Survival Period Research Articles

Prognostic value of brain perfusion by MRI in the initial study of high grade gliomas

ObjectivesTo evaluate if the tumour perfusion at the initial MRI scan is a marker of prognosis for survival in patients diagnosed with High Grade Gliomas (HGG). To analyse the risk factors which influence on the mortality from HGG to quantify the overall survival to be expected in patients. Patients and methodsThe patients diagnosed with HGG through a MRI scan in a third-level hospital between 2017 and 2019 were selected. Clinical and tumour variables were collected. The survival analysis was used to determine the association between the tumour perfusion and the survival time. The relation between the collected variables and the survival period was assessed through Wald’s statistical method, measuring the relationship via Cox’s regression model. Finally, the type of relationship that exists between the tumour perfusion and the survival was analysed through the Lineal Regression method.Those statistical analysis were carried out using the software SPSS v.17. Results38 patients were included (average age: 61.1 years old). The general average survival period was 20.6 months. A relationship between the tumour perfusion at the MRI scan and the overall survival has been identified, in detail, a group with intratumor values of relative cerebral blood volume (rCBV)>3.0 has shown a significant decline in the average survival period with regard to the average survival period of the group with values <3.0 (14.6 months vs. 22.8 months, p = 0.046). It has also been proved that variables like Karnofsky’s scale and the response time since the intervention significantly influence on the survival period. ConclusionsIt has become evident that the tumour perfusion via MRI scan has a prognostic value in the initial analysis of HGG. The average survival period of patients with rCBV less than or equal to 3.0 is significantly higher than those patients whose values are higher, which allows to be more precise with the prognosis of each patient.

Cuproptosis-related molecular classification and gene signature of hepatocellular carcinoma and experimental verification.

Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with poor overall prognosis. Cuproptosis, a recently proposed mode of copper-dependent cell death, plays a critical role in the malignant progression of various tumors; however, the expression and prognostic value of cuproptosis-related regulatory genes in HCC remain unclear. Genomic, genetic, and expression profiles of ten key cuproptosis-related regulatory genes were analyzed using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset and protein expression data from the Human Protein Atlas (HPA) database. Unsupervised clustering of HCC patients based on these ten key cuproptosis-related regulatory genes was used to identify different HCC subtypes and analyze the differences in clinical and immune characteristics among subtypes. Subsequently, univariate Cox and least absolute shrinkage and selection operator (LASSO) Cox analyses were used to establish a cuproptosis-related prognostic signature, and the accuracy of prognostic signature prediction was internally validated by Kaplan-Meier survival analysis and time-dependent receiver operating characteristic curve in TCGA training and testing cohorts. The prognostic signature was externally validated using TCGA-LIHC entire cohort and International Cancer Genome Consortium Liver Cancer (ICGC-LIRI) cohorts. Finally, the expression landscape of cuproptosis-related regulatory genes in prognostic signature was explored by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunohistochemistry (IHC) experiments. Ten cuproptosis-related genes were differentially expressed in normal and HCC tissues. Unsupervised clustering identified two subtypes and HCC patients with these two subtypes had different clinical prognoses and immune characteristics, as well as different degrees of response to immunotherapy. Lipoyltransferase 1 (LIPT1), dihydrolipoamide s-acetyltransferase (DLAT), and cyclin dependent kinase inhibitor 2A (CDKN2A) were selected to construct a prognostic signature, which significantly distinguished HCC patients with different survival periods in the TCGA training and testing cohorts and was well validated in both the TCGA-LIHC entire cohort and ICGC-LIRI cohort. The risk score of the prognostic signature was confirmed to be an independent prognostic factor, and nomograms were generated to effectively predict the probability of HCC patient survival. The qRT-PCR, western blotting and IHC results also revealed a significant imbalance in the expression of these cuproptosis-related genes in HCC. The classification and prognostic signature based on cuproptosis-related regulatory genes helps to explain the heterogeneity of HCC, which may contribute to the individualized treatment of patients with the disease.

Therapeutic approaches for spinal synovial sarcoma: a comprehensive review of the literature.

