Global, regional, and national burden of premenstrual syndrome, 1990-2019: an analysis based on the Global Burden of Disease Study 2019.

STUDY QUESTION: What is the burden of premenstrual syndrome (PMS) at the global, regional, and national levels across 21 regions and 204 countries and territories? SUMMARY ANSWER: Over the past few decades, the global prevalent cases of PMS have grown significantly from 652.5 million in 1990 to 956.0 million in 2019, representing a 46.5% increase. WHAT IS KNOWN ALREADY: PMS, which affects almost half of reproductive women worldwide, has substantial social, occupational, academic, and psychological effects on women's lives. However, no comprehensive and detailed epidemiological estimates of PMS by age and socio-demographic index (SDI) at global, regional, and national levels have been reported. STUDY DESIGN, SIZE, DURATION: An age- and SDI-stratified systematic analysis of the prevalence and years lived with disability (YLD) of PMS by age and SDI across 21 regions and 204 countries and territories has been performed. PARTICIPANTS/MATERIALS, SETTING, METHODS: The prevalence and YLD of PMS from 1990 to 2019 were retrieved directly from the Global Burden of Diseases (GBD) 2019 study. The number, rates per 100 000 persons, and average annual percentage changes (AAPCs) of prevalence and YLD were estimated at the global, regional, and national levels. MAIN RESULTS AND THE ROLE OF CHANCE: Globally, the prevalent cases of PMS increased by 46.5% from 652.5 million in 1990 to 956.0 million in 2019; in contrast, however, the age-standardized prevalence rate was approximately stable at 24 431.15/100 000 persons in 1990 and 24 406.51/100 000 persons in 2019 (AAPC, 0[95% CI: -0.01 to 0.01]). Globally, the YLD was 8.0 million in 2019 and 5.4 million in 1990, with a sizable increase over the past 30 years. The age-standardized YLD rate was stable (AAPC 0.01, P = 0.182), at 203.45/100 000 persons in 1990 and 203.76/100 000 persons in 2019. The age-standardized burden estimates were the highest in the low-middle SDI regions and the lowest in the high SDI regions. Peaks in burden rate estimates were all observed in the 40-44 years age group. Regional age-standardized burden estimates were the highest in South Asia and the lowest in Western Sub-Saharan Africa. The national age-standardized burden estimates were the highest in Pakistan and the lowest in Niger. LIMITATIONS, REASONS FOR CAUTION: The accuracy of the results depended on the quality and quantity of the GBD 2019 data. Fortunately, the GBD study endeavoured to retrieve data globally and applied multiple models to optimize the completeness, accuracy, and reliability of the data. In addition, the GBD study took the country as its basic unit and neglected the influence of race. Further study is warranted to compare differences in PMS burden associated with race. Finally, no data are available on the aetiology and risk information related to PMS, which might help us to better understand the trends and age distribution of PMS and help local governments formulate more detailed policies and comprehensive interventions. WIDER IMPLICATIONS OF THE FINDINGS: Although the age-standardized prevalence/YLD rate has been stable over the past 30 years, the absolute number of prevalent cases and YLD grew significantly worldwide from 1990 to 2019. Public health-related policies should be implemented to reduce the prevalence and alleviate the symptoms of PMS. Lifestyle changes and cognitive-behavioral therapy are critical in helping to reduce the burden of PMS. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (grant number 2022YFC2704100) and the National Natural Science Foundation of China (No. 82001498, No. 82371648). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Efficacy of immune checkpoint inhibitor monotherapy or combined with other small molecule-targeted agents in ovarian cancer.

Ovarian cancer is the most lethal female reproductive system tumour. Despite the great advances in surgery and systemic chemotherapy over the past two decades, almost all patients in stages III and IV relapse and develop resistance to chemotherapy after first-line treatment. Ovarian cancer has an extraordinarily complex immunosuppressive tumour microenvironment in which immune checkpoints negatively regulate T cells activation and weaken antitumour immune responses by delivering immunosuppressive signals. Therefore, inhibition of immune checkpoints can break down the state of immunosuppression. Indeed, Immune checkpoint inhibitors (ICIs) have revolutionised the therapeutic landscape of many solid tumours. However, ICIs have yielded modest benefits in ovarian cancer. Therefore, a more comprehensive understanding of the mechanistic basis of the immune checkpoints is needed to improve the efficacy of ICIs in ovarian cancer. In this review, we systematically introduce the mechanisms and expression of immune checkpoints in ovarian cancer. Moreover, this review summarises recent updates regarding ICI monotherapy or combined with other small-molecule-targeted agents in ovarian cancer.

