bluuebunny/crossref_metadata_2025 huggingface dataset:
Different Roles of Functional and Structural Renal Markers Measured at Discontinuation of Renal Replacement Therapy for Acute Kidney Injury
Authors: Yoshida Teruhiko , Matsuura Ryo , Komaru Yohei , Miyamoto Yoshihisa , Yoshimoto Kohei , Hamasaki Yoshifumi , Noiri Eisei , Nangaku Masaomi , Doi Kent
Published: October 2023

Introduction: Severe acute kidney injury (AKI) requiring renal replacement therapy (RRT) has been associated with an unacceptably high mortality of 50% or more. Successful discontinuation of RRT is thought to be linked to better outcomes. Although functional and structural renal markers have been evaluated in AKI, little is known about their roles in predicting outcomes at the time of RRT discontinuation. Methods: In this prospective single-center cohort study, we analyzed patients who received continuous RRT (CRRT) for AKI between August 2016 and March 2018 in the intensive care unit of the University of Tokyo Hospital (Tokyo, Japan). Clinical parameters and urine samples were obtained at CRRT discontinuation. Successful CRRT discontinuation was defined as neither resuming CRRT for 48 h nor receiving intermittent hemodialysis for 7 days from the CRRT termination. Major adverse kidney events (MAKEs) were defined as death, requirement for dialysis, or a decrease in the estimated glomerular filtration rate (eGFR) of more than 25% from the baseline at day 90. Results: Of 73 patients, who received CRRT for AKI, 59 successfully discontinued CRRT and 14 could not. Kinetic eGFR, urine volume, urinary neutrophil gelatinase-associated lipocalin (NGAL), and urinary L-type fatty acid binding protein were predictive for CRRT discontinuation. Of these factors, urine volume had the highest area under the curve (AUC) 0.91 with 95% confidence interval [0.80–0.96] for successful CRRT discontinuation. For predicting MAKEs at day 90, the urinary NGAL showed the highest AUC 0.76 [0.62–0.86], whereas kinetic eGFR and urine volume failed to show statistical significance (AUC 0.49 [0.35–0.63] and AUC 0.59 [0.44–0.73], respectively). Conclusions: Our prospective study confirmed that urine volume, a functional renal marker, predicted successful discontinuation of RRT and that urinary NGAL, a structural renal marker, predicted long-term renal outcomes. These observations suggest that the functional and structural renal makers play different roles in predicting the outcomes of severe AKI requiring RRT.
Cognitive-Behavioral Treatment of Perfectionism: An Overview of the State of Research and Practical Therapeutical Procedures
Authors: Wegerer Melanie
Published: October 2023

Background: Perfectionism represents an important transdiagnostic predisposing and maintaining factor in a number of psychological disorders. Moreover, perfectionism can complicate the treatment of psychological disorders and contribute to treatment resistance. In the present article, cognitive behavioral therapy (CBT) interventions to reduce perfectionistic patterns are explained. In addition, specifics of the therapeutic relationship with perfectionists as well as the etiology and possible functionalities of perfectionistic patterns are discussed. Summary: The effectiveness of classical CBT interventions for reducing perfectionism has been demonstrated in a number of studies. Recent research furthermore points to the (potential) benefit of interventions that fall into the third wave of CBT (such as mindfulness-based, schema therapeutic or self-compassion-based approaches) – however, there is still a lack of studies with sufficient methodological quality. Key Messages: While a number of different CBT approaches are available for the treatment of perfectionism, future studies should increasingly examine which interventions are particularly indicated for which patient characteristics.
MicroRNA-9-1 Attenuates Influenza A Virus Replication via Targeting Tankyrase 1
Authors: Bamunuarachchi Gayan , Vaddadi Kishore , Yang Xiaoyun , Dang Quanjin , Zhu Zhengyu , Hewawasam Sankha , Huang Chaoqun , Liang Yurong , Guo Yujie , Liu Lin
Published: October 2023

An unstable influenza genome leads to the virus resistance to antiviral drugs that target viral proteins. Thus, identification of host factors essential for virus replication may pave the way to develop novel antiviral therapies. In this study, we investigated the roles of the poly(ADP-ribose) polymerase enzyme, tankyrase 1 (TNKS1), and the endogenous small noncoding RNA, miR-9-1, in influenza A virus (IAV) infection. Increased expression of TNKS1 was observed in IAV-infected human lung epithelial cells and mouse lungs. TNKS1 knockdown by RNA interference repressed influenza viral replication. A screen using TNKS1 3′-untranslation region (3′-UTR) reporter assays and predicted microRNAs identified that miR-9-1 targeted TNKS1. Overexpression of miR-9-1 reduced influenza viral replication in lung epithelial cells as measured by viral mRNA and protein levels as well as virus production. miR-9-1 induced type I interferon production and enhanced the phosphorylation of STAT1 in cell culture. The ectopic expression of miR-9-1 in the lungs of mice by using an adenoviral viral vector enhanced type I interferon response, inhibited viral replication, and reduced susceptibility to IAV infection. Our results indicate that miR-9-1 is an anti-influenza microRNA that targets TNKS1 and enhances cellular antiviral state.
Risk Factors for Abnormal Small Airway Function Indicators in Nasal Polyp Patients with and without Asthma
Authors: Guo Jing , Wang Jianwei , Xu Xinjun , Yang Yujuan , Yu Pengyi , Liu Zhen , Cao Jiayu , Yang Qintai , Zhang Yu , Song Xicheng
Published: October 2023

