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Background: The SLC2A1 gene plays a vital role in brain energy metabolism. SLC2A1 variants have been reported to be associated with early-onset refractory seizures. This study aims to explore the association between the SLC2A1 gene and late-onset epilepsy. Methods: Trios-based whole-exome sequencing was performed on patients with epilepsy without acquired etiologies. The pathogenicity of the variants was assessed according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: A total of 14 heterozygous SLC2A1 variants were identified in 16 unrelated families. The variants were evaluated as "pathogenic" or "likely pathogenic" according to the ACMG guidelines. Ten cases (62.5%) presented with infantile onset seizures and developmental delay/intellectual disability and were diagnosed with developmental and epileptic encephalopathy (DEE). The other six cases (37.5%) exhibited late-onset seizures and normal development. They were diagnosed with idiopathic partial epilepsy (n = 2) or idiopathic generalized epilepsy (n = 4). Further analysis showed that DEE-associated variants tended to cluster in the transmembrane region, whereas the mild epilepsy-associated variants tended to locate in regions outside the transmembrane region, suggesting a potential molecular sub-regional effect. A total of 15 cases had delayed diagnosis, with the longest delay being 22 years. The SLC2A1 expression stage, which is expressed at relatively high level throughout the whole life span, from the embryonic to adult stages with two peaks at approximately four and 14 years, is generally consistent with the seizure onset age. In addition, patients with early-onset age had variants that were potentially associated with severe damage, suggesting a potential correlation between the age of disease onset and the damaging effects of the variants. Conclusions: SLC2A1 variants are associated with late-onset epilepsy, which is consistent with the genetic-dependent stage feature of SLC2A1. Early genetic diagnosis is important for treatment of patients with SLC2A1 variants. [ABSTRACT FROM AUTHOR]

Objective: To determine sex differences in clinical profiles and treatment outcomes in patients with spontaneous intracranial hypotension. Background: Spontaneous intracranial hypotension is associated with considerable functional disability and potentially fatal complications, and it is uncertain whether males and females should be managed differently. Methods: This was a cohort study of consecutive patients with spontaneous intracranial hypotension enrolled from a medical center. Medical records and imaging findings were reviewed. The outcome of treatment responses to epidural blood patches and risks of subdural hematoma were measured. Results: In total, 442 patients with spontaneous intracranial hypotension (165 males, 277 females) were included in the analysis. Males were more likely to have a delayed (>30 days) initial presentation than females (32.1% [53/165] vs. 19.9% [55/277], p = 0.004), and males were less likely to have nausea (55.8% [92/165] vs. 67.1% [186/277], p = 0.016), vomiting (43.0% [71/165] vs. 54.2% [150/277], p = 0.024), photophobia (9.7% [16/165] vs. 17.0% [47/277], p = 0.034), and tinnitus (26.7% [44/165] vs. 39.7% [110/277], p = 0.005) compared with females despite comparable radiologic findings. Among the 374 patients treated with epidural blood patches, males were more likely to be nonresponders to the first epidural blood patch (58.0% [80/138] vs. 39.0% [92/236], OR = 2.2, 95% CI = 1.4–3.3, p < 0.001). Males were at a higher risk of having subdural hematoma (29.7% [49/165] vs. 10.8% [30/277], OR = 3.5, 95% CI = 2.1–5.8, p < 0.001). Among patients with subdural hematoma, males had greater thickness (12.8 ± 4.3 vs. 8.1 ± 5.9 mm, p < 0.001) and were more likely to receive surgical drainage (55.1% [27/49] vs. 10.0% [3/30], OR = 11.0, 95% CI = 3.0–41.3, p < 0.001) than females. Conclusion: In the present study, spontaneous intracranial hypotension in males was characterized by a delayed presentation, poorer response to the first epidural blood patch, and a higher risk of subdural hematoma. Caution should be exercised in the management of males with spontaneous intracranial hypotension. The generalizability of the findings needs to be further confirmed. Plain Language Summary: Spontaneous intracranial hypotension is associated with considerable functional disability and potentially fatal complications, and it is uncertain whether management of this condition should differ between males and females. In this large cohort of 442 patients with spontaneous intracranial hypotension, we found that males had a longer delay in presentation, poorer response to the first epidural blood patch, and higher risks for developing subdural hematoma and having surgical drainage compared to females. The findings suggest that spontaneous intracranial hypotension in males should be managed with great caution; more aggressive measures, such as early or multiple epidural blood patches, might be necessary. [ABSTRACT FROM AUTHOR]

The spatial delays of pulmonary tuberculosis (PTB) have been less explored. In this study, a total of 151,799 notified PTB cases were included, with median patient and diagnostic delays of 15 [interquartile range (IOR), 4–35] and 2 (IOR, 0–8) days, respectively. The spatial autocorrelation analysis and spatial–temporal scan statistics were used to determine the clusters, indicating that the regions in the southwestern and northeastern parts of Zhejiang Province exhibited high rates of long-term patient delay (LPD, delay ≥ 15 days) and long-term diagnostic delay (LDD, delay ≥ 2 days). Besides, the Mantel test indicated a moderately positive correlation between public awareness of suspicious symptoms and the LPD rate in 2018 (Mantel's r = 0.4, P < 0.05). These findings suggest that PTB delays can reveal deficiencies in public health education and the healthcare system. Also, it is essential to explore methods to shift PTB knowledge towards real changes in attitude and behavior to minimize patient delay. Addressing these issues will be crucial for improving public health outcomes related to PTB in Zhejiang Province. [ABSTRACT FROM AUTHOR]

OBJECTIVE To compare the immediate, early, and delayed percutaneous coronary intervention (PCI) strategies in non-ST-segment-elevation myocardial infarction (NSTEMI) patients with high-risk. METHODS Medical records of patients treated at the Daping Hospital, Third Military Medical University, Chongqing, China between 2011 and 2021 were retrospectively reviewed. Only patients with complete available information were included. All patients assigned into three groups based on the timing of PCI including immediate (< 2 h), early (2–24 h) and delayed (≥ 24 h) intervention. Multivariable Cox hazards regression and simpler nonlinear models were performed. RESULTS A total of 657 patients were included in the study. The median follow-up length was 3.29 (interquartile range: 1.45– 4.85) years. Early PCI strategy improved the major adverse cardiac event (MACE) outcome compared to the immediate or delayed PCI strategy. Early PCI, diabetes mellitus, and left main or/and left anterior descending or/and left circumflex stenosis or/and right coronary artery ≥ 99% were predictors for MACE outcome. The optimal timing range for PCI to reduce MACE risk is 3–14 h post-admission. For high-risk NSTEMI patients, early PCI reduced primary clinical outcomes compared to immediate or delayed PCI, and the optimal timing range was 3–14 h post-admission. Delayed PCI was superior for NSTEMI with chronic kidney injury. CONCLUSIONS Delayed invasive strategy was helpful to reduce the incidence of MACE for high-risk NSTEMI with chronic kidney injury. An immediate PCI strategy might increase the rate of MACE. [ABSTRACT FROM AUTHOR]

Background: The current guidelines for managing screen‐detected pulmonary nodules offer rule‐based recommendations for immediate diagnostic work‐up or follow‐up at intervals of 3, 6, or 12 months. Customized visit plans are lacking. Purpose: To develop individualized screening schedules using reinforcement learning (RL) and evaluate the effectiveness of RL‐based policy models. Methods: Using a nested case–control design, we retrospectively identified 308 patients with cancer who had positive screening results in at least two screening rounds in the National Lung Screening Trial. We established a control group that included cancer‐free patients with nodules, matched (1:1) according to the year of cancer diagnosis. By generating 10,164 sequence decision episodes, we trained RL‐based policy models, incorporating nodule diameter alone, combined with nodule appearance (attenuation and margin) and/or patient information (age, sex, smoking status, pack‐years, and family history). We calculated rates of misdiagnosis, missed diagnosis, and delayed diagnosis, and compared the performance of RL‐based policy models with rule‐based follow‐up protocols (National Comprehensive Cancer Network guideline; China Guideline for the Screening and Early Detection of Lung Cancer). Results: We identified significant interactions between certain variables (e.g., nodule shape and patient smoking pack‐years, beyond those considered in guideline protocols) and the selection of follow‐up testing intervals, thereby impacting the quality of the decision sequence. In validation, one RL‐based policy model achieved rates of 12.3% for misdiagnosis, 9.7% for missed diagnosis, and 11.7% for delayed diagnosis. Compared with the two rule‐based protocols, the three best‐performing RL‐based policy models consistently demonstrated optimal performance for specific patient subgroups based on disease characteristics (benign or malignant), nodule phenotypes (size, shape, and attenuation), and individual attributes. Conclusions: This study highlights the potential of using an RL‐based approach that is both clinically interpretable and performance‐robust to develop personalized lung cancer screening schedules. Our findings present opportunities for enhancing the current cancer screening system. [ABSTRACT FROM AUTHOR]