Does the primary treatment sequence affect post-relapse survival in recurrent epithelial ovarian cancer? A real-world multicentre retrospective study.

OBJECTIVE: To explore the impact of the primary treatment sequence (primary debulking surgery, PDS, versus neoadjuvant chemotherapy and interval debulking surgery, NACT-IDS) on post-relapse survival (PRS) and recurrence characteristics of recurrent epithelial ovarian cancer (REOC). DESIGN: Real-world retrospective study. SETTING: Tertiary hospitals in China. POPULATION: A total of 853 patients with REOC at International Federation of Gynaecology and Obstetrics stages IIIC-IV from September 2007 to June 2020. Overall, 377 and 476 patients received NACT-IDS and PDS, respectively. METHODS: Propensity score-based inverse probability of treatment weighting (IPTW) was performed to balance the between-group differences. MAIN OUTCOME MEASURES: Clinicopathological factors related to PRS. RESULTS: The overall median PRS was 29.3 months (95% CI 27.0-31.5 months). Multivariate analysis before and after IPTW adjustment showed that NACT-IDS and residual R1/R2 disease were independent risk factors for PRS (p < 0.05). Patients with diffuse carcinomatosis and platinum-free interval (PFI) ≤ 12 months had a significantly worse PRS (p < 0.001). Logistic regression analysis revealed that NACT-IDS was an independent risk factor for diffuse carcinomatosis (OR 1.36, 95% CI 1.01-1.82, p = 0.040) and PFI ≤ 12 months (OR 1.59, 95% CI 1.08-2.35, p = 0.019). In IPTW analysis, NACT-IDS was still significantly associated with diffuse carcinomatosis (OR 1.29, 95% CI 1.05-1.58, p = 0.015) and PFI ≤ 12 months (OR 1.90, 95% CI 1.52-2.38, p < 0.001). CONCLUSIONS: The primary treatment sequence may affect the PRS of patients with REOC by altering the recurrence pattern and PFI duration.

The first Chinese National Union of Real-world Gynaecological Oncology Research and Patient Management Platform: A retrospective study.

OBJECTIVE: To produce high-quality, real-world evidence for oncologists by collating scattered gynaecologic oncology (GO) medical records in China. DESIGN: Retrospective study. SETTING: The National Union of Real-world Gynaecological Oncology Research and Patient Management Platform (NUWA platform). SAMPLE: Patient-centred data pool. METHODS: The NUWA platform integrated inpatient/outpatient clinical, gene and follow-up data. Data of 11 456 patients with ovarian cancer (OC) were collected and processed using 91 345 electronic medical records. Structured and unstructured data were de-identified and re-collated into a patient-centred data pool using a predefined GO data model by technology-aided abstraction. MAIN OUTCOME MEASURES: Recent treatment pattern shifts towards precision medicine for OC in China. RESULTS: Thirteen first-tier hospitals across China participated in the NUWA platform up to 7 December 2021. In total, 3504 (30.59%) patients were followed up by a stand-alone patient management centre. The percentage of patients undergoing breast cancer gene (BRCA) mutation tests increased by approximately six-fold between 2017 and 2018. A similar trend was observed in the administration rate of poly(ADP-ribose) polymerase inhibitors as first-line treatment and second-line treatment after September 2018, when olaparib was approved for clinical use in China. CONCLUSION: The NUWA platform has great potential to facilitate clinical studies and support drug development, regulatory reviews and healthcare decision-making.

Application of in vivo traction-assisted resection of proximal colon lesions: a case series (with video).

BACKGROUND: Endoscopic submucosal dissection (ESD) is the treatment of choice for colorectal neoplasms in Japan. ESD can completely peel off the lesion and is associated with a significantly lower recurrence rate of colorectal cancers than EMR and is widely used to treat gastrointestinal tumors. This study aimed to evaluate in vivo traction in endoscopic submucosal dissection (ESD) of proximal colon lesions. METHODS: This retrospective study included patients with lesions in the proximal colon who received ESD treatment at Qilu Hospital of Shandong University from June 2018 to December 2020. Patients were divided into two groups according to the in vivo traction method (orthodontic ring or elastic ring) during operation. The operation time, dissection time, proportion of complete resection of lesions, and complications were compared between the two groups. RESULTS: There were 28 patients in this study. In the orthodontic ring group (n = 10), the average lesion diameter was 2.0-2.5 cm, and the average operation and dissection times were 26.5 ± 7.47 and 21.5 ± 7.47 min, respectively. In the elastic ring group (n = 18), the average lesion diameter was 2.5-5.5 cm, and the average operation and dissection times were 27.39 ± 11.83 and 22.39 ± 11.83 min, respectively. All lesions were completely resected in a single operation, and no wound perforation and delayed bleeding occurred. CONCLUSION: In vivo traction-assisted ESD can be used to resect proximal colon lesions in selected patients (precancerous lesions and early colon cancer limited to the mucosa or with a submucosa infiltration depth of < 1000 µm).

