Preanalytical Phase Tumor Contaminants in Intraoperative Margins From Transoral Robotic Surgeries.

CONTEXT.­: Tumor contaminants were incidentally noted in frozen section margins of oropharyngeal squamous cell carcinoma. OBJECTIVE.­: To estimate the frequency of tumor contaminants in frozen section slides of patients who underwent surgery for pharyngeal cancer, and to characterize the surgical and pathologic context of these incidents. DESIGN.­: A retrospective search was conducted to identify pharyngeal resections from 2016 to 2022. Surgical pathology, operative reports, and frozen section slides were reviewed. Preanalytical phase tumor contaminants were defined as tumor contaminants that occurred in frozen section slides with or without occurrence in permanent slides. RESULTS.­: Eighty-one pharyngeal resections with intraoperative tumor bed margins for squamous cell carcinoma were identified. These included 308 tumor bed margins represented in 641 slides. Preanalytical contaminants occurred among 9 patients (11.1% of all and 21.4% of robotic surgeries) and in 3.8% of the 308 intraoperative tumor bed margins. A statistically significant association was found between contaminants and larger tumor size (Student t test, P = .04) and surgical approach (robotic versus open oropharyngectomy: Fisher exact test, P < .001). All patients with contaminants had intraoperative tumor disruption. Two frozen section deferrals (0.6%) and 2 discrepancies with final diagnosis (0.6%) attributed to contaminants were identified; however, clinical or surgical management was not affected in any patient. CONCLUSIONS.­: Preanalytical contaminants may cause confusion in intraoperative margin assessment. They are more likely to occur in margins of nonkeratinizing squamous cell carcinoma resected by transoral robotic surgery if there is intraoperative tumor disruption. Rarely, preanalytical contaminants lead to frozen section deferral or discrepancy with final diagnosis.

Rainfall events and daily mortality across 645 global locations: two stage time series analysis.

OBJECTIVE: To examine the associations between characteristics of daily rainfall (intensity, duration, and frequency) and all cause, cardiovascular, and respiratory mortality. DESIGN: Two stage time series analysis. SETTING: 645 locations across 34 countries or regions. POPULATION: Daily mortality data, comprising a total of 109 954 744 all cause, 31 164 161 cardiovascular, and 11 817 278 respiratory deaths from 1980 to 2020. MAIN OUTCOME MEASURE: Association between daily mortality and rainfall events with return periods (the expected average time between occurrences of an extreme event of a certain magnitude) of one year, two years, and five years, with a 14 day lag period. A continuous relative intensity index was used to generate intensity-response curves to estimate mortality risks at a global scale. RESULTS: During the study period, a total of 50 913 rainfall events with a one year return period, 8362 events with a two year return period, and 3301 events with a five year return period were identified. A day of extreme rainfall with a five year return period was significantly associated with increased daily all cause, cardiovascular, and respiratory mortality, with cumulative relative risks across 0-14 lag days of 1.08 (95% confidence interval 1.05 to 1.11), 1.05 (1.02 to 1.08), and 1.29 (1.19 to 1.39), respectively. Rainfall events with a two year return period were associated with respiratory mortality only, whereas no significant associations were found for events with a one year return period. Non-linear analysis revealed protective effects (relative risk <1) with moderate-heavy rainfall events, shifting to adverse effects (relative risk >1) with extreme intensities. Additionally, mortality risks from extreme rainfall events appeared to be modified by climate type, baseline variability in rainfall, and vegetation coverage, whereas the moderating effects of population density and income level were not significant. Locations with lower variability of baseline rainfall or scarce vegetation coverage showed higher risks. CONCLUSION: Daily rainfall intensity is associated with varying health effects, with extreme events linked to an increasing relative risk for all cause, cardiovascular, and respiratory mortality. The observed associations varied with local climate and urban infrastructure.

Temperature-mortality associations by age and cause: a multi-country multi-city study.

