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Journal of Blood Medicine 2024Immune checkpoint inhibitor-related thrombocytopenia (irTCP) is a relatively rare immune-related adverse event (irAE); however, overall survival may worsen when it...
Successful Treatment of Steroid-Refractory Immune Thrombocytopenia in a Patient Developing Multiple Myeloma While on Immune Checkpoint Inhibitor Therapy for Lung Cancer: A Case Report.
Immune checkpoint inhibitor-related thrombocytopenia (irTCP) is a relatively rare immune-related adverse event (irAE); however, overall survival may worsen when it occurs. Prolonged use of high-dose steroids can diminish the effectiveness of immune checkpoint inhibitor (ICI) therapy on the primary disease because of T lymphocyte suppression, thus early tapering is necessary. We experienced a rare case of a 79-year-old male who concurrently developed irTCP and multiple myeloma (MM) during treatment with ICIs for lung adenocarcinoma. The patient exhibited severe thrombocytopenia and elevated serum IgA levels. Based on various tests, we diagnosed MM and irTCP. Despite administering the standard bortezomib plus dexamethasone (Bd therapy) treatment for MM, there was no response and the irTCP was steroid-resistant. Consequently, we administered a regimen including daratumumab (DPd therapy) for steroid-resistant irTCP and refractory MM, which resulted in a response. As a result, we were able to avoid prolonged use of high-dose steroids and the patient is stable without exacerbation of lung adenocarcinoma for 1 year and 5 months after the onset of MM. To our knowledge, there are no cases of MM developing during ICI treatment and this is the first case report in which daratumumab was effective for the treatment of irTCP.
PubMed: 38919949
DOI: 10.2147/JBM.S468921 -
Journal of Anaesthesiology, Clinical... 2024Coronavirus disease (COVID-19)-related pneumonia is proposed to be an inflammatory process. The treatment currently includes supportive therapy and low-dose steroids....
BACKGROUND AND AIMS
Coronavirus disease (COVID-19)-related pneumonia is proposed to be an inflammatory process. The treatment currently includes supportive therapy and low-dose steroids. Anti-inflammatory drugs have been proposed to prevent cytokine storms and improve oxygenation in such cases. The study aimed to assess the efficacy of nebulized lignocaine in COVID-19 patients with pneumonia.
MATERIAL AND METHODS
This was an exploratory randomized double-blinded control trial conducted in COVID-19 patients with respiratory failure requiring oxygen therapy either by face mask or non-invasive mechanical ventilation. Patients included were of the age of more than 18 years of either gender. The patients were randomized to receive either lignocaine or distilled water nebulization. The outcomes assessed were PaO/FiO ratio, hemodynamics, respiratory parameters, and sequential organ failure score (SOFA).
RESULTS
The two groups were comparable concerning demographic variables. The PaO/FiO were significantly higher in the lignocaine group from day 2 onward. The SPO was significantly higher on day 3 in the lignocaine group and thereafter there was no significant difference. Other hemodynamic, respiratory parameters, and SOFA scores showed no difference in both the groups.
CONCLUSION
Lignocaine nebulization improved oxygenation in COVID-19 patients and can be used as adjunctive therapy along with other supportive medications.
PubMed: 38919418
DOI: 10.4103/joacp.joacp_205_22 -
Cureus May 2024Background and objective Morphea, or localized scleroderma (LS), is an autoimmune skin disorder characterized by inflammation and sclerosis. Its potential causes include...
