bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Peri-Device Leaks on Ischaemic Stroke/Transient Ischaemic Attack/Systemic Embolism after Left Atrial Appendage Closure: A Systematic Review and Meta-Analysis
Authors: He Yin-Ge , Yang Shao-Hua , Xu Liang , Wang Yan , Qin Xu-Tan , Chen Pan-Pan , Zhao Yu-Jie
Published: August 2023

Background: Left atrial appendage closure (LAAC) is a safe and effective method for preventing embolic events in patients with non-valvular atrial fibrillation. However, peri-device leaks (PDLs) are sometimes unavoidable. Controversy exists regarding whether PDLs lead to embolic events. Objectives: This study aimed to explore the association between PDLs and embolic events, including ischaemic stroke, transient ischaemic attacks (TIAs), and systemic embolism (SE). Methods: We conducted a systematic search of the PubMed, Web of Science, MEDLINE, and Cochrane Library databases for studies published up to September 25, 2022, to compare the rate of ischaemic stroke/TIA/SE between the PDL group and the non-PDL group after LAAC. Results: Thirteen studies comprising 54,405 patients were included in the meta-analysis. The PDL group detected by transoesophageal echocardiography (TEE) had a significantly higher rate of ischaemic stroke/TIA/SE than the non-PDL group (OR: 1.20, 95% CI: 1.08–1.33, p = 0.0009). However, no difference in ischaemic stroke/TIA/SE was found between the PDL and non-PDL subgroups of the cardiac computed tomography angiography (CCTA) group (OR: 1.12, 95% CI: 0.51–2.50, p = 0.77). CCTA and TEE showed different rates of PDL detection, with the CCTA group having a higher rate of PDL detection (p < 0.0001), especially for trivial leaks. Conclusions: PDL detected by TEE increases the risk of embolic events after LAAC. However, no association was found between PDL and ischaemic stroke/TIA/SE in the CCTA group, which showed a higher rate of PDL detection than TEE, particularly for trivial leaks. In the future, CCTA may be used to explore the relationship between PDL size and ischaemic stroke/TIA/SE.
Milan Ultrasound Criteria Predict Relapse of Ulcerative Colitis in Remission
Authors: Maeda Masa , Sagami Shintaro , Tashima Moyu , Yamana Yoko , Karashima Ryo , Miyatani Yusuke , Hojo Aya , Nakano Masaru , Hibi Toshifumi , Kobayashi Taku
Published: August 2023

Introduction: Bowel ultrasound is a noninvasive alternative to endoscopy for assessing the disease activity of ulcerative colitis; however, it is unclear whether bowel ultrasound can predict subsequent relapse from remission. Materials and Methods: A retrospective cohort study enrolled patients with ulcerative colitis who underwent bowel ultrasound between July 2018 and July 2021 during clinical remission (patient-reported outcome-2 ≤1 and no rectal bleeding) for at least 3 months and were followed up for 1 year. Ultrasonographic findings (bowel wall thickness, bowel wall flow, bowel wall stratification, and enlarged lymph nodes), Milan ultrasound criteria, Mayo endoscopic subscore, C-reactive protein, and fecal calprotectin levels and their association with subsequent clinical relapse were assessed. Relapse was defined as rectal bleeding score ≥1, stool frequency score ≥2, or treatment intensification for symptoms. Results: 31% of the patients (18/58) relapsed within 1 year. No single ultrasonographic finding predicted relapse, whereas Milan ultrasound criteria >6.2 (p = 0.019), Mayo endoscopic subscore ≥1 (p = 0.013), and fecal calprotectin ≥250 μg/g (p = 0.040) were associated with a shorter time to relapse in the log-rank test. Milan ultrasound criteria >6.2 (hazard ratio 3.22; 95% confidence interval 1.14–9.08, p = 0.027) and Mayo endoscopic subscore ≥1 (hazard ratio 8.70; 95% confidence interval 1.11–68.1, p = 0.039) showed a higher risk of relapse according to a Cox proportional hazards model. Conclusion: Bowel ultrasound can predict subsequent clinical relapse from remission in patients with ulcerative colitis using the Milan ultrasound criteria.
Genetic Factors in Familial Manifestation of Primary Mediastinal Large B-Cell Lymphoma over Two Generations
Authors: Juskevicius Darius , Lundberg Pontus , Tzankov Alexandar , Dirnhofer Stefan , Stenner Frank
Published: August 2023

Introduction: Primary mediastinal large B-cell lymphoma (PMBL) is a rarely occurring lymphoid malignancy which typically affects young adults and presents itself as an anterior mediastinal mass. Gene expression profiling as well as somatic genetic analysis revealed that it is closely related to classical Hodgkin lymphoma, whereas morphologically, it tends to resemble diffuse large B-cell lymphoma. Familial clustering of PMBL is rare – only two reports have been published to date. While it is generally accepted that positive family history is associated with increased risk of developing a lymphoma, genetic risk factors which might predispose to PMBL are largely unknown. Case Presentation: We performed germline and tumor genetic analyses by whole-exome sequencing and array-CGH of a family, in which the father and the son both developed a PMBL. Germline investigations of both affected patients and of their two unaffected family members have not been able to provide a single risk factor associated with lymphoma predisposition. In addition, genes that were previously implicated in increased risk for PMBL, namely MLL (KMT2A) and TIRAP, were found to be intact in all investigated family members. Somatic genetic investigations identified known as well as novel genetic aberrations in tumors of the affected subjects. Conclusion: We conclude that predisposition to a PMBL might be inherited through a combination of low- or moderate-risk factors and provide a shortlist of the most likely selected candidates, which can be used in future studies.
Same-Day Bilateral Intravitreal Dexamethasone Implants for the Treatment of Diabetic Macular Edema
Authors: Lin Tai-Chi , Tseng Po-Chen , Hsu Tsui-Kang , Huang Hsin-Wei , Huang Yi-Ming , Lo Wen-Jung , Chao Chen-Yu , Chung Yu-Chien
Published: August 2023