Background: Q fever, caused by the zoonotic pathogen Coxiella burnetii, exhibits a worldwide prevalence. In China, Q fever is not recognized as a notifiable disease, and the disease is overlooked and underestimated in clinical practice, leading to diagnostic challenges. Case presentation: We present a case series of three patients diagnosed with persistent Q fever between 2022 and 2023. The average age of our three cases was 63.33 years old, consisting of two males and one female. The medical history of the individuals included previous valve replacement, aneurysm followed by aortic stent-graft placement and prosthetic hip joint replacement. At the onset of the disease, only one case exhibited acute fever, while the remaining two cases were devoid of any acute symptoms. The etiology was initially overlooked until metagenomic next-generation sequencing test identified Coxiella burnetii from the blood or biopsy samples. Delayed diagnosis was noted, with a duration ranging from three months to one year between the onset of the disease and its confirmation. The epidemiological history uncovered that none of the three cases had direct exposure to domestic animals or consumption of unpasteurized dairy products. Case 1 and 2 resided in urban areas, while Case 3 was a rural resident engaged in farming. All patients received combination therapy of doxycycline and hydroxychloroquine, and no recurrence of the disease was observed during the follow-up period. Conclusion: Q fever is rarely diagnosed and reported in clinical practice in our country. We should be aware of persistent Q fever in high-risk population, even with unremarkable exposure history. Metagenomic next-generation sequencing holds great potential as a diagnostic tool for identifying rare and fastidious pathogens such as Coxiella burnetii. [ABSTRACT FROM AUTHOR]

Objectives Nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3-associated autoinflammatory disease (NLRP3 -AID) is a rare autosomal dominant systemic autoinflammatory disease. We aimed to summarize the phenotypic and genotypic features of Chinese adult NLRP3 -AID patients with hearing loss. Methods A retrospective cohort study of twenty-one adult patients with NLRP3 -AID was conducted in Peking Union Medical College Hospital between July 2015 and March 2023. All patients underwent whole exome sequencing and otorhinolaryngologic assessments. Clinical features and therapeutic data were collected and analysed. Results We found that 13/21 (61.90%) of patients had hearing loss with high-frequency impairment in the majority, and most patients presented with vestibular dysfunction as a new finding. The NLRP3 -AID patients with early-onset, cold or stress triggered episodes, red eyes, fatigue, hypopsia and mutations located in the NACHT domain of the NLRP3 protein were more likely to suffer from hearing loss, especially sensorineural hearing loss, perhaps as a result of pathogenic variants of high penetrance. By a series of audiological evaluations, TNF-α inhibitors were confirmed to improve or reverse hearing loss. Conclusions We reported the first cohort of Chinese adult NLRP3 -AID patients with hearing loss and characterized vestibular dysfunction, highlighted the necessity for attention to high-frequency hearing and provided potential alternative treatment. [ABSTRACT FROM AUTHOR]

Gaucher disease (GD) is an autosomal recessive ailment resulting from glucocerebrosidase deficiency caused by a mutation in the GBA1 gene, leading to multi-organ problems in the liver, spleen, and bone marrow. In China, GD is extremely uncommon and has a lower incidence rate than worldwide. In this study, we report the case of an adult male with an enlarged spleen for 13 years who presented with abdominal distension, severe loss of appetite and weight, reduction of the three-line due to hypersplenism, frequent nosebleeds, and bloody stools. Regrettably, the unexpected discovery of splenic pathology suggestive of splenic Gaucher disease was only made after a splenectomy due to a lack of knowledge about rare disorders. Our patient's delayed diagnosis may have been due to the department where he was originally treated, but it highlights the need for multidisciplinary consultation in splenomegaly of unknown etiology. We then investigated the patient's clinical phenotypes and gene mutation features using genetically phenotypical analysis. The analysis of the GBA1 gene sequence indicated that the patient carried a compound heterozygous mutation consisting of two potentially disease-causing mutations: c.907C > A (p. Leu303Ile) and c.1448 T > C (p. Leu483Pro). While previous research has linked the p. Leu483Pro mutation site to neurologic GD phenotypes (GD2 and GD3), the patients in this investigation were identified as having non-neuronopathic GD1. The other mutation, p. Leu303Ile, is a new GD-related mutation not indexed in PubMed that enriches the GBA1 gene mutation spectrum. Biosignature analysis has shown that both mutations alter the protein's three-dimensional structure, which may be a pathogenic mechanism for GD1 in this patient. [ABSTRACT FROM AUTHOR]

Background: HIV-tuberculosis (HIV-TB) co-infection is a significant public health concern worldwide. TB delay, consisting of patient delay, diagnostic delay, treatment delay, increases the risk of adverse anti-TB treatment (ATT) outcomes. Except for individual level variables, differences in regional levels have been shown to impact the ATT outcomes. However, few studies appropriately considered possible individual and regional level confounding variables. In this study, we aimed to assess the association of TB delay on treatment outcomes in HIV-TB co-infected patients in Liangshan Yi Autonomous Prefecture (Liangshan Prefecture) of China, using a causal inference framework while taking into account individual and regional level factors. Methods: We conducted a study to analyze data from 2068 patients with HIV-TB co-infection in Liangshan Prefecture from 2019 to 2022. To address potential confounding bias, we used a causal directed acyclic graph (DAG) to select appropriate confounding variables. Further, we controlled for these confounders through multilevel propensity score and inverse probability weighting (IPW). Results: The successful rate of ATT for patients with HIV-TB co-infection in Liangshan Prefecture was 91.2%. Total delay (OR = 1.411, 95% CI: 1.015, 1.962), diagnostic delay (OR = 1.778, 95% CI: 1.261, 2.508), treatment delay (OR = 1.749, 95% CI: 1.146, 2.668) and health system delay (OR = 1.480 95% CI: (1.035, 2.118) were identified as risk factors for successful ATT outcome. Sensitivity analysis demonstrated the robustness of these findings. Conclusions: HIV-TB co-infection prevention and control policy in Liangshan Prefecture should prioritize early treatment for diagnosed HIV-TB co-infected patients. It is urgent to improve the health system in Liangshan Prefecture to reduce delays in diagnosis and treatment. [ABSTRACT FROM AUTHOR]

The timing of autism spectrum disorder detection in research and clinical practice is characterised by substantial heterogeneity ranging from infancy to school age. In this study, we examined the age of diagnosis and its associated individual and socio-familial factors in Chinese children diagnosed with autism spectrum disorder. A sample of 1235 autism spectrum disorder children from 132 rehabilitation organisations in Shenzhen was investigated in 2021. We found a mean age of diagnosis of 31.4 ± 12.7 months and a median of 30.0 months. Although 71.7% of the children received their diagnosis between 25 and 36 months of age, and 13.3% were diagnosed early (⩽24 months), 15.1% did not have their symptoms detected until preschool or later years (>36 months). The diagnosis was likely delayed (>36 months) if the children were older, were less severe and presented with no intellectual impairment. The odds of delayed autism spectrum disorder diagnosis were more than 9 times higher among migrant autism spectrum disorder children than those with local household registrations. The study underscores the importance of identifying culturally sensitive socio-economic determinants in autism spectrum disorder detection in addition to clinical factors, as the former are likely to affect the quality of life of many autism spectrum disorder children and their families. Timely detection is an issue of paramount importance in the care of children with autism spectrum disorder. Whether the delayed autism spectrum disorder diagnosis can be explained by children's clinical presentations and socio-familial status in China is a question to be addressed. We investigated 1235 autism spectrum disorder children from 132 rehabilitation organisations in Shenzhen, China. These children were found to have a mean age of diagnosis of 31.4 ± 12.7 months and a median age of diagnosis of 30.0 months. The majority of these children were able to receive their diagnosis during toddlerhood. However, about one in six were not diagnosed until they entered preschool or later, thus missing the golden window of opportunity for early intervention. The age of diagnosis was likely to be late if the children were older, were less severe and presented with no intellectual impairment. The odds of having a delayed autism spectrum disorder diagnosis were more than 9 times higher among migrant autism spectrum disorder children than among those with local household registrations, thus underscoring the importance of identifying culturally sensitive socio-economic determinants in autism spectrum disorder detection, as these factors are likely to affect the quality of life of many autism spectrum disorder children and their families. [ABSTRACT FROM AUTHOR]

• A systematic analysis of typhus group rickettsiosis (TGR) and scrub typhus (ST) cases in China. • Epidemiological patterns of TGR and ST have changed from 1950 to 2022. • Distributions of the reporting institutions varied among the provinces. • Delayed diagnosis was associated with fatal outcomes of TGR and ST. • Enhanced control and prevention strategies for rickettsial diseases are necessary. We conducted a systematic analysis of the notifiable rickettsial diseases in humans in China during 1950-2022. We utilized descriptive statistics to analyze the epidemiological characteristics, clinical manifestations, and diagnostic characteristics of typhus group rickettsiosis (TGR) and scrub typhus (ST) cases. Since the 1950s, there have been variations in the incidence rate of TGR and ST in China, with a downtrend for TGR and an uptrend for ST. The South became a high-incidence area of TGR, whereas the North was previously the high-incidence area. ST cases were concentrated in the South and the geographic area of ST spread northward and westward. The seasonality of TGR and ST were similar in the South but distinct in the North. Most TGR and ST cases were reported by county-level medical institutions, whereas primary institutions reported the least. Delayed diagnosis was associated with fatal outcomes of TGR and ST. Cases in low-incidence provinces, confirmed by laboratory tests and reported from county/municipal-level institutions had higher odds of delayed diagnoses. Our study revealed significant changes in the epidemiological characteristics of TGR and ST in China, which can provide useful information to enhance the control and prevention strategies of rickettsial diseases in China. [ABSTRACT FROM AUTHOR]

