bluuebunny/crossref_metadata_2025 huggingface dataset:
Block-partitioned Rayleigh–Ritz method for efficient eigenpair reanalysis of large-scale finite element models
Authors: Jeong Yeon-Ho , Boo Seung-Hwan , Yim Solomon C
Published: April 2023

In this manuscript, we propose a new effective method for eigenpair reanalysis of large-scale finite element (FE) models. Our method utilizes the matrix block-partitioning algorithm in the Rayleigh–Ritz approach and expresses the Ritz basis matrix using thousands of block matrices of very small size. To avoid significant computational costs from the projection procedure, we derive a new formulation that uses tiny block computations instead of global matrix computations. Additionally, we present an algorithm that recognizes which blocks are changed in the modified FE model to achieve computational cost savings when computing new eigenpairs. Through selective updating for the recognized blocks, we can effectively construct the new Ritz basis matrix and the new reduced mass and stiffness matrices corresponding to the modified FE model. To demonstrate the performance of our proposed method, we solve several practical engineering problems and compare the results with those of the combined approximation method, the most well-known eigenpair reanalysis method, and ARPACK, an eigenvalue solver embedded in many numerical programs.
Host associations of biting midges (Diptera: Ceratopogonidae: Culicoides) at deer farms in Florida, USA
Authors: Sloyer Kristin E , Acevedo Carolina , Wisely Samantha M , Burkett-Cadena Nathan D
Published: April 2023

Documenting the host use of vector species is important for understanding the transmission dynamics of vector-borne pathogens. Biting midges (Diptera: Ceratopogonidae: Culicoides) are vectors of epizootic hemorrhagic disease virus (EHDV) and bluetongue virus (BTV) worldwide. However, relative to mosquitoes and many other vector groups, host associations of this group are poorly documented. In this study, we used PCR-based bloodmeal analysis to determine species-level host associations of 3,603 blood-engorged specimens belonging to 18 Culicoides species at 8 deer farms in Florida, USA. We used a binomial mixed model with a Bayesian framework to compare the effect of host composition on the feeding patterns of Culicoides spp. and employed the Morisita-Horn Index to investigate the similarity of host use between farms for Culicoides stellifer and Culicoides insignis. Results show that the estimated probability of Culicoides spp. feeding upon white-tailed deer depends on the availability of cattle or exotic game and demonstrates differences in host-feeding selection among species. Culicoides insignis had high host similarity across farms suggesting that its host-use patterns are somewhat conserved. Culicoides stellifer had lower host similarity across farms suggesting that it is a more opportunistic feeder. White-tailed deer are fed upon by many Culicoides species on deer farms in Florida, and while most Culicoides species feed on white-tailed deer, the ratio of white-tailed deer bloodmeals to other bloodmeals is likely influenced by host availability. Culicoides spp. taking a majority of their bloodmeals from farmed white-tailed deer should be assessed for their vector competence for EHDV and BTV.
A population-based characterization study of  anti-mitochondrial M2 antibodies and its consistency with anti-mitochondrial antibodies
Authors: Liang En-yu , Liu Miao , Ke Pei-feng , Han Guang , Zhang Cheng , Deng Li , Wang Yun-xiu , Huang Hui , Huang Wu-jiao , Liu Rui-ping , Li Guo-hua , Wan Ze-min , He Yi-ting , He Min , Huang Xian-zhang
Published: April 2023

Objective

This study aims to estimate the prevalence of anti-mitochondrial antibody subtype M2 (AMA-M2) and assess its consistency with AMA in a general population.

Methods

A total of 8954 volunteers were included to screen AMA-M2 using enzyme-linked immunosorbent assay. Sera with AMA-M2 >50 RU/mL were further tested for AMA using an indirect immunofluorescence assay.

Results

The population frequency of AMA-M2 positivity was 9.67%, of which 48.04% were males and 51.96% were females. The AMA-M2 positivity in males had a peak and valley value of 7.81% and 16.88% in those aged 40 to 49 and ≥70 years, respectively, whereas it showed a balanced age distribution in females. Transferrin and immunoglobulin M were the risk factors for AMA-M2 positivity and exercise was the only protective factor. Of 155 cases with AMA-M2 >50 RU/mL, 25 cases were AMA-positive, with a female-to-male ratio of 5.25:1. Only 2 people, with very high AMA-M2 of 760 and >800 RU/mL, met the diagnostic criteria of primary biliary cholangitis (PBC), making the prevalence of PBC 223.36 per million in southern China.