Background: Heterogeneity in temperature-mortality relationships across locations may partly result from differences in the demographic structure of populations and their cause-specific vulnerabilities. Here we conduct the largest epidemiological study to date on the association between ambient temperature and mortality by age and cause using data from 532 cities in 33 countries. Methods: We collected daily temperature and mortality data from each country. Mortality data was provided as daily death counts within age groups from all, cardiovascular, respiratory, or noncardiorespiratory causes. We first fit quasi-Poisson regression models to estimate location-specific associations for each age-by-cause group. For each cause, we then pooled location-specific results in a dose-response multivariate meta-regression model that enabled us to estimate overall temperature-mortality curves at any age. The age analysis was limited to adults. Results: We observed high temperature effects on mortality from both cardiovascular and respiratory causes compared to noncardiorespiratory causes, with the highest cold-related risks from cardiovascular causes and the highest heat-related risks from respiratory causes. Risks generally increased with age, a pattern most consistent for cold and for nonrespiratory causes. For every cause group, risks at both temperature extremes were strongest at the oldest age (age 85 years). Excess mortality fractions were highest for cold at the oldest ages. Conclusions: There is a differential pattern of risk associated with heat and cold by cause and age; cardiorespiratory causes show stronger effects than noncardiorespiratory causes, and older adults have higher risks than younger adults.

Effect modification of air pollution on the association between heat and mortality in five European countries.

BACKGROUND: Evidence suggests that air pollution modifies the association between heat and mortality. However, most studies have been conducted in cities without rural data. This time-series study examined potential effect modification of particulate matter (PM) and ozone (O3) on heat-related mortality using small-area data from five European countries, and explored the influence of area characteristics. METHODS: We obtained daily non-accidental death counts from both urban and rural areas in Norway, England and Wales, Germany, Italy, and the Attica region of Greece during the warm season (2000-2018). Daily mean temperatures and air pollutant concentrations were estimated by spatial-temporal models. Heat effect modification by air pollution was assessed in each small area by over-dispersed Poisson regression models with a tensor smoother between temperature and air pollution. We extracted temperature-mortality relationships at the 5th (low), 50th (medium), and 95th (high) percentiles of pollutant distributions. At each air pollution level, we estimated heat-related mortality for a temperature increase from the 75th to the 99th percentile. We applied random-effects meta-analysis to derive the country-specific and overall associations, and mixed-effects meta-regression to examine the influence of urban-rural and coastal typologies and greenness on the heat effect modification by air pollution. RESULTS: Heat-related mortality risks increased with higher PM levels, rising by 6.4% (95% CI: -2.0%-15.7%), 10.7% (2.6%-19.5%), and 14.1% (4.4%-24.6%) at low, medium, and high PM levels, respectively. This effect modification was consistent in urban and rural regions but more pronounced in non-coastal regions. In addition, heat-mortality associations were slightly stronger at high O3 levels, particularly in regions with low greenness. CONCLUSION: Our analyses of both urban and rural data indicate that air pollution may intensify heat-related mortality, particularly in non-coastal and less green regions. The synergistic effect of heat and air pollution implies a potential pathway of reducing heat-related health impacts by improving air quality.

JCV granule cell neuronopathy: A rare case manifestation.

Granule cell neuronopathy (GCN) caused by John Cunningham virus (JCV) is a rare yet significant neurological complication, particularly in immunocompromised individuals such as those with AIDS. We present a case of a 34-year-old HIV-positive male exhibiting classical symptoms of cerebellar dysfunction. Magnetic resonance imaging revealed demyelination suggestive of progressive multifocal leukoencephalopathy (PML). Histopathological examination confirmed JCV-GCN, characterized by lytic infection of cerebellar granule cell neurons. Among the 41 reported cases of JCV-GCN, histopathological data were available for only 10 cases. Ours is the 11th case with available histopathology. This case underscores the importance of considering JCV infection in the differential diagnosis of progressive cerebellar syndromes in immunocompromised patients. Early recognition and diagnosis are crucial for appropriate management and prognosis.

Radiomics features for the discrimination of tuberculomas from high grade gliomas and metastasis: a multimodal study.