Association of body mass index with clinical outcome of primary WHO grade 4 glioma.

Background: The prognostic value of body mass index (BMI) in primary WHO grade 4 gliomas is not widely acknowledged. This study aims to assess the survival outcomes of patients with different BMIs. Methods: Real-world data of patients diagnosed with primary WHO grade 4 (2021 version) glioma was assessed. All 127 patients admitted in this study were administered with standard-of-care from September 2018 to September 2021. The outcomes of overall survival and progression-free survival were analyzed. Results: The baseline characteristics of clinical features, molecular features, and secondary treatment in BMI subsets showed no significant difference. The survival analyses showed a significantly superior overall survival (OS) in the overweight group compared to the normal weight group. A trend of better OS in the overweight group compared to the obesity group was observed. The univariate Cox regression demonstrated patients of round-BMI 25 and 26 had superior OS outcomes. Conclusion: In this real-world setting, patients with a BMI between 24 and 28 have superior overall survival. Patients in the proper BMI range may acquire survival benefits undergoing standard-of-care of primary WHO grade 4 gliomas. The prospective studies on a larger scale on these subsets of patients are necessary to solve the paradox of BMI in glioma.

Impact of WeChat guidance on bowel preparation for colonoscopy: a quasi-experiment study.

Colonoscopy is a standard procedure for screening, monitoring, and treating colorectal lesions. To explore the impact of WeChat guidance on bowel preparation before colonoscopy. This quasi-experiment study included patients who underwent colonoscopy at Qingdao Endoscopy Center between March 2016 and September 2016. The primary outcome was bowel preparation quality (Ottawa score), the secondary outcomes were intubation time, withdrawal time, adenoma detection rate (ADR), and adverse reactions. Finally, 588 patients were included and divided into the WeChat guide (n = 295) and the non-WeChat guide (n = 293) groups, they were comparable in baseline characteristics. The Ottawa score (1.59 ± 1.07 vs. 6.62 ± 3.07, P < 0.001), intubation time (6.47 ± 1.81 vs. 11.61 ± 3.34, P < 0.001), withdrawal time (13.15 ± 3.93 vs. 14.99 ± 6.77, P < 0.001), and occurrence rate of adverse reactions (2.0% vs. 5.5%, P = 0.029) were significantly lower in the WeChat guide group than those in the non-WeChat guide group. ADR was significantly higher in the WeChat guide than that in the non-WeChat guide group (1.47 ± 2.30 vs. 0.84 ± 1.66, P < 0.001). WeChat guidance might improve the quality of bowel preparation and adenoma detection rate, shorten the time of colonoscopy, and reduce adverse reactions in bowel preparation.

Timing of interval debulking surgery and postoperative chemotherapy after neoadjuvant chemotherapy in advanced epithelial ovarian cancer: a multicenter real-world study.

BACKGROUND: To investigate the prognostic relevance of the time to interval debulking surgery (TTS) and the time to postoperative adjuvant chemotherapy (TTC) after the completion of neoadjuvant chemotherapy (NACT). METHODS: A retrospective real-word study included 658 patients with histologically confirmed advanced epithelial ovarian cancer who received NACT at seven tertiary hospitals in China from June 2008 to June 2020. TTS was defined as the time interval from the completion of NACT to the time of interval debulking surgery (IDS). TTC was defined as the time interval from the completion of NACT to the initiation of postoperative adjuvant chemotherapy (PACT). RESULTS: The median TTS and TTC were 25 (IQR, 20-29) and 40 (IQR, 33-49) days, respectively. Patients with TTS > 25 days were older (55 vs. 53 years, P = 0.012) and received more NACT cycles (median, 3 vs. 2, P = 0.002). Similar results were observed in patients with TTC > 40 days. In the multivariate analyses, TTS and TTC were not associated with PFS when stratified by median, quartile, or integrated as continuous variables (all P > 0.05). However, TTS and TTC were significantly associated with worse OS when stratified by median (P = 0.018 and 0.018, respectively), quartile (P = 0.169, 0.014, 0.027 and 0.012, 0.001, 0.033, respectively), or integrated as continuous variables (P = 0.018 and 0.011, respectively). Similarly, increasing TTS and TTC intervals were associated with a higher risk of death (Ptrend = 0.016 and 0.031, respectively) but not with recurrence (Ptrend = 0.103 and 0.381, respectively). CONCLUSION: The delays of IDS and PACT after the completion of NACT have adverse impacts on OS but no impacts on PFS, which indicates that reducing delays of IDS and PACT might ameliorate the outcomes of ovarian cancer patients treated with NACT.