Background: In China, rapid intraoperative diagnosis of frozen sections of thyroid nodules is used to guide surgery. However, the lack of subspecialty pathologists and delayed diagnoses are challenges in clinical treatment. This study aimed to develop novel diagnostic approaches to increase diagnostic effectiveness. Methods: Artificial intelligence and machine learning techniques were used to automatically diagnose histopathological slides. AI‐based models were trained with annotations and selected as efficientnetV2‐b0 from multi‐set experiments. Results: On 191 test slides, the proposed method predicted benign and malignant categories with a sensitivity of 72.65%, specificity of 100.0%, and AUC of 86.32%. For the subtype diagnosis, the best AUC was 99.46% for medullary thyroid cancer with an average of 237.6 s per slide. Conclusions: Within our testing dataset, the proposed method accurately diagnosed the thyroid nodules during surgery. [ABSTRACT FROM AUTHOR]

Aim: The diagnosis of inflammatory bowel disease (IBD) worldwide is complicated and results in diagnostic delay. However, the diagnostic interval of IBD and the factors associated with diagnostic delay in patients in China have not been determined.Methods: We retrospectively analyzed clinical data of hospitalized IBD patients in Peking Union Medical College Hospital from January 1998 to January 2018. Patients were divided into non-delayed and delayed groups according to their diagnostic interval.Results: A total of 516 and 848 patients were confirmed to have Crohn's disease (CD) and ulcerative colitis (UC), respectively. The median diagnostic intervals were 6 and 20 months in patients with UC and CD, respectively (P< 0.05). A decreasing trend in the diagnostic interval for IBD was observed over time, from 9 months to 1 month in UC patients and from 30 months to 3 months in CD patients. The longest diagnostic interval was 29.5 months in CD patients with first symptoms at the age of 51– 60 years and 12.5 months in UC patients at the age of 41– 50 years. In patients with CD, intestinal obstruction (OR=2.71), comorbid diabetes (OR=4.42), and appendectomy history (OR=2.18) were risk factors for diagnostic delay, whereas having fever as the first symptom may reduce its risk (OR=0.39). In patients with UC, the misdiagnosis of chronic enteritis (OR=2.10) was a risk factor for diagnostic delay.Conclusion: The diagnostic interval for IBD has decreased over the years. Some clinical manifestations, such as initial symptoms and age at symptom onset, may help to shorten this interval. Diseases such as tuberculosis and infectious enteritis should be considered during differentiation. [ABSTRACT FROM AUTHOR]

Backgrounds: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but lethal cardiac ion channelopathy. Delayed diagnosis and misdiagnosis remain a matter of concern due to its rarity and insufficient recognition of this disorder, particularly in developing countries like China. Aims and methods: We reported six catecholaminergic polymorphic ventricular tachycardia (CPVT) children diagnosed in our center along with a comprehensive review of Chinese pediatric CPVT patients reported in domestic and overseas literature between January 2013 and December 2021 to provide an essential reference for physicians to deepen their understanding of pediatric CPVT. Results: A total of 95 children with CPVT, including our six patients from 21 medical centers were identified. The median age of symptom onset is 8.7 ± 3.0 years. Diagnosis occurred at a median age of 12.9 ± 6.8 years with a delay of 4.3 ± 6.6 years. Selective beta-blockers (Metoprolol and Bisoprolol) were prescribed for 38 patients (56.7%) and 29 (43.3%) patients received non-selective beta-blocker (Propranolol and Nadolol) treatment. Six patients accepted LCSD and seven received ICD implantation at the subsequent therapy. A total of 13 patients died during the disease course. Of the 67 patients with positive gene test results, variants in RYR2 were 47 (70.1%), CASQ2 were 11 (16.4%), and RYR2 accompanied SCN5A were 7 (10.4%). Patients with CASQ2 gene mutations presented with younger symptom onset age, higher positive family history rate and better prognosis than those with RYR2 mutations. Conclusion: Chinese pediatric patients with CPVT had a poorer prognosis than other cohorts, probably due to delayed/missed diagnosis, non-standard usage of beta-blockers, unavailability of flecainide, and a lower rate of LCSD and ICD implantation. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to analyze age-specific characteristics of childhood-onset systemic lupus erythematosus (cSLE) at a health center in China. Methods: The children with SLE were grouped based on age at disease-onset: pre-pubertal (≤7 years), peri-pubertal (8–13 years), and adolescence (14–18 years). The retrospective study included patients with cSLE diagnosed at the Beijing Children's Hospital between 2013 and 2021. Results: A total of 675 females and 178 males were eligible for inclusion in this study. Among them, 160 patients were diagnosed during pre-puberty, 635 during peri-puberty, and 58 during adolescence. The female-to-male ratio of pre-pubertal, peri-pubertal, and adolescent diagnosis was 3.5: 1, 3.6: 1, and 7.28:1, respectively. The median time from onset to diagnosis during the pre-puberal period was 3.0 (IQR 1.0–24.0 months), which was longer than that during the peri-puberal period (1.4; IQR 0.7–4) months and adolescence (1.0; IQR 0.4–2) months (p = <.0001). The proportion of LN in patients diagnosed during the peri-puberal period (304, 46.6%) and during adolescence (27, 47.9%) was higher than that of patients diagnosed during the pre-puberal period (59, 36.9%) (p =.044). 46 (28.8%), 233 (36.7%), and 32 (55.2%) of children diagnosed during the pre-pubertal period, peri-pubertal period, and adolescence, respectively, suffered from leukopenia. Conclusion: The proportion of renal involvement and leukopenia in the pre-pubertal group was lower than that of the pubertal group and adolescent group. More importantly, the younger the age of the patient, the more likely the diagnosis to be delayed. [ABSTRACT FROM AUTHOR]

Objective: This study assesses the diagnostic delay, treatment duration and treatment outcomes of tuberculosis (TB) patients since the implementation of the integrated model of TB control in a county in eastern China. It further identifies factors associated with diagnostic delay and treatment duration in the integrated model. Methods: We collected data through the Chinese Tuberculosis Information Management System (TBIMS) for Cangnan County in Zhejiang Province. Chi-square and Mann-Whitney tests were adopted to identify factors associated with duration of treatment and treatment delay for TB patients within the integrated model. Multiple regression analysis was subsequently performed to confirm the identified factors. Results: In the integrated model from 2012 to 2018, the median health system delay was maintained at 1 day, and the median patient delay decreased from 14 to 9 days and the median total delay decreased from 15 to 11 days. In addition, the proportion of patients who experienced patient delay > 14 days and total delay > 28 days decreased from 49% to 35% and from 32% to 29% respectively. However, the proportion of patients who had health system delay > 14 days increased from 0.2% to 13% from 2012 to 2018. The median treatment duration increased from 199 to 366 days and the number of TB patients lost to follow-up showed an overall upward trend from 2012 to 2018. The multivariable regression analysis indicated that migrant TB patients and TB patients initially diagnosed in hospitals at the prefectural level and above tended to experience total delay > 28 days (p < 0.001). Linear regression analysis confirmed that new TB patients>60 years tended to have longer treatment duration (p < 0.05). Conclusions: While our study may suggest the potential of the integrated model in early detection and diagnosis of TB, it also suggests the importance of strengthening supervision and management of designated hospitals to optimize the treatment duration and improve retention of patients in TB care. Enhancing health education for TB patients, especially amongst migrant patients, and training in TB identification and referral for non-TB doctors are also key for early TB detection and diagnosis in the integrated model. [ABSTRACT FROM AUTHOR]

Objectives We sought to investigate the sex distribution, clinical presentations, disease outcomes and genetic background of early-onset paediatric SLE (eo-pSLE) in a single centre in China to help enable early diagnosis and timely treatment. Methods The clinical data of children aged less than 5 years old with SLE (n  = 19) from January 2012 to December 2021 were reviewed and analysed. We performed DNA sequencing in 11 out of 19 patients to survey the genetic aetiologies. Results Our study included 6 males and 13 females. The mean age at onset was 3.73 years. The median diagnostic delay was 9 months and was longer in male patients (P  = 0.02). Four patients had an SLE-relevant family history. The most common clinical manifestations at diagnosis were fever, rash and hepatosplenomegaly. ANA positivity and low C3 were identified in all children. The renal (94.74%), mucocutaneous (94.74%), haematological (89.47%), respiratory (89.47%), digestive (84.21%), cardiovascular (57.89%) and neuropsychiatric (52.63%) systems were involved to varying degrees. We identified 13 SLE-associated gene mutations in 9 out of 11 patients: TREX1 , PIK3CD , LRBA , KRAS , STAT4 , C3 , ITGAM , CYBB , TLR5 , RIPK1 , BACH2 , CFHR5 and SYK. One male patient showed a 47, XXY chromosomal abnormality. Conclusion Early-onset (<5 years) pSLE is characterized by an insidious onset, typical immunological patterns, and the involvement of multiple organs. Immunological screening and genetic testing should be performed as soon as feasible in patients with an early onset of multisystemic autoimmune diseases to confirm the diagnosis. [ABSTRACT FROM AUTHOR]