Conclusion

We found that AMA-M2 has a low coincidence rate with AMA in the general population. A new decision-making point for AMA-M2 is needed to improve consistency with AMA and diagnostic accuracy.
Variation in DNA Methylation in Avian Nestlings Is Largely Determined by Genetic Effects
Authors: Sepers Bernice , Chen Rebecca Shuhua , Memelink Michelle , Verhoeven Koen J F , van Oers Kees
Published: April 2023

As environmental fluctuations are becoming more common, organisms need to rapidly adapt to anthropogenic, climatic, and ecological changes. Epigenetic modifications and DNA methylation in particular provide organisms with a mechanism to shape their phenotypic responses during development. Studies suggest that environmentally induced DNA methylation might allow for adaptive phenotypic plasticity that could last throughout an organism's lifetime. Despite a number of studies demonstrating environmentally induced DNA methylation changes, we know relatively little about what proportion of the epigenome is affected by environmental factors, rather than being a consequence of genetic variation. In the current study, we use a partial cross-foster design in a natural great tit (Parus major) population to disentangle the effects of common origin from common rearing environment on DNA methylation. We found that variance in DNA methylation in 8,315 CpG sites was explained by a common origin and only in 101 by a common rearing environment. Subsequently, we mapped quantitative trait loci for the brood of origin CpG sites and detected 754 cis and 4,202 trans methylation quantitative trait loci, involving 24% of the CpG sites. Our results indicate that the scope for environmentally induced methylation marks independent of the genotype is limited and that the majority of variation in DNA methylation early in life is determined by genetic factors instead. These findings suggest that there may be little opportunity for selection to act on variation in DNA methylation. This implies that most DNA methylation variation likely does not evolve independently of genomic changes.
Stock Market Stimulus
Authors: Greenwood Robin , Laarits Toomas , Wurgler Jeffrey
Published: April 2023

We study the stock market effects of the arrival of the three rounds of “stimulus checks” to U.S. taxpayers and the single round of direct payments to Hong Kong citizens. The first two rounds of U.S. checks appear to have increased retail buying and share prices of retail-dominated portfolios. The Hong Kong payments increased overall turnover and share prices on the Hong Kong Stock Exchange. We cannot rule out that these price effects were permanent. The findings raise novel questions about the role of fiscal stimulus in the stock market.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Does remission in systemic lupus erythematosus according to the 2021 DORIS definition match the treating rheumatologist’s judgement?
Authors: Altabás-González Irene , Rúa-Figueroa Íñigo , Rubiño Francisco , Mouriño Coral , Hernández-Rodriguez Íñigo , Menor-Almagro Raúl , Uriarte-Isacelaya Esther , Tomero Eva , Salman-Monte Tarek C , Carrión-Barberá Irene , Galindo-Izquierdo Maria , Rodriguez-Almaraz M Esther , Inês Luís S , Jiménez Norman , Pego-Reigosa José María
Published: April 2023

Objectives

To assess agreement between the 2021 Definition Of Remission In SLE (DORIS) and physician-judged lupus activity.

Methods

A cross-sectional analysis was conducted of data from a Spanish prospective multicentre study of SLE patients. We applied the 2021 DORIS criteria and assessed whether remission status based on this definition agreed with remission as per physician clinical judgement and reasons for disagreement between them.

Results

Out of 508 patients [92% women; mean age (s.d.): 50.4 years (13.7)] studied, 267 (54.4%) met the criteria for 2021 DORIS remission. Based on physicians’ judgement, 277 (55.9%) patients were classified as in remission or serologically active clinically quiescent (SACQ). The overall rate of agreement between these assessments was 81.2% (95% CI: 79.9, 82.9%) with a Cohen’s kappa of 0.62 (0.55–0.69). Overall, 46 (9.1%) patients were classified as in remission/SACQ by rheumatologists but did not meet the 2021 DORIS criteria for remission. The main reasons for discrepancies were a clinical SLE Disease Activity Index (cSLEDAI) score >0 in 39 patients, a Physician Global Assessment score >0.5 in five patients, and prednisone >5 mg/day in another five patients.

