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Supplemental Digital Content is Available in the Text. Background: In people living with HIV (PLWH) with hepatitis C virus (HCV) infection, liver and nonliver-related mortality significantly decreased after receiving direct acting antivirals (DAAs). We aimed to assess main causes and predictors of mortality after sustained virologic response induced by DAAs. Methods: Retrospective study in antiretroviral treatment-experienced PLWH with HCV infection, followed at San Raffaele Hospital, Milan, Italy, who achieved sustained virologic response after DAAs. Kaplan–Meier analysis and log-rank test were used to estimate cumulative probability of death for any cause. Cox proportional hazards model was used to estimate adjusted hazard ratio (aHR) of death and the corresponding 95% confidence interval (95% CI); baseline variables included in the model were age, diabetes, hepatocellular carcinoma (HCC), α-fetoprotein (AFP), and albumin–bilirubin (ALBI) grade. Results: Among 663 people included with a median follow-up of 4.4 years (interquartile range = 3.5–5.5), 49 died. Overall 5-year cumulative probability of death was 8.0% (95% CI: 5.5% to 0.4%); 63.2% (n = 31/49) died from nonliver-related events [mainly nonliver malignancies (18/49) and cardiovascular events (7/49)]. At multivariate analysis, death was more likely in older people [aHR (5-year older) = 1.46, 95% CI: 1.16 to 1.83, P = 0.0009], and in people with diabetes (aHR = 2.98, 95% CI: 1.55 to 5.71, P = 0.001), ALBI grade ≥2 (aHR = 2.13, 95% CI: 1.17 to 3.90, P = 0.014), and AFP ≥3.4 ng/mL (aHR = 1.96, 95% CI: 1.01; 3.84, P = 0.049). Conclusions: In our cohort, nonliver-related events and malignancies were the most common cause of death after HCV eradication. Diabetes, ALBI grade ≥2, and AFP ≥3.4 ng/L were associated with higher risk of death. In PLWH after HCV eradication, regardless of liver disease stage, surveillance of nonliver events, particularly malignancies, should be recommended. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? The association between specific types of malignancies and the subsequent risk of dementia remains unknown. • What is the main finding of this study? Cancer survivors were more likely to develop Alzheimer's disease, unspecified dementia, and any dementia compared with controls after adjusting for potential confounders. • What is the meaning of the finding? Cancer survivors are at higher risk of subsequent dementia. Different types of cancer survivors may contribute to variable risks of specific dementias. The association between specific types of malignancies and the subsequent risk of dementia remains unknown. A retrospective population-based cohort study based on data from Taiwan National Health Insurance Research Database. We recruited 32,250 patients who survived malignancies and 322,500 controls between 1998 and 2011 and followed them up until the end of 2013. Diagnoses of dementia (including Alzheimer's disease (AD), vascular dementia (VaD), and unspecified dementia) was made during the follow-up period. Cox regression analyses were performed after adjusting for potential confounders. A sensitivity analysis was conducted to exclude patients with prodromal dementia. Cancer survivors were more likely to develop AD (hazard ratio [HR]: 1.68, 95% confidence interval [CI]: 1.38–2.06), unspecified dementia (HR: 1.19, 95% CI: 1.07–1.32), and any dementia (HR: 1.26, 95% CI: 1.16–1.37) compared with controls after adjusting for potential confounders. Importantly, cancers of the digestive and genitourinary organs seem to be associated with AD, unspecified dementia, and any dementia, whereas only malignant neoplasms of the brain are more likely to develop into VaD. Sensitivity analyses after exclusion of the first three or five years of observation and after exclusion of case enrollment before 2009 or 2007 showed consistent findings. Cancer survivors are at higher risk of subsequent dementia. Different types of cancer survivors may contribute to variable risks of specific dementias. Further studies are necessary to investigate the underlying mechanisms in cancer survivors and patients with dementia. [ABSTRACT FROM AUTHOR]

Background: Pulmonary space-occupying lesions are typical chronic pulmonary diseases that contribute significantly to healthcare resource use and impose a large disease burden in China. A time-series ecological trend study was conducted to investigate the associations between environmental factors and hospitalizations for pulmonary space-occupying lesions in North of China from 2014 to 2022. Methods: The DLNM was used to quantify the association of environmental factors with lung cancer admissions. The heating-, age-, gender-, malignancy-specific effects were further estimated to identify the susceptible groups. Results: During the study period, fluctuations in air pollutants and climate conditions closely mirrored changes in hospitalizations for pulmonary space-occupying lesions. Totally, the distributed lag surface showed clear positive associations between pulmonary tumor hospitalization and PM2.5 (RRlag30: 1.000912; 95%CI: 1.000076, 1.00175), PM10 (RRlag30: 1.002246; 95%CI: 1.000474, 1.004021), SO2 (RRlag30: 1.002714; 95%CI: 1.001071, 1.004414), CO (RRlag30: 1.002231; 95%CI: 1.000592, 1.003873). Additionally, the associations between air pollutants and hospitalizations for pulmonary space-occupying lesions were significantly stronger during the heating season. Population aged 65 or older, females and those diagnosed with malignancies were more vulnerable for the risk of pulmonary space-occupying lesions diseases due to air pollution exposure. Conclusions: The present study illustrated risk and burden for pulmonary space-occupying lesions hospitalization associated with air pollution, especially among population aged ≥ 65, or female. [ABSTRACT FROM AUTHOR]

Background: This meta‐analysis aimed to determine the incidence and overall risk of major adverse cardiovascular events (MACEs) related to immune checkpoint inhibitors (ICIs). Methods: We systematically searched all cohort studies, including the available MACE data in cancer patients receiving ICIs, in PubMed, Embase, and the Cochrane Library, from their inception to September 5, 2023. The primary outcome was the incidence of MACEs associated with ICI exposure, and the secondary outcome was the overall risk of MACEs associated with ICI exposure versus non‐ICI exposure controls. Risk ratios with 95% confidence intervals were used in the random‐ or fixed‐effects models. Results: Overall, 26 cohort studies met the inclusion criteria, involving 109,883 cancer patients. In the median follow‐up period ranging from 3.3 to 55.2 months, the incidence of MACEs associated with ICI exposure was 8.22%, ranging from 0.55% to 3.98%, among the nine MACEs, including myocarditis, tachyarrhythmia, pericarditis, pericardial effusions, cardiovascular death, myocardial infarction, heart failure, stroke, and conduction disorder. The incidence of MACE associated with non‐ICI exposure was 3.84%, ranging from 0.81% to 4.72%. The risks of all‐grade MACEs and pericardial effusions were significantly higher in the ICI group than in the non‐ICI controls. ICI treatment, age, male sex, and prior radiation therapy were significantly associated with MACEs. Conclusion: The risk of MACEs during ICI treatment in patients with cancer is more common than is currently recognized. ICI use is closely associated with an increased risk of MACEs. Patients at risk were older, male, and had a history of radiation therapy. [ABSTRACT FROM AUTHOR]

Background and Objectives: The incidence and prevalence of cancers are increasing worldwide, with special emphasis placed on prevention, early detection, and the development of new therapeutic strategies that strongly impact patient outcomes. Limited data are available about emergency care's role in treating patients with cancer. This study aims to determine the burden of end-stage and first-time diagnosis of cancer on emergency care in a high-turnover emergency care center. Materials and Methods: A retrospective observational study was conducted to identify patients requesting emergent aid for cancer-related symptoms in the Emergency Department of "St. Spiridon" Hospital from Iasi (Romania) between 1 October 2022 and 30 September 2023. The proportion and demographic characteristics of end-stage patients and those who received a first-time diagnosis during the emergency visit were evaluated. Risk analysis was performed to understand these patients' care needs (such as medical care, surgical care, specialty consults, intensive care, ward admission, and other hospital transfers) and immediate care outcomes (such as in-hospital mortality and home discharge). Results: 2318 patients with cancer requested emergent care (patient presentation rate of 3.08%), of which 444 (19.15%) were diagnosed for the first time, and 616 (26.57%) were at the end-stage. First-time diagnosed patients had a significantly different distribution of cancer types (p < 0.001), were more likely to need any form of medical care, to require a specialty consultation, or to be admitted to a ward (OR 2.65, 95% CI: 2.12–3.32; p < 0.001; OR 3.28, 95% CI: 2.48–4.35, p < 0.001; OR 2.09, 95% CI: 1.70–2.59; p < 0.001, respectively) but were less severe, while end-stage patients were more likely to address repeatedly to the emergency room (OR 1.86, 95% CI: 1.32–2.59; p = 0.001) and had higher odds of needing intensive care, assisted ventilation and death (OR-4.63, 95% CI: 1.10–19.45, p = 0.04; OR 2.59, 95% CI: 1.57–4.28; p < 0.001, and OR 4.06, 95% CI: 1.73–9.54; p = 0.001, respectively). Conclusions: The emergency department often carries the weight of diagnosing patients with cancer and treating patients with end-stage disease. These data highlight the importance of prehospital care, particularly for cancer screening and palliative care, and the importance of fostering multidisciplinary collaboration in the emergency room with oncologists, geriatricians, and palliative care specialists to improve patient outcomes. [ABSTRACT FROM AUTHOR]