BACKGROUND: Tuberculomas are prevalent in developing countries and demonstrate variable signals on MRI resulting in the overlap of the conventional imaging phenotype with other entities including glioma and brain metastasis. An accurate MRI diagnosis is important for the early institution of anti-tubercular therapy, decreased patient morbidity, mortality, and prevents unnecessary neurosurgical excision. This study aims to assess the potential of radiomics features of regular contrast images including T1W, T2W, T2W FLAIR, T1W post contrast images, and ADC maps, to differentiate between tuberculomas, high-grade-gliomas and metastasis, the commonest intra parenchymal mass lesions encountered in the clinical practice. METHODS: This retrospective study includes 185 subjects. Images were resampled, co-registered, skull-stripped, and zscore-normalized. Automated lesion segmentation was performed followed by radiomics feature extraction, train-test split, and features reduction. All machine learning algorithms that natively support multiclass classification were trained and assessed on features extracted from individual modalities as well as combined modalities. Model explainability of the best performing model was calculated using the summary plot obtained by SHAP values. RESULTS: Extra tree classifier trained on the features from ADC maps was the best classifier for the discrimination of tuberculoma from high-grade-glioma and metastasis with AUC-score of 0.96, accuracy-score of 0.923, Brier-score of 0.23. CONCLUSION: This study demonstrates that radiomics features are effective in discriminating between tuberculoma, metastasis, and high-grade-glioma with notable accuracy and AUC scores. Features extracted from the ADC maps surfaced as the most robust predictors of the target variable.

Metachronous intracranial meningiomas without dural attachment in a child - Rare case report and review of literature.

INTRODUCTION: Meningiomas in children are rare, constituting less than 5% of all paediatric brain tumours and less than 2% of all meningiomas. Multiple meningiomas (synchronous or metachronous) are even more uncommon, typically occurring due to radiation exposure or in patients with phacomatoses like Neurofibromatosis II. This report presents the case of a child with metachronous meningiomas without dural attachment in unusual locations, along with their management. PURPOSE: This report aims to describe a rare paediatric case of metachronous meningiomas without dural attachment, detailing their presentation, treatment, and outcomes. CASE DETAILS: A 2-year-old female presented with headaches, irritability, and excessive crying for one year. A CT scan revealed a mass in the fourth ventricle, causing obstruction, which was surgically decompressed. The biopsy confirmed a clear cell meningioma, WHO grade II. A follow-up MRI identified a new lesion in the suprasellar area six months later, for which she underwent right pterional craniotomy and gross total resection, which turned out to be a clear cell meningioma, WHO grade II. The patient recovered well and remained asymptomatic, with no recurrence on MRI at one-year follow-up. CONCLUSION: This case highlights the unusual presentation of metachronous clear cell meningiomas without dural attachment in a young child. Surgical excision resulted in a favourable outcome, though long-term follow-up is essential due to the high propensity for recurrence.

MAPK pathway alterations in polymorphous low-grade neuroepithelial tumor of the young: diagnostic considerations.

Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently recognised tumor type with indolent behaviour with characteristic imaging and histomolecular features. We describe the clinical, imaging, histo-molecular features of 15 cases diagnosed as low-grade glioma suggestive of PLNTY, over a period of 3 years. Immunohistochemistry (IHC) and fluorescence in situ hybridisation were used to assess molecular alterations. The tumors were seen predominantly in children (range 5-65 years). Most of the patients presented with history of seizures. Imaging revealed cortical-subcortical well demarcated solid-cystic tumor with intratumoral calcification. Histopathology revealed a low-grade tumor with oligodendroglia-Iike cells admixed with astrocytic cells immunopositive for CD34. BRAF p.V600E mutations and FGFR2 breakapart were observed in six cases each, while three showed FGFR3 breakapart. FGFR2 breakapart positive PLNTY were seen in children exclusively. The majority of cases were seizure free post-surgery, except two patients who succumbed to the illness. PLNTY, needs to be considered as a prime differential diagnosis in a solid-cystic tumor in a young patient with history of seizures. Characteristic clinical features, radiology, histomorphology with an IHC panel of OLIG2, GFAP and CD34 correlates with one of the MAPK alterations in PLNTY (BRAF p.V600E, FGFR2/3 gene rearrangement). In a resource limited setting, this limited panel may be sufficient for a correlative diagnosis.

Translation efficiency covariation across cell types is a conserved organizing principle of mammalian transcriptomes.

Characterization of shared patterns of RNA expression between genes across conditions has led to the discovery of regulatory networks and novel biological functions. However, it is unclear if such coordination extends to translation, a critical step in gene expression. Here, we uniformly analyzed 3,819 ribosome profiling datasets from 117 human and 94 mouse tissues and cell lines. We introduce the concept of Translation Efficiency Covariation (TEC), identifying coordinated translation patterns across cell types. We nominate potential mechanisms driving shared patterns of translation regulation. TEC is conserved across human and mouse cells and helps uncover gene functions. Moreover, our observations indicate that proteins that physically interact are highly enriched for positive covariation at both translational and transcriptional levels. Our findings establish translational covariation as a conserved organizing principle of mammalian transcriptomes.

