bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic diagnosis of endocrine disorders in Cyprus through the Cyprus Institute of Neurology and Genetics: an ENDO-ERN Reference Center
Authors: Neocleous Vassos , Fanis Pavlos , Toumba Meropi , Skordis Nicos , Phylactou Leonidas A.
Published: April 2024

The report covers the current and past activities of the department Molecular Genetics-Function and Therapy (MGFT) at the Cyprus Institute of Neurology and Genetics (CING), an affiliated Reference Center for the European Reference Network on Rare Endocrine Conditions (Endo-ERN).

The presented data is the outcome of > 15 years long standing collaboration between MGFT and endocrine specialists from the local government hospitals and the private sector. Up-to-date > 2000 genetic tests have been performed for the diagnosis of inherited rare endocrine disorders. The major clinical entities included Congenital Adrenal Hyperplasia (CAH) due to pathogenic variants in CYP21A2 gene and Multiple Endocrine Neoplasia (MEN) type 2 due to pathogenic variants in the RET proto-oncogene. Other rare and novel pathogenic variants in ANOS1, WDR11, FGFR1, RNF216, and CHD7 genes were also found in patients with Congenital Hypogonadotropic Hypogonadism. Interestingly, a few patients with Disorders of Sexual Differentiation (DSD) shared rare pathogenic variants in the SRD5A2, HSD17B3 and HSD3B2 while patients with Glucose and Insulin Homeostasis carried theirs in GCK and HNF1A genes. Lastly, MGFT over the last few years has established an esteemed diagnostic and research program on premature puberty with emphasis on the implication of MKRN3 gene on the onset of the disease and the identification of other prognosis biomarkers.

As an Endo-ERN member MGFT department belongs to this large European network and holds the same humanistic ideals which aim toward the improvements of health care for patients with rare endocrine conditions in respect to improved and faster diagnosis.
Pregnancy outcomes of Fabry disease in Austria (PROFABIA)-a retrospective cohort-study
Authors: Haninger-Vacariu Natalja , Anastopoulos Kyra , Aigner Christof , Sunder-Plassmann Raute , Gatterer Constantin , Ponleitner Markus , Sunder-Plassmann Gere , Schmidt Alice
Published: April 2024

Background

Pregnancy and delivery outcomes in women with Fabry disease are not well described.

Methods

Retrospective cohort-study of women with Fabry disease in Austria using a specific questionnaire and the Austrian Mother–Child Health Passport.

Results

Out of a total of 44 enrolled women (median age at study entry 44 years, p25: 30, p75: 51), 86.4% showed signs and symptoms of Fabry disease with an increase in pain burden during pregnancy, primarily in women with moderate pain before pregnancy. Thirty-two of 44 women with Fabry disease reported a total of 70 pregnancies (median age at first pregnancy 24 years, p25: 21, p75: 31), 61 (87.1%) of which resulted in 64 live births including 3 sets of twins, six miscarriages (8.6%) in five women, and three induced abortions (4.3%) in two women. Risk factors for poor maternal and foetal outcomes during pregnancy, overrepresented in our cohort as compared to the general population, were hypertension (n = 10, 16.4%), proteinuria (n = 17, 27.9%) and smoking (n = 24, 39.3%). Preeclampsia was reported in 7 pregnancies (11.5%). Fifty-one (79.7%) children were born at term and 13 (20.3%) were preterm (including one neonatal death), with a median gestational age of 39 weeks (p25: 38, p75: 40) and delivery by C-section in 15 pregnancies (24.6%). Thirteen (20.3%) children presented with low birth weight and 18 (28.1%) were small for their gestational age. In comparison to global and national data-sets, preeclampsia, prematurity, low birth weight, being small for their gestational age as well as inpatient stay were significantly more common in patients with Fabry disease.