The association of AA with malignancies has been a scope of controversy as the current literature is highly inconsistent in this regard. To evaluate the association between AA and hematological malignancies (HMs) and solid malignancies (SMs) using a large-scale, real-life computerized database. A cross-sectional study was conducted to compare the prevalence of HMs and SMs among patients with AA relative to age-, sex-, and ethnicity-matched control subjects. Chi-square and t-tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. The study included 51,561 patients with AA and 51,410 controls. AA was significantly associated with HMs (adjusted OR, 1.27; 95% CI, 1.07–1.51; P = 0.006). This association was more robust among patients with late-onset AA (≥ 50 years; OR, 1.33; 95% CI, 1.04–1.71; P = 0.025). On the other hand, AA was not found to be significantly associated with SM (adjusted OR, 0.97; 95% CI, 0.88–1.06; P = 0.487), excluding among patients with alopecia totalis and universalis (OR, 2.10; 95% CI, 1.03–4.27; P = 0.036). In a granular analysis including 5 HMs and 18 SMs, non-Hodgkin lymphoma was the only malignancy that proved positively associated with AA (adjusted OR, 1.32; 95% CI, 1.03–1.69; P = 0.028). AA is associated with HMs but not SMs. Further research is warranted to validate our observations in other study cohorts. [ABSTRACT FROM AUTHOR]

Background Malignancies are the third leading cause of death among kidney transplant recipients. These patients face increased mortality and challenges such as allograft loss and rejection, which may arise from surgical complications, changes in immunosuppressive therapy or the use of chemotherapeutics. This study aims to examine the risk of allograft rejection and loss in kidney transplant recipients diagnosed with de novo malignancies. Methods This retrospective case–control study included adult kidney transplant patients from 1986 to 2020 who developed de novo malignancies. Each patient with a malignancy was matched with a control without malignancy using the nearest neighbor matching method. The outcomes measured were biopsy-confirmed allograft rejection, death-censored allograft loss and overall mortality after the diagnosis of malignancy in the malignancy group and at any point in the control group. Results Of 2750 records reviewed, 267 patients (9.7%) had biopsy-confirmed malignancies, with a median age of 60 years and 66.3% men. The median follow-up was 218 months. Kaplan–Meier analysis showed that the allograft rejection rates were lower in the malignancy group compared with the control group (26 vs 60, P < .001). Overall mortality was higher in the malignancy group, although this difference was not statistically significant (104 vs 73, P = .25). Death-censored allograft loss was similar between groups (22 vs 32, P = .49). Chemotherapy and older recipient age were associated with reduced allograft rejection risk, as indicated by multivariable regression analysis. Conclusions In kidney transplant recipients with de novo malignancies, death with a functioning graft remains significant. However, allograft loss rates do not increase compared with those without malignancies, and rejection risk is reduced, especially in older and chemotherapy-treated patients. These findings suggest that managing immunosuppression reduction in this population may be appropriate, but further research is needed to determine optimal care strategies. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitor-associated acute kidney injury (ICI-AKI) is the most common renal complication and has attracted increasing amounts of attention. However, studies on this topic in Chinese cancer patients are very limited. Therefore, we conducted a retrospective study on the incidence, risk factors, clinical features and renal recovery of ICI-AKI in all patients with malignancies treated with ICIs in Shandong Provincial Hospital Affiliated to Shandong First Medical University. In this single-center retrospective cohort study, the data of 904 patients who received immune checkpoint inhibitors (ICIs) treatment were retrospectively analyzed. Multivariable logistic regression was used to identify the predictors of ICI-AKI. A total of 46 of 904 patients receiving ICIs developed ICI-AKI, and the incidence of ICI-AKI was 5.1%. Patients developed ICI-AKI at a median of 9 weeks (IQR 3–23) after ICIs initiation. A lower baseline estimated glomerular filtration rate (eGFR) and use of antibiotics were associated with a higher risk of ICI-AKI. Renal recovery occurred in 17 patients (46%) at a median of 4 weeks (IQR 2–8) after ICI-AKI, including 16 (43%) with complete recovery and 1 (3%) with partial recovery. Of the 14 rechallenged patients, only one developed recurrent ICI-AKI. Patients with ICI-AKI were more likely to have impaired renal function at baseline and after treatment with antibiotics. Approximately half of the patients achieved renal recovery. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a common hematologic malignancy in adults. Recent studies investigating the potential pathogenesis of AML have significantly advanced our understanding of this disease. While cytogenetics and molecular abnormalities are crucial for confirming chemotherapy response and long-term outcomes, there are additional potential therapeutic targets and prognostic factors. The CAPN1 gene, which encodes a large subunit of the ubiquitous enzyme calpain, has not been extensively studied in hematological diseases. In this study, we used data from the TCGA public database to perform a bioinformatic analysis and found that CAPN1 is differentially expressed in multiple cancers and is associated with an unfavorable prognosis in AML. We employed R software and websites such as David and STRING to conduct differential analysis, GO and KEGG analysis, and explore the correlation between CAPN1 and physiological processes and key pathways. Our findings suggest that CAPN1 is significantly associated with the structure of the extracellular matrix and receptor-ligand interactions, indicating its potential role in disease progression. Additionally, we used CYBERSORT and ssGSEA to analyze the immune environment of CAPN1 and found that it is associated with most immune components, particularly CD56 cells and neutrophils. In conclusion, CAPN1 is a key prognostic gene in AML that is significantly correlated with disease progression, clinical features, and immune invasion. [ABSTRACT FROM AUTHOR]

Purpose To investigate the phenotype of sarcoidosis according to the time when a malignancy is diagnosed (preexisting to the diagnosis of sarcoidosis, concomitant, or sequential) and to identify prognostic factors associated with malignancies in a large cohort of patients with sarcoidosis. Methods We searched for malignancies in the SARCOGEAS cohort, a multicenter nationwide database of consecutive patients diagnosed with sarcoidosis according to the ATS/ESC/WASOG criteria. Solid malignancies were classified using the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) nomenclature, and hematological malignancies using the 2016 WHO classification. We excluded patients with a biopsy-proven diagnosis of sarcoidosis based exclusively on demonstrating granulomas in tissues also involved by malignant cells. Results Out of 1942 patients with sarcoidosis, 233 (12%) developed 250 malignancies, including solid (n  = 173), hematological (n  = 57), and both types of malignancies (n  = 3). Concerning the time interval between the diagnoses of both conditions, 83 (36%) patients were diagnosed with malignancy at least 1 year before sarcoidosis diagnosis, 22 (9%) had s synchronous diagnosis of both diseases, and 118 (51%) developed malignancies at least 1 year after the diagnosis of sarcoidosis (the remaining cases developed malignancies in different time intervals). The multivariate-adjusted model showed that individuals with sarcoidosis who developed a malignancy had an hazard ratio (HR) of 2.27 [95% confidence interval (CI), 1.62–3.17] for having an asymptomatic clinical phenotype at diagnosis of sarcoidosis and that spleen (presence vs. absence: HR = 2.06; 95% CI, 1.21–3.51) and bone marrow (presence vs. absence: HR = 3.04; 95% CI, 1.77–5.24) involvements were independent predictors for the development of all-type malignancies. No predictive factors were identified when the analysis was restricted to the development of solid malignancies. The analysis limited to the development of hematological malignancies confirmed the presence of involvement in the spleen (HR = 3.73; 95% CI, 1.38–10.06) and bone marrow (presence vs. absence: HR = 8.00; 95% CI, 3.15–20.35) at the time of sarcoidosis diagnosis as predictive factors. Conclusion It is essential to consider the synchronous or metachronous timing of the diagnosis of malignancies in people with sarcoidosis. We found that half of the malignancies were diagnosed after a diagnosis of sarcoidosis, with spleen and bone marrow involvement associated with a four to eight times higher risk of developing hematological malignancies. Key messages What is already known on this topic Malignancies are one of the comorbidities more frequently encountered in people with sarcoidosis What this study adds Malignancies occur in 12% of patients with sarcoidosis Malignancy may precede, coincide with, or follow the diagnosis of sarcoidosis One-third were identified before sarcoidosis, and half were diagnosed after Spleen and bone marrow involvement are risk factors for developing hematological malignancies How this study might affect research, practice or policy Patients with sarcoidosis should be regularly monitored for neoplasms, informed of the increased risk, and educated on early detection. Those with spleen or bone marrow involvement must be closely followed. [ABSTRACT FROM AUTHOR]

