A systematic review and meta-analysis on utilizing anti-CD19 chimeric antigen receptor T-cell therapy as a second-line treatment for relapsed and refractory diffuse large B-cell lymphoma.

Introduction: Inconsistent results observed in recent phase III trials assessing chimeric antigenic receptor T (CAR-T) cell therapy as a second-line treatment compared to standard of care (SOC) in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) prompted a meta-analysis to assess the effectiveness of CAR-T cell therapy in this setting. Methods: Random-effects meta-analysis was conducted to pool effect estimates for comparison between CAR-T cell therapy and SOC. Mixed treatment comparisons were made using a frequentist network meta-analysis approach. Results: Meta-analysis of three trials with 865 patients showed significant improvement in event-free survival (EFS: HR: 0.51; 95% CI: 0.27-0.97; I2: 92%), progression-free survival (PFS: HR: 0.47; 95% CI: 0.37-0.60; I2: 0%) with CAR-T cell therapy compared to SOC. Although there was a signal of potential overall survival (OS) improvement with CAR-T cell therapy, the difference was not statistically significant between the two groups (HR 0.76; 95% CI: 0.56 to 1.03; I2: 29%). Mixed treatment comparisons showed significant EFS benefit with liso-cel (HR: 0.37; 95% CI: 0.22-0.61) and axi-cel (HR: 0.42; 95% CI: 0.29-0.61) compared to tisa-cel. Discussion: CAR-T cell therapy, as a second-line treatment, appears to be effective in achieving higher response rates and delaying the disease progression compared to SOC in R/R DLBCL.

Management of immune check-point inhibitor-associated colitis in patients with advanced metastatic cancers: A review article.

Immune check-point inhibitors (ICPi) are immunomodulating agents, which have revolutionized the management of advanced metastatic cancers. Being immunomodulating agents, they are predisposed to causing colitis. This descriptive review article emphasized on the management of ICPi-associated colitis in advanced metastatic cancers. We used PubMed, Google Scholar, Scopus, and Embase databases for literature review, and terminologies commonly searched were "management," "immune check-point inhibitors," "colitis," "metastatic," "cancers," "literature," and "review." We reviewed a total of 11 articles done in the last 15 years relevant to ICPi colitis and its management; all the articles showed that diarrhea and colitis are the most common adverse effects observed in patients on ICPi, but prior to establishing the diagnosis of ICPi-causing colitis, possibility of Clostridium difficle or cytomegalovirus infections should be ruled out. Once the diagnosis of ICPi colitis is established, treatment should be started depending upon the severity of colitis. In mild severity, discontinuation of ICPi can resolve the symptoms but, in most of the patients with moderate to high severity of colitis, corticosteroids are considered a cornerstone treatment. Patients unresponsive to steroid treatment should be re-evaluated for infections after which anti-TNF therapy-infliximab or vedolizumab, cyclosporine, mycophenolate mofetil-can be considered.

Dry-Cleaning Chemicals and a Cluster of Parkinson's Disease and Cancer: A Retrospective Investigation.

BACKGROUND: Environmental exposure to trichloroethylene (TCE), a carcinogenic dry-cleaning chemical, may be linked to Parkinson's disease (PD). OBJECTIVE: The objective of this study was to determine whether PD and cancer were elevated among attorneys who worked near a contaminated site. METHODS: We surveyed and evaluated attorneys with possible exposure and assessed a comparison group. RESULTS: Seventy-nine of 82 attorneys (96.3%; mean [SD] age: 69.5 [11.4] years; 89.9% men) completed at least one phase of the study. For comparison, 75 lawyers (64.9 [10.2] years; 65.3% men) underwent clinical evaluations. Four (5.1%) of them who worked near the polluted site reported PD, more than expected based on age and sex (1.7%; P = 0.01) but not significantly higher than the comparison group (n = 1 [1.3%]; P = 0.37). Fifteen (19.0%), compared to four in the comparison group (5.3%; P = 0.049), had a TCE-related cancer. CONCLUSIONS: In a retrospective study, diagnoses of PD and TCE-related cancers appeared to be elevated among attorneys who worked next to a contaminated dry-cleaning site. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Nano biomaterials based strategies for enhanced brain targeting in the treatment of neurodegenerative diseases: an up-to-date perspective.