Synovial sarcoma (SS) is a relatively rare type of soft-tissue sarcoma that is commonly treated with surgery, radiation, chemotherapy, and palliative care. Stereotactic radiosurgery (SRS) is an emerging approach that shows promise in treating CNS conditions, but it has not been studied for SS. The authors present a systematic review that explores the effectiveness of different treatments, with a focus on SRS, for managing spinal SS. A systematic PubMed search was conducted that covered studies from 1964 to 2022, yielding 70 relevant studies. Inclusion criteria encompassed primary and metastatic spinal SS, various treatment modalities, patient age 17 years or older, English-language studies, retrospective series, and case reports. Based on these criteria, 26 studies were included in this review and 44 were excluded. Of the included studies, 15 patients from 9 studies were treated with surgical intervention followed by both conventional radiotherapy (RT) and chemotherapy, 10 patients from 10 studies were treated with surgery followed by RT, 5 studies comprising 8 patients were exclusively treated with surgery, 5 cases in 3 studies were treated with surgery plus concomitant chemotherapy, 4 patients in 2 studies were treated with SRS, and only 1 study reported treatment without surgery and with chemotherapy and RT. The median progression-free survival and overall survival periods observed in the SRS-treated patients were 37 months and 60 months, respectively, which were higher than those of any other treatment method or combination used. The authors' study offers a thorough review of spinal SS treatments. They are hopeful that this will aid clinicians in informed decision-making for better patient outcomes.

An uncertainty-based interpretable deep learning framework for predicting breast cancer outcome

BackgroundPredicting outcome of breast cancer is important for selecting appropriate treatments and prolonging the survival periods of patients. Recently, different deep learning-based methods have been carefully designed for cancer outcome prediction. However, the application of these methods is still challenged by interpretability. In this study, we proposed a novel multitask deep neural network called UISNet to predict the outcome of breast cancer. The UISNet is able to interpret the importance of features for the prediction model via an uncertainty-based integrated gradients algorithm. UISNet improved the prediction by introducing prior biological pathway knowledge and utilizing patient heterogeneity information.ResultsThe model was tested in seven public datasets of breast cancer, and showed better performance (average C-index = 0.691) than the state-of-the-art methods (average C-index = 0.650, ranged from 0.619 to 0.677). Importantly, the UISNet identified 20 genes as associated with breast cancer, among which 11 have been proven to be associated with breast cancer by previous studies, and others are novel findings of this study.ConclusionsOur proposed method is accurate and robust in predicting breast cancer outcomes, and it is an effective way to identify breast cancer-associated genes. The method codes are available at: https://github.com/chh171/UISNet.

Genetic mutation patterns among glioblastoma patients in the Taiwanese population – insights from a single institution retrospective study

This study utilized Next-Generation Sequencing (NGS) to explore genetic determinants of survival duration in Glioblastoma Multiforme (GBM) patients. We categorized 30 primary GBM patients into two groups based on their survival periods: extended survival (over two years, N = 17) and abbreviated survival (under two years, N = 13). For identifying pathogenic or likely pathogenic variants, we leveraged the ClinVar database. The cohort, aged 23 to 66 (median: 53), included 17 patients in Group A (survival >2 years, 10 males, 7 females), and 13 patients in Group B (survival <2 years, 8 males, 5 females), with a 60% to 40% male-to-female ratio. Identified mutations included CHEK2 (c.1477 G > A, p.E493K), IDH1 (c.395 G > A, p.R132H), and TP53 mutations. Non-coding regions exhibited variants in the TERT promoter (c.-146C > T, c.-124C > T) and TP53 RNA splicing site (c.376-2 A > C, c.376-2 A > G). While Group A had more mutations, statistical significance wasn’t reached, likely due to sample size. Notably, TP53, and ATR displayed a trend toward significance. Surprisingly, TP53 mutations were more prevalent in Group A, contradicting Western findings on poorer GBM prognosis. In Taiwanese GBM patients, bevacizumab usage is linked to improved survival rates, affirming its safety and effectiveness. EGFR mutations are infrequent, suggesting potential distinctions in carcinogenic pathways. Further research on EGFR mutations and amplifications is essential for refining therapeutic approaches. TP53 mutations are associated with enhanced survival, but their functional implications necessitate detailed exploration. This study pioneers genetic analysis in Taiwanese GBM patients using NGS, advancing our understanding of their genetic landscape.