Introduction: The aim of this study was to evaluate the outcomes and complications associated with the use of same-day bilateral intravitreal dexamethasone (DEX) implants for the treatment of diabetic macular edema (DME). Methods: This retrospective analysis of an open-label, multicenter, consecutive case series included 130 eyes of 65 patients with bilateral DME who were treated with intravitreal DEX implants. The patients were divided into two groups: a control group (comprising 40 eyes treated with an alternating unilateral regimen) and a study group (comprising 90 eyes treated with concomitant bilateral DEX implants). All patients were followed up monthly after implantation. The changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to sixth month after implantation, and ocular adverse effects such as intraocular pressure, cataract, and tolerability of bilateral implantation were reviewed. The primary endpoint was to assess the safety of the same-day bilateral treatment protocol. The secondary endpoints focused on evaluating the functional and anatomical changes associated with bilateral simultaneous or alternating implantations. Results: At 6 months after implantation, mean BCVA increased and CRT decreased in both groups. Moreover, no serious ocular adverse effects were observed. In addition, no differences were observed between the two groups in the number of patients who required extra follow-up visits or the number of extra visits made in addition to the treatment schedule. Conclusions: Same-day bilateral intravitreal DEX implants are associated with a low complication rate and are well tolerated by patients. This safe practice may optimize efficiency and reduce the burden on both the health-care system and patients, when used to treat bilateral DME.
Germline Mutations in 32 Cancer Susceptibility Genes by Next-Generation Sequencing among Breast Cancer Patients
Authors: Yang Yu , Liu Chang , Zhuo Zhong-Ling , Xie Fei , Wang Ke , Wang Shu , Zhao Xiao-Tao
Published: August 2023

Introduction: BRCA1/2 germline mutations are the most well-known genetic determinants for breast cancer. However, the distribution of germline mutations in non-BRCA1/2 cancer susceptibility genes in Chinese breast cancer patients is unclear. The association between clinical characteristics and germline mutations remains to be explored. Methods: Consecutive breast cancer patients from Peking University People’s Hospital were enrolled. Clinical characteristics were collected, and next-generation sequencing was performed using blood samples of participants to identify pathogenic/likely pathogenic (P/LP) germline mutations in 32 cancer susceptibility genes including homologous recombination repair (HRR) genes. Results: A total of 885 breast cancer patients underwent the detection of germline mutations. 107 P/LP germline mutations of 17 genes were identified in 116 breast cancer patients including 79 (8.9%) in BRCA1/2 and 40 (4.5%) in 15 non-BRCA1/2 genes. PALB2 was the most frequently mutated gene other than BRCA1/2 but still relatively rare (1.1%). There were 38 novel P/LP germline variants detected. P/LP germline mutations in BRCA1/2 were significantly associated with onset age (p < 0.001), the family history of breast/ovarian cancer (p = 0.010), and molecular subtype (p < 0.001), while being correlated with onset age (p < 0.001), site of breast tumor (p = 0.028), and molecular subtype (p < 0.001) in HRR genes. Conclusions: The multiple-gene panel prominently increased the detection rate of P/LP germline mutations in 32 cancer susceptibility genes compared to BRCA1/2 alone. Onset younger than or equal to 45 years of age, bilateral and triple-negative breast cancer patients may be more likely to be recommended for detecting P/LP germline mutations in HRR genes.
Effects of Different Exercises on Physical Function, Dialysis Adequacy, and Health-Related Quality of Life in Maintenance Hemodialysis Patients: A Systematic Review and Network Meta-Analysis
Authors: Hu Huagang , Wu Chanchan , Kwok Jojo Yan Yan , Ho Mu-Hsing , Chau Pui Hing , Lok Kris Yuet Wan , Choi Edmond Pui Hang
Published: August 2023

Background: Clinical guidelines recommend exercise training for patients undergoing maintenance hemodialysis (MHD). However, the effectiveness of different types of exercise remains uncertain. Objectives: The aims of the study were to compare and rank the effect of different types of exercise on walking capacity, cardiorespiratory fitness, dialysis adequacy, and health-related quality of life (HRQOL) in patients undergoing MHD. Methods: Eight databases (four English and four Chinese) were searched from inception to January 1, 2022. Randomized controlled trials evaluating the efficacy of different exercises for patients undergoing MHD were included. Two independent reviewers screened the literature, extracted data, assessed the risk of bias, and evaluated the certainty of evidence. A frequentist random-effect network meta-analysis was conducted. Results: Ninety trials with 4,084 participants comparing 15 types of exercise were included, reporting on the six-minute walking test (45 trials), peak oxygen uptake (22 trials), dialysis adequacy (30 trials), and HRQOL (23 trials). Network meta-analysis showed that the most effective intervention for walking capacity was intradialytic aerobic exercise combined with blood flow restriction with a mean difference and 95% confidence interval of 97.35 (11.89–182.81), for peak oxygen uptake it was non-intradialytic combined aerobic and resistance exercise with a value of 4.35 (2.25–6.44), for dialysis adequacy it was intradialytic combined aerobic and resistance exercise with a value of 0.17 (0.06–0.28), for the physical component summary of HRQOL it was intradialytic aerobic exercise with a value of 4.93 (2.31–7.54), and for the mental component summary of HRQOL it was non-intradialytic combined aerobic and resistance exercise with a value of 6.36 (0.45–12.27). Ultimately, intradialytic combined aerobic and resistance exercise could improve all the above outcomes compared to usual care. Conclusions: This study concluded that intradialytic combined aerobic and resistance exercise is optimal for MHD patients due to its significant positive effects on multiple outcomes. Walking capacity can be further enhanced by combining blood flow restriction with exercise. For improving dialysis adequacy, intradialytic exercise proves to be more effective than non-intradialytic exercise. Further well-designed clinical trials are needed to investigate the effects of exercise with varying durations, intensities, and frequencies.
Dietary Flavonoid Intake and Carotid Calcification in Patients with Ischemic Stroke
Authors: Mou Tao , Jia Xuerong , Peng Min , Li Xiang , Xia Yaqian , Chen Yantong , Wang Qing , Wang Xiaoke , Liu Xinfeng , Xu Gelin
Published: August 2023