Background and Objectives: Hepatitis C virus (HCV) infection is a major global public health concern, particularly in hemodialysis (HD) patients. This study aims to evaluate the demographic, clinical, and laboratory characteristics of HCV-positive patients undergoing HD and assess the long-term impact of direct-acting antivirals (DAAs) on patient outcomes. Moreover, a narrative review aims to summarize the current knowledge regarding HCV treatment in HD patients. The search in the PubMed, Google Scholar, and Scopus databases identified 48 studies relevant to our topic, 18 regarding clinical history and 29 related to HCV treatment. Methods: A retrospective analysis was performed on 165 HD patients from Bihor County HD centers, Romania, between 2014 and 2024. The cohort was divided into two groups: 54 patients who tested positive for HCV and 111 controls who were HCV-negative. Data collected from GPs included demographic information, comorbidities, laboratory parameters, and psychological assessments. Outcomes were evaluated at over 5 years after DAA treatment. A literature review was conducted using PubMed and Google Scholar to identify relevant studies on HCV in HD patients from 1989 to 2024. Results: Laboratory results showed similar parameters across groups, except for lower serum cholesterol levels in the HCV-positive DAA-treated group vs. HCV-positive non-treated ones (155.607 mg% vs. 170.174 mg%, p = 0.040) and increased ALT levels when comparing the same groups (29.107 vs. 22.261, p = 0.027), whereas comorbidities did not differ significantly. The incidence of malignancies was significantly higher among HCV-positive compared to HCV-negative patients (20.3% vs. 8.1%, p = 0.023), mainly among those treated with DAAs, highlighted by the multivariate analysis. Cardiovascular disease remains the leading cause of mortality regardless of HCV status or the use of antiviral therapy. Psychological assessments revealed more severe depression in HCV-positive patients compared to their HCV-negative counterparts. Conclusions: HCV infection in the hemodialysis population typically follows a subclinical course. At over five years after DAA therapy, the results indicate a stabilization of the liver function and the absence of major complications. However, the incidence of malignancies remains high in HCV-positive patients. [ABSTRACT FROM AUTHOR]

Purpose: Psoriasis (PsO), a chronic inflammatory skin disorder affecting a substantial proportion of populations globally, often necessitates systemic treatment including biologics. This 14‐year cohort study, based on Danish national register data, aimed to investigate the enduring safety profile of ustekinumab compared to other systemic psoriasis treatments. Methods: Using comprehensive Danish national register data, this study scrutinized patients diagnosed with psoriasis or psoriatic arthritis (PsA) who received ustekinumab. The treatment group comparators were non‐biological systemic treatment (non‐biologic), tumor necrosis factor α inhibitor medicine groups (TNF‐α), interleukin (IL)‐17 inhibitors (IL‐17), and IL‐23 inhibitors (IL‐23). The study periods for comparisons were 2009–2022 for non‐biologic and TNF‐α, 2015–2022 for IL‐17, and 2018–2022 for IL‐23. Outcomes were malignancies, cardiovascular events, serious infections, and serious hypersensitivity reactions. Cox proportional hazards regression models were employed to analyze two estimands: a standard intention‐to‐treat (ITT) estimand and a continuous‐index‐treatment (CIT) estimand, which considered switch and re‐initiation of treatments within individuals. Results: Users of ustekinumab were found to be younger on average, with an average age of 45.1 years compared to 51.6, 47.2, 49.0, and 48.4 years in the non‐biologic, TNF‐α, IL‐17, and IL‐23 groups, respectively. Also, 57.3% of the ustekinumab users were male, compared to 46.7%, 48.9%, 50.9%, and 58.3% for the non‐biologic, TNF‐α, IL‐17, and IL‐23 groups, respectively. Although the hazard ratio estimates varied across comparators, ustekinumab was found to be safe: regardless of PsA status, no discernible safety signals in terms of malignancy, MACE, severe infections, or severe hypersensitivity reactions were observed for ustekinumab when compared to the treatment comparators. Conclusions: The present study corroborated the enduring safety of ustekinumab in the context of PsO treatment. [ABSTRACT FROM AUTHOR]

Background: Pediatric patients on chemotherapy suffer from various dermatoses due to immunosuppression or due to cutaneous adverse effects of chemotherapy. There is a paucity of literature from our country about the pattern of dermatoses in these patients. Objectives: This study has been conducted to know the pattern of dermatological manifestations in immunocompromised pediatric patients. Materials and Methods: All patients who attended the outpatient department of the division of pediatric hemato-oncology of our hospital and who were diagnosed with hematological and solid organ malignancy were screened. Those children whose guardians were willing to give consent and who fulfilled the inclusion and exclusion criteria were included in the study. The design of the study was cross-sectional. At the visit, demographic data, drug history, and history of any chronic disease were collected. The diagnosis of mucocutaneous manifestations was made by the dermatologist mainly on clinical findings. Special investigations such as potassium hydroxide mount for fungus and Tzanck smear were done in few patients when indicated. Results: A total of 76 patients were enrolled in the study. The ages of the patients ranged from 1 to 18 years with the mean age (years ± standard deviation) being 8.27 ± 4.24 years. A total of 8 patients (10.5%) had fungal infections. Ten patients (13.1%) had viral infections and six (7.9%) patients had bacterial skin infections. Generalized xerosis was the most common cutaneous manifestation which was seen in 13 patients (17.1%), followed by generalized hyperpigmentation, injection site reactions, and nevi (≤10 in number) in 10 patients (13.2%) each. In mucosal findings, mucositis was the most common manifestation seen in 13 patients (17.1%). In hair changes, anagen effluvium was the most common finding seen in 30 patients (39.5%). Discussion: Mucocutaneous findings are common in pediatric patients on chemotherapy. Prompt diagnosis and treatment reduce morbidity and improve the quality of life in these patients. Conclusion: Mucocutaneous findings are common in pediatric patients on chemotherapy due to cutaneous adverse effects of chemotherapy and immunosuppression.

Background: Urinary tract infection is one of the most common diseases in patients with cancer, making them at risk of developing opportunistic infections. Materials and Methods: A total of 110 samples from cancer patients admitted to Baqaei 2 Hospital in Ahvaz, including 55 chil-dren with malignancies and 55 adult patients, were included in the study. A questionnaire was completed with demographic items such as age, gender, type of malignancy, length of hospitalization, duration of chemotherapy and type of urinary tract infection along with an antibiogram susceptibility test (disc diffu-sion). Results: The mean age of the adult patients was 40.43±25.3 years, and the children 14.56±4.63 years. A total of 56 patients (50.9%) were male and 54 (49.1%) were female. The most frequent types of malignancy were: Leukemia, lung cancer, breast cancer, and colon cancer; the lowest frequency pertained to bladder, cerebellum, brain, uterine, and skin cancer. The mean minimum length of hospitalization of the patients was 1 day, and the maximum 21 days. In this study, no significant relationship was observed between the use of catheters and urinary infection, and Escherichia coli and Proteus were the most common bacterial infections in this category of patients. A significant relationship was observed between using a urinary catheter and the volume of excretion of RBC, WBC, and epithelial cells. A higher-than-normal WBC count alone does not confirm infection. Conclusion: Pathogens were the most common bacteria separated from the patients with malignancies in this research, which can have dangerous and fatal complications for the patient. It is therefore vital to monitor these patients for urinary infections.

Introduction: The liver is the body’s largest solid organ and receives a dual blood supply, making it an easy target for metastases from both extra-abdominal and abdominal lesions. In adults, the most common sites of primary lesions are the breast, colon, lung and pancreas. Liver biopsies are pivotal for managing patients with metastatic diseases, aiding in diagnosis and treatment planning. When primary cancer sites are undetectable, the diagnosis often falls under Carcinoma of Unknown Primary (CUP), which carries a poor prognosis. Immunohistochemistry (IHC) is critical in such cases, using antibodies to identify the cancer’s origin when other methods fail. This technique is vital for confirming known malignancies and diagnosing elusive ones, thus informing treatment and improving patient outcomes. Aim: To study the role of IHC in the categorisation of metastatic tumours of the liver. Material and Methods: A cross-sectional observational study was conducted in the Department of Pathology, Sri Aurobindo Medical College and Postgraduate (PG) Institute, Indore, Madhya Pradesh, India, between March 2021 and April 2024. Core needle biopsy samples of 65 cases were processed and analysed for Haematoxylin and Eosin (H&E) stain and IHC markers. Data on demographics and lesion characteristics were entered into Microsoft Excel and analysed with a trial version of Statistical Package for the Social Sciences (SPSS). Significance was assessed using Pearson’s Chi-square test, with a p-value

