VHL mutation drives human clear cell renal cell carcinoma progression through PI3K/AKT-dependent cholesteryl ester accumulation.

BACKGROUND: Cholesteryl ester (CE) accumulation in intracellular lipid droplets (LDs) is an essential signature of clear cell renal cell carcinoma (ccRCC), but its molecular mechanism and pathological significance remain elusive. METHODS: Enabled by the label-free Raman spectromicroscopy, which integrated stimulated Raman scattering microscopy with confocal Raman spectroscopy on the same platform, we quantitatively analyzed LD distribution and composition at the single cell level in intact ccRCC cell and tissue specimens in situ without any processing or exogenous labeling. Since we found that commonly used ccRCC cell lines actually did not show the CE-rich signature, primary cancer cells were isolated from human tissues to retain the lipid signature of ccRCC with CE level as high as the original tissue, which offers a preferable cell model for the study of cholesterol metabolism in ccRCC. Moreover, we established a patient-derived xenograft (PDX) mouse model that retained the CE-rich phenotype of human ccRCC. FINDINGS: Surprisingly, our results revealed that CE accumulation was induced by tumor suppressor VHL mutation, the most common mutation of ccRCC. Moreover, VHL mutation was found to promote CE accumulation by upregulating HIFα and subsequent PI3K/AKT/mTOR/SREBPs pathway. Inspiringly, inhibition of cholesterol esterification remarkably suppressed ccRCC aggressiveness in vitro and in vivo with negligible toxicity, through the reduced membrane cholesterol-mediated downregulations of integrin and MAPK signaling pathways. INTERPRETATION: Collectively, our study improves current understanding of the role of CE accumulation in ccRCC and opens up new opportunities for treatment. FUNDING: This work was supported by National Natural Science Foundation of China (No. U23B2046 and No. 62027824), National Key R&D Program of China (No. 2023YFC2415500), Fundamental Research Funds for the Central Universities (No. YWF-22-L-547), PKU-Baidu Fund (No. 2020BD033), Peking University First Hospital Scientific and Technological Achievement Transformation Incubation Guidance Fund (No. 2022CX02), and Beijing Municipal Health Commission (No. 2020-2Z-40713).

Clinical effectiveness of a multitarget urine DNA test for urothelial carcinoma detection: a double-blinded, multicenter, prospective trial.

Urine-based testing is promising for noninvasive diagnosis of urothelial carcinoma (UC) but has suboptimal sensitivity for early-stage tumors. Herein, we developed a multitarget urine tumor DNA test, UI-Seek, for UC detection and evaluated its clinical feasibility. The prediction model was developed in a retrospective cohort (n = 382), integrating assays for FGFR3 and TERT mutations and aberrant ONECUT2 and VIM methylation to generate a UC-score. The test performance was validated in a double-blinded, multicenter, prospective trial (n = 947; ChiCTR2300076543) and demonstrated a sensitivity of 91.37% and a specificity of 95.09%. The sensitivity reached 75.81% for low-grade Ta tumors and exceeded 93% in high-grade Ta and higher stages (T1 to T4). Simultaneous identification of both bladder and upper urinary tract tumors was enabled with sensitivities exceeding 90%. No significant confounding effects were observed regarding benign urological diseases or non-UC malignancies. The test showed improved sensitivities over urine cytology, the NMP22 test, and UroVysion FISH alongside comparable specificities. The single-target accuracy was greater than 98% as confirmed by Sanger sequencing. Post-surgery UC-score decreased in 97.7% of subjects. Overall, UI-Seek demonstrated robust performance and considerable potential for the early detection of UC.

Breaking barriers: Stereotactic ablative proton and photon radiation therapy for renal cell carcinoma with extensive metastases: A case report.