Introduction: Owing to the antioxidant and anti-inflammatory effects, flavonoids can influence the initiation and development of atherosclerosis, but the underlying mechanisms remain largely undetermined. This study aimed to evaluate the associations between dietary flavonoids and carotid calcification in patients with ischemic stroke. Methods: This study screened consecutive patients with ischemic stroke via Nanjing Stroke Registry Program from February 2016 to April 2021. A semiquantitative food frequency questionnaire was used to evaluate dietary consumption of flavonoids and other nutritional components. Presence and degree of carotid calcification were determined according to Agatston scores on computer tomography angiography. Logistic regression was performed to evaluate the association between dietary flavonoids (total flavonoids, flavonols, flavones, flavanones, flavan-3-ols, anthocyanins, and isoflavones) and carotid calcification. Results: Of the 601 enrolled patients, 368 (61.2%) were detected with carotid calcification. Patients with high intake of total flavonoids (the fifth quintile) had a 52% lower carotid calcification risk than those with low intake (the first quintile; odds ratio [OR] = 0.48; 95% confidence interval [CI], 0.26–0.90; p = 0.007 for trends) after adjusting for major confounders. Patients with high intake of flavan-3-ols (the fifth quintile) had a 51% lower carotid calcification risk than those with low intake (the first quintile; OR = 0.49; 95% CI, 0.25–0.97; p = 0.016 for trends). Conclusion: Dietary flavonoid intake is associated with carotid calcification, and, therefore, may influence the risk of stroke occurrence and recurrence.
Testing for Protein Leverage in Patients with Gastric Bypass: A Pilot Study
Authors: Rodriguez-Murguiaa Nantli , Malacara Juan M. , Kusnir Daniel , Siniego Alberto , Melendez-Rios Dora , Raubenheimer David , Simpson Steven , Martinez-Cordero Claudia
Published: August 2023

Introduction: Protein leverage (PL) is the phenomenon whereby a dominant appetite for protein drives overconsumption of energy with a decline in the ratio of protein to fat and carbohydrate in the diet. PL has been independently verified in several randomized control trials, and its predictions are supported by diet surveillance data. Our aim in the present study was to test whether surgical intervention through gastric bypass will ameliorate the PL effect. Methods: Ten patients with gastric bypass (2–5 years postsurgical time) were given ad libitum access to study food comprising 10%, 15%, or 25% protein and no access to other foods for 3 days while controlling food palatability and variety. Food intake was measured, and energy and nutrient intakes were calculated. Body weight, blood chemistry, lipid profile, hormones (insulin, leptin, and ghrelin), and creatinine were determined before and after each experimental period. Results: The gastric bypass patients in our study did not show evidence for protein intake regulation as predicted under PL but ate to constant total energy intake on the 10%, 15%, and 25% protein diets with protein intake varying significantly. Patients lost weight in the three study periods, but significant weight loss was observed only on the 15% protein diet. Conclusion: Our results suggest that gastric bypass might disengage the PL mechanism, thus ameliorating an appetite-specific mechanism that drives energy overconsumption in modern food environments.
Association of Lifelong Cognitive Reserve with Dementia and Mild Cognitive Impairment among Older Adults with Limited Formal Education: A Population-Based Cohort Study
Authors: Li Yuanjing , Ren Yifei , Cong Lin , Hou Tingting , Song Lin , Wang Mingqi , Wang Xiang , Han Xiaojuan , Tang Shi , Zhang Qinghua , Dekhtyar Serhiy , Wang Yongxiang , Du Yifeng , Qiu Chengxuan
Published: August 2023