Interim Phase II Results Using Panitumumab-IRDye800CW during Transoral Robotic Surgery in Patients with Oropharyngeal Cancer.

PURPOSE: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has continually increased during the past several decades. Using transoral robotic surgery (TORS) significantly improves functional outcomes relative to open surgery for OPSCC. However, TORS limits tactile feedback, which is often the most important element of cancer surgery. Fluorescence-guided surgery (FGS) strategies to aid surgeon assessment of malignancy for resection are in various phases of clinical research but exhibit the greatest potential impact for improving patient care when the surgeon receives limited tactile feedback, such as during TORS. Here, we assessed the feasibility of intraoperative fluorescence imaging using panitumumab-IRDye800CW (PAN800) during TORS in patients with OPSCC. PATIENTS AND METHODS: Twelve consecutive patients with OPSCC were enrolled as part of a nonrandomized, prospective, phase II FGS clinical trial using PAN800. TORS was performed with an integrated robot camera for surgeon assessment of fluorescence. Intraoperative and ex vivo fluorescence signals in tumors and normal tissue were quantified and correlated with histopathology. RESULTS: Intraoperative robot fluorescence views delineated OPSCC from normal tissue throughout the TORS procedure (10.7 mean tumor-to-background ratio), including in tumors with low expression of the molecular target. Tumor-specific fluorescence was consistent with surgeon-defined tumor borders requiring resection. Intraoperative robot fluorescence imaging revealed an OPSCC fragment initially overlooked during TORS based on brightfield views, further substantiating the clinical benefit of this FGS approach. CONCLUSIONS: The results from this patient with OPSCC cohort support further clinical assessment of FGS during TORS to aid resection of solid tumors.

Thalamic H3K27M altered diffuse midline gliomas: Clinicopathological and outcome analysis.

INTRODUCTION: Diffuse midline glioma (DMG) is a relatively new entity which was introduced in the fourth edition of the WHO classification of CNS tumours in 2016 and later underwent revision in 2021. It is an infiltrative glioma arising from midline structures, viz., thalamus, spine, and brainstem. Current literature on DMG is based majorly on brainstem lesions, and DMGs arising elsewhere remain unexplored. In our study, we have discussed our experience with thalamic DMGs. METHODOLOGY: This is a retrospective observational study of all patients with histopathologically proven DMG H3K27M altered, arising in the thalamus from 2018 to 2022. Clinical, neuroimaging, and pathology were re-reviewed, and prognostic factors for 3 months, 6 months, and overall survival (OS) were analyzed for all patients. RESULTS: There were 89 patients- 64 adults and 25 pediatric patients with thalamic DMG. The median age at presentation was 24 years. Raised ICP followed by limb weakness were the most common presenting complaints. Stereotactic biopsy was performed in 64 (71.9 %) patients and surgical decompression in 25 (28.1 %) patients. CSF diversion was required in 53 (59.6 %) patients. Median survival was 8 months in adults and 7 months in pediatric (p-value: 0.51). Raised ICP and TP53 mutation were prognostic factors in pediatric population. Radiotherapy with or without chemotherapy improved survival (p-value- <0.01). CONCLUSION: Thalamic DMGs have a poor prognosis which is comparable to brainstem DMGs. Radiotherapy improves survival in these patients. However, the disease remains an enigma and further work delving into its molecular characterization should be encouraged.

Clinicopathological Features of Amyloid Neuropathy: A Four Decade Experience.

BACKGROUND: Peripheral neuropathy is one of the manifestations of primary or familial amyloidosis. Published studies from India are limited. MATERIALS AND METHODS: We reviewed the clinical and pathological features of amyloid neuropathy diagnosed at our Institute over the last 39 years. RESULTS: Fifty-five cases of amyloid neuropathies were diagnosed between 1981 and 2019, constituting 0.28% of peripheral nerve biopsies (55/19,081). Age at presentation ranged from 24 to 81 years (mean-48 years) with male preponderance [M:F = 3.58:1]. Duration of symptoms at presentation varied from 3 months to 10 years (mean-2.31 years). Majority presented with small fiber neuropathy (85%). Pure sensory symptoms predominated in 23%, while 72% had sensorimotor neuropathy and 35.8% had autonomic involvement, with isolated autonomic failure in one patient. Amyloid neuropathy was clinically suspected in 22.6% of nonfamilial cases. Familial amyloid neuropathy was suspected in eight patients. Genetic testing detected ATTR and gelsolin mutation in one each of tested patients. Nerve biopsies revealed characteristic birefringent amyloid deposits stained mahogany brown by Congo red predominantly surrounding endoneurial microvessels (34.5%), also in perineurium and epineurium in 25.45% cases. Preferential loss of small diameter myelinated fibers was noted. Axonal degeneration or regeneration was conspicuously absent. CONCLUSION: Amyloid neuropathy is uncommon (0.28% of nerve biopsies in our series). Nerve biopsy is essential for the diagnosis. We report our experience of amyloid neuropathy and underscore the importance of making an assiduous search for amyloid deposits in the appropriate setting. Awareness of this entity is important for early diagnosis in the light of emerging therapeutic advances.