Patients with advanced renal cancer (RCC) often have limited success with systemic therapy due to tumor heterogeneity. However, stereotactic ablative radiotherapy (SABR) has been shown to have a beneficial therapeutic effect for oligometastatic disease when used early. Despite this, current guidelines recommend the use of tyrosine kinase inhibitors (TKIs) as the first-line therapeutic agent for patients with recurrent or metastatic kidney cancer. Additionally, there is limited data on the combination of systemic treatment and SABR for extensive metastatic RCC due to concerns about high toxicity. Proton therapy offers a promising treatment option as it emits energy at a specific depth, generating high target doses while minimizing damage to normal tissue. This allows for precise treatment of various tumor lesions. In this case report, we describe a high-risk 65-year-old male with extensive pleural and thoracic lymph node metastases and 2 bone metastases of clear cell renal cancer. While the targeted therapy and immunotherapy effectively treated the bone metastases, it was not effective in treating the chest metastases, including the pleural and lymph node metastases. Thus, the patient received full-coverage radiotherapy with photon for primary renal tumor and intensity-modulated proton therapy (IMPT) for thoracic metastases. The patient showed no evidence of disease for 1 year after the initial radiotherapy, and no severe SABR-related adverse effects were observed until now. The combination of targeted therapy and immunotherapy with full-coverage radiotherapy may be a promising treatment option for selected patients with extensive metastatic renal cancer, especially as proton therapy allows for more precise control of the beam and minimal damage to normal tissue. This case has motivated us to investigate the potential advantages of administering proton therapy concurrently with systemic therapy in the management of metastatic renal cell carcinoma patients.

Integration of Multiparameter MRI into Conventional Pretreatment Risk Factors to Predict Positive Surgical Margins After Radical Prostatectomy.

INTRODUCTION/BACKGROUND: Positive surgical margins (PSMs) after radical prostatectomy (RP) can increase the risk of biochemical recurrence in prostate cancer (PCa) patients. However, the prediction of the likelihood of PSMs in patients undergoing similar surgical procedures remains a challenge. We aim to develop a predictive model for PSMs in patients undergoing non-nerve-sparing RP. PATIENTS AND METHODS: In this retrospective study, we analyzed data from PCa patients who underwent minimally invasive non-nerve-sparing RP at our hospital between June 2017 and June 2021. We identified independent risk factors associated with PSMs using clinical and MRI-based parameters in univariate and multivariate logistic regression analyzes. These factors were then used to develop a nomogram for predicting the probability of PSMs. The predictive performance was validated using calibration and receiver operating characteristic curve, area under the curve ,and decision curve analysis. RESULTS: Multivariate analyzes revealed prostate-specific antigen density, tumor size, tumor location at the apex, tumor contact length, extracapsular extension (ECE) level, and apparent diffusion coefficient value as independent risk factors. A nomogram was developed and validated with high accuracy (C-index = 0.78). Furthermore, we found that 44.2% of patients diagnosed with organ-confined disease had ECE after surgery, and 29.1% of patients with Gleason scores ≤7 had higher pathological scores. Interestingly, the tumor burden calculated from PCa biopsy cores was overestimated when compared to postoperative PCa specimens. CONCLUSION: We developed a reliable nomogram for predicting the risk of PSMs in PCa patients undergoing non-nerve-sparing RP. The study highlights the importance of incorporating these parameters in personalized surgical management.

Permselective Ionic-Shield for High-Performance Lithium-Sulfur Batteries.

Lithium-sulfur batteries (LiSBs) are promising next-generation batteries because of their low cost and high theoretical energy densities. Despite remarkable advances over the decades, polysulfide (PS) shuttling during battery cycling remains a challenge in the development of commercial LiSBs and is accelerated under practical conditions. Herein, we report a permselective ionic shield between the electrodes that blocks PS shuttles and passes Li ions to high-performance LiSBs. This shield is easily built onto the separator by ionic complexation and intermolecular bonding of functional polymers, thereby improving the battery performance and safety. The LiSB with the developed shield delivers a remarkable discharge capacity of 917 mAh g-1 after 1000 cycles at 2 C. In addition, the behavior of LiSBs under practical conditions that can realize a high energy density is investigated to achieve the optimal balance in this system. This study provides new insights into the imminent development of separators for practical LiSBs.