Introduction: Early-life educational attainment contributes to cognitive reserve (CR). We investigated the associations of lifelong CR with dementia and mild cognitive impairment (MCI) among older people with limited formal education. Methods: This population-based cohort study included 2,127 dementia-free participants (≥60 years; 59.4% women; 81.5% with no or elementary school) who were examined at baseline (August-December 2014) and follow-up (March-September 2018). Lifelong CR score at baseline was generated from six lifespan intellectual factors. Dementia, MCI, and their subtypes were defined according to the international criteria. Data were analyzed using Cox proportional-hazards models. Results: During the total of 8,330.6 person-years of follow-up, 101 persons were diagnosed with dementia, including 74 with Alzheimer's disease (AD) and 26 with vascular dementia (VaD). The high (vs. low) tertile of lifelong CR score was associated with multivariable-adjusted hazards ratios (95% confidence interval) of 0.28 (0.14–0.55) for dementia and 0.18 (0.07–0.48) for AD. The association between higher CR and reduced AD risk was significant in people aged 60–74 but not in those aged ≥75 years (p for interaction = 0.011). Similarly, among MCI-free people at baseline (n = 1,635), the high (vs. low) tertile of lifelong CR score was associated with multivariable-adjusted hazard ratios of 0.51 (0.38–0.69) for MCI and 0.46 (0.33–0.64) for amnestic MCI. Lifelong CR was not related to VaD or non-amnestic MCI. Discussion: High lifelong CR is associated with reduced risks of dementia and MCI, especially AD and amnestic MCI. It highlights the importance of lifelong CR in maintaining late-life cognitive health even among people with no or limited education.
Personal Narratives of 10-Year-Old Children in Iceland: Verbal Productivity, Word Diversity, and Topics
Authors: Einarsdóttir Jóhanna T. , Þráinsdóttir Erna
Published: August 2023

Introduction: The feasibility of using a standard protocol, labelled as the Global TALES, to elicit personal stories was tested across 10 different countries between 2019 and 2021. Personal narratives have not been investigated in Iceland in a similar way. The aim was to explore personal narratives of monolingual children in Iceland by using the Global TALES (2018) protocol to investigate verbal productivity, semantic diversity, and narrative topics. Methods: Twenty-seven children (ages 9; 8–10; 9) with typical language development produced personal stories in response to six emotion-based prompts contained in the protocol. The children were interviewed by using the Zoom platform because of COVID restrictions. Children’s spoken language was analysed for total number of utterances (TNU), total number of words (TNW), number of different words (NDW), mean length of utterances in words (MLUw), and proportion of words with grammatical errors. The narrative topics were coded and documented. Results: The spoken language measures showed that there was a large individual variability within the group on all metrics examined. The mean TNU was 62.1 (SD 20.2) utterances, the mean for TNW was 546 (SD 219) words, the mean for NDW was 206 (SD 62) words, and the MLUw was 8.6 (SD 1.5) words in an utterance. Despite the variability in spoken language performance, around 70–75% of the participants produced TNU, TNW, NDW, and MLUw within +/− 1 SD from the mean. The topics of the stories were most frequently related to personal achievement or relationships with the family or friends. Conclusion: The Global TALES (2018) protocol can be used to elicit personal stories in 10-year-old children in Iceland. The results related to verbal productivity and the topics of interest were in line with previous studies around the world.
The Effect of Resolution Level and Targeted Design in the Diagnostic Performance of Prenatal Chromosomal Microarray Analysis
Authors: Papageorgiou Elena , Athanasiadis Apostolos , Fidani Stiliani , Papoulidis Ioannis , Manolakos Emmanouil , Siomou Elissavet , Chatzakis Christos , Sotiriadis Alexandros
Published: August 2023

Introduction: This study was performed to assess the optimal resolution for prenatal testing by array comparative genomic hybridization (aCGH), aiming to balance between maximum diagnostic yield and minimal detection of variants of uncertain significance (VOUS). Methods: This was a prospective study using data of 2,336 fetuses that underwent invasive prenatal diagnosis, and the samples were analyzed by aCGH. In total, six different aCGH platforms were studied; four different resolutions (0.18 Mb, 0.5 Mb, 1 Mb, and 2 Mb) and two platform designs (whole-genome [WG] and targeted). The results of these designs were compared based on their diagnostic yield and VOUS rate. The performance of the different designs was further analyzed according to indication for invasive testing. Results: The diagnostic yield of copy number variants increased with increasing level of analysis. The detection rates of clinically significant chromosomal abnormalities were almost the same across our targeted array designs; 7.2% with 0.18 Mb backbone/0.05 Mb versus 7.1% with 0.5 Mb backbone/0.05 Mb (p >0.05). However, a significant difference in the rate of VOUS was observed; 9.4% with 0.18 Mb backbone/0.05 Mb versus 6% with 0.5 Mb backbone/0.05 Mb (p <0.001). After analyzing the results across different indications for testing, we found that the application of non-targeted platform designs and lower levels of resolution analysis (such as 1 Mb WG or 0.5 MbL/1 MbG WG) would offer similar diagnostic yield in most cases with major congenital anomalies, with lower VOUS rates. However, the sample size for many indication groups was too small to extract robust associations. Conclusion: It appears that the targeted array platform with 0.5 Mb backbone resolution and 0.05 Mb on targeted gene-rich regions is optimal for routine chromosomal microarray analysis use in prenatal diagnosis. It may be beneficial to individualize the minimum resolution in specific referral indications as the indications for invasive prenatal testing may be quite heterogeneous.
Left Main Coronary Artery Revascularization in Patients with Impaired Renal Function: Percutaneous Coronary Intervention versus Coronary Artery Bypass Grafting
Authors: Daoulah Amin , Taha Baqais Rasha , Aljohar Alwaleed , Alhassoun Abdulkarim , Hersi Ahmad S. , Almahmeed Wael , Yousif Nooraldaem , Alasmari Abdulaziz , Alshehri Mohammed , Eltaieb Fakhreldein , Alzahrani Badr , Elmahrouk Ahmed , Arafat Amr A. , Jamjoom Ahmed , Alshali Khalid Z. , Abuelatta Reda , Ahmed Waleed A. , Alqahtani Abdulrahman H. , Al Garni Turki , Hashmani Shahrukh , Dahdouh Ziad , Refaat Wael , Kazim Hameedullah M. , Ghani Mohamed Ajaz , Amin Haitham , Hiremath Niranjan , Elmahrouk Youssef , Selim Ehab , Aithal Jairam , Qutub Mohammed A. , Alama Mohamed N. , Ibrahim Ahmed M. , Elganady Abdelmaksoud , Abohasan Abdulwali , Asrar Farhan M. , Farghali Tarek , Jameel Naser Maryam , Hassan Taher , Balghith Mohammed , Hussien Adnan Fathey , Abdulhabeeb Ibrahim A.M. , Ahmad Osama , Ramadan Mohamed , Ghonim Ahmed A. , Shawky Abeer M. , Noor Husam A. , Haq Ejazul , Alqahtani Abdulrahman M. , Al Samadi Faisal , Abualnaja Seraj , Khan Mushira , Alhamid Sameer , Lotfi Amir
Published: August 2023