A Rare Pituitary Tumor.

Sellar-suprasellar masses, with diverse origins ranging from infiltrative to neoplastic processes, are frequently encountered in endocrinology clinics. Evaluation involves a detailed history, hormone analysis, and imaging of the hypothalamic-pituitary axis. However, overlapping hormonal and imaging features can complicate diagnosis, often necessitating confirmation through tissue biopsy. Pituicytoma, a rare sellar tumor mimicking other masses biochemically and radiologically, exemplifies this challenge. These are benign intracranial neoplasms with characteristic bipolar spindle-shaped astrocytic cells organized in fascicular or storiform patterns with specific immunohistochemistry. The current case is of an elderly postmenopausal woman with a history of hypertension who presented with recurrent headaches and transient vision loss in the left eye. Imaging studies revealed a suprasellar mass, which was biopsied and diagnosed on histopathological examination as a pituicytoma. This case highlights the importance of considering less common etiologies when encountering such presentations.

Parkinson's disease variant detection and disclosure: PD GENEration, a North American study.

Variants in seven genes (LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7 and VPS35) have been formally adjudicated as causal contributors to Parkinson's disease; however, individuals with Parkinson's disease are often unaware of their genetic status since clinical testing is infrequently offered. As a result, genetic information is not incorporated into clinical care, and variant-targeted precision medicine trials struggle to enrol people with Parkinson's disease. Understanding the yield of genetic testing using an established gene panel in a large, geographically diverse North American population would help patients, clinicians, clinical researchers, laboratories and insurers better understand the importance of genetics in approaching Parkinson's disease. PD GENEration is an ongoing multi-centre, observational study (NCT04057794, NCT04994015) offering genetic testing with results disclosure and genetic counselling to those in the US (including Puerto Rico), Canada and the Dominican Republic, through local clinical sites or remotely through self-enrolment. DNA samples are analysed by next-generation sequencing including deletion/duplication analysis (Fulgent Genetics) with targeted testing of seven major Parkinson's disease-related genes. Variants classified as pathogenic/likely pathogenic/risk variants are disclosed to all tested participants by either neurologists or genetic counsellors. Demographic and clinical features are collected at baseline visits. Between September 2019 and June 2023, the study enrolled 10 510 participants across >85 centres, with 8301 having received results. Participants were: 59% male; 86% White, 2% Asian, 4% Black/African American, 9% Hispanic/Latino; mean age 67.4 ± 10.8 years. Reportable genetic variants were observed in 13% of all participants, including 18% of participants with one or more 'high risk factors' for a genetic aetiology: early onset (<50 years), high-risk ancestry (Ashkenazi Jewish/Basque/North African Berber), an affected first-degree relative; and, importantly, in 9.1% of people with none of these risk factors. Reportable variants in GBA1 were identified in 7.7% of all participants; 2.4% in LRRK2; 2.1% in PRKN; 0.1% in SNCA; and 0.2% in PINK1, PARK7 or VPS35 combined. Variants in more than one of the seven genes were identified in 0.4% of participants. Approximately 13% of study participants had a reportable genetic variant, with a 9% yield in people with no high-risk factors. This supports the promotion of universal access to genetic testing for Parkinson's disease, as well as therapeutic trials for GBA1 and LRRK2-related Parkinson's disease.

Safety and Efficacy of Biopsy in Patients with Diffuse Intrinsic Pontine Gliomas.