Mutational pattern off homologous recombination repair (HRR)-related genes in upper tract urothelial carcinoma.

BACKGROUND: Homologous recombination (HR) repair (HRR) has been indicated to be a biomarker for immunotherapy, chemotherapy, and poly-ADP ribose polymerase inhibitors inhibitors (PARPis). Nonetheless, their molecular correlates in upper tract urothelial carcinoma (UTUC) have not been well studied. This study aimed to explore the molecular mechanism and tumor immune profile of HRR genes and the relevance of their prognostic value in patients with UTUC. MATERIALS AND METHODS: One hundred and ninety-seven tumors and matched blood samples from Chinese UTUC were subjected to next-generation sequencing. A total of 186 patients from The Cancer Genome Atlas were included. Comprehensive analysis was performed. RESULTS: In Chinese patients with UTUC, 5.01% harbored germline HRR gene mutations, and 1.01% had Lynch syndrome-related genes. A total of 37.6% (74/197) of patients carried somatic or germline HRR gene mutations. There was marked discrepancy in the mutation landscapes, genetic interactions, and driver genes between the HRR-mut cohorts and HRR-wt cohorts. Aristolochic acid signatures and defective DNA mismatch repair signatures only existed in individuals in the HRR-mut cohorts. Inversely, the unknown signature (signature A) and signature SBS55 only existed in patients in the HRR-wt cohorts. HRR gene mutations regulated immune activities by NKT cells, plasmacytoid dendritic cells, hematopoietic stem cell, and M1 macrophages. In patients with local recurrence, patients with HRR gene mutations had poorer DFS rates than patients with wild-type HRR genes. CONCLUSIONS: Our results imply that the detection of HRR gene mutations can predict recurrence in patients with UC. In addition, this study provides a path to explore the role of HRR-directed therapies, including PARPis, chemotherapy, and immunotherapy.

Somatic and germline aberrations in homologous recombination repair genes in Chinese prostate cancer patients.

Simple summary: Somatic and germline aberrations in homologous recombinant repair (HHR) genes are associated with increased incidence and poor prognosis for prostate cancer. Through next-generation sequencing of prostate cancer patients across all clinical states from north China, here the authors identified a somatic mutational rate of 3% and a germline mutational rate of 3.9% for HRR genes using 200 tumor tissues and 714 blood specimens. Thus, mutational rates in HRR genes were lower compared with previous studies. Background: Homologous recombination repair deficiency is associated with higher risk and poorer prognosis for prostate cancer. However, the landscapes of somatic and germline mutations in these genes remain poorly defined in Chinese patients, especially for those with localized disease and those from north part of China. In this study, we explore the genomic profiles of these patients. Methods: We performed next-generation sequencing with 200 tumor tissues and 714 blood samples from prostate cancer patients at Peking University First Hospital, using a 32 gene panel including 19 homologous recombination repair genes. Results: TP53, PTEN, KRAS were the most common somatic aberrations; BRCA2, NBN, ATM were the most common germline aberrations. In terms of HRR genes, 3% (6/200) patients harbored somatic aberrations, and 3.8% (28/714) patients harbored germline aberrations. 98.0% (196/200) somatic-tested and 72.7% (519/714) germline tested patients underwent prostatectomy, of which 28.6% and 42.0% had Gleason scores ≥8 respectively. Gleason scores at either biopsy or prostatectomy were predictive for somatic aberrations in general and in TP53; while age of onset <60 years old, PSA at diagnosis, and Gleason scores at biopsy were clinical factors associated with positive germline aberrations in BRCA2/ATM. Conclusions: Our results showed a distinct genomic profile in homologous recombination repair genes for patients with prostate cancer across all clinical states from north China. Clinicians may consider to expand the prostate cancer patients receiving genetic tests to include more individuals due to the weak guiding role by the clinical factors currently available.