BACKGROUND: A considerable number of cancer patients are diagnosed following presentation at emergency department with symptoms related to their condition, yet research in this area remains scarce. This study aimed to identify the clinical characteristics and evaluate the health outcomes of patients who presented to the emergency department with symptoms of cancer. MATERIALS AND METHODS: We analyzed data for patients diagnosed with cancer postemergency department presentation at a tertiary care hospital between 2015 to 2021. Data on patient characteristics, clinical features, and health outcomes was abstracted through meticulous review of the patients’ medical record. SPPS was used for data analysis. Wilcoxon rank-sum test and Chi-square or Fisher’s exact test as appropriate, were used to determine statistical significance for continuous and categorical variables, respectively. Regression analysis determined factors associated with treatment and mortality. Kaplein-Meier analysis was performed to determine survival time. RESULTS: During the study period, 108 patients were diagnosed with new malignancies following acute medical admission. The median age of these patients was 67 years (interquartile range [IQR]: 56–75), and 58 (53.7%) of these patients were men. The most common presenting complaints were pain (55.6%), weight loss (44.4%), and poor appetite (36.1%). The median time from the onset of symptoms to hospital presentation was 30 days (IQR 8–62). The most common types of malignancies diagnosed in the study were hepatobiliary (18.5%), gastroesophageal (15.7%), and lung cancer (14.8%). Two-thirds of patients had Stage IV malignancy, and 64.81% presented with distant metastatic disease at the time of diagnosis. Older age (69 vs. 61.5 years; P = 0.04), lower level of general education and higher attainment (11.4% vs. 44.4%; P < 0.01), advanced malignancy stages (P < 0.01), and metastatic disease at diagnosis (75.4% vs. 44.4%; P = 0.01) were associated with higher mortality. CONCLUSION: Emergency presentations for newly diagnosed cancer, often seen in older patients with lower education and multiple comorbidities, were generally associated with poor survival rates owing to advanced disease with distant metastasis. Enhancing awareness of critical symptoms could improve early detection rates.

Cancer has higher incidence and mortality rates in men compared to women because of the sex genetics. Tumors and malignant diseases such as gallbladder, pancreas and liver cancers have poor prognosis which threaten the human lives. Conducive treatment strategies are thus required to improve men’s health. Herein, phenotypic screening of strains, bacteria and microbiomes by the mutational genomics is presented as novel therapeutic strategy. Mutant genomes can reduce toxicity, negative stress and sensitivity of the human body through genomic resetting and recombination. However, studies are lacking on microbial or genome-related therapeutics from the pharmacological perspective. This paper thus presents new strategies and directions in anticancer therapy including mutant genome-based human epidermal growth factor receptor 2 (HER2)/neu, vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR), mitogen-activated protein kinase (MAPK) rat sarcoma/rapidly accelerated fibrosarcoma/MAPK/ERK Kinase/extracellular signal-regulated kinase (RAS/RAF/MEK/ERK) pathway, phosphoinositide 3-Kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway, programmed death-1/programmed death-ligand 1 (PD-1/PD-L1), high tumor mutational burden (TMB) and immune checkpoint inhibitor (ICI) therapy. They are all relevant to human physiology. Moreover, strategies for treating aggressive tumors and preventive cancer are discussed along with the clinical case studies for future therapeutic applications.

Background: The treatment of psoriasis in patients with a personal history of cancer is a matter of debate and limited evidence is available to guide clinicians. Objectives: To report a multicenter real-life experience of a group of patients with psoriasis undergoing treatment with guselkumab and a history of cancer. Methods: We conducted a multicenter retrospective Spanish study enrolling patients with moderate-to-severe plaque psoriasis and neoplasia being treated with guselkumab for their psoriasis. Results: Twenty patients with moderate-to-severe psoriasis and at least 12 weeks of ongoing treatment were included. For the analysis, a 52 week follow-up period was evaluated in terms of efficacy and safety. Most of the malignancies in these patients were solid tumors. The percentage of patients achieving psoriasis area and severity index ≤3 at week 12 and week 52 was 80% and 87.5%, respectively, whereas 68.8% of patients achieved psoriasis area and severity index ≤1. A 52-week survival rate of 100% in the study population was observed (n = 20), including those patients with concomitant active cancers (n = 14). No adverse effects or dropouts related to guselkumab safety profile were detected. Limitations: Modest sample size and the retrospective nature of the study. Conclusion: Guselkumab not only demonstrates high effectiveness in treating psoriasis but also exhibits a favorable safety profile in patients with neoplasms.

Objective: There is an amelioration in mortality rates of septic shock patients with malignancies over time, but it remains uncertain in children. Therefore, the authors endeavored to compare the clinical characteristics, treatment needs, and outcomes of septic shock children with or without malignancies. Methods: The authors retrospectively analyzed the data of children admitted to the PICU due to septic shock from January 2015 to December 2022 in a tertiary pediatric hospital. The main outcome was in-hospital mortality. Results: A total of 508 patients were enrolled. The proportion of Gram-negative bacteria and fungal infections in children with malignancies was significantly higher than those without malignancies. Septic shock children with malignancies had a longer length of stay (LOS) in the hospital (21 vs. 11 days, p<0.001). However, there were no statistically significant differences in the LOS of PICU (5 vs. 5 days, p = 0.591), in-hospital mortality (43.0 % vs. 49.4 %, p = 0.276), and 28-day mortality (49.2 % vs. 44.7 %, p = 0.452). The 28-day survival analysis (p = 0.314) also showed no significant differences. Conclusion: Although there are significant differences in the bacterial spectrum of infections, the septic shock children with or without malignancies showed a similar mortality rate. The septic shock children with malignancies had longer LOS of the hospital. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to find if any significant correlation exists between C-reactive protein and Neutrophil to Lymphocyte Ratio as an indirect measure of inflammation. Methods: We selected 983 patients with any inflammatory condition who presented to a tertiary care hospital and were admitted in medical wards or Intensive Care Units (ICUs) of KRL Hospital Islamabad from December 2021 to December 2022. The study was a cross sectional study and convenience sampling was done. The patients were categorized into five groups depending upon their pathophysiology. Kolmogorov Smirnov test was used to assess the normality of the data, and Spearman’s coefficient was used to calculate the correlation between NLR and CRP. Results: A total of 983 patients were included. Mean CRP and NLR levels were 89.9±3.2 and 7.06±0.24, respectively. There was a significant positive correlation between CRP-NLR in the infectious, non-infectious non-inflammatory, and malignancy groups (0.420, 0.381, 0.642, p <0.01), and inflammatory group (0.322, p <0.05), and no correlation with chronic diseases. Conclusion: A significant correlation was shown to exist between CRP and NLR in patients with malignancies, noninfective non-inflammatory, inflammatory, and infective conditions and can therefore be used interchangeably to detect the presence of inflammation. Further exploration of these associations may contribute to a more nuanced understanding of the intricate relationships between different markers of inflammation and response to treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND: A considerable number of cancer patients are diagnosed following presentation at emergency department with symptoms related to their condition, yet research in this area remains scarce. This study aimed to identify the clinical characteristics and evaluate the health outcomes of patients who presented to the emergency department with symptoms of cancer. MATERIALS AND METHODS: We analyzed data for patients diagnosed with cancer postemergency department presentation at a tertiary care hospital between 2015 to 2021. Data on patient characteristics, clinical features, and health outcomes was abstracted through meticulous review of the patients' medical record. SPPS was used for data analysis. Wilcoxon rank-sum test and Chi-square or Fisher's exact test as appropriate, were used to determine statistical significance for continuous and categorical variables, respectively. Regression analysis determined factors associated with treatment and mortality. Kaplein-Meier analysis was performed to determine survival time. RESULTS: During the study period, 108 patients were diagnosed with new malignancies following acute medical admission. The median age of these patients was 67 years (interquartile range [IQR]: 56–75), and 58 (53.7%) of these patients were men. The most common presenting complaints were pain (55.6%), weight loss (44.4%), and poor appetite (36.1%). The median time from the onset of symptoms to hospital presentation was 30 days (IQR 8–62). The most common types of malignancies diagnosed in the study were hepatobiliary (18.5%), gastroesophageal (15.7%), and lung cancer (14.8%). Two-thirds of patients had Stage IV malignancy, and 64.81% presented with distant metastatic disease at the time of diagnosis. Older age (69 vs. 61.5 years; P = 0.04), lower level of general education and higher attainment (11.4% vs. 44.4%; P < 0.01), advanced malignancy stages (P < 0.01), and metastatic disease at diagnosis (75.4% vs. 44.4%; P = 0.01) were associated with higher mortality. CONCLUSION: Emergency presentations for newly diagnosed cancer, often seen in older patients with lower education and multiple comorbidities, were generally associated with poor survival rates owing to advanced disease with distant metastasis. Enhancing awareness of critical symptoms could improve early detection rates. [ABSTRACT FROM AUTHOR]

AbstractTriciribine (TCN) is a tricyclic nucleoside. Its synthesis was first described in 1971. Subsequent studies have indicated that TCN plays a role in inhibiting DNA synthesis and was revealed to possess a higher selectivity for Akt. Although a single dose of TCN demonstrated limited activity in solid tumors at the clinical level, combinations of TCN with various agents, such as specific inhibitors, tyrosine kinase inhibitor dasatinib, ErbB inhibitor tipifarnib, IGF1-R inhibitor NVP-AEW541, mTORC1 inhibitor RAD-001, TNF-related apoptosis-inducing ligand, PPARγ agonist, 1,25(OH)2D3, gemcitabine, and paclitaxel, have been reported to be efficient against various malignancies such as pancreatic, breast, prostate cancer, insulinoma, gut neuroendocrine tumor, and hepatocellular carcinoma at the preclinical level. Other than malignancies, through Akt inhibition activity, TCN has also been demonstrated potential for treating lung injuries, including those encountered in COVID-19 infections. [ABSTRACT FROM AUTHOR]