Conclusions

The 2021 DORIS remission is an achievable target in clinical practice. There is substantial agreement between the DORIS definition and physician-judged remission. The discordance was mainly due to physicians classifying some patients with ongoing mild disease activity as in remission. Thus, the standardized DORIS definition should be used to define the target in a treat-to-target strategy for the management of SLE.
Outcomes of Open Reduction in Children With Developmental Hip Dislocation: A Multicenter Experience Over a Decade
Authors: Cummings Jason L. , Oladeji Afolayan K. , Rosenfeld Scott , Johnson Megan , Goldstein Rachel , Georgopoulos Gaia , Stephenson Lindsay , White Nathan W. , Hosseinzadeh Pooya
Published: April 2023

Background:

Open reduction of the hip is commonly performed in children with severe developmental dysplasia of the hip, or in cases that are refractory to nonoperative forms of treatment. The open reduction has been associated with numerous complications including avascular necrosis (AVN) of the femoral head, the need for reoperation, and residual radiographic dysplasia. This study seeks to determine the effects of preoperative severity of dysplasia, associated procedures (femoral and acetabular osteotomies), age on AVN, and the need for reoperation.

Methods:

Children with developmental dysplasia of the hip and a minimum of 2 years of follow-up who underwent open reduction were identified. The following data points were recorded: sex, laterality of hip involvement, simultaneous procedures, surgical approach used, age, acetabular index, and International Hip Dysplasia Institute grade. We analyzed the effects of preoperative International Hip Dysplasia Institute, age, surgical approach (anterior/medial), bilateral reduction, and simultaneous femoral shortening or pelvic osteotomy on the outcomes of AVN and reoperation.

Results:

One hundred eighty-five hips in 149 patients were included in this study with an average follow-up of 4 years (range: 2 to 5 y). The average age at index surgery was 23 months (range: 1 to 121 mo). Overall, 60 hips (32.4%) required secondary surgical procedures at an average age of 58.5 months. High-grade AVN was noted in 24 hips (13.0%) and was found to be associated with the severity of the hip dislocation (P = 0.02). A higher rate of reoperation was found in children over 18 months at the time of open reduction who did not receive an acetabular osteotomy (P = 0.012).

Conclusion:

Approximately 1/3 of patients require another operative intervention within the first 4 years after open reduction of the hip. We found the severity of hip dislocation to be associated with a higher risk of AVN development. These findings support performing an acetabular osteotomy in children over 18 months of age at the time of open reduction to decrease the likelihood of requiring future reoperation during the first 4 years after the index procedure.

Level of Evidence:

Level III.
Hodgkin lymphoma in Brazil: trends in incidence and mortality over 4 decades
Authors: Silveira Talita Maira Bueno da , Mendonça e Silva Diego Rodrigues , Fernandes Gisele Aparecida , Lucio da Silva Thaina , Curado Maria Paula
Published: April 2023

Background

In Brazil, there is lack of studies on the incidence and mortality of this malignancy. The aim of this study was to describe the profile of HL in Brazil for incidence, mortality and trends.

Methods

Data on incidence in Brazil were collected from Population-Based Cancer Registries (1988–2017) and mortality for 1979–2019. Age-standardized incidence and mortality rates were calculated. Average annual percent change was estimated and analyzed in two calendar periods for mortality (1979–1999 and 2000–2019).

Results

Trends in the incidence of HL for males in Brazil declined in two state capitals – Belo Horizonte, −3.7% (95% CI, −7.1 to −0.3); and Salvador, −8.5% (95% CI, −13.0 to −3.8) – and remained stable in other cities. For females, two capitals showed a decrease in incidence: Salvador, −9.5% (95% CI, −15.3 to −3.2) and Porto Alegre, −3.9% (95% CI, −7.0 to −0.8). Mortality rates in males were higher than those in females. However, the decrease in mortality was greater in males, −2.2% (95% CI, −2.5 to −1.8). Age incidence distribution across Brazilian capitals showed a higher incidence among younger (15–30 years) individuals yet no clear incidence among older adults (>60 years).

