bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of immunotherapy as second-line or later-line therapy and prognostic significance of KRAS or TP53 mutations in advanced non-small cell lung cancer patients
Authors: Liu Jingya , Gao Jianing 
Published: April 2023

Objective
In this retrospective study, we aimed to assess the relationship between mutations in the Kirsten rats sarcoma viral oncogene (KRAS)/ tumor protein p53 (TP53) genes and the efficacy of immune checkpoint inhibitors (ICIs) therapy as a second-line or later-line treatment for patients with stage IIIB/IV non-small cell lung cancer (NSCLC).

Methods
We retrospectively analyzed the clinical data of 143 patients with stage IIIB/IV NSCLC who were admitted to the Cancer Hospital of Harbin Medical University between January 2019 and September 2022. Kaplan–Meier survival curve analysis was performed to analyze the survival outcomes. Univariate and multivariate Cox proportional risk models were used to analyze the factors associated with the progression-free survival (PFS) and overall survival (OS) of advanced-stage NSCLC patients who received ICIs as second-line or later-line therapy.

Results
NSCLC patients with KRAS or TP53 mutations treated with ICIs showed significantly higher objective response rate, disease control rate, PFS, and OS compared to NSCLC patients with wild-type KRAS/TP53 (P < 0.05). Multivariate Cox regression analysis showed that a combined treatment regimen of ICIs plus chemotherapy was significantly associated with prolonged PFS [hazard ratio = 0.192; 95% confidence interval (CI), 0.094–0.392; P < 0.001] and OS (hazard ratio = 0.414; 95% CI, 0.281–0.612; P < 0.001).

Conclusion

KRAS or TP53 mutations were associated with improved PFS of advanced NSCLC patients treated with ICIs as second-line or later-line therapy. KRAS or TP53 mutations show great potential as clinical biomarkers to predict the efficacy of ICIs therapy.
Cancer mortality predictions for 2023 in Latin America with focus on stomach cancer
Authors: Santucci Claudia , Malvezzi Matteo , Levi Fabio , Camargo Maria Constanza , Boffetta Paolo , La Vecchia Carlo , Negri Eva 
Published: April 2023

Objective
We estimated cancer mortality statistics for the current year in seven major Latin American countries.

Methods
We retrieved official death certification data and population figures from the WHO and the United Nations databases for the 1970–2020 calendar period. We considered mortality from all neoplasms combined and for 10 major cancer sites. We estimated the number of deaths and age-standardized mortality rates for the year 2023.

Results
Age-standardized mortality rates for all cancers combined are predicted to decline in all countries, in both sexes, apart from Venezuelan women. The lowest predicted total cancer mortality rates are in Mexico, 69.8/100 000 men and 62.5/100 000 women. The highest rates are in Cuba with 133.4/100 000 men and 90.2/100 000 women. Stomach cancer is predicted to decline steadily in all countries considered, but remains the first-ranking site for men in Chile (14.3/100 000) and Colombia (11/100 000). Colorectal cancer rates also tended to decline but remain comparatively high in Argentina (14/100 000 men). Breast cancer rates were high in Argentinian women (16.5/100 000) though they tended to decline in all countries. Lung cancer mortality rates are also predicted to decline, however, rates remain exceedingly high in Cuba (30.5/100 000 men and 17.2/100 000 women) as opposed to Mexico (5.6/100 000 men and 3.2/10 000 women). Declines are also projected for cancer of the uterus, but rates remain high, particularly in Argentina and Cuba (10/100 000 women), and Venezuela (13/100 000 women) due to inadequate screening and cervical cancer control.

Conclusion
Certified cancer mortality remains generally lower in Latin America (apart from Cuba), as compared to North America and Europe; this may be partly due to death certification validity.
Unknown Causes of Death in Cancer Patients
Authors: Chinniah Siven , Chiam Mckenzee , Mani Kyle , Liang Menglu , Trifiletti Daniel M. , Spratt Daniel E. , Prasad Vinayak K. , Wang Ming , Tchelebi Leila T. , Zaorsky Nicholas G. 
Published: April 2023

Objectives:
Deaths from an unknown cause are difficult to adjudicate and oncologic studies of comparative effectiveness often demonstrate inconsistencies in incorporating these deaths and competing events (eg, heart disease and stroke) in their analyses. In this study, we identify cancer patients most at risk for death of an unknown cause.

Methods:
This retrospective, population-based study used cancer registry data from the Surveillance, Epidemiology, and End Results database (1992-2015). The absolute rate of unknown causes of death (COD) cases stratified by sex, marital status, race, treatment, and cancer site were calculated and a multivariable logistic regression model was applied to obtain adjusted odds ratios with 95% CIs.