Neurons and their connecting axons gradually degenerate in neurodegenerative diseases (NDs), leading to dysfunctionality of the neuronal cells and eventually their death. Drug delivery for the treatment of effected nervous system is notoriously complicated because of the presence of natural barriers, i.e., the blood-brain barrier and the blood cerebrospinal fluid barrier. Palliative care is currently the standard care for many diseases. Therefore, treatment programs that target the disease's origin rather than its symptoms are recommended. Nanotechnology-based drug delivery platforms offer an innovative way to circumvent these obstacles and deliver medications directly to the central nervous system, thereby enabling treatment of several common neurological problems, i.e., Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. Interestingly, the combination of nanomedicine and gene therapy enables targeting of selective mutant genes responsible for the progression of NDs, which may provide a much-needed boost in the struggle against these diseases. Herein, we discussed various central nervous system delivery obstacles, followed by a detailed insight into the recently developed techniques to restore neurological function via the differentiation of neural stem cells. Moreover, a comprehensive background on the role of nanomedicine in controlling neurogenesis via differentiation of neural stem cells is explained. Additionally, numerous phytoconstituents with their neuroprotective properties and molecular targets in the identification and management of NDs are also deliberated. Furthermore, a detailed insight of the ongoing clinical trials and currently marketed products for the treatment of NDs is provided in this manuscript.

Classic IgA-Vasculitis With Nephrotic Range Proteinuria - Rare Presentation in an Adult.

IgA vasculitis formerly known as Henoch-Schonlein Purpura is characterized by leukocytoclastic vasculitis and IgA immune complex in small vessels of the affected organ. IgA vasculitis can involve any organ system depending upon the deposition of the IgA immune complex. IgA vasculitis is a clinical diagnosis which manifest with abdominal pain, arthralgia/arthritis, palpable purpura, and kidney involvement. Occasionally, serum IgA levels or skin or kidney biopsy can help in confirming the diagnosis. Treatment is usually supportive, but studies have proved that prednisone or immunosuppressive agents can help in the prevention or progression of the disease. Hereby we present a case of 54-year-old Caucasian male who developed classic tetrad findings of IgA vasculitis most likely after receiving monkeypox vaccine which patient received three weeks prior to presentation to the hospital. Kidney involvement was present but surprisingly proteinuria was above nephrotic range making it as a rare presentation of IgA vasculitis.

Death receptor pathway genes (Caspase and BID) expression analysis in cancerous cells in response to extracts of amla and turmeric.

Plant extracts antiproliferative effects were determined by using mammalian cells along the expression profile of Caspases 3, 8 and the BID gene of the death receptor-induced pathway. Two medicinal plants viz., Turmeric (Curcuma longa) and Amla (Emblica officinalis) extracts were examined for antiproliferative effect through Neutral Red-Dye uptake assay on Vero and MDA-MB 231 cell lines. A reverse transcriptase polymerase chain reaction was used to determine the expression of genes while GAPDH expression was used as an internal control. Expression of BID was up-regulated in methanolic turmeric extract-induced MDA-MB 231 cells while Caspases 3,8 expressions were the same in induced and uninduced MDA-MB 231 cells. Activated BID cleaved into tBID and activated the intrinsic pathway which caused death in methanolic turmeric extract-induced cancerous cells. Ethanolic extracts of turmeric exerted the strongest antiproliferative effects on Vero and methanolic extracts on MDA-MB 231 cells. The morphological studies of cell lines and gene expression analysis of turmeric methanolic extract-treated cells showed activation of apoptosis via converting BID into t-BID (intrinsic pathway) and activating Caspase-3 and Caspase-8 (extrinsic pathway). With the differential cytotoxicity and induction of apoptosis in induced cancer cells in comparison to uninduced cancerous cells, hence turmeric is a natural source of new anti-cancerous compounds.