Introduction: The evidence about the optimal revascularization strategy in patients with left main coronary artery (LMCA) disease and impaired renal function is limited. Thus, we aimed to compare the outcomes of LMCA disease revascularization (percutaneous coronary intervention [PCI] vs. coronary artery bypass grafting [CABG]) in patients with and without impaired renal function. Methods: This retrospective cohort study included 2,138 patients recruited from 14 centers between 2015 and 2,019. We compared patients with impaired renal function who had PCI (n= 316) to those who had CABG (n = 121) and compared patients with normal renal function who had PCI (n = 906) to those who had CABG (n = 795). The study outcomes were in-hospital and follow-up major adverse cardiovascular and cerebrovascular events (MACCE). Results: Multivariable logistic regression analysis showed that the risk of in-hospital MACCE was significantly higher in CABG compared to PCI in patients with impaired renal function (odds ratio [OR]: 8.13 [95% CI: 4.19–15.76], p < 0.001) and normal renal function (OR: 2.59 [95% CI: 1.79–3.73]; p < 0.001). There were no differences in follow-up MACCE between CABG and PCI in patients with impaired renal function (HR: 1.14 [95% CI: 0.71–1.81], p = 0.585) and normal renal function (HR: 1.12 [0.90–1.39], p = 0.312). Conclusions: PCI could have an advantage over CABG in revascularization of LMCA disease in patients with impaired renal function regarding in-hospital MACCE. The follow-up MACCE was comparable between PCI and CABG in patients with impaired and normal renal function.
Retrospective Study of Treatment Patterns and Natural History of Patients with T1a/b N0 Triple-Negative Breast Cancers: A Single-Institution Experience
Authors: Liu Langfeier , Lewis Nicholas , Sun Weihong , Whiting Junmin , Hoover Susan , Costa Ricardo L.B.
Published: August 2023

Introduction: T1a/b, node-negative (node−), triple-negative breast cancers (TNBCs) are underrepresented in randomized drug-approving clinical trials. Given their low incidence, the clinicopathological features, natural history, and treatment patterns of these tumors remain insufficiently understood. Methods: We conducted a single-institution retrospective cohort study of patients with T1a/b, N0, M0 TNBCs. Deidentified patient- and tumor-related data were collected and summarized. Kruskal-Wallis, χ2, or Fisher exact tests were used to evaluate associations of interest. Kaplan-Meier methods, log-rank tests, and Cox’s proportional hazards models were applied for survival analyses. Results: Of 108 cases of node– TNBCs measuring ≤2 cm, 34 node– T1a/b tumors were included in our analysis. All cases had an intermediate to high histological grade, and most had a Ki-67 score of ≥20%. All patients received adjuvant chemotherapy, and many underwent mastectomy (47%). Docetaxel combined with cyclophosphamide was the most common adjuvant chemotherapy regimen (75%). We did not observe significant associations between improved outcomes and treatment with anthracycline-containing regimens. Among patients with node– pT1a/b tumors, the estimated 3-year recurrence-free survival (RFS) and distant RFS rates were both 96.3% (95% CI: 76.5–99.5), and the overall survival rate was estimated to be 100% (95% CI: 100–100). There were no cases of local recurrences observed. Conclusions: In our cohort, all patients with T1a/b node– TNBCs were treated with adjuvant chemotherapy and had favorable outcomes even when treated with anthracycline-sparing regimens.
Optimization of a Validated Protocol That Determines Bioavailable Fluoride in Toothpastes
Authors: Miranda Luis Fernando Bandeira , Tabchoury Cinthia Pereira Machado , Cury Jaime Aparecido
Published: August 2023

A validated protocol used to determine how much of total fluoride is bioavailable in toothpaste formulations was evaluated if it could be simplified regarding the following parameters: (1) concentration of the slurry (0.25–4%), (2) centrifugation speed (1,000–12,000 g) and time (1–10 min), and (3) incubation time for FPO32− ion hydrolysis and insoluble-F dissolution (15–60 min). Fresh and aged Na2FPO3/CaCO3 and fresh NaF/SiO2-based toothpastes were analyzed (n = 9). The improvements were the centrifugation at 1,000 g for 5 min is enough to separate insoluble-F and the time for FPO32− ion hydrolysis and insoluble-F dissolution can be shortened to 30 min.
Safety and Efficacy of the Phototherapeutic Keratectomy for Treatment of Recurrent Corneal Erosions: A Systematic Review and Meta-Analysis
Authors: Chen Sijing , Chu Xiaoran , Zhang Chen , Jia Zhe , Yang Liu , Yang Ruibo , Huang Yue , Zhao Shaozhen
Published: August 2023