Conclusions

Our cohort-study in women with Fabry disease shows an increase of pain burden during pregnancies and clearly points to an increased risk for preeclampsia, prematurity, and neonates small for gestational age. With a substantial number of high-risk pregnancies, neonatal outcomes are somewhat worse in Fabry disease than in the general public. Thus, we provide valuable data enabling informed decision-making in pregnancy counselling for Fabry disease.
The emergence of highly resistant and hypervirulent Klebsiella pneumoniae CC14 clone in a tertiary hospital over 8 years
Authors: Hala Sharif , Malaikah Mohammed , Huang Jiayi , Bahitham Wesam , Fallatah Omniya , Zakri Samer , Antony Chakkiath Paul , Alshehri Mohammed , Ghazzali Raeece Naeem , Ben-Rached Fathia , Alsahafi Abdullah , Alsaedi Asim , AlAhmadi Ghadeer , Kaaki Mai , Alazmi Meshari , AlhajHussein Baraa , Yaseen Muhammad , Zowawi Hosam M. , Alghoribi Majed F. , Althaqafi Abdulhakeem O. , Al-Amri Abdulfattah , Moradigaravand Danesh , Pain Arnab
Published: April 2024

Background

Klebsiella pneumoniae is a major bacterial and opportunistic human pathogen, increasingly recognized as a healthcare burden globally. The convergence of resistance and virulence in K. pneumoniae strains has led to the formation of hypervirulent and multidrug-resistant strains with dual risk, limiting treatment options. K. pneumoniae clones are known to emerge locally and spread globally. Therefore, an understanding of the dynamics and evolution of the emerging strains in hospitals is warranted to prevent future outbreaks.

Methods

In this study, we conducted an in-depth genomic analysis on a large-scale collection of 328 multidrug-resistant (MDR) K. pneumoniae strains recovered from 239 patients from a single major hospital in the western coastal city of Jeddah in Saudi Arabia from 2014 through 2022. We employed a broad range of phylogenetic and phylodynamic methods to understand the evolution of the predominant clones on epidemiological time scales, virulence and resistance determinants, and their dynamics. We also integrated the genomic data with detailed electronic health record (EHR) data for the patients to understand the clinical implications of the resistance and virulence of different strains.

Results

We discovered a diverse population underlying the infections, with most strains belonging to Clonal Complex 14 (CC14) exhibiting dominance. Specifically, we observed the emergence and continuous expansion of strains belonging to the dominant ST2096 in the CC14 clade across hospital wards in recent years. These strains acquired resistance mutations against colistin and extended spectrum β-lactamase (ESBL) and carbapenemase genes, namely blaOXA-48 and blaOXA-232, located on three distinct plasmids, on epidemiological time scales. Strains of ST2096 exhibited a high virulence level with the presence of the siderophore aerobactin (iuc) locus situated on the same mosaic plasmid as the ESBL gene. Integration of ST2096 with EHR data confirmed the significant link between colonization by ST2096 and the diagnosis of sepsis and elevated in-hospital mortality (p-value < 0.05).

Conclusions

Overall, these results demonstrate the clinical significance of ST2096 clones and illustrate the rapid evolution of an emerging hypervirulent and MDR K. pneumoniae in a clinical setting.
Accuracy of automated computer-aided risk scoring systems to estimate the risk of COVID-19: a retrospective cohort study
Authors: Faisal Muhammad , Mohammed Mohammed Amin , Richardson Donald , Fiori Massimo , Beatson Kevin
Published: April 2024

Background

In the UK National Health Service (NHS), the patient’s vital signs are monitored and summarised into a National Early Warning Score (NEWS) score. A set of computer-aided risk scoring systems (CARSS) was developed and validated for predicting in-hospital mortality and sepsis in unplanned admission to hospital using NEWS and routine blood tests results. We sought to assess the accuracy of these models to predict the risk of COVID-19 in unplanned admissions during the first phase of the pandemic.

Methods

Adult ( > = 18 years) non-elective admissions discharged (alive/deceased) between 11-March-2020 to 13-June-2020 from two acute hospitals with an index NEWS electronically recorded within ± 24 h of admission. We identified COVID-19 admission based on ICD-10 code ‘U071’ which was determined by COVID-19 swab test results (hospital or community). We assessed the performance of CARSS (CARS_N, CARS_NB, CARM_N, CARM_NB) for predicting the risk of COVID-19 in terms of discrimination (c-statistic) and calibration (graphically).