Background and objective Morphea, or localized scleroderma (LS), is an autoimmune skin disorder characterized by inflammation and sclerosis. Its potential causes include infections, genetic predisposition, and trauma. The disease involves cycles of inflammation and fibrosis, leading to skin hardening and scarring, which can cause deformities if untreated. Research exploring the link between morphea and rheumatoid factor (RF), a marker associated with other autoimmune conditions, is ongoing. This study aimed to examine the less-explored role of RF, a marker typically linked to rheumatoid arthritis (RA), in the severity of morphea. It focused on assessing the levels of RF among morphea patients and its correlation with disease severity, intending to provide deeper insights into the condition and its management. Methods This study involved a simple randomized cross-sectional analysis to evaluate the role of the RF in measuring morphea severity among patients at the Dermatology and Venereology Department of Al-Sader Teaching Hospital from October 2022 to December 2023. We included participants with clinically and laboratory-confirmed morphea while excluding those with other autoimmune dermatological diseases, recent systemic steroid or immunosuppressive therapy, and pregnant women. The assessment of disease severity was done by utilizing the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT). Statistical analyses were performed using SPSS Statistics version 27 (IBM Corp., Armonk, NY), with a significance threshold of p<0.05. Results Elevated RF levels were significantly associated with increased morphea severity, with severe cases showing higher RF levels (mean: 30.34 U/mL) compared to moderate (25.83 U/mL) and mild cases (21.56 U/mL) (p = 0.028). However, no significant correlation was found between RF levels and demographic factors such as age, gender, or occupation. Patients with high RF levels had a longer disease duration (mean: 57.15 years) compared to those with normal levels (25.83 years, p = 0.020). Significant differences were observed in lesion distribution on the back (p = 0.002). Logistic regression indicated that severe morphea patients were more likely to have elevated RF levels [odds ratio (OR): 1.158, p = 0.014]. Conclusions This study enriches our understanding of RF's role in morphea, revealing no significant correlation with demographic factors but suggesting its potential role in disease chronicity and severity.
PubMed: 38919251
DOI: 10.7759/cureus.61105 -
Cureus May 2024Cocaine is a widely abused controlled substance. Cocaine use is associated with a myriad of side effects and a sequelae of consequences secondary to its harmful nature...
Cocaine is a widely abused controlled substance. Cocaine use is associated with a myriad of side effects and a sequelae of consequences secondary to its harmful nature and potential adulterants, the most recently described and less known sequelae being leukoencephalopathy. In our case, we describe a 58-year-old male who presented to the ED with agitation and acute stroke-like symptoms with reported rapid onset. Cocaine induced toxic leukoencephalopathy is a diagnosis of exclusion, thus other etiologies of disease were ruled out in a full neurological and infectious workup; most importantly consisting of extensive brain imaging, alluding to the diagnosis of acute cocaine induced toxic leukoencephalopathy in an individual with a confirmed history of cocaine and cannabinoid abuse. Although there is no targeted therapy for the condition to our knowledge, we utilized a supportive approach to treatment in contrast to other reported treatment modalities which included the use of steroids, plasma exchange, and intravenous immunoglobulin. Furthermore, we describe the clinical evaluation and treatment throughout the patient's hospital course with his eventual marked improvement from initial presentation.
PubMed: 38919221
DOI: 10.7759/cureus.61098 -
World Journal of Surgical Oncology Jun 2024This study aimed to evaluate the oncological and reproductive outcomes of fertility-preserving re-treatment in progestin-resistant endometrial carcinoma (EC) and...
OBJECTIVE
This study aimed to evaluate the oncological and reproductive outcomes of fertility-preserving re-treatment in progestin-resistant endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) women who desire to maintain their fertility.
METHODS
Our study included 61 progestin-resistant EC/AEH patients. These patients underwent treatment with gonadotropin-releasing hormone agonist (GnRHa) solely or a combination of GnRHa with levonorgestrel-releasing intrauterine system (LNG-IUD) or aromatase inhibitor (AI). Histological evaluations were performed every 3-4 months. Upon achieving complete remission (CR), we recommended maintenance treatments including LNG-IUD, cyclical oral contraceptives, or low-dose cyclic progestin until they began attempting conception. Regular follow-up was conducted for all patients. The chi-square method was utilized to compare oncological and fertility outcomes, while the Cox proportional hazards regression analysis helped identify risk factors for CR, recurrence, and pregnancy.