Background: Phototherapeutic keratectomy (PTK) has been increasingly used to treat severe recurrent corneal erosion syndrome (RCES) patients who do not respond to other treatments. However, the efficacy and complication of each study are currently uncertain due to varying rates. Objectives: The objective of this study was to investigate the safety and efficacy of the PTK for recurrent corneal erosions. Methods: This article performed a systematic literature research in Cochrane, Embase, PubMed, Scopus, and the Web of Science for the literature on PTK treatment of RCES until December 20, 2022. The extracted data including recurrence rate and the adverse event rate were used for meta-analysis. Results: The recurrence rate was 18% (95% CI, 13%–24%) (129/700 eyes). Subgroup analysis showed that the RCE recurrence was 17% (95% CI, 9%–24%) after trauma and 22% (95% CI, 11%–32%) in the corneal dystrophy group. Treatment-related adverse events included subepithelial haze, hyperopic shift, and decrease of the best spectacle-corrected visual acuity. In this study, the incidence of these events was 13% (95% CI, 6%–21%), 20% (95% CI, 11%–28%), and 11% (95% CI, 5%–16%), respectively. Conclusions: PTK represented a valuable treatment option for patients with recurrent corneal erosions, especially those with traumatic injuries, which had minimal side effects.
Addenda to ISCN 2020
Authors: Hastings Ros , McGowan-Jordan Jean , Moore Sarah ,   On behalf of the ISCN Standing Committee
Published: August 2023

Since the publication of ISCN 2020, the ISCN Standing Committee have noted some clarification of the text and additional examples were needed. These addenda have already been published online (https://iscn.karger.com/) and this short report summarises the ISCN 2020 addenda for the benefit of participants. These addenda will be included in the release of the next version of ISCN.
Diagnostic and Management Performance of ChatGPT in Obstetrics and Gynecology
Authors: Allahqoli Leila , Ghiasvand Mohammad Matin , Mazidimoradi Afrooz , Salehiniya Hamid , Alkatout Ibrahim
Published: August 2023

Objectives: The use of artificial intelligence (AI) in clinical patient management and medical education has been advancing over time. ChatGPT was developed and trained recently, using a large quantity of textual data from the internet. Medical science is expected to be transformed by its use. The present study was conducted to evaluate the diagnostic and management performance of the ChatGPT AI model in obstetrics and gynecology. Design: A cross-sectional study was conducted. Participants/Materials, Setting, Methods: This study was conducted in Iran in March 2023. Medical histories and examination results of 30 cases were determined in six areas of obstetrics and gynecology. The cases were presented to a gynecologist and ChatGPT for diagnosis and management. Answers from the gynecologist and ChatGPT were compared, and the diagnostic and management performance of ChatGPT were determined. Results: Ninety percent (27 of 30) of the cases in obstetrics and gynecology were correctly handled by ChatGPT. Its responses were eloquent, informed, and free of a significant number of errors or misinformation. Even when the answers provided by ChatGPT were incorrect, the responses contained a logical explanation about the case as well as information provided in the question stem. Limitations: The data used in this study were taken from the electronic book and may reflect bias in the diagnosis of ChatGPT. Conclusions: This is the first evaluation of ChatGPT’s performance in diagnosis and management in the field of obstetrics and gynecology. It appears that ChatGPT has potential applications in the practice of medicine and is (currently) free and simple to use. However, several ethical considerations and limitations such as bias, validity, copyright infringement, and plagiarism need to be addressed in future studies.
The Evaluation of Sarcopenia before Neoadjuvant Chemotherapy Is Important for Predicting Postoperative Pneumonia in Patients with Esophageal Cancer
Authors: Nishi Satoshi , Miki Yuichiro , Imai Takumi , Nambara Mikio , Miyamoto Hironari , Tamura Tatsuro , Yoshii Mami , Toyokawa Takahiro , Tanaka Hiroaki , Lee Shigeru , Maeda Kiyoshi
Published: August 2023

Introduction: Sarcopenia is often observed in patients with esophageal cancer (EC). However, the influence of sarcopenia during neoadjuvant chemotherapy (NAC) on complications has not been fully investigated. Thus, we aimed to investigate the best way of evaluating sarcopenia for predicting complications, especially postoperative pneumonia (PP), in patients with EC undergoing NAC and esophagectomy. Methods: We retrospectively reviewed 113 patients. The skeletal muscle mass index (SMI) was evaluated by bioelectrical impedance analysis and/or computed tomography. Patients were diagnosed with sarcopenia at pre-NAC and preoperative timing. Different criteria were compared in terms of the predictability of PP. Next, we evaluated which factors were related to sarcopenia with the best PP predictability. Results: Fifteen (13.2%) patients developed grade III or higher PP. Pre-NAC modified European Working Group on Sarcopenia in Older People (EWGSOP) criteria showed the highest sensitivity (100%) and acceptable specificity (75.8%) for predicting PP. Low pre-NAC body mass index and %VC were significantly associated with sarcopenia by the modified EWGSOP criteria. Conclusion: Pre-NAC sarcopenia by modified EWGSOP was a significant predictor of PP after esophagectomy. Appropriate interventions for these patients should be explored to prevent PP.
Stand der Forschung und neue therapeutische Perspektiven in der Immuntherapie des Prostatakarzinoms
Authors: Maselli Felicia Maria , Giuliani Francesco , Laface Carmelo , Perrone Martina , Melaccio Assunta , De Santis Pierluigi , Santoro Anna Natalizia , Guarini Chiara , Iaia Maria Laura , Fedele Palma
Published: August 2023