Introduction: Small airway dysfunction (SAD) is associated with type 2 inflammation in patients who have non-asthmatic chronic rhinosinusitis with nasal polyps (CRSwNPs); however, the risk factors for abnormal small airway function indicators in CRSwNP patients with and without asthma remain unclear. Methods: We retrospectively analyzed 41 asthmatic and 109 non-asthmatic CRSwNP patients. Clinical characteristics were compared between groups, correlations between small airway function and clinical parameters were calculated, and independent risk factors for every small airway indicator were identified in each group. Results: Asthmatic CRSwNP patients had significantly reduced small airway function, and the proportion of patients with SAD was higher in asthmatic CRSwNP patients (65.85%) than in patients without asthma (9.17%). With regard to specific airway function indicators, age and a patient’s blood eosinophil (%) were identified as independent risk factors for lower FEF50% %pred and FEF25–75% pred, with age being an independent risk factor for FEF75% %pred in asthmatic CRSwNP patients. In non-asthmatic CRSwNP patients, allergic rhinitis comorbidity was found to be an independent risk factor for FEF50% %pred, FEF75% %pred, and FEF25–75% %pred. Conclusion: Physicians should pay greater attention to risk factors for abnormal small airway function indicators in patients with CRSwNPs to prevent the occurrence of SAD.
Postoperative Early Body Weight Loss Is a Risk Factor for Recurrence in Patients with pStage III Gastric Cancer
Authors: Fujimoto Daisuke , Taniguchi Keizo , Takashima Junpei , Kobayashi Hirotoshi
Published: October 2023

Introduction: The goal of this study was to determine whether postoperative early body weight loss (EWL) after radical gastrectomy is a risk factor for recurrence in patients with pathological stage III (pStage III) gastric cancer who received postoperative adjuvant chemotherapy, which included tegafur/gimeracil/oteracil (S-1). Methods: Patients who underwent gastrectomy for gastric cancer were identified from a prospectively managed gastric cancer database. We analyzed 58 consecutive patients who underwent radical gastrectomy with D2 lymph node dissection for confirmed pStage III gastric cancer treated postoperatively with adjuvant chemotherapy including S-1 between 2010 and 2019. Clinical and pathologic characteristics, baseline body mass index (BMI), and postoperative weights were extracted. Weight changes were evaluated from the preoperative period to the start of adjuvant chemotherapy. EWL was defined as % BMI change = (preoperative BMI – postoperative BMI at the start of adjuvant chemotherapy) × 100/preoperative BMI. Results: Of the 58 consecutive patients who underwent radical resection for gastric cancer, 72.4% were male, with a mean age of 65.5 years, and a mean preoperative BMI of 21.2 (range: 15.4–29.1) kg/m2. The degree of EWL was found to be closely correlated to compliance with adjuvant chemotherapy. Multivariate analysis by Cox proportional hazard analysis revealed that EWL was an independent factor for relapse-free survival (RFS), and patients with an EWL of 15.9% or more severe had poorer RFS. Conclusion: EWL above a certain rate at the start of adjuvant chemotherapy was a predictor of poor compliance with adjuvant chemotherapy and a high risk of disease recurrence in patients with pStage III gastric cancer.
Efficacy of Autologous Hematopoietic Stem Cell Transplantation versus Chemotherapy or Allogeneic Hematopoietic Stem Cell Transplantation for Follicular Lymphoma: Systematic Review and Meta-Analysis
Authors: Liu Xinsheng , Zheng Yaxin , Li Hongtao , Wang Meiyi , You M. James , Tian Chen
Published: October 2023

Background: The effect of autologous hematopoietic stem cell transplantation (auto-HSCT) versus conventional chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the survival of patients with advanced follicular lymphoma (FL) is uncertain. Objectives: To elucidate this, FL and HSCT were used as keywords to search in PubMed, Embase, Web of Science, and Cochrane Library databases. Method: After data extraction and quality evaluation, a total of 13 studies were included, seven of which compared auto-HSCT with conventional chemotherapy and the other six compared allo-HSCT with auto-HSCT to the survival of FL patients. Results: The results showed that auto-HSCT improved overall survival (OS), progression-free survival, and event-free survival of FL patients compared with conventional chemotherapy without auto-HSCT. Compared with allo-HSCT, the patients receiving auto-HSCT had longer OS and lower non-recurrent mortality. Conclusions: Auto-HSCT can provide a survival advantage for patients with FL compared with conventional chemotherapy and allo-HSCT did not result in a survival benefit.
A Case of Lip Psoriasis in a 14-Year-Old Boy Successfully Treated with Adalimumab
Authors: Caroppo Francesca , Gnesotto Laura , Deotto Maria Ludovica , Salmaso Roberto , Belloni Fortina Anna
Published: October 2023

Psoriasis is a common chronic skin disease mainly located in areas of friction. Psoriasis of the lips as an exclusive presentation is rare and often misdiagnosed. Different anti-psoriatic therapies have been proposed, but the literature is limited to case studies with partial results. Biologic therapies have revolutionized the management of many dermatologic conditions, including psoriasis, and they are approved for pediatric use. We report the case of a 14-year-old boy with a 2-year history of white-yellowish scaling lesions on his lips, without intraoral involvement. Lip biopsy showed a psoriasiform pattern. Treatment with adalimumab 40 mg every other week was started, and after 6 months of therapy, we obtained a complete remission of the patient’s lip psoriasis.
Fibro-Osseus Pseudotumor of the Digit: A Case Report and Review of Literature
Authors: Grover Chander , Gupta Pratibha , Gupta Chhavi , Nambiyar Kaniyappan , Goel Shitij
Published: October 2023