Impact of Operation on Disease Progression and Survival of Patients With Pleural Mesothelioma

BackgroundThe effects of surgery on the survival of patients with pleural mesothelioma remain poorly understood. We compared the therapeutic outcomes of patients receiving neoadjuvant chemotherapy, followed by surgery or refusing surgery, for pleural mesothelioma. MethodsThis retrospective study included consecutive patients who were eligible for curative-intent surgery after 3 cycles of neoadjuvant chemotherapy with platinum plus pemetrexed at our hospital during January 2011 to December 2021. Patients were divided into 2 groups. The surgery group comprised patients who underwent curative-intent surgery for pleural mesothelioma. The refusal-of-surgery group comprised patients who were medically eligible for surgery but refused to consent to surgery. Overall survival and progression-free survival were calculated using the Kaplan-Meier method with the generalized Wilcoxon test. ResultsOf the 296 eligible patients for the study, 272 underwent surgery and 24 refused surgery. During the surgery, 204 patients (75.0%), 43 (15.8%), and 25 (9.2%) underwent pleurectomy/decortication, extrapleural pneumonectomy, and exploratory thoracotomy, respectively. The median follow-up length was 28.4 months. The median overall survival periods were 40.7 months (95% CI, 32.2-45.6 months) for surgery and 23.6 months (95% CI, 15.2-43.0 months) for refusal of surgery (P = .03). The median progression-free survival periods were 20.2 months (95% CI, 17.0-22.5 months) for surgery and 12.9 months (95% CI, 8.3-16.8 months) for refusal of surgery (P < .001). ConclusionsOverall survival and progression-free survival were significantly better in surgery than in refusal of surgery. Surgery may improve the survival outcomes of patients with pleural mesothelioma.

Exploring the impact of traumatic injury on mortality: An analysis of the certified cause of death within one year of serious injury in the Scottish population

BackgroundFew studies effectively quantify the long-term incidence of death following injury.The absence of detailed mortality and underlying cause of death data results in limited understanding and a potential underestimation of the consequences at a population level. This study takes a nationwide approach to identify the one-year mortality following injury in Scotland, evaluating survivorship in relation to pre-existing comorbidities and incidental causes of death. Study DesignThis retrospective cohort study assessed the one-year mortality of adult trauma patients with an Injury Severity Score ≥ 9 during 2020 using the Scottish Trauma Audit Group (STAG) registry linked to inpatient hospital data and death certificate records. Patients were divided into three groups: trauma death, trauma-contributed death, and non-trauma death. Kaplan-Meier curves were used for survival analysis to evaluate mortality, and cox proportional hazards regression analysed risk factors linked to death. Results4056 patients were analysed with a median age 63 years (58–88) and male predominance (55.2 %). Falls accounted for 73.1 % of injuries followed by motor vehicle accidents (16.3 %) and blunt force (4.9 %). Extremity was the most commonly injured region overall followed by chest and head. However, head injury prevailed in those who died. The registry demonstrated a one-year mortality of 19.3 % with 55 % deaths occurring post-discharge. Of all deaths reported, 35.3 % were trauma deaths, and 47.7 % were trauma-contributed deaths. These groups accounted for over 70 % of mortality within 30 days of hospital admission and continued to represent the majority of deaths up to 6 months post-injury. Patients who died after 6 months were mainly the result of non-traumatic causes, frequently circulatory, neoplastic, and respiratory diseases (37.7 %, 12.3 %, 9.1 %, respectively). Independent risk factors for one-year mortality included a GCS ≤ 8, modified Charlson Comorbidity score >5, Injury Severity Score >25, serious head injury, age and sex. ConclusionWith a one-year mortality of 19.3 %, and post-discharge deaths higher than previously appreciated, patients can face an extended period of survival uncertainty.As mortality due to index trauma lasted up to 6 months post-admission, short-term outcomes fail to represent trauma burden and so cogent survival predictions should be avoided in clinical and patient settings.