Results:
Out of 7,154,779 cancer patients across 22 cancer subtypes extracted from Surveillance, Epidemiology, and End Results, 3,448,927 died during follow-up and 276,068 (7.4%) of these deaths were from unknown causes. Patients with an unknown COD had a shorter mean survival time compared with patients with known COD (36.3 vs 65.7 mo, P < 0.001). The contribution of unknown COD to total mortality was highest in patients with more indolent cancers (eg, prostate [12.7%], thyroid [12.3%], breast [10.7%]) and longer follow-up (eg, >5 to 10 y). One, 3, and 5-year cancer-specific survival (CSS) calculations including unknown COD were significantly decreased compared with CSS estimates excluding cancer patients with unknown COD.

Conclusion:
Of the patients, 7.4% died of unknown causes during follow-up and the proportion of death was higher with longer follow-up and among more indolent cancers. The attribution of high percentages of unknown COD to cancer or non-cancer causes could impact population-based cancer registry studies or clinical trial outcomes with respect to measures involving CSS and mortality.
Early assessment of circulating exosomal lncRNA-GC1 for monitoring neoadjuvant chemotherapy response in gastric cancer
Authors: Guo Xin , Gao Yunge , Song Qiying , Wei Jiangpeng , Wu Jianfeng , Dong Jian , Chen Ligang , Xu Shenhui , Wu Di , Yang Xisheng , Chen Lubin , Li Xiaohua , Ji Gang , Lv Xiaohui , Wei Bo 
Published: April 2023

Background:
The timing of surgery for patients with gastric cancer (GC) who undergo neoadjuvant chemotherapy (neoCT) was mainly guided by serial radiologic imaging. However, an earlier assessment was indispensable to avoid delayed treatment for nonresponders and excessive toxicity for responders. Our previous study has identified circulating extracellular vesicles-derived lncRNA-GC1 as a biomarker for early detection and monitoring progression of GC. However, the potential role of neoCT remains poorly understood.

Methods:
In this explorative biomarker analysis, we conducted a multi-cohort study to examine longitudinal levels of circulating extracellular vesicles-derived lncRNA-GC1 in 798 patients enrolled in the RESONANCE study (NCT01583361). Both circulating extracellular vesicles-derived lncRNA-GC1 and traditional gastrointestinal biomarkers were assessed at defined time nodes. Computed tomography (CT) scans were performed before treatment and 8–10 weeks and assessed based on the RECIST criteria.

Results:
Circulating extracellular vesicles-derived lncRNA-GC1 could be detected in 96.3% of patients at baseline, and significant reductions were observed before cycle 2 (P<0.0001). Levels of circulating extracellular vesicles-derived lncRNA-GC1 showed a stronger correlation with tumor burden and exhibited earlier dynamic changes than the traditional gastrointestinal biomarkers during the first cycle of neoCT. Strong agreement was observed between circulating extracellular vesicles-derived lncRNA-GC1 response (reduction >50%) and radiographic response (Cohen’s κ, 0.704). Importantly, circulating extracellular vesicles-derived lncRNA-GC1 maintained predictive value in two external cohorts. Patients with circulating extracellular vesicles-derived lncRNA-GC1 response showed superior disease-free survival [hazard ratio (HR), 0.6238; 95% CI, 0.4095–0.9501; P=0.0118] and overall survival (HR, 0.6131; 95% CI, 0.4016–0.9358; P=0.0090).

Conclusion:
Circulating extracellular vesicles-derived lncRNA-GC1 is an early marker of neoCT efficacy and predicts superior survival in GC patients treated with neoCT.
SurgSmart: an artificial intelligent system for quality control in laparoscopic cholecystectomy: an observational study
Authors: Wu Shangdi , Chen Zixin , Liu Runwen , Li Ang , Cao Yu , Wei Ailin , Liu Qingyu , Liu Jie , Wang Yuxian , Jiang Jingwen , Ying Zhiye , An Jingjing ,   Youth Committee of Pancreatic Disease of Sichuan Doctor Association (YCPD), Peng Bing , Wang Xin 
Published: April 2023

Background:
The rate of bile duct injury in laparoscopic cholecystectomy (LC) continues to be high due to low critical view of safety (CVS) achievement and the absence of an effective quality control system. The development of an intelligent system enables the automatic quality control of LC surgery and, eventually, the mitigation of bile duct injury. This study aims to develop an intelligent surgical quality control system for LC and using the system to evaluate LC videos and investigate factors associated with CVS achievement.