Introduction: Bony subungual growths arising on the digital tip are uncommon. Among these, subungual exostosis is a common cause. Case Presentation: We describe a 35-year-old-male patient with a rare occurrence of a fibro-osseus pseudotumor of the digit. It presents with reactive intramembranous ossification, with no continuity with the distal phalanx, helping differentiate it from a subungual exostosis. The patient presented with an asymptomatic subungual growth, lifting up the nail plate distally causing onycholysis. The characteristic clinical, radiological, and histopathological features of the case are described, which helped confirm the diagnosis. Conclusion: Cases with fibro-osseus pseudotumor of the digit reported in literature are reviewed comprehensively. The factors helping differentiate this from the other bony tumors affecting the distal phalanx, including subungual exostosis, myositis ossificans, and osteosarcoma are also highlighted.
Advanced Female Primary Urethral Carcinoma with Nodal Extension Managed with Exclusive Use of Chemoradiotherapy: Report of a Case and Review of the Relevant Current Literature
Authors: Al Barajraji Moncef , Holz Serge , Moussa Ilan , Naudin Michel , Coscarella Mathieu , Martin Martinez Maria-Dolores , Dingenen Stéphanie , Baize Adèle , Taylor Stephen
Published: October 2023

Primary urethral carcinoma (PUC) is a rare disease with frequent nodal metastasis at the time of diagnosis. Few risk factors have been established and overall prognosis remains poor. As of now, no clear therapeutic guidelines are established and management of advanced PUC often involves surgery which can have negative functional and psychological outcomes for the patient. Few authors have already reported the use of chemoradiotherapy alone to avoid surgery with some good short-term results. We report the case of a 48-year-old woman with advanced high-grade urothelial carcinoma of distal urethra associated to bilateral inguinal nodal metastasis. She was similarly and successfully treated using chemoradiotherapy exclusively without significant adverse effects. This experience reinforces benefits of a surgery-sparing management, when possible, as recommended in current guidelines.
Double-Layered Hand-Sewn versus Stapled Intestinal Anastomosis in Patients Who Underwent Ileal Urinary Diversion in Radical Cystectomy: A Comparative and Cost Effective Study
Authors: Tulone Gabriele , Pavan Nicola , Giannone Sofia , Abrate Alberto , Mannone Piero , Baiamonte Davide , Claps Francesco , Giaimo Rosa , Rossanese Marta , Ficarra Vincenzo , Simonato Alchiede
Published: October 2023

Introduction: Intestinal anastomosis can be performed by hand suturing (single layer or double layer) or by a mechanical suturing machine. The aim of the study was to compare complications, operative time, and costs of the intestinal anastomosis techniques. Methods: A retrospective comparative study was conducted including patients who underwent radical cystectomy and uretero-ileo-cutaneostomy or vescica ileale Padovana orthotopic neobladder. Double-layered hand-sewn intestinal anastomosis (HS-IA) were performed using Vicryl stitches. Mechanical-stapled intestinal anastomosis (MS-IA) were performed with a mechanical stapler. Results: Data of 195 patients who underwent were collected. 100 (51.3%) patients underwent HS-IA and 95 (48.7%) patients underwent MS-IA. Considering the complications classified according to Clavien-Dindo, a statistical difference with higher incidence for grade one in the HS-IA both in the ileal conduit group and in the neobladder one than the MS-IA (15.8% and 8.7%, respectively, in HS-IA vs. 1.7% and none in MS-IA). There is not a significant difference in time to flatus and time to defecation. Difference is recorded in the ileal conduit groups for the length of stay (10 days, range 9–12 with HS-IA vs. 13 days range 12–16 days with MS-IA (p < 0.001). The cost of the suture thread used for a single operation was 0.40 euros, whereas the overall cost of a disposable mechanical stapler and one refill was 350.00 €. Conclusion: Both HS-IA and MS-IA are safe and effective for patients. The cost for the stapling device is 350 €, in contrast, the cost for Vicryl sutures is negligible.
Epstein Barr Virus-Positive Lymphoproliferative Disorder Following Lymphodepletion for MAGE A4 Adoptive Cellular Therapy in a Patient with Synovial Sarcoma: A Case Report
Authors: Zhou Maggie , Jawed Ghazal , Ganjoo Kristen N.
Published: October 2023

Lymphoproliferative disorder (LPD) associated with viral reactivation is a known risk of immunocompromised patients. With development of novel cellular therapies utilizing lymphodepletion regimens in advanced cancer, the risk of LPDs should be a consideration. Here, we report a case of a 61-year-old treated male with history of metastatic synovial sarcoma and multiple treatment lines treated with cell therapy (lymphodepleting chemotherapy and afami-cel, formerly ADP-A2M4, T-cell treatment) on clinical study that developed Epstein Barr virus-positive LPD. Patient was treated with rituximab and achieved a complete response. New cellular therapies present promising treatment options for patients and adverse events should be monitored carefully.
Associations of the P300 Event-Related Potentials and Self-Reported Craving in Substance Use Disorders: A Systematic Review
Authors: Epp Tanisse , Skrenes Asal , Chao Thomas , Krigolson Olave E. , Schütz Christian G.
Published: October 2023