We analyzed data on pediatric invasive fungal diseases of the central nervous system (CNS-IFDs) reported by five of a total of eight Pediatric Hematology-Oncology Departments in Greece for 16 years (2007–2022). A total of twelve patients (11 boys, median age: 9.5 years, range: 2–16) were reported suffering from CNS-IFDs. The underlying malignancy was acute lymphoblastic leukemia in 9/12 and acute myeloid leukemia, Ewing sarcoma, and rhabdomyosarcoma in one each. Eleven patients presented with CNS-related symptoms (i.e., seizures, headache, cerebral palsy, ataxia, hallucination, seizures, blurred vision, amaurosis). All patients had pathological MRI findings. Multifocal fungal disease was observed in 6/12 patients. Nine proven and three probable CNS-IFD cases were diagnosed. Causative pathogens in proven cases were Aspergillus spp. and Candida albicans (n = 2 each), Mucor spp., Rhizopus arrhizus, Absidia spp., Fusarium oxysporum and Cryptococcus neoformans (n = 1 each). Causative pathogens in probable cases were Aspergillus spp. (n = 2) and Candida spp. (n = 1). All patients received appropriate antifungal therapy (median duration: 69.5 days, range 19–364). Two patients underwent additional surgical treatment. Six patients were admitted to the Intensive Care Unit due to complications. Three patients (25%) died, two due to IFD and one due to an underlying disease. Early recognition and prompt intervention of CNS-IFDs may rescue the patients and improve overall survival. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) and cancer are the two leading causes of death worldwide. Given their high prevalence, it is important to understand the disease burden of cancer mortality in CVD patients. Objective: We aimed to evaluate whether patients with incident CVD have a higher risk of malignancy‐related mortality, compared to the general population without CVD. Methods: We performed a national population‐based cohort study selecting patients with incident CVD in the Netherlands between 01 April 2000 and 31 December 2005. A reference cohort was selected from the Dutch population using age, sex and ethnicity. Mortality follow‐up data were evaluated after data linkage of national registries from Statistics Netherlands until 31 December 2020. Results: A total of 2,240,879 individuals were selected with a mean follow‐up of 12 years (range 0.4–21.0), of which 738,666 patients with incident CVD with a mean age of 71 ± 15 years. Malignancy mortality per 1000 person years was 84 for the reference group and 118 for patients with CVD, with the highest rate of 258 in patients with heart failure. Patients with CVD had a higher malignancy mortality risk, compared to the reference group: HR 1.35 (95%CI 1.33–1.36). Highest risks were observed in patients with venous diseases (HR 2.27, 95%CI 2.17–2.36) and peripheral artery disease (HR 1.87, 95%CI 1.84–2.01). Conclusion: Results show that CVD predisposes to a higher cancer mortality rate. Of all CVD subtypes, HF patients have the highest cancer mortality rate and the hazards were highest in patients with venous diseases and peripheral artery disease. [ABSTRACT FROM AUTHOR]

Background: Cancer is widely recognized as a prominent contributor to global mortality due to factors such as delayed diagnosis, unfavorable prognosis, and high likelihood of recurrence. FGD5 transcription factor G antisense RNA 1 (FGD5-AS1), a newly identified long non-coding RNA, has emerged as a promising prognostic biomarker, for malignancy prognosis. This meta-analysis aimed to assess the prognostic significance of FGD5-AS1 in various carcinomas. Methods: A systematic search was performed through five electronic databases to identify studies that investigating the role of FGD5-AS1 expression as a prognostic factor in carcinomas. The value of FGD5-AS1 in malignancies was estimated by odds ratios (ORs) and hazard ratios (HRs) with a corresponding 95% confidence intervals (CIs). Furthermore, the GEPIA database was used to further supplement our results. Results: This analysis included 12 studies with 642 cases covering eight cancer types. High FGD5-AS1 expression exhibited a significant correlation with poor overall survival(OS) (HR = 2.04, 95%CI [1.72, 2.42], P < 0.00001), advanced tumor stage (OR = 3.47, 95%CI [2.34, 5.14], P < 0.00001), lymph node metastasis(LNM) (OR = 1.79, 95% CI [1.20,2.67], P = 0.004), and larger tumor size (OR= 5.25, 95%CI [2.68, 10.30], P < 0.00001). Furthermore, the FGD5-AS1 expression was notably upregulated in six types of malignancies as verified using the GEPIA online gene analysis tool. Conclusions: The findings of this meta-analysis indicated that high FGD5-AS1 expression was significantly associated with poor prognosis in diverse cancer types, suggesting that FGD5-AS1 may be a promising biomarker for predicting cancer prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Kidney diseases frequently complicate cancer and its treatment, contributing to both morbidity and mortality. Malignancies can give rise to various kidney issues, such as glomerulonephritis and Chronic Kidney Disease (CKD). This association operates bidirectionally, with patients experiencing the development of renal diseases due to cancer, and CKD predisposing to cancer. Furthermore, nephrotoxicity induced by chemotherapy can result in Acute Tubular Injury (ATI) and necrosis, imposing limitations on its application. Aim: To evaluate the spectrum of renal pathology in autopsies of malignancies. Materials and Methods: This was a retrospective cross-sectional study of complete autopsies of all cases of malignancies performed in the Department of Pathology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India. The study was carried out over a 5-year period from January 2015 to December 2019. Analysis of cases with respect to demographics, type of primary malignancy, gross and microscopic features, and the final cause of death was conducted. These findings were meticulously tabulated, with frequencies and percentages calculated for each category. Results: A total of 4392 autopsies were conducted throughout the study period, with 120 of them revealing the presence of malignancies. A total of 38 (31.6%) malignancies were diagnosed for the first time at autopsy. The commonest renal findings on gross were scars (superficial and deep) seen in 40 (33.33%), followed by cortical cysts in 25 (20.83%), granular contracted kidney in 15 (12.50%), mass lesions in 7 (5.83%), abscesses in 7 (5.83%), and swollen, oedematous kidneys in 6 (5%) autopsies. The most frequent renal pathology on microscopy were infective lesions seen in 43 (35.83%), Acute Tubular Necrosis (ATN) in 32 (26.66%), ATI in 30 (25%), followed by malignancies- primary and secondary in 11 (9.16%), tubular casts in 6 (5%), etc. Rare findings included membranous glomerulonephritis and Tumour Lysis Syndrome (TLS) (Acute urate nephropathy) in 1 (0.83%) each. The TLS case had classic histomorphological features of TLS, apart from laboratory parameters. Extensive deposits of uric acid crystals were seen obstructing the tubules as well as some of the glomeruli on microscopy. Conclusion: In one-third of the cases, the malignancy was exclusively discovered during the autopsy. The study revealed a diverse array of lesions, encompassing pyelonephritis, ATN, primary and metastatic renal tumours, cast nephropathy, membranous glomerulonephritis, and TLS. One-fifth of the cases had end-stage renal disease (advanced renal disease). A significant number of the cases exhibited tumour masses within the kidneys. One-fifth of the cases had renal pathology contributing to the final cause of death, further highlighting the association between malignancies and renal pathology.

To analyze the Big Three diagnostic errors (malignant neoplasms, cardiovascular diseases, and infectious diseases) through internists' self-reflection on their most memorable diagnostic errors. This secondary analysis study, based on a web-based cross-sectional survey, recruited participants from January 21 to 31, 2019. The participants were asked to recall the most memorable diagnostic error cases in which they were primarily involved. We gathered data on internists' demographics, time to error recognition, and error location. Factors causing diagnostic errors included environmental conditions, information processing, and cognitive bias. Participants scored the significance of each contributing factor on a Likert scale (0, unimportant; 10, extremely important). The Big Three comprised 54.1 % (n=372) of the 687 cases reviewed. The median physician age was 51.5 years (interquartile range, 42–58 years); 65.6 % of physicians worked in hospital settings. Delayed diagnoses were the most common among malignancies (n=64, 46 %). Diagnostic errors related to malignancy were frequent in general outpatient settings on weekdays and in the mornings and were not identified for several months following the event. Environmental factors often contributed to cardiovascular disease-related errors, which were typically identified within days in emergency departments, during night shifts, and on holidays. Information gathering and interpretation significantly impacted infectious disease diagnoses. The Big Three accounted for the majority of cases recalled by Japanese internists. The most relevant contributing factors were different for each of the three categories. Addressing these errors may require a unique approach based on the disease associations. [ABSTRACT FROM AUTHOR]