Conclusion

The incidence trend of HL in Brazil has remained stable. While the mortality has decreased for both sex. Age distribution for mortality in young age and older ages follows the bimodal pattern for Brazil as a whole. Finally, further studies are necessary to understand age incidence distribution of HL in Brazil.
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.
Feasibility of personalized circulating tumor DNA detection in stage II and III melanoma
Authors: Brunsgaard Elise K. , Bowles Tawnya L. , Asare Elliot A. , Grossmann Kenneth , Boucher Kenneth M. , Grossmann Allie , Jackson Julie A. , Wada David A. , Rathore Richa , Budde Griffin , Grandemange Andrew , Hyngstrom John R.
Published: April 2023

The objective of this study was to evaluate the feasibility of developing personalized, tumor-informed assays for patients with high-risk resectable melanoma and examine circulating tumor DNA (ctDNA) levels in relation to clinical status. Pilot prospective study of clinical stage IIB/C and resectable stage III melanoma patients. Tumor tissue was used to design bespoke somatic assays for interrogating ctDNA in patients’ plasma using a multiplex PCR (mPCR) next-generation sequencing (NGS)-based approach. Plasma samples for ctDNA analysis were collected pre-/post-surgery and during surveillance. Out of 28 patients (mean 65 years, 50% male), 13 (46%) had detectable ctDNA prior to definitive surgery and 96% (27/28) tested ctDNA-negative within 4 weeks post-surgery. Pre-surgical detection of ctDNA was significantly associated with the later-stage (P = 0.02) and clinically evident stage III disease (P = 0.007). Twenty patients continue in surveillance with serial ctDNA testing every 3–6 months. With a median follow-up of 443 days, six out of 20 (30%) patients developed detectable ctDNA levels during surveillance. All six of these patients recurred with a mean time to recurrence of 280 days. Detection of ctDNA in surveillance preceded the diagnosis of clinical recurrence in three patients, was detected concurrent with clinical recurrence in two patients and followed clinical recurrence in one patient. One additional patient developed brain metastases without detection of ctDNA during surveillance but had positive pre-surgical ctDNA. Our results demonstrate the feasibility of obtaining a personalized, tumor-informed mPCR NGS-based ctDNA assay for patients with melanoma, particularly in resectable stage III disease.
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.
Extracorporeal Rewarming Is Associated With Increased Survival Rate in Severely Hypothermic Patients With Preserved Spontaneous Circulation
Authors: Podsiadło Paweł , Smoleń Agata , Brožek Tomáš , Kosiński Sylweriusz , Balik Martin , Hymczak Hubert , Cools Evelien , Walpoth Beat , Nowak Ewelina , Dąbrowski Wojciech , Miazgowski Bartosz , Witt-Majchrzak Anna , Jędrzejczak Tomasz , Reszka Kacper , Segond Nicolas , Debaty Guillaume , Dudek Michał , Górski Stanisław , Darocha Tomasz
Published: April 2023

Treatment recommendations for rewarming patients in severe accidental hypothermia with preserved spontaneous circulation have a weak evidence due to the absence of randomized clinical trials. We aimed to compare the outcomes of extracorporeal versus less-invasive rewarming of severely hypothermic patients with preserved spontaneous circulation. We conducted a multicenter retrospective study. The patient population was compiled based on data from the HELP Registry, the International Hypothermia Registry, and a literature review. Adult patients with a core temperature <28°C and preserved spontaneous circulation were included. Patients who underwent extracorporeal rewarming were compared with patients rewarmed with less-invasive methods, using a matched-pair analysis. The study population consisted of 50 patients rewarmed extracorporeally and 85 patients rewarmed with other, less-invasive methods. Variables significantly associated with survival included: lower age; outdoor cooling circumstances; higher blood pressure; higher PaCO2; higher BE; higher HCO3; and the absence of comorbidities. The survival rate was higher in patients rewarmed extracorporeally (p = 0.049). The relative risk of death was twice as high in patients rewarmed less invasively. Based on our data, we conclude that patients in severe accidental hypothermia with circulatory instability can benefit from extracorporeal rewarming without an increased risk of complications.
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.