Introduction: The phenomenon of craving and attention bias towards drug cues is theorized to operate cooperatively, owing to the principles of associative learning. In this context, the conditioned response to drug-related stimuli activates reward mechanisms within the brain, consequently inducing craving and fostering the underlying mechanisms that contribute to relapse in individuals with substance use disorders. Multiple studies have assessed the relationship between attention to substance-related cues and subjective craving through electroencephalography (EEG), but their findings have yet to be synthesized and examined. This review summarizes the association between the amplitude of the P300 event-related potential (ERP) and substance use craving, compares discrepancies in results by type of substance, and discusses gaps in the literature to inform future research. Methods: A systematic search was conducted on Embase, Web of Science, CINAHL, and PsychINFO databases. Studies were published in English and included peer-reviewed human research investigating the relationship between EEG P300 ERP and self-reported substance use craving. The included study samples comprised of in treatment or non-treatment-seeking participants who use substances. The primary outcomes of interest were those derived from inferential statistics assessing P300 amplitude and substance use craving. Results: Ten studies were included in the final search and were organized by substance type: three alcohol, three cocaine, two tobacco, one heroin, and one cannabis. Results were mixed for alcohol and cocaine. Studies on tobacco, heroin, and cannabis use were congruent for associations between the P300 amplitude and craving. Conclusions: Overall findings are mixed between studies addressing the association of the EEG P300 amplitude and craving. These results should be considered in the context of the limited sample size, underpowered analyses, and methodological differences that potentially contribute to discrepancies in outcomes. Further research is required to assess the role of craving assessment, EEG methodology, and substance-related factors on the association between P300 amplitude and self-reported craving.
The Involvement of PGRMC1 Signaling in Cognitive Impairment Induced by Long-Term Clozapine Treatment in Rats
Authors: Cao Ting , Wang LiWei , Jiao ShiMeng , Chen Hui , Lin ChenQuan , Zhang BiKui , Cai HuaLin
Published: October 2023

Introduction: Progesterone receptor component 1 (PGRMC1) has been identified as a potential target in atypical antipsychotic drug-induced metabolic disturbances as well as neuroprotection in the central nervous system. In our study, we aimed to figure out the essential role of PGRMC1 signaling pathway underlying clozapine-induced cognitive impairment. Methods: In male SD rats, we utilized recombinant adeno-associated viruses (BBB 2.0) and the specific inhibitor of PGRMC1 (AG205) to regulate the expression of PGRMC1 in the brain, with a special focus on the hippocampus. Treatments of clozapine and AG205 were conducted for 28 days, and subsequent behavioral tests including modified elevated plus maze and Morris water maze were conducted to evaluate the cognitive performance. Hippocampal protein expressions were measured by Western blotting. Results: Our study showed that long-term clozapine administration led to cognitive impairment as confirmed by behavioral tests as well as histopathological examination in the hippocampus. Clozapine inhibited neural survival through the PGRMC1/EGFR/GLP1R-PI3K-Akt signaling pathway, leading to a decrease in the downstream survival factor, brain-derived neurotrophic factor (BDNF), and simultaneously promoted neural apoptosis in the rat hippocampus. Intriguingly, by targeting at the hippocampal PGRMC1, we found that inhibiting PGRMC1 mimics, while its upregulation notably mitigates clozapine-induced cognitive impairment through PGRMC1 and its downstream signaling pathways. Conclusion: PGRMC1-overexpression could protect hippocampus-dependent cognitive impairment induced by clozapine. This effect appears to arise, in part, from the upregulated expression of PGRMC1/EGFR/GLP1R and the activation of downstream PI3K-Akt-BDNF and caspase-3 signaling pathways.
Bibliometric and Correlation Analysis of Bariatric Surgery Researches in Asia-Pacific from 2000 to 2021
Authors: Lu Guanhua , Hu Ruixiang , Dong Zhiyong , Wang Jianxue , Yang Wah , Wang Cunchuan
Published: October 2023

Introduction: Bariatric surgery has grown in popularity over the past two decades, especially in the Asia-Pacific. Correspondingly, researchers’ interest in this field has also increased. This study aims to perform a bibliometric analysis of publications from Asia-Pacific represented by the International Federation for the Surgery of Obesity and Metabolic Disorders Asia-Pacific Chapter (IFSO-APC) and investigate the relevant factors that might affect the publications. Methods: The search terms for bariatric surgery were searched in Web of Science focusing on the period 2000–2021. Bibliometric analysis was performed after screening the search results. Univariate and multivariate regression analyses were performed on the number of publications and corresponding indicators obtained from official agencies. Results: A total of 9,547 publications in IFSO-APC were retrieved, of which China had the largest number with 2,782 publications. Authors and journals with major contributions were listed. The authors’ or affiliations’ cooperation networks mainly were limited to domestic. “Bariatric surgery” was the most frequent keyword with 2,063 times and also the largest cluster. “Morbid obesity” was the strongest citation bursts. Multivariate analysis found that the number of publications in each country/region was associated with body mass index ≥25 kg/m2, gross domestic product, and total population. Conclusion: Generally, Asia-Pacific represented by IFSO-APC scientific publications on bariatric surgery has grown significantly in the last two decades, but cooperation between countries/regions should be strengthened. “Morbid obesity” is the focus and frontier of research in this field.
Gastrointestinal Angiodysplasia in Patients with Severe Aortic Stenosis: The Endoscopic Features of Heyde’s Syndrome
Authors: Sugino Satoshi , Inoue Ken , Zen Kan , Yashige Masaki , Kobayashi Reo , Takamatsu Kazuaki , Ito Nobuyasu , Iwai Naoto , Hirose Ryohei , Doi Toshifumi , Dohi Osamu , Yoshida Naohisa , Uchiyama Kazuhiko , Takagi Tomohisa , Ishikawa Takeshi , Konishi Hideyuki , Matoba Satoaki , Itoh Yoshito
Published: October 2023