Conditional survival analysis and dynamic survival prediction for intracranial solitary-fibrous tumor/hemangiopericytoma

BackgroundAs the form of World Health Organization Central Nervous System (WHO CNS) tumor classifications is updated, there is a lack of research on outcomes for intracranial combined solitary-fibrous tumor and hemangiopericytoma (SFT/HPC). This study aimed to explore conditional survival (CS) pattern and develop a survival prediction tool for intracranial SFT/HPC patients.MethodsData of intracranial SFT/HPC patients was gathered from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. The patients were split into training and validation groups at a 7:3 ratio for our analysis. CS is defined as the likelihood of surviving for a specified period of time (y years), given that the patient has survived x years after initial diagnosis. Then, we used this definition of CS to analyze the intracranial SFT/HPC patients. The least absolute shrinkage and selection operator (LASSO) regression and best subset regression (BSR) were employed to identify predictive factors. The Multivariate Cox regression analysis was applied to establish a novel CS-based nomogram, and a risk stratification system was developed using this model.ResultsFrom the SEER database, 401 patients who were diagnosed with intracranial SFT/HPC between 2000 and 2019 were identified. Among them, 280 were included in the training group and 121 were included in the internal validation group for analysis. Our study revealed that in intracranial SFT/HPC, 5-year survival rates saw significant improvement ranging from 78% at initial diagnosis to rates of 83%, 87%, 90%, and 95% with each successive year after surviving for 1–4 years. The LASSO regression and BSR identified patient age, tumor behavior, surgery and radiotherapy as predictors of CS-based nomogram development. A risk stratification system was also successfully constructed to facilitate the identification of high-risk patients.ConclusionThe CS pattern of intracranial SFT/HPC patients was outlined, revealing a notable improvement in 5-year survival rates after an added period of survival. Our newly-established CS-based nomogram and risk stratification system can provide a real-time dynamic survival estimation and facilitate the identification of high-risk patients, allowing clinicians to better guide treatment decision for these patients.

Pre-operative predictors of post-operative seizure control in low-grade glioma: a systematic review and meta-analysis.

As many as 80% of low-grade gliomas (LGGs) present with seizures, negatively impacting quality of life. While seizures are associated with gliomas regardless of grade, the importance of minimizing impact of seizures for patients with low grade tumors cannot be understated given the prolonged survival period in this population.The objective of this systematic review and meta-analysis was to summarize existing literature and identify factors associated with post-operative seizure control (defined as Engel I classification) in patients with LGGs, with a focus on pre-operative factors. Patient data extracted include tumor location and histology, pre-operative anti-seizure medication use, extent of resection (EOR), adjuvant treatment, pre-operative seizure type, duration, and frequency, and post-operative Engel classification. A random-effects model was used to calculate the effects of EOR, pre-operative seizure duration, adjuvant radiation, and adjuvant chemotherapy on post-operative seizure control. The effect of tumor location and histology on post-operative Engel I classification was determined using contingency analyses.Thirteen studies including 1628 patients with seizures were included in the systematic review. On meta-analyses, Engel I classification was associated with pre-operative seizure type (OR = 0.79 (0.63-0.99), p = 0.0385, focal versus generalized), frontal lobe LGGs (OR = 1.5 (1.1-2.0), p = 0.0195), and EOR (OR (95% CI) = 4.5 (2.3-6.7), p < 0.0001 gross-total versus subtotal). Pre-operative seizure duration less than one year, adjuvant radiation, adjuvant chemotherapy, and tumor histology were not associated with achieving Engel I classification. In addition to the known effects of EOR, Engel I classification is less likely to be achieved in patients with focal pre-operative seizures and more likely to be achieved in patients with frontal lobe LGGs.

A novel ferroptosis-related gene signature for overall survival prediction in patients with gastric cancer.

The global diagnosis rate and mortality of gastric cancer (GC) are among the highest. Ferroptosis and iron-metabolism have a profound impact on tumor development and are closely linked to cancer treatment and patient's prognosis. In this study, we identified six PRDEGs (prognostic ferroptosis- and iron metabolism-related differentially expressed genes) using LASSO-penalized Cox regression analysis. The TCGA cohort was used to establish a prognostic risk model, which allowed us to categorize GC patients into the high- and the low-risk groups based on the median value of the risk scores. Our study demonstrated that patients in the low-risk group had a higher probability of survival compared to those in the high-risk group. Furthermore, the low-risk group exhibited a higher tumor mutation burden (TMB) and a longer 5-year survival period when compared to the high-risk group. In summary, the prognostic risk model, based on the six genes associated with ferroptosis and iron-metabolism, performs well in predicting the prognosis of GC patients.