Materials and methods:
SurgSmart, an intelligent system capable of recognizing surgical phases, disease severity, critical division action, and CVS automatically, was developed using training datasets. SurgSmart was also applied in another multicenter dataset to validate its application and investigate factors associated with CVS achievement.

Results:
SurgSmart performed well in all models, with the critical division action model achieving the highest overall accuracy (98.49%), followed by the disease severity model (95.45%) and surgical phases model (88.61%). CVSI, CVSII, and CVSIII had an accuracy of 80.64, 97.62, and 78.87%, respectively. CVS was achieved in 4.33% in the system application dataset. In addition, the analysis indicated that surgeons at a higher hospital level had a higher CVS achievement rate. However, there was still considerable variation in CVS achievement among surgeons in the same hospital.

Conclusions:
SurgSmart, the surgical quality control system, performed admirably in our study. In addition, the system’s initial application demonstrated its broad potential for use in surgical quality control.
Limited sampling strategies for individualized BAX 855 prophylaxis in severe hemophilia A: in silico evaluation
Authors: Bukkems Laura H. , Goedhart Tine M.H.J. , Zwaan C. Michel , Cnossen Marjon H. , Mathôt Ron A.A. 
Published: April 2023

Objective
Limited sampling strategies (LSS) lower the burden of pharmacokinetic (PK)-guided dosing, but an extensive evaluation of LSS for BAX 855 (Adynovi) is currently lacking. This study aimed to develop a LSS for BAX 855 and combine this with a LSS of a standard half-life (SHL) factor VIII (FVIII) concentrate in a clinical setting.

Methods
Individual PK parameters of BAX 855 were estimated for 10 000 virtual patients with severe hemophilia A using Monte Carlo simulations. Several LSS consisting of 2–6 samples were examined based on patient burden, bias and accuracy of clearance, elimination half-life, volume of distribution and trough levels at 72 h (C72). Analyses were performed separately for adults and children <12 years.

Results
The preferred LSS for BAX 855 consisted of three sampling points at 15–30 min, 48 h and 72 h for both adults (mean accuracy C72: 14.0% vs. 10.8% using six samples) and children (mean accuracy C72: 14.9% vs. 11.4% using six samples). The best strategy with two samples (peak, 48 h) resulted in an adequate, but lower accuracy than strategies with ≥3 samples (mean accuracy C72: 22.3%). The optimal combination of the LSS of SHL FVIII and BAX 855 led to six samples during four clinical visits.

Conclusion
This in silico study has identified that two to three samples are necessary to estimate the individual PK of BAX-855 adequately. These samples can be collected in one or two clinical visits. When combining PK profiling of SHL FVIII and BAX 855, six samples during four clinical visits are needed.
Adjuvant Radiofrequency Ablation Along With Stenting Versus Stenting Alone for Biliary Tree Drainage in Patients With Malignant Biliary Strictures
Authors: Hayat Umar , Ashfaq Muhammad Z. , Haseeb Muhammad , Farhan Muhammad L. , Kamal Muhammad Umar , Talib Khandokar A. , Khan Hafiz M.A. , Siddiqui Ali A. 
Published: April 2023

Objective:
This metanalysis aims to assess the efficacy and safety of biliary stenting along with radiofrequency ablation compared with stents alone to treat malignant biliary obstruction (MBO) due to extrahepatic biliary strictures secondary to cholangiocarcinoma, pancreatic cancer, and metastatic cancer.

Methods:
A systemic search of major databases through April 2022 was done. All original studies were included comparing radiofrequency ablation with stenting versus stenting alone for treating malignant biliary strictures. The primary outcomes of interest were the difference in the mean stent patency and overall survival (OS) days between the 2 groups. The secondary outcome was to compare the adverse events of the 2 groups. The mean difference in the stent patency and OS days was pooled by using a random-effect model. We calculated the odds ratio to compare the adverse events between the 2 groups.

Results:
A total of 13 studies with 1339 patients were identified. The pooled weighted mean difference in stent patency was 43.50 days (95% CI, 25.60–61.41), favoring the RFA plus stenting. Moreover, the pooled weighted mean difference in OS was 90.53 days (95% CI, 49.00–132.07), showing improved survival in the RFA group. Our analysis showed no statistically significant difference in adverse events between the 2 groups OR 1.13 (95% CI, 0.90–1.42).