Introduction: Aortic stenosis (AS) is sometimes associated with gastrointestinal bleeding, and this phenomenon is known as Heyde’s syndrome. Such bleeding is most often considered to originate from gastrointestinal angiodysplasias, but the frequency and endoscopic features of such bleeding remain unclear. This study aimed to determine the frequency and endoscopic features of gastrointestinal angiodysplasia in patients with severe AS. Patients and Methods: In this multicenter, retrospective study, we evaluated consecutive patients who underwent transcatheter aortic valve implantation (TAVI) with severe AS from May 2016 to December 2019. We extracted the data on the clinicopathological features according to the status of anemia, the proportion of patients who underwent gastrointestinal endoscopic examinations and demonstrated gastrointestinal angiodysplasia, and identified the endoscopic features associated with such patients. Results: In 325 patients, the rates of moderate/severe anemia (hemoglobin < 11 g/dL) were 52%. Regarding medicine, there were no significant differences between the patients with and without moderate/severe anemia. Patients were examined by esophagogastroduodenoscopy (21%), colonoscopy (12%), and balloon-assisted enteroscopy or small bowel capsule endoscopy (1.5%). Patients with moderate/severe anemia had significantly more angiodysplasia (38.3% vs. 7.7%; p < 0.0001) and active bleeding (23.4% vs. 0%; p < 0.01). Angiodysplasia was detected in 21 patients (stomach, n = 9; small intestine, n = 5, and colon, n = 10). Conclusions: The results suggest, for the first time, that patients with severe AS who underwent TAVI and moderate/severe anemia frequently had gastrointestinal angiodysplasia and active bleeding throughout the entire gastrointestinal tract.
Synchronous Urinary Bladder Urothelial Carcinoma and Transitional Cell Carcinoma of the Ovary: A Case Report
Authors: Rizzuto Ivana , Slade Laura , Yanling Yang , Oehler Martin Klaus
Published: October 2023

Transitional cell carcinoma (TCC) of the ovary is a rare subtype of epithelial ovarian tumours defined as a tumour composed of epithelial elements, histologically resembling urothelium and its neoplasms. Ovarian metastases from primary urinary tract carcinomas are rare. The differential diagnosis of primary TCC of the ovary versus metastatic bladder TCC is challenging because of histological similarity. We present the case of a 49-year-old premenopausal woman who was initially diagnosed with non-invasive papillary urothelial carcinoma of bladder (NIPUC) and after 2 years with a synchronous TCC of the ovary while being investigated for suspected relapse. She underwent a radical cystectomy, total hysterectomy, bilateral salpingo-oopharectomy, and pelvic lymph node dissection. The final diagnosis of synchronous NIPUC of the bladder and TCC of the ovary was made by histopathology and immunohistochemical studies.
Retinoblastoma with MYCN Amplification Diagnosed from Cell-Free DNA in the Aqueous Humor
Authors: Joseph Sarah , Pike Sarah , Peng Chen-Ching , Brown Brianne , Xu Liya , Berry Jesse L. , Chévez-Barrios Patricia , Hubbard G. Baker , Grossniklaus Hans E.
Published: October 2023

Introduction: The objective of this study was to report the clinicopathologic features of three cases of MYCN-amplified retinoblastoma identified genetically by aqueous humor sampling. Methods: Whole-genome sequencing was performed using isolated cell-free DNA (cfDNA) from aqueous humor of 3 retinoblastoma patients. We analyzed genomic copy number and mutational alterations, histologic and pathologic features, and clinical data. Results: The most common genetic alteration identified in these three retinoblastoma cases was a focal MYCN amplification on 2p. All tumors showed an early age of diagnosis with a median of 9 months. The tumor histopathologic features included neovascularization and subretinal seeding in case 1, diffuse nature with choroidal and prelaminar optic nerve invasion in case 2, and complete vitreous seeding in case 3. Case 1 expressed RB protein and had no RB1 mutation, case 2 did not express RB protein and had an RB1 mutation, and case 3 did not express RB protein and likely had an epigenetic effect on RB expression. Conclusions: Our report shows 3 cases of unilateral retinoblastomas diagnosed in patients ranging from 4 months to 18 months old. Genomic analysis from AH cfDNA revealed MYCN amplification with intact RB protein staining in case 1 and lack of RB staining in cases 2 and 3. RB1 mutational analysis in the AH confirmed a pathogenic variant in case 2. Clinical pathology showed features requiring aggressive treatment, specifically enucleation. Importance: MYCN-amplified retinoblastomas demonstrate unique pathogenesis and aggressive behavior, regardless if MYCN is a primary or secondary driver of disease. Genomic analysis from aqueous humor may be useful when deciding to enucleate as opposed to treating conservatively. Focal MYCN amplification on 2p might be relevant for tumor growth in this subset of the retinoblastoma population in terms of targeted therapeutics.
Risk Factors for Acute Rhinosinusitis in Childhood Asthma
Authors: Wang Hanrui , Wang Jianwei , Song Zheying , Guo Jing , Yang Yujuan , Liu Zi , Sun Yuemei , Liu Liping , Zhang Yu , Song Xicheng
Published: October 2023