BACKGROUND: Diffuse intrinsic pontine gliomas are aggressive tumors that carry a poor prognosis with a 2-year survival rate of <10%. The imaging appearance is often pathognomonic, and surgical biopsy is not mandatory to initiate treatment in children. Studies of biopsy samples provide insight into the disease's molecular pathobiology and open prospects for targeted therapy. This study was conducted to determine the diagnostic yield and safety of stereotactic biopsies. METHODS: This is a prospective observational study from a single tertiary health care center. All patients with clinical and radiological features diagnostic of diffuse intrinsic pontine gliomas (DIPGs) who underwent biopsy from July 2018 to June 2023 were included. Biopsies were performed using either stereotactic frame-based, frameless, or endoscopic techniques. RESULTS: A total of 165 patients with DIPGs were evaluated in the study period. The option of biopsy with its associated risks and benefits was offered to all patients. A total of 76 biopsies were performed in 74 patients (40 children and 34 adults, including 2 repeat biopsies). The median age was 15 years. Diffuse midline gliomas, H3K27M altered, was the most common histopathological diagnosis (85% pediatric and 55.9% adults). The diagnostic efficacy of the procedure was 94.7%. The complication rate was 10.8%, with no permanent neurological deficits due to surgery. There was no procedure-related mortality. CONCLUSIONS: Establishing the safety of the procedure could be an important step toward popularizing the concept, which might offer a better understanding of the disease. Brainstem eloquence and a lack of direct benefit to patients are the primary obstacles to brainstem biopsy.

Clinicopathological Features in Morvan's Syndrome: An Autopsy Case Study.

Morvan's syndrome is a rare, complex autoimmune syndrome comprising peripheral nerve hyperexcitability, dysautonomia, insomnia, and encephalopathy. In this case report, we highlight the clinical and pathological findings of an elderly gentleman who presented to us with clinical features of Morvan's syndrome associated with anti-contactin-associated protein 2 (CASPR-2) antibodies. Histopathology [Figure 3] revealed cortical atrophy with gliosis and mild microglial proliferation. Microglial activation and gliosis were observed in the hippocampus, hypothalamus, and thalamus. Brainstem showed multifocal inflammation. Mild inflammation was observed in the leptomeninges. Morvan's syndrome is an autoimmune disease with antibodies targeted against CASPR within the voltage-gated potassium channel (VGKC) complex. Early diagnosis and treatment play a key role in the management of patients. Most patients show a good response when treated with plasmapheresis and steroids. This patient presented to us late into the illness and succumbed.

Comparison for the effects of different components of temperature variability on mortality: A multi-country time-series study.

BACKGROUND: Temperature variability (TV) is associated with increased mortality risk. However, it is still unknown whether intra-day or inter-day TV has different effects. OBJECTIVES: We aimed to assess the association of intra-day TV and inter-day TV with all-cause, cardiovascular, and respiratory mortality. METHODS: We collected data on total, cardiovascular, and respiratory mortality and meteorology from 758 locations in 47 countries or regions from 1972 to 2020. We defined inter-day TV as the standard deviation (SD) of daily mean temperatures across the lag interval, and intra-day TV as the average SD of minimum and maximum temperatures on each day. In the first stage, inter-day and intra-day TVs were modelled simultaneously in the quasi-Poisson time-series model for each location. In the second stage, a multi-level analysis was used to pool the location-specific estimates. RESULTS: Overall, the mortality risk due to each interquartile range [IQR] increase was higher for intra-day TV than for inter-day TV. The risk increased by 0.59% (95% confidence interval [CI]: 0.53, 0.65) for all-cause mortality, 0.64% (95% CI: 0.56, 0.73) for cardiovascular mortality, and 0.65% (95% CI: 0.49, 0.80) for respiratory mortality per IQR increase in intra-day TV0-7 (0.9 °C). An IQR increase in inter-day TV0-7 (1.6 °C) was associated with 0.22% (95% CI: 0.18, 0.26) increase in all-cause mortality, 0.44% (95% CI: 0.37, 0.50) increase in cardiovascular mortality, and 0.31% (95% CI: 0.21, 0.41) increase in respiratory mortality. The proportion of all-cause deaths attributable to intra-day TV0-7 and inter-day TV0-7 was 1.45% and 0.35%, respectively. The mortality risks varied by lag interval, climate area, season, and climate type. CONCLUSIONS: Our results indicated that intra-day TV may explain the main part of the mortality risk related to TV and suggested that comprehensive evaluations should be proposed in more countries to help protect human health.