An intelligent framework to measure the effects of COVID-19 on the mental health of medical staff.

The mental and physical well-being of healthcare workers is being affected by global COVID-19. The pandemic has impacted the mental health of medical staff in numerous ways. However, most studies have examined sleep disorders, depression, anxiety, and post-traumatic problems in healthcare workers during and after the outbreak. The study's objective is to evaluate COVID-19's psychological effects on healthcare professionals of Saudi Arabia. Healthcare professionals from tertiary teaching hospitals were invited to participate in the survey. Almost 610 people participated in the survey, of whom 74.3% were female, and 25.7% were male. The survey included the ratio of Saudi and non-Saudi participants. The study has utilized multiple machine learning algorithms and techniques such as Decision Tree (DT), Random Forest (RF), K Nearest Neighbor (KNN), Gradient Boosting (GB), Extreme Gradient Boosting (XGBoost), and Light Gradient Boosting Machine (LightGBM). The machine learning models offer 99% accuracy for the credentials added to the dataset. The dataset covers several aspects of medical workers, such as profession, working area, years of experience, nationalities, and sleeping patterns. The study concluded that most of the participants who belonged to the medical department faced varying degrees of anxiety and depression. The results reveal considerable rates of anxiety and depression in Saudi frontline workers.

Trichloroethylene: An Invisible Cause of Parkinson's Disease?

The etiologies of Parkinson's disease (PD) remain unclear. Some, such as certain genetic mutations and head trauma, are widely known or easily identified. However, these causes or risk factors do not account for the majority of cases. Other, less visible factors must be at play. Among these is a widely used industrial solvent and common environmental contaminant little recognized for its likely role in PD: trichloroethylene (TCE). TCE is a simple, six-atom molecule that can decaffeinate coffee, degrease metal parts, and dry clean clothes. The colorless chemical was first linked to parkinsonism in 1969. Since then, four case studies involving eight individuals have linked occupational exposure to TCE to PD. In addition, a small epidemiological study found that occupational or hobby exposure to the solvent was associated with a 500% increased risk of developing PD. In multiple animal studies, the chemical reproduces the pathological features of PD.Exposure is not confined to those who work with the chemical. TCE pollutes outdoor air, taints groundwater, and contaminates indoor air. The molecule, like radon, evaporates from underlying soil and groundwater and enters homes, workplaces, or schools, often undetected. Despite widespread contamination and increasing industrial, commercial, and military use, clinical investigations of TCE and PD have been limited. Here, through a literature review and seven illustrative cases, we postulate that this ubiquitous chemical is contributing to the global rise of PD and that TCE is one of its invisible and highly preventable causes. Further research is now necessary to examine this hypothesis.

Bevacizumab combined with platinum-based chemotherapy in primary or relapsed ovarian cancer patients: Meta-analysis and literature to review.

Introduction: Earlier, patients with advanced ovarian cancer were treated with a combination of cytoreductive surgery and platinum-based chemotherapy, which had significant outcomes in the past until an increase in relapse and resistance to treatment, which led to the use or development of bevacizumab (a vascular endothelial growth factor inhibitor) in the treatment of primary or relapsed ovarian cancer. Method and Methodology: This study includes five-phase three randomized controlled clinical trials designed to study the impact of bevacizumab in combination with platinum-based chemotherapy compared with platinum-based chemotherapy alone. Results: This study demonstrated significant improvement in the progression-free span but no improvement in overall survival in the treatment group when compared with the control group. Also, adverse effects reported with combination therapy were tolerable and easily manageable by decreasing the infusion rate or by decreasing the frequency of infusion.

Safety Profile of Mutant EGFR-TK Inhibitors in Advanced Non-Small Cell Lung Cancer: A Meta-analysis.