Introduction: Specific pathogen infections associated with acute rhinosinusitis (ARS) in infants are risk factors for allergic asthma in adolescents. However, the risk factors for ARS onset remain largely unknown in asthmatic children. In this study, we aim to investigate the risk factors for ARS in childhood asthma. Methods: This study retrospectively compared and analyzed the clinical characteristics of asthmatic children with (n = 194) or without ARS (n = 799). Univariate regression analyses were performed to identify ARS-associated risk factors in asthmatic children, and subsequent multivariate backward stepwise logistic regression analyses were performed to identify independent risk factors. Results: The onset age, values of blood eosinophils (EOS) (%), and total IgE were significantly lower in patients with ARS than in those without ARS. Moreover, the proportions of patients allergic to Dermatophagoides pteronyssinus (d1) and Dermatophagoides farinae (d2) were significantly smaller in children with ARS (all p values <0.05). Univariate analyses showed that an older onset age, a higher body mass index, a higher value of blood EOS (%) were protective factors, while a higher value of blood lymphocytes (%) and a higher degree of sensitization to d1 and d2 were risk factors for ARS. Further backward stepwise multivariate logistic regression analyses confirmed that a younger onset age and allergic sensitization to d1 were independent risk factors for ARS in childhood asthma. Conclusion: Younger onset age and allergic sensitization to d1 are risk factors for the onset of ARS in childhood asthma, so allergen intervention should be performed as early as possible in asthmatic children.
Automatic Positive and Negative Emotion Regulation in Adolescents with Major Depressive Disorder
Authors: Zhang Wenhai , Zhao Cancan , Tang Fanggui , Luo Wenbo
Published: October 2023

Introduction: Adolescents with major depressive disorder (MDD) exhibit hypoactivity to positive stimuli and hyperactivity to negative stimuli in terms of neural responses. Automatic emotion regulation (AER) activates triple networks (i.e., the central control network, default mode network, and salience network). Based on previous studies, we hypothesized that adolescents with MDD exhibit dissociable spatiotemporal deficits during positive and negative AER. Methods: We first collected EEG data from 32 adolescents with MDD and 35 healthy adolescents while they performed an implicit emotional Go/NoGo task. Then, we characterized the spatiotemporal dynamics of cortical activity during AER. Results: In Go trials, MDD adolescents exhibited reduced N2 amplitudes, enhanced theta power for positive pictures, and stronger bottom-up information flow from the left orbitofrontal cortex (OFC) to the right superior frontal gyrus compared to top-down information flow than the controls. In contrast, in NoGo trials, MDD adolescents exhibited elevated P3 amplitudes, enhanced theta power, and stronger top-down information flows from the right middle frontal gyrus to the right OFC and the left insula than the controls. Conclusion: Overall, adolescents with MDD exhibited impaired automatic attention to positive emotions and impaired automatic response inhibition. These findings have potential implications for the clinical treatment of adolescents with MDD.
Niños con fibrosis quística: Impacto en la vida real de la terapia moduladora de CFTR altamente efectiva
Authors: Álvarez-Arroyo Maria René
Published: October 2023

Introduction: Recently, cystic fibrosis transmembrane regulator modulator therapy with elexacaftor/tezacaftor/ivacaftor has become available for children with cystic fibrosis (CF) carrying at least one F508del mutation. Objective: To assess the intermediate term effects of elexacaftor/tezacaftor/ivacaftor in children with cystic fibrosis in a real-world setting. Methods: We performed a retrospective analysis of records of children with cystic fibrosis, who started elexacaftor/tezacaftor/ivacaftor between 8/2020 and 10/2022. Pulmonary function tests, nutritional status, sweat chloride and laboratory data were assessed before, 3 and 6 months after the start of elexacaftor/tezacaftor/ivacaftor respectively. Results: Elexacaftor/tezacaftor/ivacaftor was started in 22 children 6–11 years and in 24 children 12–17 years. Twenty-seven (59%) patients were homozygous for F508del (F/F) and 23 (50%) patients were transitioned from ivacaftor/lumacaftor (IVA/LUM) or tezacaftor/ivacaftor (TEZ/IVA) to elexacaftor/tezacaftor/ivacaftor. Overall, mean sweat chloride concentration decreased by 59.3 mmol/L (95% confidence interval: -65.0 to -53.7 mmol/L, p < 0.0001) under elexacaftor/tezacaftor/ivacaftor. Sweat chloride concentration also decreased significantly after transition from IVA/LUM or TEZ/IVA to elexacaftor/tezacaftor/ivacaftor (-47.8 mmol/l; 95% confidence interval: -57.6 to -37.8 mmol/l, n = 14, p < 0.0001). Sweat chloride reduction was more marked in children with the F/F than in those with the F/MF genotype (69.4 vs 45.9 mmol/L, p < 0.0001). At 3 months follow-up, body-mass-index-z-score increased by 0.31 (95% CI, 0.2–0.42, p < 0.0001) with no further increase at 6 months. BMI-for-age-z-score was more markedly improved in the older group. Overall pulmonary function (percent predicted FEV1) at 3 months follow-up increased by 11.4% (95% CI: 8.0–14.9, p < 0.0001) with no further significant change after 6 months. No significant differences were noted between the age groups. Children with the F/MF genotype had a greater benefit regarding nutritional status and pulmonary function tests than those with the F/F genotype. Adverse events led to elexacaftor/tezacaftor/ivacaftor dose reduction in three cases and a temporary interruption of therapy in four cases. Conclusion: In a real-world setting, elexacaftor/tezacaftor/ivacaftor therapy had beneficial clinical effects and a good safety profile in eligible children with cystic fibrosis comparable to previously published data from controlled clinical trials. The positive impact on pulmonary function tests and nutritional status seen after 3 months of elexacaftor/tezacaftor/ivacaftor therapy was sustained at 6 months follow-up.
Association between the Dietary Inflammatory Index and All-Cause Mortality in Adults with Obesity
Authors: Zheng Xin , Ge Yi-Zhong , Ruan Guo-Tian , Lin Shi-Qi , Chen Yue , Liu Chen-An , Xie Hai-Lun , Song Meng-Meng , Liu Tong , Wang Zi-Wen , Shi Jin-Yu , Zhang He-Yang , Yang Ming , Liu Xiao-Yue , Deng Li , Shi Han-Ping
Published: October 2023