Das Prostatakarzinom ist die häufigste Art von Tumor bei Männern. Im Frühstadium der Erkrankung ist es empfindlich gegenüber einer Androgenentzugstherapie. Bei Patienten mit metastasiertem kastrationssensitivem Prostatakarzinom (mHSPC) haben Chemotherapie und Androgenrezeptortherapien der zweiten Generation zu einer Verlängerung der Überlebenszeit geführt. Trotz der Fortschritte bei der Behandlung des mHSPC ist eine Kastrationsresistenz unvermeidlich, und viele Patienten entwickeln eine metastasierende kastrationsresistente Erkrankung (mCRPC). In den letzten Jahrzehnten hat die Immuntherapie die onkologische Landschaft dramatisch verändert und die Überlebensraten bei vielen Krebsarten erhöht. Allerdings hat die Immuntherapie beim Prostatakarzinom noch nicht die bahnbrechenden Ergebnisse gebracht, die sie bei anderen Tumorarten erzielt hat. Die Erforschung neuer Behandlungsmöglichkeiten ist für Patienten mit mCRPC aufgrund der schlechten Prognose sehr wichtig. In dieser Übersichtsarbeit konzentrieren wir uns auf die Gründe für die scheinbare intrinsische Resistenz des Prostatakarzinoms gegenüber der Immuntherapie, die Möglichkeiten zur Überwindung dieser Resistenz sowie die klinische Evidenz und auf neue therapeutische Perspektiven für die Immuntherapie des Prostatakarzinoms mit einem Blick in die Zukunft.
Klarzellkarzinom der Prostata vom renalen Typ: Bericht eines seltenen Falls
Authors: Ansari Jamshid , Khaleghi Shima , Seif Fatemeh
Published: August 2023

Das Auftreten eines klarzelligen Karzinoms der Prostata ist äußerst selten und stellt ein diagnostisches Dilemma dar. Wir beschreiben den Fall eines 47-jährigen männlichen Nichtrauchers, der seit 6 Monaten über häufiges, tröpfelndes Wasserlassen und Dysurie klagte. Bei einer digitalen rektalen Untersuchung wurde eine vergrößerte Prostata mit einer harten Konsistenz festgestellt. Alle Ergebnisse der hämatologischen und biochemischen Tests waren normal. Außerdem lag der Serumspiegel des prostataspezifischen Antigens (PSA) bei 2,7 ng/ml (im Normbereich). Es wurde eine offene Prostatektomie durchgeführt, die ein 300 g schweres Präparat ergab, und die histopathologische Untersuchung ergab ein klarzelliges Karzinom. Bei einer Computertomografie und einer Ultraschalluntersuchung wurde keine Masse in den Nieren festgestellt, aber 3 Knoten in beiden Lungen, die für eine Metastasierung sprachen. 3 Monate nach der Operation ergab ein PET-Scan eine Hyperaktivität in der Bauchdecke, den Beckenlymphknoten und den Lungenfeldern, was für eine Metastasierung sprach; daraufhin wurde eine systemische Therapie mit einem Tyrosinkinaseinhibitor verordnet. Soweit wir wissen, ist über klarzellige Karzinome der Prostata sehr selten berichtet worden.
Immune Dysfunction and Infection – Interaction between CLL and Treatment: A Reflection on Current Treatment Paradigms and Unmet Needs
Authors: Gargiulo Ernesto , Teglgaard Rebecca Svanberg , Faitová Tereza , Niemann Carsten Utoft
Published: August 2023

Background: Chronic lymphocytic leukemia (CLL) is a hematological malignancy characterized by immune dysfunction, which significantly contributes to increased morbidity and mortality due to infections. Summary: Advancement in therapeutic strategies based on combination chemoimmunotherapy and targeted treatment have increased life expectancy for patients affected by CLL. However, mortality and morbidity due to infection showed no improvement over the last decades. Although therapy options are highly efficient in targeting leukemic cells, several studies highlighted the interactions of different treatments with the tumor microenvironment immune components, significantly impacting their clinical efficacy and fostering increased risk of infections. Key Messages: Given the profound immune dysfunction caused by CLL itself, treatment can thus represent a double-edged sword. Thus, it is essential to increase our understanding and awareness on how conventional therapies affect the disease-microenvironment-infection axis to ensure the best personalized strategy for each patient. This requires careful consideration of the advantages and disadvantages of efficient treatments, whether chemoimmunotherapy or targeted combinations, leading to risk of infectious complications. To this regard, our machine learning-based algorithm CLL Treatment-Infection Model, currently implemented into the local electronic health record system for Eastern Denmark, aims at early identification of patients at high risk of serious infections (PreVent-ACaLL; NCT03868722). We here review strategies for management of immune dysfunction and infections in CLL.
Correlation between PainDETECT Questionnaire and Quantitative Sensory Testing for the Detection of Neuropathic Pain in Hidradenitis Suppurativa
Authors: Speck Patrick J. , Alsouhibani Ali , Mustin Danielle E. , Cole Emily F. , Harper Daniel E. , Orenstein Lauren A.V.
Published: August 2023