Conclusion:
Our analysis showed that RFA, along with stent, is safe and is associated with improved stent patency and overall patient survival in malignant biliary strictures. More robust prospective studies should assess this association further.
Lung transplantation for coronavirus disease 2019 acute respiratory distress syndrome/fibrosis: silver lining of a global pandemic
Authors: Cerier Emily J. , Bharat Ankit 
Published: April 2023

Purpose of review
The COVID-19 pandemic revolutionized the field of lung transplantation, as lung transplant is now an acceptable life-saving therapy for select patients with COVID-19-associated acute respiratory distress syndrome (ARDS), while prior to the pandemic, few transplants were performed for ARDS. This review article details the establishment of lung transplantation as a viable therapy for COVID-19-related respiratory failure, how to evaluate COVID-19 patients for lung transplant, and specific technical considerations for the operation.

Recent findings
Lung transplantation is a life-altering treatment for two distinct cohorts of COVID-19 patients: those with irrecoverable COVID-19-associated ARDS and those who recover from the initial COVID-19 insult but are left with chronic, debilitating post-COVID fibrosis. Both cohorts require stringent selection criteria and extensive evaluation to be listed for lung transplantation. As the first COVID-19 lung transplantation was recently performed, long-term outcomes are lacking; however, short-term outcome data of COVID-19-related lung transplants are promising.

Summary
Given the challenges and complexities associated with COVID-19-related lung transplantation, strict patient selection and evaluation are required with an experienced multidisciplinary team at a high-volume/resource center. With promising short-term outcome data, ongoing studies are needed to assess long-term outcomes of COVID-19-related lung transplants.
Gut Microbiota Dysbiosis in Suspected Food Protein Induced Proctocolitis—A Prospective Comparative Cohort Trial
Authors: Wurm Philipp , Stampfer Laura , Greimel Theresa , Leitner Eva , Zechner Ellen L. , Bauchinger Sebastian , Hauer Almuthe C. , Gorkiewicz Gregor , Högenauer Christoph , Hoffmann K. Martin 
Published: April 2023

Objectives:
In infants with suspected food protein induced proctocolitis (sFPIP) only a minority of patients are finally diagnosed with the disease following diagnostic dietary intervention (DDI). There is a need for a pathophysiological explanation for the cause of hematochezia in the majority of sFPIP infants.

Methods:
We prospectively recruited infants with sFPIP and healthy controls. Fecal samples were collected at inclusion, week 4 (end of DDI in sFPIP), and week 8. For 16S rRNA sequencing (515F/806R) we used Illumina MiSeq sequencing system. Amplicon sequence variants were generated using Qiime2 and DADA2. Qiime diversity alpha and beta group comparisons and linear discriminant analysis effect size analysis was performed. For shotgun metagenomic analysis on species level we used KneadData and MetaPhlAn2.

Results:
Fourteen sFPIP infants were compared to 55 healthy infants. At inclusion overall microbial composition of sFPIP infants differed significantly from controls (weighted UniFrac; Pairwise PERMANOVA, P = 0.002, pseudo-F = 5.008). On genus level healthy infant microbiota was significantly enriched with Bifidobacterium (B) compared to sFPIP patients (linear discriminant analysis [LDA] = 5.5, P < 0.001, 31.3% vs 12.1%). sFPIP stool was significantly enriched by Clostridium sensu stricto 1 over controls (LDA = 5.3, P = 0.003, 3.5% vs 18.3%). DDI caused a significant and sustained increase of Bifidobacterium (LDA = 5.4, P = 0.048, 27.9%) in sFPIP infants. Species level analysis revealed significant reduction of abundance of B longum in sFPIP patients, which after DDI was reversed by B. species other than B longum.

Conclusions:
We revealed a gut microbiota dysbiosis phenomenon in sFPIP infants. DDI induces a microbiota composition comparable to that of healthy infants. In most sFPIP infants hematochezia might be triggered by a gut microbiota dysbiosis phenomenon.
Activated phosphoinositide 3-kinase delta syndrome 2 associated with Kikuchi–Fujimoto disease: a rare Palestinian case report
Authors: Abulaila Karim J. , Sabha Mosa A. , Misk Momin R. , Alhalabeye Amr A. , Jobran Afnan W.M. , Abunejma Fawzy M. , Bakri Izzeddin A. 
Published: April 2023

Introduction:
Histiocytic necrotic lymphadenitis (HNL), also known as Kikuchi–Fujimoto disease (KFD), is a rare local lymphadenopathy with a benign course and clinical manifestations such as fever, lymphadenopathy, rash, hepatosplenomegaly, central nervous system (CNS) symptoms, and hemophilic cell syndrome. It was first identified by Japanese pathologists Kikuchi and Fujimoto. KFD damages the meninges, the brain parenchyma, and peripheral nerves in addition to the CNS. Neurological symptoms may even be the most obvious clinical manifestations or initial symptoms of the disease.