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. An increasing number of researchers have found extra motor features in ALS, which are also called ALS-plus syndromes. Besides, a great majority of ALS patients also have cognitive impairment. However, clinical surveys of the frequency and genetic background of ALS-plus syndromes are rare, especially in China. Methods: We investigated a large cohort of 1015 patients with ALS, classifying them into six groups according to different extramotor symptoms and documenting their clinical manifestations. Meanwhile, based on their cognitive function, we divided these patients into two groups and compared demographic characteristics. Genetic screening for rare damage variants (RDVs) was also performed on 847 patients. Results: As a result, 16.75% of patients were identified with ALS-plus syndrome, and 49.5% of patients suffered cognitive impairment. ALS-plus group had lower ALSFRS-R scores, longer diagnostic delay time, and longer survival times, compared to ALS pure group. RDVs occurred less frequently in ALS-plus patients than in ALS-pure patients (P = 0.042) but showed no difference between ALS-cognitive impairment patients and ALS-cognitive normal patients. Besides, ALS-cognitive impairment group tends to harbour more ALS-plus symptoms than ALS-cognitive normal group (P = 0.001). Conclusion: In summary, ALS-plus patients in China are not rare and show multiple differences from ALS-pure patients in clinical and genetic features. Besides, ALS-cognitive impairment group tends to harbour more ALS-plus syndrome than ALS-cognitive normal group. Our observations correspond with the theory that ALS involves several diseases with different mechanisms and provide clinical validation. [ABSTRACT FROM AUTHOR]

Background: Patients with schizophrenia in rural areas of China face severe delays in getting appropriate treatment due to poverty, transportation, and limited availability of mental healthcare services. However, the experiences of care-seeking among patients with delayed diagnosis and treatment in rural areas remain poorly understood, and it remains unclear how these experiences influence patients' medical mistrust or expectations of care. This study aims to fill that void. Methods: We applied a qualitative phenomenological method. Patients were recruited through purposive sampling at a psychiatric hospital in Harbin, China. Semi-structured, one-to-one interviews were conducted, guided by an interview outline. Thematic analysis was performed using Colaizzi's seven-step method. Results: Data saturation was achieved after interviewing 13 participants aged 21 to 53 years. Three themes with eight subthemes were identified: (i) Barriers to seeking care, (ii) Feelings for psychiatric treatment, and (iii) Demand for mental healthcare. Several factors that may impede the timely diagnosis and treatment were identified, including patients, physicians, and institutions. The participants described their feelings of adverse treatment experiences, as well as expectations arising from this process. It predominantly covers awareness of the disease, supportive access to care, and geographic accessibility of services. Conclusion: Patients with delayed diagnosis and treatment in rural areas often have negative experiences and various needs for mental health services in the pursuit of effective treatments. Policymakers and health planners should seriously consider the current challenges in rural mental healthcare to develop comprehensive strategies for improving prehospital delays and medical experience for this group of patients. [ABSTRACT FROM AUTHOR]

Background: Ataxia-telangiectasia (A-T) is a multisystem genetic disorder involving ataxia, oculocutaneous telangiectasia, and immunodeficiency caused by biallelic pathogenic variants in the ATM gene. To date, most ATM variants have been reported in the Caucasian population, and few studies have focused on the genotype-phenotype correlation of A-T in the Chinese population. We herein present a Chinese patient with A-T who carries compound heterozygous variants in the ATM gene and conducted a literature review for A-T in China. Case presentation: A 7-year-old Chinese girl presented with growth retardation, ataxia, medium ocular telangiectasia, cerebellar atrophy, and elevated serum alpha-fetoprotein (AFP) level, which supported the suspicion of A-T. Notably, the serum levels of immunoglobulins were all normal, ruling out immunodeficiency. Exome sequencing and Sanger sequencing revealed two likely pathogenic ATM variants, namely NM_000051.4: c.4195dup (p.Thr1399Asnfs 15) and c.6006 + 1G>T (p.), which were inherited from her father and mother, respectively. From the Chinese literature review, we found that there was a marked delay in the diagnosis of A-T, and 38.9% (7/18) of A-T patients did not suffer from immunodeficiency in China. No genotype-phenotype correlation was observed in this group of A-T patients. Conclusion: These results extend the genotype spectrum of A-T in the Chinese population and imply that the diagnosis of A-T in China should be improved. [ABSTRACT FROM AUTHOR]

Simple Summary: Signet-ring-cell carcinoma (SRCC) is a specific subtype of gastric cancer with a lower incidence and poor prognosis. At the same time, the prognosis of early SRCC and late SRCC remains controversial. Early SRCC and SRCC have different prognostic features, especially lymph-node metastasis. Therefore, the accurate assessment of lymph-node metastasis is important for SRCC. We retrospectively analyzed the prognostic value of different lymph-node staging systems for early and advanced SRCCs. We demonstrated that the predictive performance of log odds of positive lymph nodes (LODDS) is superior to pN-stage and lymph-node metastasis rate (LNR) regardless of early or late SRCC, and is an independent risk factor associated with patient outcomes. This provides a theoretical basis for the further exploration of lymph-node metastasis in SRCC. Background: The lymph-node staging system can predict the prognosis of gastric signet-ring-cell carcinoma (SRCC). However, there are significant differences in lymph-node status between early SRCC and advanced SRCC. Additionally, the optimal system for early and advanced SRCC remains unknown. Methods: This study retrospectively analyzed 693 SRCC patients who underwent radical resection in the Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital. The predicted performance of three lymph-node staging systems, including pN staging, lymph-node metastasis rate (LNR), and log odds of positive lymph nodes (LODDS), was compared using the receiver characteristic operating curve (ROC) and c-index. The Kaplan–Meier method and the log-rank test analyzed the overall survival of patients. The Cox risk regression model identified independent risk factors associated with patient outcomes. The nomogram was made by R studio. Results: The 693 SRCC included 165 early SRCC and 528 advanced SRCC. ROC showed that LODDS had better predictive performance than pN and LNR in predicting prognosis regardless of early or advanced SRCC. LODDS can be used to predict the prognosis of early and advanced SRCC and was an independent risk factor associated with patient outcomes (p = 0.002, p < 0.001). Furthermore, the nomogram constructed by LODDS and clinicopathological features had good predictive performance. Conclusions: LODDS showed clear prognostic superiority over both pN and LNR in early and advanced SRCC. [ABSTRACT FROM AUTHOR]

Underrated and neglected, talaromycosis is a life-threatening fungal disease endemic to the tropical and subtropical regions of Asia. In China, it has been reported that talaromycosis mortality doubles from 24 to 50% when the diagnosis is delayed, and reaches 100% when the diagnosis is missed. Thus, the accurate diagnosis of talaromycosis is of utmost importance. Herein, in the first part of this article, we provide an extensive review of the diagnostic tools used thus far by physicians in the management of cases of talaromycosis. The challenges encountered and the perspectives which may aid in the discovery of more accurate and reliable diagnostic approaches are also discussed. In the second part of this review, we discuss the drugs used to prevent and treat T. marneffei infection. Alternative therapeutic options and potential drug resistance reported in the contemporary literature are also discussed. We aim to guide researchers towards the discovery of novel approaches to prevent, diagnose, and treat talaromycosis, and therefore improve the prognosis for those afflicted by this important disease. [ABSTRACT FROM AUTHOR]

Background: Registry-based studies on pediatric pulmonary arterial hypertension (PPAH) are scarce in developing countries, including China. The PPAH risk assessment tool needs further evaluation and improvement.Research Question: What are the characteristics and long-term survival of PPAH in China and how is the performance of the PPAH risk model in Chinese patients?Study Design and Methods: Patients with PAH were enrolled in the national prospective multicenter registry from August 2009 to December 2019. Children aged 3 months to 18 years at the time of PAH diagnosis were analyzed.Results: A total of 247 children with PAH were enrolled. The median patient age was 14.8 years, and 58.3% were female. PAH associated with congenital heart disease (APAH-CHD, 61.5%) and idiopathic/heritable PAH (IPAH/HPAH, 37.7%) comprised the majority of patients. The median time from symptom onset to PAH diagnosis was 24 months. The mean pulmonary artery pressure and pulmonary vascular resistance index were 70.78±19.80 mmHg and 21.82±11.18 Wood unit·m2, respectively. Patients with APAH-CHD had a longer diagnostic delay, and a higher pulmonary artery pressure but better cardiac performance than those with IPAH/HPAH. An increased number of patients received targeted therapy at the last follow-up compared with baseline. The 5- and 10-year survival rates of the whole cohort were 74.9% and 55.7%, with better survival in patients with APAH-CHD than in those with IPAH/HPAH. Patients with "low risk" had better survival than those with "high risk" according to the simplified noninvasive risk score model with weight, function class, and echocardiographic right ventricular size, both at baseline and follow-up.Interpretation: Patients with PPAH in China had severely compromised hemodynamics with marked diagnostic delay. The long-term survival of PPAH is poor despite the increased utility of targeted drugs. The simplified noninvasive risk model demonstrated good performance for predicting survival in Chinese children with PAH.Clinical Trial Registration: ClinicalTrials.gov (NCT01417338). [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer-related death in China and the world, mainly attributed to delayed diagnosis, given that currently available early screening strategies exhibit limited value. Endobronchial optical coherence tomography (EB-OCT) has the characteristics of non-invasiveness, accuracy, and repeatability. Importantly, the combination of EB-OCT with existing technologies represents a potential approach for early screening and diagnosis. In this review, we introduce the structure and strengths of EB-OCT. Furthermore, we provide a comprehensive overview of the application of EBOCT on early screening and diagnosis of lung cancer from in vivo experiments to clinical studies, including differential diagnosis of airway lesions, early screening for lung cancer, lung nodules, lymph node biopsy and localization and palliative treatment of lung cancer. Moreover, the bottlenecks and difficulties in developing and popularizing EB-OCT for diagnosis and treatment during clinical practice are analyzed. The characteristics of OCT images of normal and cancerous lung tissues were in good agreement with the results of pathology, which could be used to judge the nature of lung lesions in real time. In addition, EB-OCT can be used as an assistant to biopsy of pulmonary nodules and improve the success rate of biopsy. EB-OCT also plays an auxiliary role in the treatment of lung cancer. In conclusion, EB-OCT is non-invasive, safe and accurate in real-time. It is of great significance in the diagnosis of lung cancer and suitable for clinical application and is expected to become an important diagnostic method for lung cancer in the future. [ABSTRACT FROM AUTHOR]