A recently discovered type of copper-driven cell death is regarded as Cuproptosis. The significance of copper and copper-triggered cell death in the development of malignancies has garnered attention recently. Cuproptosis has shown remarkable promise for cancer therapy, which has sparked a great deal of interest in the cancer research community. Treatments based on copper have the potential to treat malignancies that are resistant to chemotherapy by impeding the growth of the tumor. We offer a critical examination of copper homeostasis and the part copper dysregulation plays in the onset and spread of cancer in this review. After outlining the fundamental molecular underpinnings of Cuproptosis and its connection to cancer, the present state of knowledge regarding copper-based cancer treatment agents - copper chelators, copper ionophores, and copper complexes-based dynamic therapy is summarized. We also provide an overview of the latest research on the use of copper ionophores and complexes-based medicines to reduce tumor treatment resistance in various cancer types. We also go over the small-molecule substances and nanoparticles (NPs) that have the potential to induce Cuproptosis in cancer cells, which will provide fresh insight into the future development of Cuproptosisinducing anticancer medications. Ultimately, the key ideas and urgent issues surrounding Cuproptosis that need to be addressed in further research were covered. Targeting Cuproptosis may be a potential anticancer therapy and treatment approach to overcome drug resistance in cancer, according to this review article. [ABSTRACT FROM AUTHOR]

Introduction: Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder, characterized by microcephaly, immunodeficiency, and impaired DNA repair. NBS is most prevalent among Slavic populations, including Ukraine. Our study aimed to comprehensively assess the prevalence, diagnosis, clinical data, immunological parameters, and treatment of NBS patients in Ukraine. Methods: We conducted a retrospective review that included 84 NBS patients from different regions of Ukraine who were diagnosed in 1999-2023. Data from the Ukrainian Registry of NBS and information from treating physicians, obtained using a developed questionnaire, were utilized for analysis. Results: Among 84 NBS patients, 55 (65.5%) were alive, 25 (29.8%) deceased, and 4 were lost to follow-up. The median age of patients was 11 years, ranging from 1 to 34 years. Most patients originate from western regions of Ukraine (57.8%), although in recent years, there has been an increase in diagnoses from central and southeastern regions, expanding our knowledge of NBS prevalence. The number of diagnosed patients per year averaged 3.4 and increased from 2.7 to 4.8 in recent years. The median age of NBS diagnosis was 4.0 years (range 0.1-16) in 1999-2007 and decreased to 2.7 in the past 6 years. Delayed physical development was observed in the majority of children up to the age of ten years. All children experienced infections, and 41.3% of them had recurrent infections. Severe infections were the cause of death in 12%. The second most common clinical manifestation of NBS was malignancies (37.5%), with the prevalence of lymphomas (63.3%). Malignancies have been the most common cause of death in NBS patients (72% of cases). Decreased levels of CD4+ and CD19+ were observed in 89.6%, followed by a reduction of CD3+ (81.8%) and CD8+ (62.5%). The level of NK cells was elevated at 62.5%. IgG concentration was decreased in 72.9%, and IgA - in 56.3%. Immunoglobulin replacement therapy was administered to 58.7% of patients. Regular immunoglobulin replacement therapy has helped reduce the frequency and severity of severe respiratory tract infections. Conclusion: Improvements in diagnosis, including prenatal screening, newborn screening, monitoring, and expanding treatment options, will lead to better outcomes for NBS patients. [ABSTRACT FROM AUTHOR]

Background: Bronchoalveolar lavage (BAL) is a widely used diagnostic procedure in pulmonology, yet its utility across diverse pulmonary conditions warrants further evaluation. Methods: This prospective study involved 47 patients suspected of having pulmonary diseases, where conventional diagnostics were inconclusive. BAL was performed to diagnose infections, interstitial lung diseases (ILDs), and malignancies, with subsequent analysis for sensitivity, specificity, and diagnostic yield. Results: BAL identified tuberculosis in 15 cases (31.9%), bacterial pneumonia in 10 (21.3%), fungal infections in 2 (4.3%), ILDs in 5 (10.6%), and malignancies in 6 (12.8%). The procedure demonstrated high diagnostic accuracy with sensitivity and specificity rates notably high across conditions: tuberculosis (88.2%, 97.0%; p<0.001), bacterial pneumonia (76.9%, 98.5%; p<0.001), fungal infections (66.7%, 99.0%; p=0.005), ILDs (83.3%, 96.7%; p=0.001), and malignancies (85.7%, 97.5%; p<0.001). Conclusion: The study highlights BAL's substantial diagnostic value in pulmonary diseases, reinforcing its role in enhancing diagnostic accuracy and informing therapeutic strategies. BAL emerges as an indispensable tool in the early detection and management of complex lung diseases. [ABSTRACT FROM AUTHOR]

Introduction: Kidney diseases frequently complicate cancer and its treatment, contributing to both morbidity and mortality. Malignancies can give rise to various kidney issues, such as glomerulonephritis and Chronic Kidney Disease (CKD). This association operates bidirectionally, with patients experiencing the development of renal diseases due to cancer, and CKD predisposing to cancer. Furthermore, nephrotoxicity induced by chemotherapy can result in Acute Tubular Injury (ATI) and necrosis, imposing limitations on its application. Aim: To evaluate the spectrum of renal pathology in autopsies of malignancies. Materials and Methods: This was a retrospective crosssectional study of complete autopsies of all cases of malignancies performed in the Department of Pathology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India. The study was carried out over a 5-year period from January 2015 to December 2019. Analysis of cases with respect to demographics, type of primary malignancy, gross and microscopic features, and the final cause of death was conducted. These findings were meticulously tabulated, with frequencies and percentages calculated for each category. Results: A total of 4392 autopsies were conducted throughout the study period, with 120 of them revealing the presence of malignancies. A total of 38 (31.6%) malignancies were diagnosed for the first time at autopsy. The commonest renal findings on gross were scars (superficial and deep) seen in 40 (33.33%), followed by cortical cysts in 25 (20.83%), granular contracted kidney in 15 (12.50%), mass lesions in 7 (5.83%), abscesses in 7 (5.83%), and swollen, oedematous kidneys in 6 (5%) autopsies. The most frequent renal pathology on microscopy were infective lesions seen in 43 (35.83%), Acute Tubular Necrosis (ATN) in 32 (26.66%), ATI in 30 (25%), followed by malignancies- primary and secondary in 11 (9.16%), tubular casts in 6 (5%), etc. Rare findings included membranous glomerulonephritis and Tumour Lysis Syndrome (TLS) (Acute urate nephropathy) in 1 (0.83%) each. The TLS case had classic histomorphological features of TLS, apart from laboratory parameters. Extensive deposits of uric acid crystals were seen obstructing the tubules as well as some of the glomeruli on microscopy. Conclusion: In one-third of the cases, the malignancy was exclusively discovered during the autopsy. The study revealed a diverse array of lesions, encompassing pyelonephritis, ATN, primary and metastatic renal tumours, cast nephropathy, membranous glomerulonephritis, and TLS. One-fifth of the cases had end-stage renal disease (advanced renal disease). A significant number of the cases exhibited tumour masses within the kidneys. One-fifth of the cases had renal pathology contributing to the final cause of death, further highlighting the association between malignancies and renal pathology. [ABSTRACT FROM AUTHOR]

Background: With the emergence of cytotoxic T lymphocyte‐associated protein‐4 (CTLA‐4) inhibitors, the outcomes of patients with malignant tumors have improved significantly. However, the incidence of cardiovascular adverse events has also increased, which can affect tumor treatment. In this study, we evaluated the incidence and severity of adverse cardiovascular events caused by CTLA‐4 inhibitors by analyzing reported trials that involved CTLA‐4 inhibitor therapy. Methods: Randomized clinical trials published in English from January 1, 2013, to November 30, 2022, were searched using the Cochrane Library and PubMed databases. All included trials examined all grade and grades 3–5 cardiac and vascular adverse events. These involved comparisons of CTLA‐4 inhibitors to placebo, CTLA‐4 inhibitors plus chemotherapy to chemotherapy alone, CTLA‐4 inhibitors combined with PD‐1/PD‐L1 inhibitors to PD‐1/PD‐L1 inhibitors alone, and CTLA‐4 inhibitors plus target agent to PD‐1/PD‐L1 inhibitors plus target agent. The odds ratio (OR) and corresponding 95% confidence intervals (CIs) were calculated using the Mantel‐Haenszel method. Results: Overall, 20 trials were included. CTLA‐4 inhibitors significantly increased the incidence of all‐grade cardiovascular toxicity (OR = 1.33, 95% CI: 1.00–1.75, p = 0.05). The incidence of all‐grade cardiovascular toxicity increased in malignant tumor patients who received single‐agent CTLA‐4 inhibitors (OR = 1.73, 95% CI: 1.13–2.65, p = 0.01), as well as the incidence rate of grades 3–5 cardiovascular adverse events (OR = 2.00, 95% CI: 1.08–3.70, p = 0.03). Compared with the non‐CTLA‐4 inhibitor group, CTLA‐4 inhibitors plus chemotherapy, PD‐1/PD‐L1 inhibitors, or target agent did not significantly affect the incidence of cardiac and vascular toxicity. The incidence of grades 3–5 cardiac failure, hypertension, pericardial effusion, myocarditis, and atrial fibrillation were much higher among patients exposed to CTLA‐4 inhibitor, but the data were not statistically significant. Conclusion: Our findings suggest that the incidence rate of all cardiovascular toxicity and severe cardiovascular toxicity increased in patients who were administered CTLA‐4 inhibitors. In addition, the risk of serious cardiovascular toxic events was independent of the type of adverse event. From these results, physicians should assess the benefits and risks of CTLA‐4 inhibitors when treating malignancies. [ABSTRACT FROM AUTHOR]