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

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.
Deficits in Analytic and Common-Sense Reasoning in Schizophrenia
Authors: Bora Emre , Yalincetin Berna , Akdede Berna Binnur , Alptekin Köksal
Published: April 2023

Human rationality has a dual nature including analytic and common-sense thinking. Symptoms of schizophrenia have been suggested to be related to deficits in these aspects of logical reasoning. However, empirical studies investigating logical reasoning errors in schizophrenia and their clinical and neurocognitive correlates are scarce. Formal thought disorder and theory of mind (ToM) might be particularly important for understanding logical reasoning errors in schizophrenia. The current study compared the performances of 80 patients with schizophrenia with those of 49 healthy controls on syllogistic and counterfactual reasoning tasks and investigated clinical, neuropsychological, and social cognitive correlates of logical reasoning in schizophrenia. Patients with schizophrenia were impaired in both analytic and common-sense thinking. ToM impairment was a significant predictor of analytic reasoning abilities in schizophrenia. Executive functions and verbal memory were also significantly associated with analytic reasoning in schizophrenia. Further studies investigating logical reasoning errors in the early phases of the illness are needed.
Hernia Prevention Using Biologic Mesh and/or Small Bites: A Multi-Specialty 2x2 Factorial Randomized Controlled Trial
Authors: Coelho Rainna , Dhanani Naila H , Lyons Nicole B , Bernardi Karla , Askenasy Erik P , Millas Stefanos , Holihan Julie L , Ali Zuhair , Liang Mike K
Published: April 2023

Background:

VIH are the most common surgical complication following abdominal surgery. Randomized trials have shown efficacy of prophylactic synthetic mesh and small bites. Adoption of these practices has been limited due to concerns with placement of synthetic mesh in contaminated cases and small bites in an overweight population. We sought to assess the efficacy of prophylactic biologic mesh and small bites to prevent post-operative major complications: ventral incisional hernias (VIH), surgical site infection (SSI), reoperation, and death.

Study Design:

High-risk patients (overweight/obese, current smoker) undergoing abdominal surgery with a midline incision (≥5cm) were randomized (2x2 factorial trial) to receive either sublay biologic mesh or no mesh and either small bites (0.5x0.5cm) or large bites (1x1cm) fascial closure. The primary outcome measure was major complications at one-year post-operative. CONSORT guidelines were followed, and this study was registered on clinicaltrials.gov (NCT03148496). Assuming α=0.05, β=0.20, Δ=20%, it was estimated that 105 patients were needed. Primary outcome was assessed using Fisher’s exact test.

Results:

107 patients were randomized: 52 (49%) to mesh, 55 (51%) to no mesh, 55 (51%) to small bites, 52 (49%) to large bites. 16% were smokers, 31% overweight, 55% obese. At one-year post-operative, there were no differences in major complications between groups (mesh vs no mesh 21% vs 16%, p=0.62; small vs large bites 18% vs 19%, p=1.00).

Conclusion:

In this trial, biologic mesh and small bites appear to have no benefit. Further randomized trials are needed among high-risk patients prior to widespread adoption of prophylactic biologic mesh or small bites.
Longitudinal effects of early psychosocial deprivation on macaque executive function: Evidence from computational modelling
Authors: Massera Alice , Bonaiuto James J. , Gautier-Martins Marine , Costa Sara , Rayson Holly , Ferrari Pier Francesco
Published: April 2023

Executive function (EF) describes a group of cognitive processes underlying the organization and control of goal-directed behaviour. Environmental experience appears to play a crucial role in EF development, with early psychosocial deprivation often linked to EF impairment. However, many questions remain concerning the developmental trajectories of EF after exposure to deprivation, especially concerning specific mechanisms. Accordingly, using an ‘A-not-B’ paradigm and a macaque model of early psychosocial deprivation, we investigated how early deprivation influences EF development longitudinally from adolescence into early adulthood. The contribution of working memory and inhibitory control mechanisms were examined specifically via the fitting of a computational model of decision making to the choice behaviour of each individual. As predicted, peer-reared animals (i.e. those exposed to early psychosocial deprivation) performed worse than mother-reared animals across time, with the fitted model parameters yielding novel insights into the functional decomposition of group-level EF differences underlying task performance. Results indicated differential trajectories of inhibitory control and working memory development in the two groups. Such findings not only extend our knowledge of how early deprivation influences EF longitudinally, but also provide support for the utility of computational modelling to elucidate specific mechanisms linking early psychosocial deprivation to long-term poor outcomes.