Background: Despite the use of platinum-based chemotherapy, lung cancer continues to be the leading cause of cancer-related death in the world. To overcome the rate of lung cancer-related death, scientists discovered advanced therapies, including mutant epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitors. Observations: We conducted a meta-analysis to determine the safety profile of mutant EGFR-TK inhibitors in the management of advanced non-small cell lung cancer (NSCLC). Included in this study are 9 phase 3 randomized controlled trials designed to study the safety profile of mutant EGFR-TK inhibitors in patients with advanced NSCLC. The study showed that mutant EGFR-TK inhibitors have an incidence of adverse effects that is less reported when compared with platinum-based chemotherapy. Conclusions: We recommend continuing using mutant EGFR-TK inhibitors in patients with advanced NSCLC especially in patients having mutant EGFR receptors. Adverse effects caused by mutant EGFR-TK inhibitors are significant but are usually tolerable and can be avoided by reducing the dosage of it with each cycle or by skipping or delaying the dose until patient is symptomatic.

Role of daratumumab in relapsed or refractory multiple myeloma patient: A meta-analysis and literature to review.

Introduction: With an increase in number of cases of relapsed or refractory multiple myeloma (RRMM), scientist have discovered various combination of medications among which one is daratumumab, Daratumumab is a mono-clonal antibody which attacks CD-38 markers present in abundance on the surface of myeloma cells and is used universally for the treatment of primary newly diagnosed multiple myeloma patients. Methods and Methodology: This meta-analysis was conducted according to Cochrane Collaboration guidelines in which initially 679 articles were evaluated for relevance on abstract level followed by full text screening of final list of 45 articles. Out of the 45 articles, only 10 articles qualified for selection criteria for eligibility. Three Phase 3 randomized control clinical trials which includes primary outcomes of progression free span and secondary outcomes including complete response, partial response or very good partial response and adverse effects reported were included in this study. Results: A total of three studies including 1533 patients (849 in Daratumumab treatment group while 684 patients in control group) were included in the study. All three of these studies were phase 3 clinical trial conducted to observe the role of daratumumab in relapsed and refractory multiple myeloma. Mean age reported was 65 years in both treatment and control groups. This study showed that daratumumab improves primary and secondary outcomes including progression free span, overall response rate, very good partial response, and complete response. However, daratumumab increases drug induced adverse effects. Conclusion: Our study confirmed that daratumumab in combination therapy improved primary and secondary outcomes when compared with platinum-based chemotherapy, but more adverse effects were reported in the combination group. So, we recommend that combination therapy should include daratumumab in treatment of relapsed and refractory multiple myeloma patients.

IoT Framework for a Decision-Making System of Obesity and Overweight Extrapolation among Children, Youths, and Adults.

Approximately 30% of the global population is suffering from obesity and being overweight, which is approximately 2.1 billion people worldwide. The ratio is expected to surpass 40% by 2030 if the current balance continues to grow. The global pandemic due to COVID-19 will also impact the predicted obesity rates. It will cause a significant increase in morbidity and mortality worldwide. Multiple chronic diseases are associated with obesity and several threat elements are associated with obesity. Various challenges are involved in the understanding of risk factors and the ratio of obesity. Therefore, diagnosing obesity in its initial stages might significantly increase the patient's chances of effective treatment. The Internet of Things (IoT) has attained an evolving stage in the development of the contemporary environment of healthcare thanks to advancements in information and communication technologies. Therefore, in this paper, we thoroughly investigated machine learning techniques for making an IoT-enabled system. In the first phase, the proposed system analyzed the performances of random forest (RF), K-nearest neighbor (KNN), support vector machine (SVM), decision tree (DT), logistic regression (LR), and naïve Bayes (NB) algorithms on the obesity dataset. The second phase, on the other hand, introduced an IoT-based framework that adopts a multi-user request system by uploading the data to the cloud for the early diagnosis of obesity. The IoT framework makes the system available to anyone (and everywhere) for precise obesity categorization. This research will help the reader understand the relationships among risk factors with weight changes and their visualizations. Furthermore, it also focuses on how existing datasets can help one study the obesity nature and which classification and regression models perform well in correspondence to others.