At the beginning of the eighteenth century, most physicians recognized cancer as an aggressive process that gradually spreads, leading to cachexia and death. Thyroid malignancies had long been underestimated because the majority of the population of West Europe suffered from diffuse goiters that masked malignant processes in the neck. Moreover, the life expectancy at that time was very low (about 37-40 years), so the majority of people died of other causes before metastatic thyroid cancer could develop and manifest. Nevertheless, in 1817, French dermatologist Jean Louis Alibert described the first case of a malignant tumor involving the thyroid gland. From the 1820s the number of case reports describing thyroid cancer increased. Even though Jean Claude Recamier described metastases in 1829, secondary lesions on various organs in patients with thyroid malignancies were not themselves considered malignant until 1876. [ABSTRACT FROM AUTHOR]

Disease-modifying anti-rheumatic drugs (DMARDs) have improved the outcomes of patients with rheumatoid arthritis (RA). DMARDs are classified into three categories: conventional synthetic DMARDs, biological DMARDs (including biosimilars), and targeted synthetic DMARDs. DMARDs, by way of their effect on the immune system, are associated with increased risk of adverse events, including infections, malignancies, cardiovascular disease, gastrointestinal perforations, and other less common events. In this narrative literature review performed with searches of the PubMed database from 1 January 2010 through 1 January 2023, we compare the risk of safety events between DMARDs using data from both randomized clinical trials and observational studies. DMARD use in RA is associated with higher rates of serious infections, tuberculosis reactivation, opportunistic infections, and possibly malignancies. Specific biologic DMARDs and higher doses are associated with elevated risks of various adverse events (gastrointestinal perforations, thromboembolism, serious infection). Shared decision-making is paramount when choosing a treatment regimen for patients based on their own comorbidities. JAKi are the newest class of medications used for RA with robust safety data provided in clinical trials. However, more real-world evidence and phase-IV pharmacovigilance data are needed to better understand comparative safety profile of DMARDs in RA. [ABSTRACT FROM AUTHOR]

Background: Eswatini has a high HIV prevalence in adults and, despite being one of the first countries to achieve the UNAIDS 95-95-95 targets, AIDS-related deaths are still high. Objectives: This study describes the causes of death among people living with HIV (PLHIV) receiving care at five clinics in Eswatini. Method: A cross-sectional review of sociodemographic, clinical and mortality data of deceased clients who received care from 01 January 2021 to 30 June 2022, was conducted. Data were extracted from the deceased clients’ clinical records, and descriptive and comparative analysis was performed. Results: Of 257 clients, 52.5% (n = 135) were male, and the median age was 47 years (interquartile range [IQR]: 38, 59). The leading causes of death were non-communicable diseases (NCDs) (n = 59, 23.0%), malignancies (n = 37, 14.4%), COVID-19 (n = 36, 14.0%), and advanced HIV disease (AHD) (n = 24, 9.3%). Clients who had been on antiretroviral therapy (ART) for 12–60 months (OR: 0.01; 95% confidence interval [CI]: 0.0006, 0.06) and 60 months (OR: 0.006; 95% CI: 0.0003, 0.029) had lower odds of death from AHD compared to those on ART for 12 months. Clients aged ≥ 40 years had higher odds of dying from COVID-19, while female clients (OR: 2.64; 95% CI: 1.29, 5.70) had higher odds of death from malignancy. Conclusion: Most clients who died were aged 40 years and above and died from NCD-related causes, indicating a need to integrate prevention, screening, and treatment of NCDs into HIV services. Specific interventions targeting younger PLHIV will limit their risk for AHD.

Multiple studies have demonstrated the importance of androgen receptor (AR) splice variants (SVs) in the progression of prostate cancer to the castration-resistant phenotype and their utility as a diagnostic. However, studies on AR expression in non-prostatic malignancies uncovered that AR-SVs are expressed in glioblastoma, breast, salivary, bladder, kidney, and liver cancers, where they have diverse roles in tumorigenesis. AR-SVs also have roles in non-cancer pathologies. In granulosa cells from women with polycystic ovarian syndrome, unique AR-SVs lead to an increase in androgen production. In patients with nonobstructive azoospermia, testicular Sertoli cells exhibit differential expression of AR-SVs, which is associated with impaired spermatogenesis. Moreover, AR-SVs have been identified in normal cells, including blood mononuclear cells, neuronal lipid rafts, and the placenta. The detection and characterization of AR-SVs in mammalian and non-mammalian species argue that AR-SV expression is evolutionarily conserved and that AR-SV-dependent signaling is a fundamental regulatory feature in multiple cellular contexts. These discoveries argue that alternative splicing of the AR transcript is a commonly used mechanism that leads to an expansion in the repertoire of signaling molecules needed in certain tissues. Various malignancies appropriate this mechanism of alternative AR splicing to acquire a proliferative and survival advantage.

Shasha Zhang,1,&ast; Jianhua Wu,2,&ast; Yue Zhao,3 Jingjing Zhang,1 Xiaoyun Zhang,1 Chensi Wu,3 Zhidong Zhang,4 Zhanjun Guo1 1Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China; 2Animal Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China; 3Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China; 4Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhidong Zhang, Department of Surgery, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, People’s Republic of China, Email zzd407@163.com Zhanjun Guo, Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, People’s Republic of China, Tel +86 311 86095734, Email zjguo5886@aliyun.comPurpose: Immune checkpoint inhibitors (ICIs) have significantly improved the outcomes of patients with cancer; however, these agents may initiate immune-related adverse events (irAEs). Previous studies have demonstrated a robust correlation between disease prognosis and the occurrence of irAEs, specifically skin or endocrine irAEs. Herein, we aimed to evaluate the correlation between irAE-related adrenal insufficiency (AI) and ICI treatment efficacy.Patients and methods: Patients diagnosed with gastrointestinal, respiratory, head and neck, urological, skin and gynecologic cancers treated with anti-programmed cell death 1 (PD-1)/anti-programmed cell death ligand 1 (PD-L1) antibody as monotherapy or combined therapy (combined with chemotherapy or targeted therapy) were divided into irAE-A (patients with irAE-related AI), irAE-B (patients with other irAEs) and non-irAE groups. Immunotherapy efficacy was assessed based on the disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Survival probabilities were estimated using the Kaplan–Meier method with the log–rank test.Results: Of the 192 patients enrolled in our study, 17 developed irAE-related AI and 83 developed other irAEs. The DCR of the irAE-A and irAE-B groups were higher than that of the non-irAE group (P< 0.05). Multiple extended Cox regression analyses showed that irAE status (irAE-A vs non-irAE, P=0.008; irAE-B vs non-irAE, P=0.020), Eastern Cooperative Oncology Group (ECOG) status (P=0.045), tumor-node-metastasis (TNM) stage (P=0.000), and treatment line (P=0.002) were independent predictors of PFS. Contrarily, irAE status (irAE-A vs non-irAE, P=0.009; irAE-B vs non-irAE, P=0.013), ECOG status (P=0.007), TNM stage (P=0.035), treatment line (P=0.001) and treatment modality (P=0.008) were independent predictors for OS.Conclusion: IrAE-related AI was significantly associated with ICI treatment efficacy in patients with cancer, which could be a potentially predictable marker. Due to the destruction of adrenal tissue by T cells with enhanced activity, AI reflects enhanced T cell activity to some extent.Keywords: endocrine adverse event, malignancies, monoclonal antibody therapy, immune-related side effects, treatment efficacy