Corrigendum: Modulation of colonic function in irritable bowel syndrome rats by electroacupuncture at ST25 and the neurobiological links between ST25 and the colon.

[This corrects the article DOI: 10.3389/fnins.2022.930489.].

Letter to the Editor: clinical utility of urine DNA for noninvasive detection and minimal residual disease monitoring in urothelial carcinoma.

Current methods for the early detection and minimal residual disease (MRD) monitoring of urothelial carcinoma (UC) are invasive and/or possess suboptimal sensitivity. We developed an efficient workflow named urine tumor DNA multidimensional bioinformatic predictor (utLIFE). Using UC-specific mutations and large copy number variations, the utLIFE-UC model was developed on a bladder cancer cohort (n = 150) and validated in The Cancer Genome Atlas (TCGA) bladder cancer cohort (n = 674) and an upper tract urothelial carcinoma (UTUC) cohort (n = 22). The utLIFE-UC model could discriminate 92.8% of UCs with 96.0% specificity and was robustly validated in the BLCA_TCGA and UTUC cohorts. Furthermore, compared to cytology, utLIFE-UC improved the sensitivity of bladder cancer detection (p < 0.01). In the MRD cohort, utLIFE-UC could distinguish 100% of patients with residual disease, showing superior sensitivity compared to cytology (p < 0.01) and fluorescence in situ hybridization (FISH, p < 0.05). This study shows that utLIFE-UC can be used to detect UC with high sensitivity and specificity in patients with early-stage cancer or MRD. The utLIFE-UC is a cost-effective, rapid, high-throughput, noninvasive, and promising approach that may reduce the burden of cystoscopy and blind surgery.

Modulation of colonic function in irritable bowel syndrome rats by electroacupuncture at ST25 and the neurobiological links between ST25 and the colon.

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disease characterized by abdominal pain and defecation disorders. Acupuncture therapy positively affects IBS, with ST25 being the main point. However, ST25 has mostly been used in conjunction with other acupoints. This study aimed to observe the therapeutic effect of electroacupuncture at ST25 alone in IBS and the neurobiological mechanism of ST25 associated with the colon. First, we observed the effect of electroacupuncture at ST25 on the visceral pain threshold and slow-wave discharge of the colon in IBS model rats. Second, we explored the neurobiological mechanism of ST25 associated with the colon using a neural tracer technique. The results showed that (1) electroacupuncture at ST25 alone can alleviate visceral hypersensitivity and restore normal slow-wave frequency and rhythm of the colon in IBS rats; (2) there is a close neuroanatomical connection between ST25 and the colon, i.e., in the dorsal root ganglion (DRG), ST25 is similar in innervation to the colon, mainly in the T8-L1 segment, while the presence of double-labeled positive neurons is present in a part of the DRG; retrogradely labeled motor neurons associated with ST25 were observed in the anterior horn of the spinal cord, and retrogradely labeled sympathetic postganglionic neurons associated with ST25 were observed in the sympathetic nerve chain. These findings suggested that the DRGs and the dorsal horn of the spinal cord are important targets for electroacupuncture at ST25 to reduce visceral hypersensitivity in IBS rats. The sympathetic ganglia may be an important site for ST25 to regulate intestinal motility. The neurobiological mechanism of ST25 action in IBS rats should be further investigated in the future by combining related techniques, such as pseudorabies virus, optogenetics, calcium imaging, and electrophysiology.