Background: Hereditary spastic paraplegia (HSP) constitutes a group of clinically and genetically rare neurodegenerative diseases characterized by progressive corticospinal tract degeneration. The phenotypes and genotypes of HSP are still expanding. In this study, we aimed to analyse the differential diagnosis, clinical features, and genetic distributions of a Chinese HSP patients in a 14-year cohort and to improve our understanding of the disease. Methods: The clinical data of patients with a primary diagnosis of HSP at the initial visit to the Department of the Neurology, Peking University Third Hospital, from 2008 to 2022 were retrospectively collected. Next-generation sequencing gene panels (NGS) combined with a multiplex ligation-amplification assay (MLPA) were conducted. Epidemiological and clinical features and candidate variants in HSPrelated genes were analyzed and summarized. Results: 54 cases (probands from 25 different pedigrees and 29 sporadic cases) from 95 patients with a primary diagnosis of HSP were finally confirmed to have a clinical diagnosis of HSP based on clinical criteria, including their clinical findings, family history and long-term follow-up. Earlier disease onset was associated with longer diagnostic delay and longer disease duration and was associated with a lower risk of loss of ability to walk independently. In addition, 20 candidate variants in reported HSP-related genes were identified in these clinically diagnosed HSP patients, including variants in SPAST, ALT1, WASHC5, SPG11, B4GALNT1, and REEP1. The genetic diagnostic rate in these 54 patients was 35.18%. Conclusion: Hereditary spastic paraplegia has high clinical and genetic heterogeneity and is prone to misdiagnosis. Long-term follow-up and genetic testing can partially assist in diagnosing HSP. Our study summarized the clinical features of Chinese HSP patients in a 14-year cohort, expanded the genotype spectrum, and improved our understanding of the disease. [ABSTRACT FROM AUTHOR]

Objective: To identify the clinical characteristics, treatment, and prognosis of relapsing polychondritis patients with airway involvement. Methods: Twenty-eight patients with relapsing polychondritis, hospitalised in the First Hospital of Shanxi Medical University between April 2011 and April 2021, were retrospectively analysed. Results: Fifty per cent of relapsing polychondritis patients with airway involvement had a lower risk of ear and ocular involvement. Relapsing polychondritis patients with airway involvement had a longer time-to-diagnosis (p < 0.001), a poorer outcome following glucocorticoid combined with immunosuppressant treatment (p = 0.004), and a higher recurrence rate than those without airway involvement (p = 0.004). The rates of positive findings on chest computed tomography and bronchoscopy in relapsing polychondritis patients with airway involvement were 88.9 per cent and 85.7 per cent, respectively. Laryngoscopy analysis showed that 66.7 per cent of relapsing polychondritis patients had varying degrees of mucosal lesions. Conclusion: For relapsing polychondritis patients with airway involvement, drug treatment should be combined with local airway management. [ABSTRACT FROM AUTHOR]

Background. The number of people suffering from dementia is increasing rapidly in China. Early identification, referral, and intervention for dementia patients within communities are important to public health. However, these measures could be impacted by misconceptions about dementia and associated psychiatric stigma from community health professionals and relatives of dementia patients. Methods. A cross-sectional survey was conducted on 249 participants, which included community doctors, community nurses, and relatives of diagnosed and suspected dementia patients in Guiyang, China. Participants were recruited through convenient sampling. The Chinese version of Dementia Knowledge Assessment Scale (DKAS) and the Perceived Psychiatric Stigma Scale (PPSS) were used to evaluate the participants' knowledge of dementia and dementia-related psychiatric stigma. Results. A total of 249 participants completed the questionnaire. The participants had moderate overall knowledge of dementia and the associated psychiatric stigma. Participants who were -45 years old, had a low level of education, had a low monthly income, or gained knowledge of dementia through non-media channels had lower awareness of dementia and stronger psychiatric stigma. In the "Communication & behavior" subscale of DKAS, all participants had a low level of awareness. Relatives of diagnosed and suspected dementia patients had higher total PPSS and "Marital preclusion" subscale scores than community doctors and nurses but lower psychiatric stigma based on the PPSS "Self-deprecation" subscale score. Conclusions. Despite their profession, community doctors and nurses did not show an absolute advantage over relatives of diagnosed and suspected dementia patients in the dementia knowledge, and they even showed higher psychiatric stigma in some subscales. The self-deprecation subscale is related to the identification with negative labels such as "people with a mental illness are the weak". This study shows that reducing stigma on the "Self-deprecation" subscale should be a core component of training and educational programs targeted at improving dementia knowledge among community health service providers. [ABSTRACT FROM AUTHOR]

This paper aimed to quantify and characterize the prevalence and associated factors for late diagnosis in older adults living with human immunodeficiency virus (HIV) in Liuzhou, China, from 2010 to 2020. The characteristics of older adults living with HIV were described separately in time, space and population. Multivariate logistic regression analysis evaluates the factors influencing late diagnosis in HIV‐positive adults ≥ 50 years of age. The majority of older adults living with HIV were over 60 years old, male, and with CD4 counts < 200 cells/μl at diagnosis, with most late diagnoses being more likely to report heterosexual transmission. These two factors may potentially provide a positive influence on late diagnosis: older and CD4 counts < 500 cells/μl. In contrast, females and those with homosexual or other transmission provide a negative. These results suggest that late diagnosis of HIV‐positive adults ≥ 50 years of age remains a severe and growing epidemiological issue. [ABSTRACT FROM AUTHOR]

Background: Whether medical insurance impacts the timely diagnosis in chronic kidney disease (CKD) children is unknown. We aim to examine the extent to which insurance is associated with access to timely diagnosis and different stages of CKD among a large population of children in China. Methods: A retrospective, cross-sectional study based on China's national hospitalized record database was carried out. Children aged 0–17 years diagnosed as CKD stages 1–5 between June 1, 2013, and December 31, 2018, were included. A diagnosis of advanced CKD stage (CKD stage 4 or 5) was the primary outcome. Multivariable logistic regression model adjusted for age, sex, cross-regional hospitalization, year of diagnosis, and cause of CKD was used to assess the association between insurance status and the stage of CKD when diagnosed. Results: A total of 10,256 children (median [interquartile range, IQR] age, 12.4 [7.9, 15.4] years) were included. There were 4716 (46.0%) uninsured children in the included population. The insurance coverage was highest in children 13–17 years old (60.9%). The hospitalized charge was highest in stage 5 uninsured children (median [IQR], ¥13,000.89 [7640.63, 24,585.00]). More uninsured children are diagnosed in CKD stage 4 or 5 (48.1%) than insured children (47.5%). Uninsured children had higher odds (odds ratio [OR] 1.20, [95% CI, 1.08–1.32]) of receiving a diagnosis of CKD stage 4 or 5 compared with insured children. Conclusions: Lack of medical insurance was associated with a more advanced stage of CKD when diagnosed in hospitalized children. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) seriously threatens individual and public health. Recently, TB outbreaks in schools have been reported more frequently in China and have attracted widespread attention. We reported three TB outbreaks in high schools in Hunan Province, China. Methods: When a tuberculosis patient was reported in a school, we carried out field epidemiological investigations, including tuberculin skin testing (TST), chest X-ray (CXR) and laboratory test for all close contacts, and whole-genome sequencing (WGS) analyses to understand the transmission patterns, the causes and the risk factors for the outbreaks, thereby providing a foundation for the control of TB epidemics in schools. Results: A total of 49 students with TB patients were identified in the three schools where TB outbreaks occurred, including nine patients in School A, 14 patients in School B, and 26 patients in School C. In Schools A, B and C, the putative attack rates in the classes of the index case were 13.8% (8/58), 7.6% (5/66), and 40.4% (21/52), while the putative attack rates of expanding screening in the school were 0.3% (1/361), 0.2% (9/3955), and 0.2% (5/2080), respectively. Thirteen patients had patient delay, with a median delay interval of 69 days (IQR 30.5– 113 days). Twelve patients had a healthcare diagnostic delay with a median delay interval of 32 days (IQR 24– 82 days). Phylogenetic analysis of culture-positive patients revealed that most of them shared a small genetic distance (≤ 12 SNPs), with three separate genetic clusters (including one MDR-TB genomic cluster), indicating the recent transmission of Mycobacterium tuberculosis strains. Conclusion: This combination of field investigation and WGS analysis revealed the transmission of three TB outbreaks in schools. Reinforced implementation is needed to improve timely case finding and reduce diagnosis delay in routine TB control in the school population. [ABSTRACT FROM AUTHOR]

This study examined the prevalence of HIV late diagnosis (LD) and identified associated factors with LD among people living with HIV (PLWH). We extracted sociodemographic, epidemiological, and immunological information between 2018 and 2021 in Hunan, China from the HIV/AIDS Comprehensive Response Information Management System of China. The chi-squared test and multivariable logistic regression model were used to identify the factors associated with LD. Among 22,504 PLWH, 14,988 (66.6%) were diagnosed late. PLWH aged 50 and older had a higher proportion of LD (71.2%) than the younger group (60.0%). Older age, being male, Han ethnicity, being registered in Western Hunan, being transferred from health facilities, and being infected through heterosexual intercourse were associated with LD. Among PLWH younger than 50 years, apart from the factors mentioned above, individuals who had primary school or lower education, were non-student, and were divorced or widowed were more likely to be diagnosed late. Unlike younger PLWH, these factors were not associated with LD in the older group. But regional disparities in LD were more significant among them. LD in PLWH remains a severe issue, especially among older people. The study findings provided valuable insights into designing programs targeting groups at higher risk of LD to reduce its prevalence., (© 2024. The Author(s).)