Results

The risk of in-hospital mortality following emergency medical admission was 8.4% (500/6444) and 9.6% (620/6444) had a diagnosis of COVID-19. For predicting COVID-19 admissions, the CARS_N model had the highest discrimination 0.73 (0.71 to 0.75) and calibration slope 0.81 (0.72 to 0.89) compared to other CARSS models: CARM_N (discrimination:0.68 (0.66 to 0.70) and calibration slope 0.47 (0.41 to 0.54)), CARM_NB (discrimination:0.68 (0.65 to 0.70) and calibration slope 0.37 (0.31 to 0.43)), and CARS_NB (discrimination:0.68 (0.66 to 0.70) and calibration slope 0.56 (0.47 to 0.64)).

Conclusions

The CARS_N model is reasonably accurate for predicting the risk of COVID-19. It may be clinically useful as an early warning system at the time of admission especially to triage large numbers of unplanned admissions because it requires no additional data collection and is readily automated.
Intravenous infusion of dexmedetomidine during the surgery to prevent postoperative delirium and postoperative cognitive dysfunction undergoing non-cardiac surgery: a meta-analysis of randomized controlled trials
Authors: Wang Di , Liu Zhi , Zhang Wenhui , Zu Guo , Tao He , Bi Congjie
Published: April 2024

Background

Dexmedetomidine plays a pivotal role in mitigating postoperative delirium and cognitive dysfunction while enhancing the overall quality of life among surgical patients. Nevertheless, the influence of dexmedetomidine on such complications in various anaesthesia techniques remains inadequately explored. As such, in the present study, a meta-analysis was conducted to comprehensively evaluate its effects on postoperative delirium and cognitive dysfunction.

Methods

A number of databases were searched for randomised controlled trials comparing intravenous dexmedetomidine to other interventions in preventing postoperative delirium and cognitive dysfunction in non-cardiac and non-neurosurgical patients. These databases included PubMed, Embase, and Cochrane Library. Statistical analysis and graphing were performed using Review Manager, STATA, the second version of the Cochrane risk-of-bias tool for randomised controlled trials, and GRADE profiler.

Main results

This meta-analysis comprised a total of 24 randomised controlled trials, including 20 trials assessing postoperative delirium and 6 trials assessing postoperative cognitive dysfunction. Across these 24 studies, a statistically significant positive association was observed between intravenous administration of dexmedetomidine and a reduced incidence of postoperative delirium (RR: 0.55; 95% CI 0.47 to 0.64, p < 0.00001, I2 = 2%) and postoperative cognitive dysfunction (RR: 0.60; 95% CI 0.38 to 0.96, p = 0.03, I2 = 60%). Subgroup analysis did not reveal a significant difference in the incidence of postoperative delirium between the general anaesthesia and non-general anaesthesia groups, but a significant difference was observed in the incidence of postoperative cognitive dysfunction. Nonetheless, when the data were pooled, it was evident that the utilisation of dexmedetomidine was associated with an increased incidence of hypotension (RR: 1.42; 95% CI 1.08 to 1.86, p = 0.01, I2 = 0%) and bradycardia (RR: 1.66; 95% CI 1.23 to 2.26, p = 0.001, I2 = 0%) compared with other interventions. However, there was no significantly higher occurrence of hypertension in the DEX groups (RR = 1.35, 95% CI 0.81–2.24, p = 0.25, I2 = 0%).

Conclusion

Compared with other interventions, intravenous dexmedetomidine infusion during non-cardiac and non-neurosurgical procedures may significantly reduce the risk of postoperative delirium and cognitive dysfunction. The results of subgroup analysis reveal a consistent preventive effect on postoperative delirium in both general and non-general anaesthesia groups. Meanwhile, continuous infusion during general anaesthesia was more effective in reducing the risk of cognitive dysfunction. Despite such findings, hypotension and bradycardia were more frequent in patients who received dexmedetomidine during surgery.
Accelerated construction of projection-based reduced-order models via incremental approaches
Authors: Agouzal Eki , Taddei Tommaso
Published: April 2024