Histological Changes in Adrenal Glands in Suicidal and Sudden Death Cases: A Postmortem Study.

Introduction Various studies have linked suicidal behavior, stress, affective disorders, and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis resulting from chronic stress. Chronic stress has been shown to cause enlargement of the adrenal glands, altering their function and potentially leading to suicidal behaviors in individuals with depression. This study aimed to compare the histological changes in the adrenal glands of individuals who died by suicide with those who experienced sudden death. Suicide victims are exposed to chronic stress, while individuals with sudden deaths face acute stress related to the act of dying. Methods This analytical study, approved by the Institutional Ethics Committee (IEC), was conducted in the Department of Forensic Medicine and Toxicology at Gandhi Medical College, Bhopal. The study included 100 confirmed cases of suicide, irrespective of gender, aged 15-60 years, with notable autopsy findings, relevant history, no signs of decomposition, and varying survival periods (including immediate deaths within 24 hours). Additionally, 20 controls were selected, involving individuals who died suddenly from causes other than suicide within 24 hours of the incident. Informed consent was obtained using a prescribed proforma from relatives and the police. Histological examination slides of the adrenals were prepared and analyzed. Data were collected and statistically analyzed using GraphPad software and Epi Info 7. Results Capsular hemorrhage was observed in 98% of suicide cases and 40% of controls. Nodulation was present in 48% of suicidal cases and 20% of controls. Zonal extension of zona fasciculata was specific to chronic stress in suicidal cases. In 25% of suicidal cases, a prominent extension of the medulla was noted. Irregular thinning of zona glomerulosa with shrunken cells and increased nuclear density in 88% of cases were considered specific to chronic stress conditions and suicide, not observed in controls. Lipid depletion was observed in all suicidal cases, with diffuse depletion in 47% and focal depletion in 53% of cases. In contrast, 45% of those exposed to the acute stress of dying showed focal depletion, with none exhibiting diffuse depletion. Suicidal cases displayed dilated prominent sinusoids in all three zones and the adrenal medulla (98-99%), absent in controls. Adrenal hemorrhage and necrosis were specific to chronic stress conditions, with 7%, 8%, 32%, and 16% of cases showing hemorrhage in all three zones and adrenal medulla, respectively, and none in controls. Conclusion Histological changes observed in acute stress conditions included focal lipid depletion, capsular hemorrhage, nodular hyperplasia, and hemorrhage and necrosis with edema. However, the proportion and severity of these changes were lower than those observed in the suicidal group, suggesting that these findings may be considered non-specific for differentiating between acute and chronic stress.

HMGB1 promotes mitochondrial transfer between hepatocellular carcinoma cells through RHOT1 and RAC1 under hypoxia

Mitochondrial transfer plays an important role in various diseases, and many mitochondrial biological functions can be regulated by HMGB1. To explore the role of mitochondrial transfer in hepatocellular carcinoma (HCC) and its relationship with HMGB1, field emission scanning electron microscopy, immunofluorescence, and flow cytometry were used to detect the mitochondrial transfer between HCC cells. We found that mitochondrial transfer between HCC cells was confirmed using tunnel nanotubes (TNTs). The transfer of mitochondria from the highly invasive HCC cells to the less invasive HCC cells could enhance the migration and invasion ability of the latter. The hypoxic conditions increased the mitochondrial transfer between HCC cells. Then the mechanism was identified using co-immunoprecipitation, luciferase reporter assay, and chromatin immunoprecipitation. We found that RHOT1, a mitochondrial transport protein, promoted mitochondrial transfer and the migration and metastasis of HCC cells during this process. Under hypoxia, HMGB1 further regulated RHOT1 expression by increasing the expression of NFYA and NFYC subunits of the NF-Y complex. RAC1, a protein associated with TNTs formation, promoted mitochondrial transfer and HCC development. Besides, HMGB1 regulated RAC1 aggregation to the cell membrane under hypoxia. Finally, the changes and significance of related molecules in clinical samples of HCC were analyzed using bioinformatics and tissue microarray analyses. We found that HCC patients with high HMGB1, RHOT1, or RAC1 expression exhibited a relatively shorter overall survival period. In conclusion, under hypoxic conditions, HMGB1 promoted mitochondrial transfer and migration and invasion of HCC cells by increasing the expression of mitochondrial transport protein RHOT1 and TNTs formation-related protein RAC1.