Depersonalization/derealization disorder (DPD) is a prevalent yet inadequately understood clinical condition characterized by a recurrent or persistent sense of unreality. This study aims to provide insight into DPD through descriptive and comparative analyses involving a large group of Chinese participants. The socio-demographic details (age, gender proportion, education, occupational status, marital status), depersonalized and dissociative symptom characteristics (symptomatic factors or subscales of the Cambridge Depersonalization Scale and the Dissociative Experiences Scale), development trajectory (age of onset, potential precipitating factors, course characteristics), treatment history (duration of delayed healthcare attendance, duration of delayed diagnosis, previous diagnoses), and adverse childhood experiences of the DPD patients are presented. Comparisons of anxiety and depressive symptoms, alongside psychosocial functioning, between DPD participants and those diagnosed with generalized anxiety disorder, bipolar disorders, and major depressive disorder were conducted. The analysis highlights a higher male preponderance and early onset of DPD, symptomatology marked by derealization, notable impairment in psychosocial functioning, and prolonged periods of delayed healthcare attendance and diagnosis associated with symptom severity. Furthermore, noteworthy relationships between adverse childhood experiences and symptom levels were identified. The findings substantiate the view that DPD is a serious but neglected mental disorder, urging initiatives to improve the current condition of DPD patients., (© 2024. The Author(s).)

Background: Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a serious and potentially life-threatening form of wheat allergy. Further episodes can only be prevented by avoiding wheat ingestion or avoiding exercise after wheat intake. Anaphylaxis may recur in some patients post-diagnosis. This study aimed to analyze the clinical features and management/outcomes of WDEIA in China. Methods: We retrospectively analyzed the clinical characteristics, and laboratory testing of 197 patients with WDEIA. After diagnosis, the patients were followed up as outpatients to evaluate dietary/exercise choice and clinical outcomes. Results: Among the 197 WDEIA patients (median age, 37 years), 53.8% were male and 28.4% had other allergic disorders. The median duration of anaphylaxis before diagnosis was 16 months. Significant delays in diagnosis (> 1 years) were recorded in 52.7% of the patients, which has not decreased by years (P = 0.064). Exercise (83.8%), alcohol (12.2%), and nonsteroidal anti-inflammatory drugs (7.1%) were the most common cofactors. The most common clinical features were urticaria (100%), loss of consciousness (82.7%), dyspnea (50.8%), and hypotension (47.2%). Of the 197 eligible patients, 155 responded (78.7%), and 124 (80.0%) of which had no anaphylaxis post-diagnosis. A wheat-free diet prevented future anaphylaxis in 91.7% of the patients, followed by the avoidance of wheat combined with exercise (87%) and reduced wheat intake combined with exercise avoidance (80.5%). Conclusion: The diagnosis of WDEIA is frequently delayed. Therefore, when patients present with unexplained anaphylaxis, the possibility of WDEIA should be considered. A wheat-free diet or avoiding wheat combined with exercise or reduced wheat combined with exercise avoidance helps to significantly reduce the onset of future anaphylaxis. However, approximately one-fifth of patients continue to experience anaphylaxis post-diagnosis. Thus, these patients must always carry epinephrine autoinjectors. [ABSTRACT FROM AUTHOR]

To investigate the clinical and genetic factors influencing the survival of amyotrophic lateral sclerosis (ALS) patients in China. Patients were enrolled in the study between December 2013 and December 2018. Clinical variables were recorded upon patient diagnosis. Causative genes related to ALS were screened by whole-exome sequencing and validated by Sanger sequencing. Each patient was followed up every 3–6 months until the endpoint (death or tracheotomy) or the last connection time on 31 December 2020. Propensity score matching analysis was performed to match the genetic and non-genetic ALS patients. The Kaplan–Meier method and multivariable Cox regression were performed for survival analysis. A total of 337 patients, including 32 with genetic ALS and 305 with non-genetic ALS, were enrolled in the study. Before matching, in univariate analysis, age of onset (P < 0.001), site of onset (P = 0.036), diagnostic delay (P < 0.001), ALSFRS-R score at diagnosis (P < 0.001), ΔALSFRS-R (P < 0.001), and causative mutations (P = 0.020) were significant prognostic factors. These factors remained statistically significant after multivariate analysis. After matching, in the multivariate analysis, age of onset (P = 0.003), site of onset (P = 0.014), diagnostic delay (P = 0.007), ALSFRS-R score at diagnosis (P = 0.010), ΔALSFRS-R (P = 0.007), and causative mutations (P = 0.003) were found to be significant prognostic factors. Both clinical factors and genetic factors influenced survival in our ALS cohort. Clarifying of the underlying mechanisms is crucial for the development of future therapies. [ABSTRACT FROM AUTHOR]

Coccidioidomycosis is caused by the dimorphic fungi Coccidioides species which is endemic in the Western hemisphere. Reports on the characteristics of travel-related disseminated coccidioidomycosis in immunocompetent patients are rare, especially in non-endemic regions. The multifaceted symptoms of this condition present a diagnostic challenge to clinicians. This study aimed to review immunocompetent patients diagnosed with disseminated coccidioidomycosis in a tertiary hospital in Eastern China and other non-endemic areas, and to emphasize the importance of combining travel history with clinical manifestations and proper diagnostic examinations. This study retrospectively reviewed a case series of disseminated coccidioidomycosis diagnosed in an academic hospital in Eastern China. We conducted a global literature review of disseminated coccidioidomycosis in immunocompetent patients with travel history. We identified six patients in our case series and reviewed 42 cases in the literature. Travel history included Mexico, Arizona, California, and regions of low endemicity. Extrapulmonary sites of infection, which presented with diverse signs and symptoms, involved the skin and soft tissue, musculoskeletal system, lymph nodes, and central nervous system. Misdiagnoses and diagnostic delays were common. Next-generation sequencing substantially promoted precise diagnosis in our series. The overall prognosis for immunocompetent individuals was positive, mainly benefited from long-term azole therapies. The patients that succumbed had either central nervous system involvement or multiorgan dissemination. Progressive pneumonia with varied symptoms and travel history should alert healthcare professionals in non-endemic areas to consider the possibility of Coccidioides species infection. We recommend detailed history-taking and hypothesis-free detection of pathogens for cases with diagnostic delay. [ABSTRACT FROM AUTHOR]

Ultrasonography is the most widely used technique to diagnose echinococcosis; however, challenges in using this technique and the demand on medical resources, especially in low-income or remote areas, can delay diagnosis. We aimed to develop a deep convolutional neural network (DCNN) model based on ultrasonography to identify echinococcosis and its types, especially alveolar echinococcosis. • This study used 9631 ultrasound images from patients assessed at 84 hospitals in China, obtained between Jan 1, 2002, and Dec 31, 2021. Patients with a diagnosis of cystic echinococcosis, alveolar echinococcosis, or seven other types of focal liver lesions were included. • We tested ResNet-50, ResNext-50, and VGG-16 as the backbone network architecture for a classification DCNN model and input the perinodular information from the ultrasound images. We trained and validated the DCNN model to diagnose and classify echinococcosis using still greyscale ultrasound images of focal liver lesions. • We then tested the algorithm on internal, external, and prospective test datasets. The performance of DCNN was also compared with that of 12 radiologists in a subset of ultrasound data that were randomly chosen from the prospective test dataset. Results The DCNN model was shown to be accurate and robust, and could improve the ultrasound diagnostic ability of radiologists for Echinococcosis and its types for highly endemic and remote regions. [ABSTRACT FROM AUTHOR]

Primary care serves as the cornerstone to ensure positive health outcomes for diseases. Autism spectrum disorder (ASD) has attracted more attention as a lifelong neurodevelopmental disorder with a prevalence that is increasing yearly. Although the demand for primary care for ASD is rapidly expanding, there are many challenges that need to be faced. Here, the current status of primary care for ASD in China is described. i) Identification of and care for ASD includes pre-diagnosis, diagnosis and evaluation, and treatment; the complexity of the disease and the lack of public understanding increase delays in diagnosis and treatment. ii) Most instruments, which are indispensable for diagnosing and evaluating ASD, are of foreign origin. iii) Treatments for ASD are based on mainstream Western interventions with complementary approaches. iv) The scale of rehabilitation and educational institutions has gradually grown and their expertise has gradually increased but rehabilitation costs are relatively high. [ABSTRACT FROM AUTHOR]