Background and Objectives: The incidence and prevalence of cancers are increasing worldwide, with special emphasis placed on prevention, early detection, and the development of new therapeutic strategies that strongly impact patient outcomes. Limited data are available about emergency care’s role in treating patients with cancer. This study aims to determine the burden of end-stage and first-time diagnosis of cancer on emergency care in a high-turnover emergency care center. Materials and Methods: A retrospective observational study was conducted to identify patients requesting emergent aid for cancer-related symptoms in the Emergency Department of “St. Spiridon” Hospital from Iasi (Romania) between 1 October 2022 and 30 September 2023. The proportion and demographic characteristics of end-stage patients and those who received a first-time diagnosis during the emergency visit were evaluated. Risk analysis was performed to understand these patients’ care needs (such as medical care, surgical care, specialty consults, intensive care, ward admission, and other hospital transfers) and immediate care outcomes (such as in-hospital mortality and home discharge). Results: 2318 patients with cancer requested emergent care (patient presentation rate of 3.08%), of which 444 (19.15%) were diagnosed for the first time, and 616 (26.57%) were at the end-stage. First-time diagnosed patients had a significantly different distribution of cancer types (p < 0.001), were more likely to need any form of medical care, to require a specialty consultation, or to be admitted to a ward (OR 2.65, 95% CI: 2.12–3.32; p < 0.001; OR 3.28, 95% CI: 2.48–4.35, p < 0.001; OR 2.09, 95% CI: 1.70–2.59; p < 0.001, respectively) but were less severe, while end-stage patients were more likely to address repeatedly to the emergency room (OR 1.86, 95% CI: 1.32–2.59; p = 0.001) and had higher odds of needing intensive care, assisted ventilation and death (OR-4.63, 95% CI: 1.10–19.45, p = 0.04; OR 2.59, 95% CI: 1.57–4.28; p < 0.001, and OR 4.06, 95% CI: 1.73–9.54; p = 0.001, respectively). Conclusions: The emergency department often carries the weight of diagnosing patients with cancer and treating patients with end-stage disease. These data highlight the importance of prehospital care, particularly for cancer screening and palliative care, and the importance of fostering multidisciplinary collaboration in the emergency room with oncologists, geriatricians, and palliative care specialists to improve patient outcomes.

Background and Objectives: Hepatitis C virus (HCV) infection is a major global public health concern, particularly in hemodialysis (HD) patients. This study aims to evaluate the demographic, clinical, and laboratory characteristics of HCV-positive patients undergoing HD and assess the long-term impact of direct-acting antivirals (DAAs) on patient outcomes. Moreover, a narrative review aims to summarize the current knowledge regarding HCV treatment in HD patients. The search in the PubMed, Google Scholar, and Scopus databases identified 48 studies relevant to our topic, 18 regarding clinical history and 29 related to HCV treatment. Methods: A retrospective analysis was performed on 165 HD patients from Bihor County HD centers, Romania, between 2014 and 2024. The cohort was divided into two groups: 54 patients who tested positive for HCV and 111 controls who were HCV-negative. Data collected from GPs included demographic information, comorbidities, laboratory parameters, and psychological assessments. Outcomes were evaluated at over 5 years after DAA treatment. A literature review was conducted using PubMed and Google Scholar to identify relevant studies on HCV in HD patients from 1989 to 2024. Results: Laboratory results showed similar parameters across groups, except for lower serum cholesterol levels in the HCV-positive DAA-treated group vs. HCV-positive non-treated ones (155.607 mg% vs. 170.174 mg%, p = 0.040) and increased ALT levels when comparing the same groups (29.107 vs. 22.261, p = 0.027), whereas comorbidities did not differ significantly. The incidence of malignancies was significantly higher among HCV-positive compared to HCV-negative patients (20.3% vs. 8.1%, p = 0.023), mainly among those treated with DAAs, highlighted by the multivariate analysis. Cardiovascular disease remains the leading cause of mortality regardless of HCV status or the use of antiviral therapy. Psychological assessments revealed more severe depression in HCV-positive patients compared to their HCV-negative counterparts. Conclusions: HCV infection in the hemodialysis population typically follows a subclinical course. At over five years after DAA therapy, the results indicate a stabilization of the liver function and the absence of major complications. However, the incidence of malignancies remains high in HCV-positive patients.

This document provides a list of references to studies and articles related to CAR-T cell therapy for various types of lymphoma and multiple myeloma. The studies mentioned discuss the outcomes, safety, and efficacy of CAR-T cell therapies such as lisocabtagene maraleucel, axicabtagene ciloleucel, brexucabtagene autoleucel, ciltacabtagene autoleucel, and idecabtagene vicleucel. The document also includes references to studies that discuss the potential risk of secondary malignancies and other long-term effects associated with CAR-T cell therapy. [Extracted from the article]

Simple Summary: Myelofibrosis is a rare bone marrow disorder, leading to an increasing failure to generate healthy blood cells. Defining clinical prognosis scores for rare diseases is difficult, as sufficient numbers of patients for score validation are difficult to obtain. The current study investigates the utility of the TriNetX database, containing electronic medical records for over 140 million patients, to identify risk factors and establish clinical scores. TriNetX includes more than 64,000 myelofibrosis patients, and the present study explores factors influencing survival and common complications. Age over 65, anemia, an increased number of leukocytes, a low platelet count and an increased number of monocytes are associated with increased risks, while high numbers of eosinophiles and basophiles show positive associations. We demonstrate that the TriNetX database offers insights to refine predictive models, crucial for tailoring treatments to individual patient risks in the complex landscape of rare diseases like myelofibrosis. Myelofibrosis (MF) is a myeloproliferative neoplasia arising de novo as primary myelofibrosis (PMF) or secondary to polycythemia vera or essential thrombocythemia. Patients experience a high symptom burden and a marked reduction in life expectancy. Despite progress in molecular understanding and treatment, the clinical and prognostic heterogeneity of MF complicates treatment decisions. The International Prognostic Scoring System (IPSS) integrates clinical factors for risk stratification in MF. This study leverages the TriNetX database with more than 64,000 MF patients to assess the impact of accessible parameters on survival and complicating events, including AML transformation, cachexia, increased systemic inflammation, thrombosis and hemorrhage. Age over 65 years correlated with increased risks of death, AML transformation, thrombosis and hemorrhage. Anemia (Hb < 10 g/dL), leukocytosis (>25 × 103/µL) and thrombocytopenia (<150 × 103/µL) reduced survival and increased risks across all assessed events. Monocytosis is associated with decreased survival, whereas eosinophilia and basophilia were linked to improved survival. Further, as proof of concept for the applicability of TriNetX for clinical scores, we devised a simplified IPSS, and confirmed its value in predicting outcomes. This comprehensive study underscores the importance of age, anemia, leukocytosis and thrombocytopenia in predicting disease trajectory and contributes to refining prognostic models, addressing the challenges posed by the disease's heterogeneity. [ABSTRACT FROM AUTHOR]

Objectives Patients with SLE have an increased risk of comorbidities and impaired survival. We aimed to assess whether various thresholds of oral CS (OCS) can predict development of infections, comorbidities, malignancies and survival in SLE using data from national health registries in Sweden. Methods All incident SLE cases, age >18 years, in Sweden (n  = 5309) between 2005 and 2020 and matched population controls (n  = 26 545) were included and followed until 2020, a total of 257 942 patient years. Data from national registers were retrieved including information from the National Prescribed Drug Register. Risk factors were analysed using time-dependent Cox regression models. Results Compared with no OCS, >0 to <5.0 mg/day, 5.0–7.5 mg/day as well as >7.5 mg/day OCS predicted development of infections (pneumonia, influenza, herpes zoster and urinary tract infection), osteoporosis, osteonecrosis, gastroduodenal ulcers, cataracts, hypertension and mortality (all P  < 0.05). OCS >0 to <5.0 mg/day was associated with lower hazard ratios for these comorbidities than higher doses of OCS. Fifteen years after diagnosis, 48% of patients were taking OCS at a median dose of 5.7 mg/day. A small reduction of OCS treatment 5 years after diagnosis in patients diagnosed with SLE 2006–10 compared with 2011–15 was observed, 49% vs 46% respectively (P  = 0.039). Conclusion Results highlight the potential harm associated with even low OCS dose treatment in SLE and the need to judiciously use OCS at the lowest possible dose to maximize efficacy and minimize harm. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infection is one of the most common diseases in patients with cancer, making them at risk of developing opportunistic infections. Materials and Methods: A total of 110 samples from cancer patients admitted to Baqaei 2 Hospital in Ahvaz, including 55 chil-dren with malignancies and 55 adult patients, were included in the study. A questionnaire was completed with demographic items such as age, gender, type of malignancy, length of hospitalization, duration of chemotherapy and type of urinary tract infection along with an antibiogram susceptibility test (disc diffusion). Results: The mean age of the adult patients was 40.43±25.3 years, and the children 14.56±4.63 years. A total of 56 patients (50.9%) were male and 54 (49.1%) were female. The most frequent types of malignancy were: Leukemia, lung cancer, breast cancer, and colon cancer; the lowest frequency pertained to bladder, cerebellum, brain, uterine, and skin cancer. The mean minimum length of hospitalization of the patients was 1 day, and the maximum 21 days. In this study, no significant relationship was observed between the use of catheters and urinary infection, and Escherichia coli and Proteus were the most common bacterial infections in this category of patients. A significant relationship was observed between using a urinary catheter and the volume of excretion of RBC, WBC, and epithelial cells. A higher-than-normal WBC count alone does not confirm infection. Conclusion: Pathogens were the most common bacteria separated from the patients with malignancies in this research, which can have dangerous and fatal complications for the patient. It is therefore vital to monitor these patients for urinary infections. [ABSTRACT FROM AUTHOR]