Introduction: The dietary inflammatory index (DII) is associated with numerous chronic noncommunicable diseases. Previous studies have shown that the pro-inflammatory DII categories are associated with abdominal and simple obesity. However, the association between DII and mortality in patients with abdominal obesity and simple overweight or obesity remains unclear. Methods: We used data from the US National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. A DII >0 (positive DII) was defined as a pro-inflammatory diet. A restricted cubic spline curve was used to describe the trend between DII and all-cause mortality. We then examined the association between DII and all-cause mortality in different body types using a Cox regression analysis and investigated the differences between sexes. Finally, the mediating effects of systemic inflammation were explored. Results: A pro-inflammatory diet increased all-cause mortality in adults with abdominal obesity (aHR: 1.31, 95% confidence interval [CI]: 1.11–1.54; p < 0.001) and with simple overweight or obesity (aHR: 1.30, 95% CI: 1.11–1.53; p < 0.001). In addition, the most pro-inflammatory DII increased the risk of mortality by 43% (hazard ratio [HR]: Q4 vs. Q1 = 1.43, 95% CI = 1.14–1.79; p = 0.002; p for trend = 0.003) and 39% (HR: Q4 vs. Q1 = 1.39, 95% CI = 1.13–1.74; p = 0.003; p for trend = 0.009) in participants with abdominal obesity and with simple overweight or obesity, respectively. However, this association was not present in normal-sized participants. Compared with men, women resisted the effects of a pro-inflammatory diet. Mediation analysis showed that white blood cell and neutrophil were mediators of the association between DII and all-cause mortality (p < 0.001). Conclusion: A pro-inflammatory diet is associated with all-cause mortality in adults with abdominal obesity and simple overweight or obesity, and this effect differs between men and women. Systemic inflammation may mediate the association between DII and all-cause mortality.
Bullous Lichen Planus of the Nails: A Case Report and Review of the Literature
Authors: Hwang Jonathan K. , Magro Cynthia M. , Lipner Shari R.
Published: October 2023

Lichen planus is a chronic inflammatory disorder that may affect the skin, nails, and/or oral mucosa. Bullous lichen planus is a rare variant of lichen planus, which is even less common in the nails. We present a case of nail bullous lichen planus, in a 48-year-old male presenting with a 10-month history of onychodystrophy of all ten fingernails. A longitudinal excision of the left thumbnail was performed, with histopathology consistent with lichen planus with focal transition to bullous lichen planus. He was treated with intralesional triamcinolone injections to the fingernails monthly, with improvements noted after three treatments. Our patient’s nail bullous lichen planus manifested with longitudinal ridging, white-yellow discoloration, onycholysis, subungual hyperkeratosis, and v-shaped nicking. Histopathological findings included classical lichen planus changes, as well as formation of subepidermal bullae, colloid bodies, and extensive inflammatory infiltrate. Increased awareness and high index of suspicion for this condition are necessary, given the often late diagnosis reported in previously published cases.
Mismatch Repair Deficiency in Biliary Tract Cancer: Prognostic Implications and Correlation with Histology
Authors: Vivaldi Caterina , Genovesi Virginia , Ugolini Clara , Bernardini Laura , Casadei-Gardini Andrea , Formica Vincenzo , Salani Francesca , Orsi Giulia , Massa Valentina , Cacciato-Insilla Andrea , Caccese Miriam , Cesario Silvia , Andrikou Kalliopi , Graziani Jessica , Campani Daniela , Vasile Enrico , Fontanini Gabriella , Fornaro Lorenzo , Masi Gianluca
Published: October 2023

Introduction: Mismatch repair (MMR) deficiency represents a biomarker and therapeutic target in various neoplasms, but its role in biliary tract cancers (BTCs) remains misunderstood. Methods: MMR status was retrospectively assessed using immunohistochemistry in 163-BTCs patients. We identified MMR proficiency (pMMR)/deficiency (dMMR) according to the loss of MMR proteins (MLH1, PMS2, MSH2, MSH6). The primary objective of the study was to assess the incidence of dMMR in BTCs; the secondary purpose was to explore its association with prognosis and clinical features. Results: dMMR was recorded in 9 patients, and it was strongly associated with mucinous histology (p < 0.01). Regarding the prognostic effect, in 122-radically resected patients, disease-free survival (DFS) resulted significantly shorter in dMMR patients compared to pMMR patients (10.7 vs. 31.3 months, p = 0.025) and so did nodal status (48.2 vs. 15.3 months in N0 vs. N+) (p < 0.01). Moreover, dMMR confirmed its prognostic role in terms of DFS at multivariate analysis (p = 0.03), together with nodal status (p = 0.01), and resection margin (p = 0.03). In 103 M+ patients (encompassing 41 metastatic de novo and 62 recurred after surgery patients) there were not differences between dMMR and pMMR regarding survival analyses. Conclusions: dMMR status is strongly correlated with mucinous histology and represents an independent prognostic factor in terms of disease relapse in patients with resected BTC. Implications for Practice: MMR may play an independent role in promoting an aggressive behaviour in patients with radically resected BTC. These results could be useful in improving the selection of patients after resection and, above all, should justify the evaluation of MMR status as a therapeutic target in BTC, especially in patients with atypical histology.
Survival Outcome in Early-Onset Metastatic Colorectal Cancer: A Multicenter-Matched Pair Analysis
Authors: Doleschal Bernhard , Niedersüß-Beke Dora , Kirchweger Patrick , Petzer Andreas , Thaler Josef , Rumpold Holger
Published: October 2023