Background: Rare disease patients often experience diagnosis delays or misdiagnosis, which may be due to lack of knowledge on rare diseases among physicians.Objective: To assess Chinese physicians' knowledge on specific rare diseases and identify its associated factors.Methods: Thirty-four patient organizations with a unique disease of interest were invited to develop 3 knowledge questions for each rare disease to assess physicians' knowledge on the disease that they felt most experienced in. The total knowledge score for each participant ranged from a score of 0 to 3. A national cross-sectional study conducted in a cohort of 3197 physicians from 6 provinces across western, central and eastern China. The demographic information of the participants was collected including gender, age, birthplace, income, education, hospital class, working title, working years, and specialty. A multiple linear regression analysis was performed to assess the independent associations between the physician variables and the total knowledge score.Results: Two thousand, one hundred and fifteen (66.16%) of the involved physicians obtained a total knowledge score of 2 or 3. The median knowledge scores of 10 (29.4%) rare diseases were a score of 1.5 or below. Physicians with female gender (β = 0.08, p < 0.05 for females vs. males), and a monthly income of 5000-10,000 RMB (β = 0.11, p < 0.01 for 5000-10,000 vs. < 5000) and 10,000-30,000 RMB (β = 0.14, p < 0.05) were associated with a higher score. Specialties of physicians who received a relatively higher score included internal medicine, obstetrics and gynecology, radiology, intensive care unit, and surgery.Conclusions: Almost two thirds of the participants had an average or good level of knowledge on the specific rare disease that they felt most experienced in. Physicians with female gender, a monthly income of 5000-10,000 RMB and 10,000-30000 RMB, and specialties of internal medicine, obstetrics and gynecology, radiology, intensive care unit, and surgery, were associated with a relatively higher knowledge score. [ABSTRACT FROM AUTHOR]

Background: The lack of simple and affordable spirometry has led to the missed and delayed diagnoses of chronic respiratory diseases in communities. The PUS201P is a portable spirometry developed to solve this problem.Objective: We aimed to verify the consistency of the PUS201P spirometer with conventional Jaeger spirometer.Methods: In this cross-sectional study, we randomly recruited 202 subjects aged > 40 years. Testing with the portable spirometry and conventional spirometry were performed on all participants. We compared forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC measured by the PUS201P device with the conventional spirometer. Pearson correlation coefficient and Interclass Correlation Coefficient (ICC) were assessed to confirm the consistency of the measures from two instruments. Bland-Altman graph was created to assess the agreement of the measures from two devices.Results: 202 participants were included in this study. The ICC on FEV1, FVC, FEV1/FVC measured by the portable spirometer and the conventional spirometer were 0.95 (95% confidence interval [CI]: 0.94-0.96), 0.92 (95% CI: 0.90-0.94], 0.93 (95% CI: 0.91-0.95), respectively. The Bland-Altman plots showed that the mean difference between the measures from two spirometers are always located in the 95% limits of agreement.Conclusions: Our results support that the measures from the portable spirometer and the conventional spirometer have a good agreement and reproducibility. And the portable spirometer is a reliable tool to screen and diagnose chronic airway diseases in the primary care settings. [ABSTRACT FROM AUTHOR]

Objectives: Delay in diagnosis and treatment, called total delay, could probably result in lower survival rates in breast cancer patients. This study aimed to investigate the factors associated with the comprehensive delay behaviors and to evaluate its effect on outcomes in patients with breast cancer in Dalian, a northeast city of China. Methods: A retrospective chart review was conducted using a cancer registry dataset including 298 patients. The Kaplan–Meier survival analysis was used to identify the threshold of total delay, dividing the patients into a group with significant uncertainty and a group without substantial delay. The factors associated with the significant total delay were investigated from the potential candidates, like income level and marital status, by using the chi-squared test. The difference of the clinicopathologic characteristics between the patients grouped by the significant total delay, like tumor size and lymph node metastasis, was also investigated to find out the effect of the total delay. Results: A total of 238 charts were used for analysis. The mean age was 57.3. The median of total delays was 3.75 months. Thirty days was identified as a threshold, more than which the total delay can lead to worse survival. Patients' marital status (p = 0.010), income levels (p = 0.003), smoking status (p = 0.031), initial visiting hospital level (p = 0.005), self-health care (p = 0.001), and self-concern about initial symptom (p ≈ 0.000) were identified as the independent predictors of the total delay. Metastasis (p ≈ 0.000) was identified as the significant result relating to the significant total delay. Conclusions: A total delay of more than 30 days predicts worse survival in breast cancer patients in Dalian. Several factors, like patients' marital status and income levels, can be considered to be relevant to the significant total delay. We recommend that these factors be used to predict the potential patients with the significant total delay in the clinical practice. [ABSTRACT FROM AUTHOR]

Background: Since the spreading of SARS-CoV-2 from China, all deferrable medical activities have been suspended, to redirect resources for the management of COVID patients. The goal of this retrospective study was to investigate the impact of COVID-19 on head and neck cancers' diagnosis in our Academic Hospital. Methods: A retrospective analysis of patients treated for head and neck cancers between March 12 and November 1, 2020 was carried out, and we compared these data with the diagnoses of the same periods of the 5 previous years. Results: 47 patients were included in this study. We observed a significative reduction in comparison with the same period of the previous 5 years. Conclusions: Our findings suggest that the COVID-19 pandemic is associated with a decrease in the number of new H&N cancers diagnoses, and a substantial diagnostic delay can be attributable to COVID-19 control measures. [ABSTRACT FROM AUTHOR]

Objectives: To assess whether recurrent gestational diabetes mellitus (GDM) and newly diagnosed GDM share similar risk factors. Methods: The study recruited a cohort of 10,151 multipara women with singleton pregnancy who delivered between 2016 and 2019 in Beijing, China. The prevalence of recurrent GDM and associated risk factors were analyzed between women with and without prior GDM history. Results: Eight hundred and seventy-five (8.6%) multipara women had a diagnosis of GDM during previous pregnancies. The prevalence of GDM and pre-gestational diabetes mellitus were 48.34% (423/875) and 7.89% (69/875) if the women were diagnosed with GDM during previous pregnancies, as compared to 16.00% (1484/9276) and 0.50% (46/9276) if the women were never diagnosed with GDM before. In women without a history of GDM, a variety of factors including older maternal age, higher pre-pregnancy body mass index (PPBMI), prolonged interval between the two pregnancies, higher early pregnancy weight gain, family history of type 2 diabetes mellitus (T2DM), maternal low birth weight, and higher early pregnancy glycemic and lipid indexes were generally associated with an increased risk of GDM at subsequent pregnancy. In women with a history of GDM, higher PPBMI, higher fasting glucose level and maternal birthweight ≥4000 g were independent risk factors for recurrent GDM. Conclusions: GDM reoccurred in nearly half of women with a history of GDM. Risk factors for recurrent GDM and newly diagnosed GDM were different. Identifying additional factors for GDM recurrence can help guide clinical management for future pregnancies to prevent GDM recurrence. [ABSTRACT FROM AUTHOR]

Background: To investigate the association between geographic, clinical, socioeconomic factors and delayed management of pediatric testicular torsion (TT) in West China.Methods: A retrospective study was conducted on TT at Children's Hospital of Chongqing Medical University in West China from November 2004 to December 2020. Univariate analysis and logistic regression analysis were conducted to determine the association between these factors and delayed management of TT.Results: A total of 301 cases were included in this study. The misdiagnosis rate of TT in primary, secondary healthcare units and tertiary hospitals was 93.8, 71.1, and 8.9%, respectively. Approximately 26.9% of TT boys received timely surgical management (within 12 h from symptoms inset to surgery). Logistic regression analyses suggested the following factors were associated with delayed repair of TT: age less than 6 years (P = 0.001), with a history of symptoms progress (P = 0.001) or former treatment (P <0.001), absence of other diagnosis (P = 0.011) and those boys living far away from the main city zones (P <0.001).Conclusions: Delayed surgical management for TT was more likely for boys with age less than 6 years, the absence of other diagnosis, with a history of former treatment or symptoms progress, and those living far away from the main city zone. To maximize the possibility of timely surgical management for TT, it is vital to strengthen the public awareness of TT and conduct continuously re-education and update physicians working at primary and secondary healthcare units. [ABSTRACT FROM AUTHOR]

Objective: High prevalence of undiagnosed psoriatic arthritis (PsA) and prolonged diagnostic delay are key troubles in the appropriate management of PsA. To analyze the possible causes for this phenomenon, a web-based nationwide survey was conducted to investigate rheumatologists' perceptions on PsA diagnosis in China. Methods: The electronic questionnaire consisting of 38 questions were designed by an expert panel and distributed with the online survey tool Sojump, which is a professional online survey platform. The completed questionnaires by real-name rheumatologists were collected. Results: A total of 1594 valid questionnaires were included. More than half of Chinese rheumatologists reported it was challenging to make a diagnosis of PsA. The four major challenges were "Difficulties in identification of atypical or hidden psoriasis", "Absence of diagnostic biomarkers", "No active self-report of history or family history of psoriasis" and "Various musculoskeletal manifestations". In diagnosing PsA, minor participants had incorrect knowledge of inflammatory arthropathy (13.7%), acute phase reactant (23.8%), and rheumatoid factor (28.7%). There were no significant differences in the knowledge of PsA and practice habits in diagnosing PsA between modern western medicine (WM)- and traditional Chinese medicine (TCM)-rheumatologists. The part-time rheumatologists were not as good as full-time rheumatologists in diagnosing PsA. Conclusions: About three quarters of Chinese rheumatologists are familiar with the elements in PsA diagnosis and have good practice habits in diagnosing PsA. Four main challenges in making PsA diagnosis are revealed. There was no significant difference in the knowledge of PsA between WM- and TCM-rheumatologists. [ABSTRACT FROM AUTHOR]