Outcomes of High-Dose Stereotactic Ablative Radiotherapy to All/Multiple Sites for Oligometastatic Renal Cell Cancer Patients.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is one of the treatment options for oligometastatic renal cell carcinoma (RCC) but is limited by a lack of data to evaluate high-dose SABR to all/multiple sites. OBJECTIVE: This study retrospectively investigated the efficacy and prognostic factors of high-dose SABR for oligometastatic RCC patients. DESIGN, SETTING, AND PARTICIPANTS: Patients with oligometastatic RCC on systemic therapy were retrospectively collected. INTERVENTION(S): All patients were treated with SABR (40-50 Gy/5 fractions) for small tumors or partial-SABR (tumor center boosted with 6-8 Gy/3-5 fractions with 50-60 Gy/20-25 fractions to the whole tumor volume) for bulky tumors or tumors adjacent to critical organs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS AND LIMITATIONS: In total, 35 patients were enrolled, of which 88.5% had intermediate- or high-risk disease, with 60% on second- to fourth-line systemic therapy. The median follow-up time was 17 months. The median PFS and OS times were 11.3 and 29.7 months, respectively. Univariate analysis showed that an OS benefit was found in patients who received radiation before tyrosine kinase inhibitor (TKI) failure (p = 0.006) and where there was a short time interval (

Highly Stable Potassium-Ion Battery Enabled by Nanoengineering of an Sb Anode.

We present the nanoengineering of Sb particles assisted by a conductive and stress-relieving network of carbon quantum dots (CQDs) and poly(3,4-ethylene dioxythiophene) poly(styrenesulfonate) (PEDOT:PSS), in the proper design of anode materials with high specific capacity and excellent stability for potassium-ion batteries (KIBs). The nanosized Sb particles are prepared by the CQDs as functional tuners in the morphology and surface, which tune the size to nanolevel and provide fast ionic channels and a soft matrix to relieve the volume changes. As the additional conductive and stress-relieving network layer, PEDOT:PSS offers enhanced electron/ion pathways and maintains the integrity of the Sb@CQD composite electrode. In the KIB, the prepared Sb anode exhibits battery performance with a high specific capacity of 480 mA h g-1 at 0.5 A g-1 and a high-capacity retention of 95.4% over 350 cycles.

Binder-Free and High-Loading Cathode Realized by Hierarchical Structure for Potassium-Sulfur Batteries.

Potassium-sulfur batteries have attracted significant research attention owing to the naturally abundant resources of potassium and sulfur, and have promising applications in large-scale energy storage systems. However, the sluggish reaction kinetics of K+ , low reaction activity of sulfur species, shuttling effect of polysulfides, and large volume change impede the development of these batteries. Moreover, the conventional electrode fabrication method with binders and current collectors renders it difficult to improve the areal sulfur loading and energy density. In this study, a binder-free and freestanding sulfur cathode is prepared by phase inversion and sulfurization of polyacrylonitrile. This sulfur cathode, with a hierarchically porous network, enables a high reversible capacity of 1345 mAh g-1 and a stable cycling performance with a capacity decay of 0.15% per cycle. Importantly, areal capacities of 3.1 and 4.2 mAh cm-2 are achieved even at high sulfur loadings of 3 and 7 mg cm-2 , owing to the favorable electron/ion transport in the cathode. The facile preparation method and excellent electrochemical properties reported herein can pave the way for developing high-performance K-S batteries.

Recycling respirator masks to a high-value product: From COVID-19 prevention to highly efficient battery separator.

COVID-19 is a pandemic that has caused serious disruption in almost every day-to-day life around the world, and wearing a mask is essential for human safety from this virus. However, masks are non-recyclable materials, and the accumulation of masks used every day causes serious environmental issues. In this study, we investigate the recycling of mask materials for addressing the environmental problems and transforming as a high value-added material through chemical modification of masks. The recycled mask is applied as a separator for aqueous rechargeable batteries, and shows outstanding safety and electrochemical performance than the existing separator. This approach will lead to an advanced energy technology considering nature after overcoming COVID-19.

Analysis of acupoint selection and prescription rules of acupuncture for treatment of stable angina pectoris based on a Traditional Chinese Medicine inheritance calculation platform: A systematic review.