Introduction: Survival of patients suffering from metastatic colorectal cancer (mCRC) has increased over the last decades. These benefits appear to be restricted to patients aged 50 and above. However, among the population aged <50, colorectal cancer incidence and mortality rates are significantly rising. The clinical benefit of treatment in this population still is a matter of debate. We aim to compare the clinical outcome between patients aged 50 and younger. Methods: In this retrospective, observational study, we analyzed data from 1,077 patients treated for mCRC at three cancer centers in Austria from January 2005 to December 2019. Patients were divided into two groups based on age at diagnosis: <50 years (eo-CRC) and >50 years (regular-onset CRC, ro-CRC). Propensity score matching was used to control for potential biases, and survival outcomes were compared between the two groups. Results: The differences in tumor characteristics between eo-CRC and ro-CRC in the overall population were primarily related to tumor sidedness and disease-free survival following intended curative resection. Our data show that eo-CRC patients underwent metastases resection more often and received significantly more lines of treatment in the palliative setting. Overall survival was superior in eo-CRC compared to ro-CRC, even after adjusting for sidedness, timing of metastases, sex, number of treatment lines, and resection of metastases by propensity scoring. Conclusion: Our study suggests that younger patients benefit at least to the same magnitude or even more from mCRC-treatment than patients aged 50 or above.
Síndrome de reacción a fármaco con eosinofilia y síntomas sistémicos en un niño con fibrosis quística
Authors: Abushahin Ahmed , Toma Haneen , Hamad Sara G. , Abu-Hasan Mutasim
Published: October 2023

Antecedentes: El síndrome de reacción a fármacos con eosinofilia y síntomas sistémicos (DRESS) es una reacción idiosincrásica inducida por fármacos que rara vez se produce en niños, pero que puede dar lugar a complicaciones graves. Se manifiesta sobre todo con fiebre, erupciones cutáneas extensas y eosinofilia. Los síntomas suelen aparecer entre dos y seis semanas después de la administración del fármaco desencadenante. También pueden verse afectados los órganos viscerales, especialmente el hígado, y si no se detecta de forma temprana y no se interrumpe de inmediato la administración del fármaco desencadenante, puede producirse insuficiencia hepática. Por tanto, un diagnóstico temprano es importante, aunque puede ser muy difícil debido a la rareza de la enfermedad, la falta de una prueba diagnóstica y su similitud con otras afecciones alérgicas e infecciosas pediátricas comunes. Presentación del caso: Un niño de 2.5 años con diagnóstico conocido de fibrosis quística, bronquiectasias bilaterales, insuficiencia pancreática y colonización crónica de las vías respiratorias por Pseudomonas aeruginosa ingresó en nuestro hospital con una exacerbación aguda de enfermedad pulmonar por FQ. Se le trató con piperacilina-tazobactam y amikacina, ambos por vía intravenosa, y se despejaron las vías respiratorias. En el día 18 de tratamiento, el paciente desarrolló fiebre elevada seguida de erupción maculopapular eritematosa y pruriginosa difusa. Los análisis de sangre mostraron eosinofilia, proteína C reactiva (CRP) elevada y niveles altos de enzimas hepáticas. Las manifestaciones clínicas y los resultados de laboratorio fueron compatibles con el síndrome DRESS. Por tanto, se suspendieron todos los antibióticos. Se observó una resolución progresiva de los síntomas en dos días. Las anomalías de laboratorio también se normalizaron en la visita clínica de seguimiento cuatro meses después.
Blood Pressure in Children with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency
Authors: Balagamage Chamila , Lawrence Neil R. , Krone Ruth , Bacila Irina A. , Krone Nils P.
Published: October 2023

Background: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) leads to impaired glucocorticoid and mineralocorticoid synthesis with excess production of androgens. Replication of the normal circadian cortisol secretion is challenging and supraphysiological doses of glucocorticoids are often required. Most patients experience transient episodes of hyper- and hypocortisolaemia during the day leading to adverse metabolic outcomes such as insulin resistance, visceral adiposity, and cardiovascular morbidity, including hypertension. These health problems are commonly diagnosed in adolescence and adulthood. Summary: Herein, we review the published data on the variation in blood pressure in CAH due to 21OHD and the interrelation with disease and treatment factors. Key Messages: Hypertension in childhood is a well-known risk factor for poor cardiovascular health in later life. Children with CAH have a higher prevalence of hypertension, which is more commonly transient. The prevalence is higher at younger ages, while relatively fewer patients remain hypertensive in adolescence, requiring antihypertensive treatment. Most studies suggest, transient hypertension in early childhood is associated with mineralocorticoid replacement; however, its direct association with adverse cardiovascular and metabolic outcome is not well established. There is insufficient evidence to support a relationship between hypertension and either glucocorticoid dose or salt supplementation in infancy. Androgen excess has been suggested as a possible reason for the absence of gender dimorphism in the incidence of hypertension and cardiovascular risks in CAH. There is no conclusive evidence for a direct association between hypertension and hyperandrogenism or insulin resistance. Increased carotid intima media thickness is commonly found in children with CAH and is thought to be driven by increased blood pressure.