo 3 foram significativamente maiores em comparação ao grupo 2. Os níveis de IL-9 e IL-1β foram elevados no grupo 3, como em comparação com os outros grupos. Conclusão: Este estudo mostrou associação positiva entre depressão e IL-1β, IL-9 em pacientes com DM2. Além disso, os pacientes diabéticos têm pior QdV, o que é ainda piorado pela presença de depressão. Assim, a avaliação rotineira da presença de depressão é sugerida em pacientes com DM2.