This study investigated the association between serum albumin concentration and 12-weeks mortality of HIV/AIDS with late diagnosis in China. This retrospective cohort study included, 1079 inpatients diagnosis with late HIV/AIDS between January 2018 and December 2021. Disease progression was estimated based on the 12-weeks mortality rate. Cox proportional hazards regression models were used to evaluate the relationship between serum albumin levels and disease progression. The effects of serum albumin levels on mortality was estimated via Kaplan-Meier curves. The mortality risk decreased by 7% with every 1 g/L increase in serum albumin after adjustment ([HR] = 0.93, 95% CI: 0.88-0.97). Compared with that of the low (< 28 g/L) serum albumin group, the middle (28-34 g/L) group's mortality risk decreased by 70% (HR = 0.30, 95% CI: 0.15-0.59), and that of the high (≥ 34 g/L) group decreased by 40% (HR = 0.6, 95% CI: 0.29-1.23) after adjustment. Our findings suggest a positive correlation between the increase in serum albumin levels upon admission and a decrease in mortality at 12 weeks post-discharge among patients with late AIDS/HIV diagnosis. Further research is needed to characterize the role of serum albumin in 12-weeks mortality prevention in patients with a late diagnosis., (© 2024. The Author(s).)

Background and Aims: The significance of different ages of perianal disease (PD) onset in patients with perianal Crohn's disease (PCD) remains unknown. We aimed to investigate the impact of paediatric-onset PD (POP) and adult-onset PD (AOP) on the Crohn's disease (CD) course in a Chinese cohort.Methods: The medical records of diagnosed PCD patients from 2008 to 2018 were reviewed retrospectively. The cumulative incidence and predictors of intestinal resection were calculated using the Kaplan-Meier and logistic regression analysis.Results: Complex perianal fistulas (71.7% vs 50.0%, p = 0.011) and infliximab (IFX) treatment (33.3% vs 22.0%, p = 0.044) were more common among the POP patients (age < 18 years old, n = 84). A younger PD onset age (15.1 ± 2.9 vs 30.2 ± 10.5 years, p < 0.001) and shorter PCD diagnostic delay (12 vs 24 months, p = 0.033) was found in the POP cohort. AOP patients (age ≥ 18 years old, n = 209) had a higher rate of current smoking (12.9% vs 4.8%, p = 0.040), stricturing behaviour (42.1% vs 27.4%, p = 0.024) and intestinal resection (21.1% vs 4.8%, p = 0.001). The cumulative probability of intestinal resection in AOP patients was higher than that in POP patients (p = 0.007). In multivariable analysis, AOP (OR: 4.939, 95% CI 1.538-15.855, p = 0.007), stricturing behaviour (OR: 1.810, 95% CI 1.008-3.251, p = 0.047) and rectal inflammation (OR: 3.166, 95% CI 1.119-8.959, p = 0.030) were predictive factors for CD-related intestinal resection in all PCD patients. AOP patients with complex perianal fistula (OR: 2.257, 95% CI 1.041-4.891, p = 0.039) and POP patients with rectal inflammation (OR: 3.166, 95% CI 1.119-8.959, p = 0.030) were more likely to suffer intestinal resection. The IFX administration significantly decreased the rate of intestinal resection in AOP patients (r = - 0.900, p = 0.037).Conclusions: The AOP patients have more complicated luminal disease and higher rate of intestinal resection than COP patients. The perianal diseases onset-age can provide clinical treatment guidance for individual management of CD patients. [ABSTRACT FROM AUTHOR]

Background: Mutations in superoxide dismutase 1 gene (SOD1) are the most frequent high penetrant genetic cause for amyotrophic lateral sclerosis (ALS) in the Chinese population. A detailed natural history of SOD1 -mutated ALS patients will provide key information for ongoing genetic clinical trials. Methods: We screened for SOD1 mutations using whole exome sequencing (WES) in Chinese ALS cases from 2017 to 2021. Functional studies were then performed to confirm the pathogenicity of novel variants. In addition, we enrolled previously reported SOD1 mutations in our centers from 2007 to 2017. The SOD1 mutation spectrum, age at onset (AAO), diagnostic delay, and survival duration were analyzed. Results: We found two novel SOD1 variants (p.G17H and p.E134*) that exerted both gain-of-function and loss-of-function effects in vitro. Combined with our previous SOD1 -mutated patients, 32 probands with 21 SOD1 mutations were included with the four most frequently occurring mutations of p.V48A, p.H47R, p.C112Y, and p.G148D. SOD1 mutations account for 58.9% of familial ALS (FALS) cases. The mean (SD) AAO was 46 ± 11.4 years with a significant difference between patients carrying mutations in exon 1 [ n = 5, 34.6 (12.4) years] and exon 2 [ n = 8, 51.4 (8.2) years] (p = 0.038). The mean of the diagnostic delay of FALS patients is significantly earlier than the sporadic ALS (SALS) patients [9.5 (4.8) vs. 20.3 (9.3) years, p = 0.0026]. In addition, male patients survived longer than female patients (40 vs. 16 months, p = 0.05). Conclusion: Our results expanded the spectrum of SOD1 mutations, highlighted the mutation distribution, and summarized the natural history of SOD1 -mutated patients in southeastern China. Male patients were found to have better survival, and FALS patients received an earlier diagnosis. Our findings assist in providing a detailed clinical picture, which is important for ongoing genetic clinical trials. [ABSTRACT FROM AUTHOR]

Background: There are over 16.8 million rare disease patients in China, representing a large community that should not be neglected. While the public lack the awareness of their existence and difficult status quo, for one reason that they exist as a rare and special group in our society, for another reason that all sectors of the community haven't introduced and propagandized them suitably. However, as a special group with more difficulties in all aspects than normal healthy persons, they need enough care and love from us. To provide a basis for policy-makers to better understand the status quo of rare disease patients and care-givers in China and to devise some new policies to improve their quality of life, a comprehensive analysis of the status quo, unmet needs, difficulty caused by the rare disease is essential.Methods: A questionnaire-based online study of patients and care-givers (usually family members) was performed. The questionnaire was composed of 116 questions, such as the diagnosis process, treatment access, financial burden, views on patients' organizations, and a series of standardized tests to assess the quality of their life, including the SF-36, PHQ-9, PHQ-15, GAD-7, and PSQI. To examine the influence of age, disease type, and relationship to patients on the scores in these tests, statistical analysis with a general linear model was conducted.Findings: A total of 1959 patients and care-givers participated in the survey, representing 104 rare diseases, such as lysosomal storage diseases, hemophilia, and muscular dystrophy diseases. The diagnosis was delayed for 1.4 ± 3.0 years, and patients experienced 1.6 ± 3.8 misdiagnoses between 3.2 ± 2.4 hospitals. The hospitals where diagnoses were made were highly concentrated in 10 large hospitals (43.8%) and 5 big cities (42.1%), indicating a significant inequality of medical resources. The disease often led to difficulty in social life, education, and employment, as well as financial burden that was seldom covered by medical insurance. A battery of standardized tests demonstrated poor health status, depression, somatization, anxiety, and sleeping issues among both patients and care-givers (p < 0.05). Statistical analysis of the questionnaire also showed that poor health, anxiety, depression, somatization, and sleeping problems were more prevalent in patients than in care-givers, and more prevalent in more severe diseases (e.g., hemophilia, Dravet) or undiagnosed than in other diseases.Interpretations: This study identified the lack of rare disease awareness and legislative support as the major challenge to rare diseases in China, and makes key recommendations for policy-makers, including legislating orphan drug act, raising rare disease awareness, providing sufficient and fair opportunities about education and employment, expanding the medical insurance coverage of treatments, and protecting rights in education and employment. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the factors impacting time to diagnosis in pediatric central nervous system tumors.Methods: A descriptive, cross-sectional design was used in this study. A self-developed questionnaire for health-seeking behavior and influencing factors was used in children with intracranial tumors. The factors related to time to diagnosis and the long-term prognosis of children were analyzed.Results: A total of 433 families replied to the questionnaire. The median parental interval was 50 days (range 0 ~ 884), the median diagnostic interval was 97 days (range 4 ~ 1646), and the median prediagnostic symptomatic interval (PSI) was 123 days (range 8 ~ 1844). Higher education was associated with a shorter parental interval (mother: P = 0.048; father: P = 0.035). The diagnostic interval was shortened in patients with dizziness (P = 0.022), abnormal eye movement (P = 0.034), or drowsiness (P = 0.021). A shorter PSI was observed in patients who presented with high intracranial pressure such as headache (P = 0.016), dizziness (P = 0.009), or drowsiness (P = 0.023) and those who went to a higher-level health institution or patients who went to neurology or neurosurgery department as the first medical consultation. No statistically significant difference was found in the interval time (parental interval, diagnostic interval, and PSI) regarding patients' outcomes.Conclusion: Different time intervals showed different factors influencing the long delay in diagnosing central nervous system tumors, highlighting the need for increased awareness to improve the treatment efficacy. [ABSTRACT FROM AUTHOR]