The use of acupuncture to treat stable angina pectoris is increasing popularity. Based on the prevalence of this treatment over the past 20 years, the rule of acupoint selection and prescription were summarized in this study. The China National Knowledge Infrastructure, China Academic Journal Database, Chinese Science and Technology Periodical Database, PubMed and Web of Science were used for literature search clinical studies on acupuncture in the treatment of stable angina pectoris conducted over the past 20 years were identified, 225 studies were included. Prescriptions were entered into the Traditional Chinese Medicine heritage calculation platform and association rule analysis and complex entropy clustering analysis were performed. Of the sixty-seven acupoints were regularly used and PC6, BL15 and RN17 were the most common. Commonly used meridians were the foot sun bladder meridian, Renmai and hand Shaoyin pericardium meridian; Get the basic prescription of PC6, RN17 and BL15and have two new prescriptions: BL15, ST36 and GB39; DU10, DU11 and RN17. All acupoints act on the heart through neural regulation mechanism. There are many clinical practice guidelines worldwide for writing acupuncture into the recommended therapy. Acupuncture has a clear therapeutic effect on stable angina pectoris. In the treatment of stable angina pectoris, all acupoints directly or indirectly act on the heart, dredge meridians and relieve angina symptoms.

Wide range detector of plasma induced charging effect for advanced CMOS BEOL processes.

This work proposed a modified plasma induced charging (PID) detector to widen the detection range, for monitoring the possible plasma damage across a wafer during advanced CMOS BEOL processes. New antenna designs for plasma induced damage patterns with extended capacitors are investigated. By adapting the novel PID detectors, the maximum charging levels of the detectors have been enhanced.

Comparison of Genomic Characterization in Upper Tract Urothelial Carcinoma and Urothelial Carcinoma of the Bladder.

BACKGROUND: Different genomic characterization in urothelial carcinoma (UC) by site of origin may imply contrasting therapeutic opportunities and pathogenetic mechanisms. The aim of this study was to investigate whether differences between upper tract UC (UTUC) and UC of the bladder (UCB) result from intrinsic biological diversity. MATERIALS AND METHODS: We prospectively sequenced 118 tumors and matched blood DNA from Chinese patients with UC using next-generation sequencing techniques, including 45 UTUC and 73 UCB. Two hundred twenty-six patients with UTUC and 350 patients with UCB for The Cancer Genome Atlas were acquired from the cbioportal. RESULTS: There were marked disparities in the mutational landscape for UC according to race and site of origin. Signature 22 for exposure to aristolochic acid was only observed in the UTUC cohort. Conversely, signature 6 for defective DNA mismatch repair only existed in the UCB cohort. Compared with UCB, UTUC had higher clonal and subclonal mutation numbers. TP53, PIK3CA, and FGFR3 mutations may be the driver genes for UTUC, whereas for UCB, the driver gene may be BRCA1. Patients with UTUC had lower PD-L1 than those with UCB. There was no significant difference in the number of DDR mutations, copy number variation counts, and tumor mutational burden between UTUC and UCB. CONCLUSION: UTUC and UCB exhibit significant differences in the prevalence of genomic landscape and carcinogenesis. Consequently, molecular subtypes differ according to location, and these results may imply the site-specific management of patients with urothelial carcinoma. Mutational signature may be used as a screening tool to assist clinical differential diagnosis between UTUC and UCB. IMPLICATIONS FOR PRACTICE: This study's findings lay the foundation for a deeper understanding of distinct molecular mechanisms and similar treatment opportunities between upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) and had important implications for the site-specific management of patients with urothelial carcinoma. A comprehensive understanding of the biology of UTUC and UCB is needed to identify new drug targets in order to improve clinical outcomes.

Lead poisoning due to incense burning: an outbreak in a family.