Comprehensive Analysis of Oral Squamous Cell Carcinomas: Clinical, Epidemiological, and Histopathological Insights With a Focus on Prognostic Factors and Survival Time.

Oral squamous cell carcinoma(OSCC) is one of the most common malignancies in the head and neck region. Particularly, high incidence rates are observed in South and Southeast Asia, attributed to the widespread use of the carcinogenic areca nut. This study aimed to investigate the clinical, epidemiological, and histopathological features of OSCC, identify prognostic factors impacting disease-free survival, and determine a post-diagnosis disease-free survival time of OSCC patients. Employing a descriptive cross-sectional design, the study conducted a thorough examination of the clinical, epidemiological, and histopathological aspects of OSCC among patients seeking care at a tertiary healthcare facility. Participants were personally interviewed if available, while information for unreachable or deceased individuals was extracted from archival patient records in the Oral and Maxillofacial Surgery Department, Bakhtawar Amin Medical and Dental College, Multan, Pakistan. Data analysis was performed with a significance level set at p ≤ 0.05. The mean age of the patients was 54.16 ± 11.1, with a notable concentration in the 41 years and above age group, indicating a significant prevalence of OSCC in this population. The data revealed a gender bias towardmales, and a substantial proportion of patients, particularly those aged 41 years and above, had unfortunately passed away. Statistical analysis using the Fisher exact test showed a significant association between age groups and patients' current living status (p-value < 0.05). Histopathologically, moderately differentiated OSCC was the most frequently encountered grade, and surgery emerged as the predominant treatment modality. The majority of patients studied had a survival period of three years or less, emphasizing the need for further exploration of factors influencing prognosis and treatment outcomes in OSCC.

Studies on the embryonic development and larval infection potential of the stomach bot flies, Gasterophilus pecorum

Endangered Przewalski's horses have faced severe infections from Gasterophilus pecorum (Diptera, Gastrophilidae) in Xinjiang's Kalamaili Nature Reserve (KNR). This study examines G. pecorum's development and infection patterns in embryonic and larval stages, crucial for understanding horse botfly disease in desert grasslands. For the incubation of G. pecorum fertilized eggs, we established the six distinct temperature gradients: 16 °C, 20 °C, 24 °C, 28 °C, 30 °C, and 32 °C. Using the least squares method, we calculated the correlation between the developmental threshold temperature of the eggs and their cumulative effective temperature. Furthermore, we meticulously recorded the survival duration of the larvae across a spectrum of temperature gradients (−20 °C, −10 °C, 4 °C, 10 °C, 20 °C, and 30 °C) and under varying conditions (dark and light). This method allows us to analyze and interpret the impact of these environmental factors on larval survival durations. 1) The formula for predicting the embryonic development period of G. pecorum was N = (182.7 ± 12.03)/[T-(3.191 ± 1.48)], where the developmental threshold temperature was 3.191 ± 1.48 °C, and the effective accumulated temperature was 182.7 ± 12.03 d°C 2) The model describing the relationship between the embryonic development rate and temperature was: y = 0.0001x2+0.0007x+0.0378, demonstrating a positive correlation between the development rate and temperature (R-sq = 0.989, p < 0.001). 3) Larvae in the dark group exhibited a longer survival time, with the longest being 9 months at 4 °C. The adaptation of G. pecorum's embryonic development to cold temperature, combined with the extended survival period of larvae in the egg state, significantly increases the infection potential of G. pecorum in colder climates. This discovery offers essential insights into the predominance of G. pecorum in the KNR region and provides a crucial biological basis for the prevention of myiasis and the conservation of vulnerable species, such as Przewalski's horses.

Clinical and Real-World Effectiveness of Mogamulizumab: A Narrative Review.