Influence of End-Capped Modifications in the Nonlinear Optical Amplitude of Nonfullerene-Based Chromophores with a D-π-A Architecture: A DFT/TDDFT Study.

Nonlinear optical (NLO) materials have several uses in many fields such as solid physics, biology, medicine, nuclear physics, and material research. Therefore, a series of nonfullerene-based derivatives (CC10D1-CC10D8) with a D-π-A configuration was planned for the NLO investigation using CC10R as the reference molecule with structural alternations at acceptor moieties. Natural bonding orbital (NBO), UV-vis spectra, frontier molecular orbitals (FMOs), global reactivity parameters (GRPs), transition density matrix (TDM), and density of states (DOS) were analyzed using the M06/6-311G(d,p) functional in chloroform solvent to understand the NLO responses of CC10R and CC10D1-CC10D8. The highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) band gaps of CC10D1-CC10D6 were illustrated to be lower than that of CC10R, with the larger bathochromic shift (726.408-782.674 nm) resulting in a significant NLO response. Along with the band gap, the FMO method also identified an efficient interfacial charge transfer from D to A moieties via a π-bridge, which was further supported by the DOS and TDM map. Moreover, NBO calculations demonstrated that extended hyperconjugation and strong internal molecular interactions were important in their stabilization. The dipole moment (µ), linear polarizability ⟨α⟩, hyperpolarizability (ßtotal), and second-order hyperpolarizability (γtotal.) were studied for CC10R and CC10D1-CC10D8. Among all of the derivatives, CC10D2 was proven to be the most appropriate candidate because of its suitable NLO behavior such as being well-supported by a reduced band gap (2.093 eV) and having a suitable maximum absorption wavelength (782.674 nm). Therefore, CC10D2 was reported to have a greater value of first hyperpolarizability (208 659.330 a.u.) compared with other derivatives and CC10R. For the second hyperpolarizability, a greater value was obtained for CC10R (5.855 × 107 a.u.), and its derivatives showed results comparable to that of the parent chromophore for γtotal. This theoretical framework reveals that structural customization with different acceptor units plays a significant role in obtaining attractive NLO materials for optoelectronic applications.

Subcutaneous gluteal abscess from Trichosporon asahii in an immunocompetent adult.

Fungal infections have been drastically increasing in incidence in recent years, preferentially affecting immunocompromised hosts and causing potentially fatal outcomes. One of the emerging fatal fungal pathogens is Trichosporon asahii, a non-Candida yeast that has been increasingly reported in recent years. Previous literature has described T. asahii as primarily affecting immunocompromised hosts, specifically those who are neutropenic, and causing fatal disseminated infections. Herein, we describe a case of an isolated subcutaneous abscess with T. asahii in an immunocompetent host without overlying skin manifestations or predisposing factors that resulted in complete mycotic cure when treated with voriconazole and terbinafine.

Role of steroids in critically-ill sepsis patients: a review article and literature to review.

Sepsis, a life-threatening condition, commonly affecting critically ill patients, is a major cause of death worldwide. It is thus of great importance to determine the optimum management to cure this condition. This review article summarizes the role and effects of corticosteroids in the treatment of sepsis and septic shock, and to determine its mortality benefits. We used PubMed, Google scholar, Scopus, and Embase databases for literature review, and terminologies commonly searched were 'sepsis', 'septic shock', 'therapeutic use' and 'corticosteroids'. In this review article, we reviewed a total of eight different articles being done in last 10 years, relevant to the clinical outcome and effects of corticosteroids. Among those, two demonstrated improved clinical outcomes, two showed both improved clinical outcomes and decreased mortality, three showed increased adverse effects, and the remaining one showed unequivocal results.