RESULTS
Overall, 55 (90.2%) patients achieved CR, including 90.9% of AEH patients and 89.7% of EC patients. The median re-treatment time was 6 months (ranging from 3 to 12 months). The CR rate for GnRHa alone, GnRHa + LNG-IUD and GnRHa + AI were 80.0%, 91.7% and 93.3%, respectively. After a median follow-up period of 36 months (ranging from 3 to 96 months), 19 women (34.5%) experienced recurrence, 40.0% in AEH and 31.4% in EC patients, with the median recurrence time of 23 months (ranging from 6 to 77 months). Among the patients who achieved CR, 39 expressed a desire to conceive, 20 (51.3%) became pregnant, 11 (28.2%) had successfully deliveries, 1 (5.1%) was still pregnant, while 8 (20.5%) suffered miscarriages.
CONCLUSION
GnRHa-based fertility-sparing treatment exhibited promising oncological and reproductive outcomes for progestin-resistant patients. Future larger multi-institutional studies are necessary to confirm these findings.
Topics: Humans; Female; Endometrial Neoplasms; Adult; Retrospective Studies; Fertility Preservation; Endometrial Hyperplasia; Progestins; Follow-Up Studies; Pregnancy; Drug Resistance, Neoplasm; Gonadotropin-Releasing Hormone; Levonorgestrel; Middle Aged; Prognosis; Intrauterine Devices, Medicated; Neoplasm Recurrence, Local; Pregnancy Rate; Aromatase Inhibitors; Antineoplastic Agents, Hormonal
PubMed: 38918837
DOI: 10.1186/s12957-024-03439-w -
BMC Pulmonary Medicine Jun 2024The efficacy of immune checkpoint inhibitors (ICIs) has been widely recognized in several cancers and is now being used in the perioperative setting for lung cancer.We...
The efficacy of immune checkpoint inhibitors (ICIs) has been widely recognized in several cancers and is now being used in the perioperative setting for lung cancer.We recently encountered an immune-related adverse event that has not been previously reported: thoracic lymphangitis, which occurred after postoperative ICI treatment for lung cancer. The patient complained of breathlessness and her condition rapidly progressed to hypoxia grade 3. Chest computed tomography revealed significant lymphostasis. With high-dose steroid treatment, the patient showed improvement.Therefore, as the frequency of neoadjuvant, adjuvant, and perioperative ICI use is expected to increase, it is crucial to understand and monitor this adverse event.
Topics: Humans; Lymphangitis; Female; Lung Neoplasms; Tomography, X-Ray Computed; Immune Checkpoint Inhibitors; Aged; Middle Aged
PubMed: 38918749
DOI: 10.1186/s12890-024-03123-5 -
BMC Cancer Jun 2024Cancer is among the leading cause of death worldwide. Chemotherapy is commonly used in cancer management and among the challenges in managing cancer patients is renal...
Prevalence of renal insufficiency and factors associated among selected cancer patients on chemotherapy at Ocean Road Cancer Institute in Tanzania: a cross-sectional study.
BACKGROUND
Cancer is among the leading cause of death worldwide. Chemotherapy is commonly used in cancer management and among the challenges in managing cancer patients is renal insufficiency (RI), which can be due to cancer or anticancer treatment and can be potentiated by different factors. Data regarding the prevalence of RI and associated factors in Tanzania is scanty. This study aims to assess the prevalence of RI and associated factors among selected cancer patients on chemotherapy.
METHODS
This analytical cross-sectional study was conducted at Ocean Road Cancer Institute (ORCI) in Dar es Salaam, Tanzania, from March to May 2023. The study included cancer patients on chemotherapy. Data was collected using semi-structured questionnaires whereby socio-demographics, clinical and laboratory data were recorded. Data was analyzed by using STATA version 15. Categorical data was presented as frequencies and percentages, and continuous data was summarized using means. A modified Poisson regression model was used to assess factors associated with RI. The p-values ≤ 0.05 was considered statistically significant.
RESULTS
Out of 354 patients, the majority (76.6%) were female. The enrolled patients' mean age was 53 ± 13.19 years. The proportion of cancer patients with RI was 62.2% with most (60%) having stage 2 and stage 3 (37.7%). Age, hypertension (HTN), human immunodeficiency virus (HIV), diabetes mellitus (DM) and non-steroidal anti-inflammatory drugs (NSAIDs) use were significantly associated with increased risk of RI (p ≤ 0.05).