BACKGROUND: In Asia and some other regions of the world, incense burning is an important folk and cultural activity. However, this ritual can cause health impacts, such as chronic respiratory diseases and neoplasms. Herein, we describe a family with lead poisoning possibly related to the frequent use of incense sticks at home. CASE REPORT: A 65-year-old homemaker with severe anemia, pitting edema of the lower legs, bone pain, abdominal pain, and exertional dyspnea for several months presented to our clinic. Her blood workup indicated severe anemia with basophilic stippling in red blood cells and blood lead level (BLL) of 59.75 µg/dL. Her husband, three children, and four grandchildren who lived with her also had high BLLs. As a Daoist clergy person, she had been exposed to a large amount of smoke from every day use of incense for >30 years. In the field investigation, the chronic dust deposited in hidden corners of their home had considerably higher lead content and other toxic metals. DISCUSSION: Our observations indicated chronic, frequent exposure to smoke from incense burning may be a cause of lead poisoning. Strict avoidance of incense smoke is a significant step toward preventing lead poisoning in children in societies with the custom of incense burning.

The prevalence of esophageal cancer after caustic and pesticide ingestion: A nationwide cohort study.

Habits such as smoking and alcohol drinking and existing esophageal malfunction are considered the main risk factors for esophageal carcinogenesis. Caustic ingestion of acidic or alkaline agents or strong irritants can induce severe esophageal corrosive injury and increase esophageal cancer risk. We studied the relationship between esophageal carcinoma and acute detergent or pesticide poisoning by using nationwide health insurance data. Methodology/Principle findings: We compared a pesticide/detergent intoxication cohort (N = 21,840) and an age- and gender-matched control cohort (N = 21,840) identified from the National Health Insurance Research Database between 2000 and 2011. We used the multivariable Cox proportional model to determine esophageal carcinoma risk. The overall incidence density of esophageal cancer was 1.66 per 10,000 person-years in the comparison cohort and 4.36 per 10,000 person-years in the pesticide/detergent intoxication cohort. The corresponding adjusted hazard ratio (HR) for esophageal cancer was 2.33 (95% confidence interval [CI] = 1.41-3.86) in the pesticide/detergent intoxication cohort compared with the control cohort. Patients with corrosive and detergent intoxication did not have a higher risk of esophageal cancer (adjusted HR = 0.98, 95% CI = 0.29-3.33) than those without pesticide/detergent intoxication. However, patients with pesticide intoxication had a significantly higher risk of esophageal cancer (adjusted HR = 2.52, 95% CI = 1.52-4.18) than those without pesticide/detergent intoxication. Conclusion: In the present study, after adjusting for conventional risk factors, we observed that pesticide intoxication could exert substantial effects through increased esophageal cancer risk. However, patients with detergent intoxication may not have an increased risk of esophageal cancer.

Risk of Seizures in Patients with Organophosphate Poisoning: A Nationwide Population-Based Study.

OBJECTIVE: Previous research has demonstrated that patients with a history of organophosphate poisoning tend to have a higher risk of neurological disorder. However, research on the rate of seizure development in patients after organophosphate poisoning is lacking. This study examined whether individuals with organophosphate poisoning have an increased risk of seizures through several years of follow-up. PATIENTS AND METHODS: We conducted a retrospective study on a cohort of 45,060 individuals (9012 patients with a history of organophosphate poisoning and 36,048 controls) selected from the Taiwan National Health Insurance Research Database. The individuals were observed for a maximum of 12 years to determine the rate of new-onset seizure disorder. We selected a comparison cohort from the general population that was randomly frequency-matched by age, sex, and index year and further analyzed the risk of seizures using a Cox regression model adjusted for sex, age, and comorbidities. RESULTS: During the study period, the risk of seizure development was 3.57 times greater in patients with organophosphate poisoning compared with individuals without, after adjustments for age, sex, and comorbidities. The absolute incidence of seizures was highest in individuals aged 20 to 34 years in both cohorts (adjusted hazard ratio = 13.0, 95% confidence interval = 5.40-31.4). A significantly higher seizure risk was also observed in patients with organophosphate poisoning and comorbidities other than cirrhosis. CONCLUSIONS: This nationwide retrospective cohort study demonstrates that seizure risk is significantly increased in patients with organophosphate poisoning compared with the general population.