Hemophagocytic lymph histiocytosis (HLH): etiologies, pathogenesis, treatment, and outcomes in critically ill patients: a review article and literature to review.

Hemophagocytic lymph histiocytosis (HLH) is not an independent disease but is instead a clinical syndrome that occurs in many underlying conditions involving all age groups. HLH is the consequence of a severe, uncontrolled hyperinflammatory reaction that in most cases is triggered by an infectious agent. Acquired HLH is much more common than primary HLH syndrome but primary is more fatal, and it does have the worst prognosis with no definitive treatment available to date. This review article mentioned all the latest advancements regarding etiologies, pathogenesis, treatment, and outcomes in critically ill patients who got diagnosed with HLH syndrome in last 15 years.

Prognostic importance of deranged sodium level in critically ill patients: A systemic literature to review.

It is common upon admission or during stay at a hospital or intensive care unit (ICU) for patients to present with or acquire a serum sodium abnormality. Hyponatremia, serum sodium level less than 135 mmol/L, frequently associated with critical illnesses such as heart failure and liver cirrhosis, is an indicator of disease severity as well as a risk factor for poor prognosis. Hypernatremia, serum sodium level greater than 145 mmol/L, results due to any ailment disabling a patient's modality of thirst or the ability to relieve it once sensed. Hypernatremia has a more frequent iatrogenic component than hyponatremia. It can develop insidiously among patients through IV fluid administration of saline; both its presentation upon admission and development during stay is associated with mortality. Hyponatremia is associated with increased mortality and its treatment with morbidity as it carries a risk of overcorrection and consequently the development of central pontine myelinolysis. This review article covers the findings, and subsequent correlation between findings sought, of six articles catering to underscore the correlation between sodium disorders and prognosis of hospitalized or critically ill patients. PubMed search engine was utilized to select articles befitting the purpose of this review. Cumulatively, this review article substantiates the need to diligently evaluate and treat serum sodium disorders in hospitalized patients to achieve better prognosis.

Acute Interstitial Pancreatitis With a Normal Lipase Level in the Background of Inflammatory Bowel Disease: A Case Report.

Acute interstitial pancreatitis is usually diagnosed on the basis of clinical findings, elevated lipase level, and imaging. However, herein we present a case of a 44-year-old Caucasian male who presented with pancreatitis diagnosed on the clinical grounds in the background of inflammatory bowel disease.

Role of immature platelet fraction (IPF) in sepsis patients: A systematic review.

Sepsis is extremely common amongst critically ill patients and requires early diagnosis. Hence, identifying a biomarker that could acknowledge sepsis at its prior stage is of vital significance. Immature platelets are a percentage of circulating platelets that contain RNA and is a newer parameter that is measured using automated hematology analyzers in diagnosing sepsis. This review article discusses 10 articles that reveal the role of immature platelet fraction in predicting the onset of sepsis and its relationship with mortality in sepsis. Literature search was done using PubMed, Scopus and Google Scholar and words like platelet indices and immature platelet fraction were typed in the search bar. The aim of this review article is to present a precise form of data that talk about immature platelet fraction (IPF) and its association with the severity and mortality of sepsis. Five out of 10 articles suggest that immature platelet fraction can predict the onset of sepsis and eight out of 10 articles suggest that increased IPF values are associated with high mortality.

Antibiotic-Resistant Pyrexia of Unknown Origin: An Unusual Presentation of Myelodysplastic Syndrome.

A 74-year-old male presented to the emergency department (ED) with complaints of high-grade fever, productive cough, and difficulty breathing for three weeks, and a significant weight loss in the past six months. Despite a detailed investigation, diagnosis could not be achieved. Multiple empiric regimens were tried but no response was observed. Bone marrow biopsy was conducted after suspicious peripheral film result, which concluded that the patient was having myelodysplastic syndrome. Although pyrexia of unknown origin has a diverse group of diseases to evaluate for, and rare entities are difficult to diagnose, meticulous evaluation may give significant evidence for targeted diagnostic workup.