CONCLUSION
This study showed that RI is common among cancer patients on chemotherapy. Age, HTN, DM, HIV and NSAIDS use were associated with RI. Close monitoring of kidney function is necessary for cancer patients with other factors associated with RI. Use of creatinine clearance (CrCl) rather than serum creatinine in estimating kidney function is important.
Topics: Humans; Female; Cross-Sectional Studies; Middle Aged; Male; Tanzania; Neoplasms; Prevalence; Adult; Aged; Renal Insufficiency; Risk Factors; Antineoplastic Agents
PubMed: 38918707
DOI: 10.1186/s12885-024-12419-y -
Asian Pacific Journal of Cancer... Jun 2024Cytochrome P450 (CYP) are phase I metabolizing enzymes involved in detoxification of chemotherapeutic agents. Among the CYP gene family, including CYP1A1, CYP1B1, CYP2C,...
BACKGROUND
Cytochrome P450 (CYP) are phase I metabolizing enzymes involved in detoxification of chemotherapeutic agents. Among the CYP gene family, including CYP1A1, CYP1B1, CYP2C, CYP2D, CYP2E and CYP17, their significance in cancer susceptibility is well established. However, there remains limited understanding regarding the polymorphisms of CYP2C19*2 and CYP17 and their potential correlation with chemotherapy-induced toxicity reactions in breast cancer (BC) patients. In this study we intended to identify the association of CYP2C19*2 and CYP17 gene polymorphisms on drug response as well as toxicity reactions in BC patients undergoing adriamycin/paclitaxel based chemotherapy within Indian population.
METHODS
Two hundred BC patients receiving adriamycin and paclitaxel chemotherapy were enrolled in this study and chemotherapy induced hematological and non-hematological toxicity reactions were noted. The polymorphisms of CYP2C19*2 (681G>A) and CYP17 (34T>C) isoforms of cytochrome p 450 gene was studied by PCR and RFLP analysis.
RESULTS
The univariate logistic regression analysis revealed significant associations between CYP2C19*2 (681 G>A) polymorphisms with hematological toxicities i.e., anemia (OR=9.77, 95% CI: 2.84-33.52; p=0.0003), neutropenia (OR=5.72, 95% CI: 1.75-18.68; p=0.003), febrile neutropenia (OR=4.29, 95% CI: 1.32-13.87; p=0.014) and thrombocytopenia (OR=5.86, 95% CI: 1.15-29.72); p=0.032) in BC patients. Additionally BC patients treated with adriamycin exhibited significant association between CYP2C19*2 polymorphism with chemotherapy induced nausea and vomiting (CINV) (OR=99.73, 95% CI: 5.70-174.64); p=0.001), fatigue (OR=83.29, 95% CI: 4.77-145.69); p=0.002), bodyache (OR=4.44, 95% CI: 1.24-15.91); p=0.021) and peripheral neuropathy (OR=12.00, 95% CI: 1.80-79.89); p=0.010. Furthermore, the regression analysis indicated an association between CYP17 with body ache (OR=2.77, 95% CI: 1.21-6.34; p=0.015) and peripheral neuropathy (OR=3.90, 95% CI: 1.59-9.53; p=0.002) in BC patients treated with paclitaxel chemotherapy.
CONCLUSION
The findings obtained from this study illustrated significant association of CYP2C9*2 (681G>A) polymorphism with adreamicin based chemotherapy induced toxicities and CYP17 (34T>C) polymorphism with paclitaxel induced bodyache and peripheral neuropathy in BC patients.