Peroral endoscopic myotomy assisted with an elastic ring for achalasia with obvious submucosal fibrosis: A case report.

BACKGROUND: Peroral endoscopic myotomy (POEM) is an established treatment option for esophageal achalasia. However, technical challenges and failures exist. Submucosal fibrosis is a rare cause of aborted POEM procedures. CASE SUMMARY: We performed POEM with an elastic ring for achalasia with obvious submucosal fibrosis. The short-term outcome was excellent, surgery time was significantly shorter, and success rate was higher with POEM for achalasia with obvious submucosal fibrosis. CONCLUSION: POEM performed with an elastic ring is a feasible and effective endoscopic treatment modality for achalasia with obvious submucosal fibrosis.

Case report: Chronic lymphocytic leukemia/small lymphocytic lymphoma and monomorphic epitheliotropic intestinal T-cell lymphoma: A composite lymphoma.

Background: Composite lymphomas involving B-cell and T-cell lymphomas is very rare. Case presentation: We reported a 63-year-old gentleman with composite chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL). The patient was admitted to our hospital due to abdominal pain, and was diagnosed with CLL/SLL after bone marrow (BM) biopsy, BM aspiration, and flow cytometry. Two weeks later, he was diagnosed with MEITL based on pathological analysis after intestine excision. Next gene sequencing (NGS) findings identified two hotspot mutation sites (STAT5B and DNMT3A) closely related with the pathogenesis of CLL/SLL and MEILT. Additionally, BCOR mutation was only detected in the CLL/SLL area. The likely pathogenic mutations of CLL were SETD2, NOTCH1, SF3B1, and PTPN11, while the likely pathogenic mutations related with the MEILT were TET2 and ZRSR2. Mutations of GATA3, PLCG2, and FAT1 were identified in both CLL/SLL and MEITL areas, but the clinical significance was unknown. Finally, the patient died in the 12-month follow-up after surgery. Conclusion: We report a rare case of composite CLL/SLL and MEITL that highlights the importance of careful inspection of hematologic neoplasms. We also present the results of NGS of different gene mutations in CLL and MEITL tissues.

Submucosal esophageal abscess evolving into intramural submucosal dissection: A case report.

BACKGROUND: Here we report a rare case of submucosal esophageal abscess evolving into intramural submucosal dissection. CASE SUMMARY: An 80-year-old woman was admitted to our emergency department with a chief complaint of dysphagia and fever. Laboratory tests showed mild leukocytosis and elevated C-reactive protein level. Computed tomography showed thickening of the esophageal wall. Upper endoscopy showed a laceration of the esophageal mucosa and a submucosal mass. Spontaneous drainage occurred, and we could see purulent exudate from the crevasse. We closed the laceration with endoscopic clips. The patient did not remember swallowing a foreign body; however, she ate crabs before the symptoms occurred. We prescribed the patient with antibiotic, and the symptoms were gradually relieved. Two months later, upper endoscopy showed that the laceration was healed, and the submucosal abscess disappeared. However, intramural esophageal dissection was formed. We performed endoscopic incision of the septum using dual-knife effectively. CONCLUSION: In conclusion, we are the first to report the case of esophageal submucosal abscess evolving into intramural esophageal dissection. The significance of this case lies in clear presentation of the evolution process between two disorders. In addition, we recommend that endoscopic incision be considered as one of the routine therapeutic modalities of intramural esophageal dissection.

Gastric ulcer treated using an elastic traction ring combined with clip: A case report.

BACKGROUND: There is a high annual incidence of acute, nonvariceal upper gastrointestinal bleeding in Chinese adults. Early endoscopic intervention can reduce rates of rebleeding, surgery, and mortality. The metal clip is the most common method for establishing homeostasis; however, it possesses several limitations. In patients with bleeding secondary to large gastric ulcers, the clip will often fail to stop the bleeding. This article highlights the use of an elastic traction ring as a novel hemostatic method for patients with upper gastrointestinal bleeding. CASE SUMMARY: An elderly male presented to the emergency room with complaints of hematemesis and melena. Endoscopic examination revealed an ulcer (Forrest IIa) in the lesser curvature of the gastric antrum. Six tissue clips and one elastic traction ring were inserted into the stomach cavity to suture the ulcer. The patient recovered quickly without postoperative gastrointestinal bleeding. Two months later, the patient's ulcer was significantly healed. CONCLUSION: To our best knowledge, this is the first report to demonstrate the safety and efficacy of elastic traction rings for upper gastrointestinal bleeding. Elastic traction rings should be considered a routine therapeutic modality for patients with upper gastrointestinal bleeds.