Mogamulizumab (MOG) is an antibody targeting the CCR4 receptor, authorized for relapsed or refractory peripheral T-cell (PTCL) and cutaneous T-cell lymphomas (CTCL). Its adoption in guidelines and endorsement by FDA and EMA established it as a systemic treatment, especially for advanced disease stages due to its comparatively lower toxicity. Clinical trials and real-world evidence have underscored its efficacy in advanced CTCLs, including mycosis fungoides and Sézary syndrome; PTCLs; and adult T-cell leukemia/lymphoma (ATLL), showcasing positive outcomes. Notably, the drug has demonstrated significant response rates, disease stability, and extended periods of progression-free survival, suggesting its applicability in cases with multiple treatment lines. Its safety profile is generally manageable, with adverse events (AEs) primarily related to the skin, infusion-related reactions, drug eruptions, autoimmune diseases, and skin disorders. The latter seem to appear as CCR4 can promote the skin-specific homing of lymphocytes, and MOG is directed against this receptor. While combination with immunostimulatory agents like interferon alpha and interleukin 12 has shown promising results, caution is urged when combining with PD1 inhibitors due to the heightened risk of immune-mediated AEs. The introduction of MOG as a systemic treatment implies a significant advancement in managing these diseases, supported by its favorable safety profile and complementary mechanisms.

Proton Pump Inhibitors and Cyclin-Dependent Kinase 4/6 Inhibitors in Patients With Breast Cancer.

Proton pump inhibitors (PPIs) reduce the bioavailability of several anticancer drugs. The impact of PPIs co-administered with cyclin-dependent kinase 4 and 6 inhibitors is controversial. We aimed to clarify whether the concomitant use of PPIs impacts palbociclib and abemaciclib effectiveness in breast cancer treatment. This multicenter, retrospective, observational study, conducted across 4 medical institutions in Japan, consecutively included patients with endocrine-resistant metastatic breast cancer, receiving palbociclib or abemaciclib between December 2017 and August 2022. Propensity score-matched analyses were performed. Treatment efficacy and safety with and without PPIs were compared. Progression-free survival and overall survival were estimated using the Kaplan-Meier method and compared using a log-rank test. A Cox proportional hazards model was used to estimate the hazard ratio. The study included 240 patients. After 1:1 matching, 112 patients were treated with and without PPIs. The median progression-free survival period was 1.2 years in the PPI group and 1.3 years in the non-PPI group (hazard ratio, 1.19; 95% CI, 0.70-2.02). The median overall survival period was 3.6 years in the PPI group, whereas it was not reached in the non-PPI group (hazard ratio, 1.23; 95% CI, 0.61-2.47). Consistent results were obtained for subgroups receiving palbociclib (n = 177) and abemaciclib (n = 63) without propensity score matching. Adverse event incidence and severity were similar in both groups. The effectiveness of cyclin-dependent kinase 4/6 inhibitors is unlikely to be affected by concomitant PPI use. Future prospective pharmacokinetic studies are warranted.

Microscopic Growth Pattern of Metastatic Colorectal Carcinomas, Morphological Findings of the Non-Neoplastic Liver, andTheir Relationship With Prognosis and Survival.

Introduction. Various clinicopathological, radiological, and molecular parameters are predictive of prognosis in patients with colorectal carcinoma and distant organ metastases continue to have a significant place among them. Recent studies reveal that not only the presence of metastases but also the histopathological growth pattern of the metastatic tumor significantly affects prognosis. This study aimed to investigate the prognostic significance of the histopathological growth patterns of metastatic tumors, the morphological findings in the peritumoral non-neoplastic liver, and its relationship with survival in patients who have metastatic colorectal carcinoma. Materials and Method. Hematoxylin and eosin-stained slides of the tumors were re-examined in terms of histopathological diagnosis, growth pattern, presence and degree of peritumoral lymphocytic infiltration, steatosis, cholestasis, and peritumoral ductular reaction in the non-neoplastic liver. Results. In terms of histopathological growth patterns, 24 (47%) tumors showed replacement, 19 (37%) showed desmoplastic and 8 (16%) showed pushing growth pattern. In terms of total survival, there was a significant difference (P = .011) between desmoplastic and replacement growth patterns, and the survival period was shorter in patients with replacement growth patterns. Conclusion. Recent studies show that histopathological growth patterns in metastatic liver tumors may be a promising prognostic and predictive parameter. It is important to include this parameter in the pathology reports as it does not require additional equipment for evaluation in routine pathology practice, does not bring additional costs, or takes a long time to evaluate. This feature can be evaluated standardly by every pathologist.

Electronic Cigarette Vape Exposure Exacerbates Post-Ischemic Outcomes in Female but Not in Male Rats.