Topics: Humans; Female; Breast Neoplasms; Paclitaxel; Doxorubicin; Cytochrome P-450 CYP2C19; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Polymorphism, Single Nucleotide; Adult; Steroid 17-alpha-Hydroxylase; Prognosis; Follow-Up Studies; Aged
PubMed: 38918659
DOI: 10.31557/APJCP.2024.25.6.1977 -
Translational Psychiatry Jun 2024Major depressive disorder (MDD) is a debilitating illness that includes depressive mood. Repetitive Transcranial Magnetic Stimulation (rTMS) is a therapy method used in... (Randomized Controlled Trial)
Randomized Controlled Trial
Major depressive disorder (MDD) is a debilitating illness that includes depressive mood. Repetitive Transcranial Magnetic Stimulation (rTMS) is a therapy method used in the treatment of MDD. The purpose of this study was to assess neurotrophic factors, and oxidative stress levels in MDD patients and evaluate the changes in these parameters as a result of rTMS therapy. Twenty-five patients with MDD and twenty-six healthy volunteers with the same demographic characteristics were included in the study. Brain-derived neurotrophic factors were measured photometrically with commercial kits. Oxidative stress parameters were measured by the photometric method. Oxidative stress index (OSI) and disulfide (DIS) levels were calculated with mathematical formulas. In this study, total antioxidant status (TAS), total thiol (TT), and native thiol (NT) antioxidant parameters and brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and allopregnanolone (ALLO) levels were reduced in pre-rTMS with regard to the healthy control group; TOS, OSI, DIS, and S100 calcium-binding protein B (S100B) levels were increased statistically significantly (p < 0.01). Moreover, owing to TMS treatment; TAS, TT, NT, BDNF, GDNF, and ALLO levels were increased compared to pre-rTMS, while DIS, TOS, OSI, and S100B levels were decreased significantly (p < 0.01). The rTMS treatment reduces oxidative stress and restores thiol-disulfide balance in MDD patients. Additionally, rTMS modulates neurotrophic factors and neuroactive steroids, suggesting its potential as an antidepressant therapy. The changes in the biomarkers evaluated may help determine a more specific approach to treating MDD with rTMS therapy.
Topics: Humans; Depressive Disorder, Major; Male; Female; Adult; Transcranial Magnetic Stimulation; Oxidative Stress; Case-Control Studies; Brain-Derived Neurotrophic Factor; Middle Aged; S100 Calcium Binding Protein beta Subunit; Glial Cell Line-Derived Neurotrophic Factor; Antioxidants; Sulfhydryl Compounds
PubMed: 38918365
DOI: 10.1038/s41398-024-02942-8 -
JCO Clinical Cancer Informatics Jun 2024The estimation of prognosis and life expectancy is critical in the care of patients with advanced cancer. To aid clinical decision making, we build a prognostic strategy...
PURPOSE
The estimation of prognosis and life expectancy is critical in the care of patients with advanced cancer. To aid clinical decision making, we build a prognostic strategy combining a machine learning (ML) model with explainable artificial intelligence to predict 1-year survival after palliative radiotherapy (RT) for bone metastasis.
MATERIALS AND METHODS
Data collected in the multicentric PRAIS trial were extracted for 574 eligible adults diagnosed with metastatic cancer. The primary end point was the overall survival (OS) at 1 year (1-year OS) after the start of RT. Candidate covariate predictors consisted of 13 clinical and tumor-related pre-RT patient characteristics, seven dosimetric and treatment-related variables, and 45 pre-RT laboratory variables. ML models were developed and internally validated using the Python package. The effectiveness of each model was evaluated in terms of discrimination. A Shapley Additive Explanations (SHAP) explainability analysis to infer the global and local feature importance and to understand the reasons for correct and misclassified predictions was performed.
RESULTS
The best-performing model for the classification of 1-year OS was the extreme gradient boosting algorithm, with AUC and F1-score values equal to 0.805 and 0.802, respectively. The SHAP technique revealed that higher chance of 1-year survival is associated with low values of interleukin-8, higher values of hemoglobin and lymphocyte count, and the nonuse of steroids.
CONCLUSION
An explainable ML approach can provide a reliable prediction of 1-year survival after RT in patients with advanced cancer. The implementation of SHAP analysis provides an intelligible explanation of individualized risk prediction, enabling oncologists to identify the best strategy for patient stratification and treatment selection.
Topics: Humans; Machine Learning; Bone Neoplasms; Palliative Care; Male; Female; Prognosis; Aged; Middle Aged; Algorithms
PubMed: 38917384
DOI: 10.1200/CCI.24.00027