Sintilimab combined with bevacizumab in relapsed/persistent ovarian clear cell carcinoma (INOVA): an investigator-initiated, multicentre clinical trial-a study protocol of clinical trial.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) has an abysmal prognosis with a median overall survival (OS) of 25.3 months because of a low response to chemotherapy. The 5-year disease-specific survival rate after recurrence is 13.2%, with more than two-thirds of the patients dying within a year. Therefore, it is urgent to explore new therapeutic options for OCCC. Based on the characteristic immune-suppressive tumour microenvironment derived from the gene expression profile of OCCC, the combination of immunoantiangiogenesis therapy might have certain efficacy in recurrent/persistent OCCC. This trial aims to evaluate the efficacy and safety of sintilimab and bevacizumab in patients who have failed platinum-containing chemotherapy with recurrent or persistent OCCC. METHOD AND ANALYSIS: In this multicentre, single-arm, open-label, investigator-initiated clinical trial, 38 patients will be assigned to receive sintilimab 200 mg plus bevacizumab 15 mg/kg every 3 weeks. The eligibility criteria include histologically diagnosed patients with recurrent or persistent OCCC who have been previously treated with at least one-line platinum-containing chemotherapy; patients with Eastern Cooperative Oncology Group (ECOG) performance status 0-2 with an expected survival greater than 12 weeks. The exclusion criteria include patients previously treated with immune checkpoint inhibitor and patients with contraindications of bevacizumab and sintilimab. The primary endpoint is the objective response rate. The secondary endpoints are progression-free survival, time to response, duration of response, disease control rate, OS, safety and quality of life. Statistical significance was defined as p<0.05. ETHICS AND DISSEMINATION: This trial was approved by the Research Ethics Commission of Tongji Medical College of Huazhong University of Science and Technology (2020-S337). The protocol of this study is registered at www. CLINICALTRIALS: gov. The trial results will be published in peer-reviewed journals and at conferences. TRIAL REGISTRATION NUMBER: NCT04735861; Clinicaltrials. gov.

Global Evidence of Temperature Acclimation of COVID-19 D614G Linage.

The novel D614G linage is becoming the dominating species of SARS-CoV-2. The impact of meteorological and geographical factors on SARS-CoV-2 pandemic are presently not well understood. This research article presents a retrospective case series. Pandemic and meteorological data from 30 countries and 49 states from USA are collected as of June 10th, 2020. The primary outcome are the coefficients of correlations between meteorological factors and pandemic data. Hierarchical clustering analysis are used on SARS-CoV-2 genome, meteorological factors, and pandemic. Disseminating velocity of SARS-CoV-2 is negatively correlated with average temperature in majority of included countries and states from USA. Proportion of the GR clade is positively associated with temperature, but is negatively correlated with altitude in countries-set. Virus disseminating velocities in states from cluster A (Overwhelming proportion of G + GR + GH clades, GH > 60%) and C (Overwhelming proportion of G + GR + GH clades, G 20-30%) both has negative correlations with temperature, while cluster C has more significant negative correlation than cluster A. Climate and geographical environment are revealed to affect virus spreading. GH and GR clades of SARS-CoV-2 are probably acquiring higher temperature tolerance, while G clade may retain high temperature intolerance.

Landscape of Myeloid-derived Suppressor Cell in Tumor Immunotherapy.

Myeloid-derived suppressor cells (MDSC) are a group of immature cells that produced by emergency myelopoiesis. Emerging evidences have identified the vital role of MDSC in cancer microenvironment, in which MDSC exerts both immunological and non-immunological activities to assist the progression of cancer. Advances in pre-clinical research have provided us the understanding of MDSC in cancer context from the perspective of molecular mechanism. In clinical scenario, MDSC and its subsets have been discovered to exist in peripheral blood and tumor site of patients from various types of cancers. In this review, we highlight the clinical value of MDSC in predicting prognosis of cancer patients and the responses of immunotherapies, therefore to propose the MDSC-inhibiting strategy in the scenario of cancer immunotherapies. Phenotypes and biological functions of MDSC in cancer microenvironment are comprehensively summarized to provide potential targets of MDSC-inhibiting strategy from the aspect of molecular mechanisms.