Nicotine-containing electronic cigarette (EC) vaping has become popular worldwide, and our understanding of the effects of vaping on stroke outcomes is elusive. Using a rat model of transient middle cerebral artery occlusion, the current exploratory study aims to evaluate the sex-dependent effects of EC exposure on brain energy metabolism and stroke outcomes. Adult Sprague-Dawley rats of both sexes were randomly assigned to air/EC vapor (5% nicotine Juul pods) exposure for 16 nights, followed by randomization into 3 cohorts. The first cohort underwent exposure to air/EC preceding randomization to transient middle cerebral artery occlusion (90 minutes) or sham surgery, followed by survival for 21 days. During the survival period, rats underwent sensorimotor and Morris water maze testing. Subsequently, brains were collected for histopathology. A second cohort was exposed to air/EC after which brains were collected for unbiased metabolomics analysis. The third cohort of animals was exposed to air/EC and received transient middle cerebral artery occlusion/sham surgery, and brain tissue was collected 24 hours later for biochemical analysis. In females, EC significantly increased (P<0.05) infarct volumes by 94% as compared with air-exposed rats, 165±50 mm3 in EC-exposed rats, and 85±29 mm3 in air-exposed rats, respectively, while in males such a difference was not apparent. Morris water maze data showed significant deficits in spatial learning and working memory in the EC sham or transient middle cerebral artery occlusion groups compared with the respective air groups in rats of both sexes (P<0.05). Thirty-two metabolites of carbohydrate, glycolysis, tricarboxylic acid cycle, and lipid metabolism were significantly altered (P≤0.05) due to EC, 23 of which were specific for females. Steady-state protein levels of hexokinase significantly decreased (P<0.05) in EC-exposed females; however, these changes were not seen in males. Even brief EC exposure over 2 weeks impacts brain energy metabolism, exacerbates infarction, and worsens poststroke cognitive deficits in working memory more in female than male rats.

Breeding for Bacterial Wilt Disease Resistance in Brinjal

Brinjal is a warm–season vegetable that belongs to the Solanaceae family. Among the biotic stresses of brinjal, bacterial wilt is a major disease caused by a soil-borne bacterium, Ralstonia solanacearum. Both cultural and chemical disease control methods are not effective due to the wide host range and prolonged spore survival periods in soil. In recent past, the use of resistant varieties and hybrids are recognized as the effective method to control bacterial wilt disease. Information on genetics of resistance to bacterial wilt disease is of prime importance for improvement of varieties and hybrids in brinjal. The bacterial wilt resistance response and resistance mechanisms are strictly based on the environmental conditions and cultivars. In traditional crop improvement methods, the development of varieties and hybrids is expensive and time consuming. The discovery of molecular marker systems increases the speed and precision for developing of varieties and hybrids with desired agronomic traits.

Effects of Frankliniella occidentalis (Pergande) density and loofah pollen on development and fecundity of Orius similis Zheng

AbstractOrius similis Zheng, a predatory bug that feeds on Frankliniella occidentalis (Pergande), a pest that damages vegetables and ornamental plants by feeding and transforming plant viruses. O. similis is an omnivorous predator on thrips, as well as pollen. Our study investigated the impact of five different amount densities of thrips and abundant loofah pollen on the survival, development, fecundity, and consumption of O. similis. The performance of O. similis nymphs and adults was significantly affected by the density of thrips and loofah pollen on which they fed. The highest survival and shortest development period of O. similis nymphs after feeding on 40 thrips/d, while the lowest survival rate and longest period were observed after feeding on only 5 thrips. Feeding on loofah pollen alone also significantly increased survival and decreased the nymph development period compared with feeding on 20 thrips/d. The highest prey consumption occurred at densities of 30 and 40 thrips/d, while the lowest prey consumption occurred at a thrips density of 5, regardless of whether the O. similis were nymphs or female adults. However, adding loofah pollen decreased prey consumption of nymphs and adult females. In addition, O. similis showed higher fecundity and longevity when feeding on 40 thrips/d compared to other thrips densities and adding loofah pollen. Adding loofah pollen also increased fecundity and longevity compared to feeding on thrips alone at the same density, regardless of the thrips' density. Therefore, a high thrips abundant density daily was beneficial for the development, fecundity, and longevity of O. similis, and adding loofah pollen can enhance their performance.