Case presentation:
We present a unique case of a 7-year-old male patient who was diagnosed with activated phosphoinositide 3-kinase delta syndrome 2 (APDS 2) associated with KFD, a HNL during a workup for fever without a focus and cervical lymphadenopathy.

Conclusion:
Highlighted the unique relationship between two uncommon conditions and stressed the significance of adding KFD to the list of possible diagnoses for lymphadenopathy in APDS 2. Furthermore, we demonstrate that patients with APDS 2 may exhibit low immunoglobulin M levels.
Nonparaneoplastic anti-NMDA receptor encephalitis in an adolescent girl: a case report
Authors: Ghimire Sharmila , Bhattarai Madhur , Ghimire Sandeep , Bista Kumar B. , Sharma Prakash , Kharel Arun , Gautam Niraj 
Published: April 2023

Introduction:
Anti-N-methyl D-aspartate (NMDA) receptor encephalitis is an autoimmune neurologic disorder that classically presents with psychiatric, neurologic, and autonomic symptoms, often with a viral prodrome.

Case presentation:
A 17-year-old female presented to the hospital with an 11-day history of fever, altered behavior, abnormal body movements, and altered sensorium. Upon examination, she was found to be febrile, tachycardic, and tachypneic, with a Glasgow Coma Scale score of 8.

Discussion:
The diagnosis of anti-NMDA receptor encephalitis is usually confirmed by the presence of anti-NMDA receptor antibodies in the cerebrospinal fluid. The first-line treatment options include steroids, intravenous immunoglobulin, and plasmapheresis, while second-line therapies such as rituximab and cyclophosphamide may be necessary for some patients. While most patients respond well to treatment, complications can arise, and as in this case, death can occur.

Conclusion:
New onset symptoms like alteration in behavior, abnormal body movement, altered sensorium, and psychiatric symptoms in a young female should raise suspicion of this disease. Immunotherapy is promising; however, anticipation and management of complication are essential in reducing mortality.
A thalamic epidermoid cyst presenting with memory disturbances: a case report
Authors: Paudel Kumar , Shrestha Ramesh , Karki Sijan , Jha Prabhat , Jha Rajiv 
Published: April 2023

Introduction and importance:
Epidermoid cysts are benign, slow-growing tumors. They account for 0.2–1.8% of all intracranial tumors and rarely appear as intraparenchymal masses. The most prevalent symptom in people of middle age is an insidious-onset headache.

Case presentation:
We present a 20-year-old college student who presented with memory disturbances. The imaging revealed a left thalamic mass. The tumor was excised and diagnosed histopathologically as an epidermoid cyst.

Clinical discussion:
Epidermoid cysts resemble epidermal skin cells in histology. The lesion of the thalamus involving the ventrolateral and anterior regions is involved with memory and language. Of note, to our knowledge, no cases of memory issues associated with thalamic epidermoid cysts have been reported in the literature.

Conclusion:
The ideal treatment is cystic component removal with complete capsule excision. Sometimes, in cases of incomplete excision, radiotherapy can be another option.
Feasibility and Acceptability of Group Compassion-Focused Therapy to Treat the Consequences of Childhood Maltreatment in People With Psychiatric Disorders in France
Authors: Riebel Marie , Weiner Luisa 
Published: April 2023

Abstract
Childhood maltreatment contributes to the development of psychiatric disorders. Shame appears to be an important mediating factor. Compassion-focused therapy (CFT) targets shame and seems relevant for adults with hard-to-treat psychiatric disorders associated with childhood maltreatment. Nevertheless, few studies have examined the feasibility and relevance of group CFT for this population and none in a French routine care setting. The aim of our study was to evaluate the feasibility and acceptability of group CFT for psychiatric disorders associated with childhood maltreatment. Eight adult patients with a history of childhood maltreatment participated in the 12-session group CFT. Feasibility and acceptability were assessed via a standardized satisfaction questionnaire, dropout rates, and attendance. Clinical benefits were assessed via changes in scores on scales of self-compassion, shame, and psychopathological dimensions. Adherence to therapy (75%) and attendance (88.3%) were high, and all participants reported high satisfaction. Posttreatment, self-compassion significantly increased (p = 0.016), and depression, anxiety, and posttraumatic scores decreased. Our study is the first to show that transdiagnostic group CFT (difficult-to-treat psychiatric disorders associated with a history of child maltreatment) is feasible in a French routine care setting. Changes in clinical scale scores after the intervention suggest the clinical value of the intervention and encourage further research of its effectiveness.