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that is often severely painful due to nociceptive mechanisms (i.e., stimulation of cutaneous nociceptors). However, patient-reported pain character suggests that neuropathy may also drive HS pain in a subset of patients. Quantitative sensory testing (QST) can help identify neuropathic pain by testing for heightened and paradoxical pain responses in patients, but it is less feasible for routine clinical use compared with brief questionnaires. We therefore tested the suitability of a standardized neuropathic questionnaire (PainDETECT; PD-Q) for use as a surrogate clinical measure by directly comparing it with QST-identified neuropathic pain in HS. Methods: This observational, cross-sectional study included 22 adults with painful HS lesions who completed the PD-Q and underwent QST. A receiver operating characteristic curve was generated and Cohen’s Kappa, sensitivity, and specificity were examined at three scoring thresholds. Results: Of the 22 participants, 14 (64%) exhibited dynamic mechanical allodynia and/or paradoxical thermal sensations in QST, which are characteristically found in neuropathic pain. According to the PD-Q, 8 participants (36%) were unlikely, 8 (36%) were possible, and 6 (27%) were likely to have neuropathic pain. A PD-Q Score indicating possible or likely neuropathic pain (i.e., ≥13) demonstrated 82% agreement with QST-determined neuropathic pain (Cohen’s Kappa = 0.61 [p = 0.004]; sensitivity = 86%; specificity = 75%). Conclusion: The PD-Q demonstrates moderate agreement with QST in screening for neuropathic pain in HS and may be a helpful clinical tool.
Detection of Atrial Fibrillation after Ischemic Stroke with an Insertable Cardiac Monitor: A Systematic Review and Individual Patient Data Meta-Analysis of Randomized Clinical Trials
Authors: Wong Zi Yi , Yuen Linus Z.H. , Tan Ying Kiat , Goh Claire X.Y. , Teo Yao Neng , Ho Jamie S.Y. , Seow Swee Chong , Lee Edward C.Y. , Teoh Hock-Luen , Yeo Leonard L.L. , Sia Ching-Hui , Tan Benjamin Y.Q.
Published: August 2023

Introduction: We compared the use of insertable cardiac monitor (ICM) versus non-ICM methods of cardiac monitoring in ischemic stroke patients on the detection of atrial fibrillation (AF) and other clinical outcomes. Current guidelines recommend the routine use of 12-lead electrocardiography or Holter monitoring for AF detection after ischemic stroke. Recent randomized controlled trials have investigated the impact of ICM versus non-ICM methods of cardiac monitoring for AF detection in this population. However, precise recommendations for monitoring poststroke AF are lacking, including the optimal timing, duration, and method of electrocardiography monitoring. Methods: A systematic search was conducted on Embase and PubMed from database inception until October 27, 2022, to include randomized controlled trials that compared ICM with non-ICM methods of cardiac monitoring for poststroke AF detection. This yielded 3 randomized controlled trials with a combined cohort of 1,233 patients with a recent ischemic stroke. Individual patient data (IPD) were then reconstructed from Kaplan-Meier curves and analyzed using the shared-frailty Cox model. An aggregate data meta-analysis was conducted for 1,233 patients across all 3 studies for outcomes that could not be reconstructed using IPD. Results: One-stage meta-analysis demonstrated an increase in the hazard ratio (6.00 95% CI: 3.40–10.58; 195 p < 0.001) of AF detection in patients undergoing monitoring via ICM compared to standard care. The cumulative incidence curves of AF events in patients undergoing ICM and non-ICM separated significantly at 24 days. Aggregate data meta-analysis revealed a significant increase in initiation of anticoagulation (RR: 2.76, 95% CI: 1.89–4.02, p < 0.00001) in the ICM group. However, no significant differences in the incidence of recurrent ischemic stroke, transient ischemic attack, or death were found. Conclusions: In this meta-analysis, we found that the use of ICM increased the detection rate of poststroke AF and the rate of anticoagulation initiation in ischemic stroke patients. However, this did not translate into a reduced incidence of recurrent ischemic stroke.
MYC Promotes Aggressive Growth and Metastasis of a WNT-Medulloblastoma Mouse Model
Authors: Hartley Rachel , Phoenix Timothy N.
Published: August 2023

Medulloblastoma (MB), the most common malignant pediatric brain tumor, comprises four molecularly and clinically distinct subgroups (termed WNT, SHH, group 3, and group 4). Prognosis varies based on genetic and pathological features associated with each molecular subgroup. WNT-MB, considered low-risk, is rarely metastatic and contains activating mutations in CTNNB1; group 3-MB (GRP3-MB), commonly classified as high-risk, is frequently metastatic and can contain genomic alterations, resulting in elevated MYC expression. Here, we compare model systems of low-risk WNT-MB and high-risk GRP3-MB to identify tumor and microenvironment interactions that could contribute to features associated with prognosis. Compared to GRP3-MB, we find that WNT-MB is enriched in gene sets related to extracellular matrix (ECM) regulation and cellular adhesion. Exogenous expression of MycT58A in a murine WNT-MB model significantly accelerates growth and results in metastatic disease. In addition to decreased ECM regulation and cell adhesion pathways, we also identified immune system interactions among the top downregulated signaling pathways following MycT58A expression. Taken together, our data provide evidence that increased Myc signaling can promote the growth and metastasis in a murine model of WNT-MB.
The Biggest Unmet Needs in Cardiovascular Disease Prevention in 2023
Authors: Graham Ian M.
Published: August 2023

Background: While the major causes of atherosclerotic cardiovascular disease (CVD) are known, clinical audits continue to show inadequate risk factor control, even in the highest risk subjects. More effective risk estimation methods may help, and advances in this field are outlined. There exist excellent guidelines on CVD prevention, but their very length and complexity may limit their use. Other factors inhibiting guideline implementation are explored. Summary: While new medications continue to be developed, the real challenges to effective CVD prevention are societal and political. Both nationally and at European levels, cohesive, integrated strategies with defined responsibilities and accountability are needed, together with empowerment of people to understand the concept of risk and what they can do about it. Key Messages: There are profound health inequalities between and within countries that need to be addressed.