We present an accelerated greedy strategy for training of projection-based reduced-order models for parametric steady and unsteady partial differential equations. Our approach exploits hierarchical approximate proper orthogonal decomposition to speed up the construction of the empirical test space for least-square Petrov–Galerkin formulations, a progressive construction of the empirical quadrature rule based on a warm start of the non-negative least-square algorithm, and a two-fidelity sampling strategy to reduce the number of expensive greedy iterations. We illustrate the performance of our method for two test cases: a two-dimensional compressible inviscid flow past a LS89 blade at moderate Mach number, and a three-dimensional nonlinear mechanics problem to predict the long-time structural response of the standard section of a nuclear containment building under external loading.
Reducing anti-fat bias toward the self and others: a randomized controlled trial
Authors: Kramer Emily B. , Pietri Evava S. , Bryan Angela D.
Published: April 2024

Despite strong evidence linking anti-fat bias directed toward others with markers of self-directed anti-fat bias, there is a dearth of theory-based research examining the cognitive pathways underlying this relationship, and existing bias-reduction intervention efforts have thus far been conducted with exclusive focus on one domain or the other. Cognitive dissonance (CD)-based interventions have been identified as viable for reducing anti-fat bias directed toward the self and others. However, no study has yet examined whether the effects of these domain-specific interventions (e.g., anti-fat bias towards the self) extend to anti-fat bias in the non-targeted domain (e.g., anti-fat bias towards others). The present study aimed to address these gaps in the literature by comparing effects of brief CD-based interventions targeting anti-fat bias directed toward either the self or others on measures of anti-fat bias. Participants (N = 197, female-identifying undergraduates) were randomized to a writing activity prompting cognitive dissonance about either self-directed or other-directed anti-fat bias, or a bias-consistent control condition. Results indicated that participants in the CD intervention conditions showed significantly greater reductions in both explicit self- and other-directed anti-fat biases than those in the control condition, but results did not significantly differ across CD conditions. This supports the potential utility of interventions simultaneously targeting anti-fat bias in both domains and provides insight into the cognitive pathways underlying these related forms of bias.
Ineffectiveness of hemoadsorption in large animals with abdominal sepsis: a randomized controlled porcine study
Authors: Tegl Vaclav , Horak Jan , Nalos Lukas , Horakova Michala , Stengl Milan , Matejovic Martin , Benes Jan
Published: April 2024

Objectives

The use of hemoadsorption (HA) has become popular in the treatment of vasoplegic states associated with massive cytokine release, including septic shock. However, this approach does not seem to be based on robust evidence, and it does not follow international guidelines. To understand the pathophysiological rationale and timing of HA, we conducted a large animal septic shock experiment.

Design

Prospective randomized large-animal peritoneal septic shock experiment.

Setting

Laboratory investigation.

Subjects

Twenty-six anesthetized, mechanically ventilated, and instrumented pigs randomly assigned into (1) sham-operated group with HA (SHAM, n = 5); (2) sepsis animals without HA (SEPSIS, n = 5); (3) sepsis group with HA at norepinephrine initiation (EARLY, n = 8); and (4) sepsis group with HA initiated at norepinephrine rate reaching 0.5 μg/kg/min (LATE, n = 8).

Interventions

Peritoneal sepsis was induced by cultivated autologous feces inoculation. A CytoSorb cartridge (200 g) with a blood flow rate of 200 mL/min and heparin anticoagulation was used to perform HA. The animals received sedation and intensive organ support up to 48 h or until they experienced cardiovascular collapse.

Measurements and main results

Systemic hemodynamics, multiple-organ functions, and immune-inflammatory response were measured at predefined periods. The HA treatment was not associated with any measurable benefit in terms of systemic hemodynamics and organ support. The systemic inflammatory markers were unaffected by any of the treatment timings. In contrast, the HA resulted in higher vasopressor load and decreased 36-h survival (5 animals in SHAM (100%), 4 (80%) in SEPSIS, 4 (57%) in EARLY, and 2 (25%) in LATE; p = 0.041). The HA exposure in healthy animals was associated with hemodynamic deterioration, systemic inflammatory response, and cytopenia.

Conclusions

In this large-animal-controlled fulminant sepsis study, the HA was unable to counteract the disease progression in the early or advanced septic shock phase. However, findings from the HA-exposed sham animals suggest potential safety concerns.
A cross-sectional survey of hepatitis B virus screening in patients who received immunosuppressive therapy for rheumatoid arthritis in Japan
Authors: Yanagisawa Yuki , Imai Shungo , Kizaki Hayato , Hori Satoko
Published: April 2024

Background

Patients with a history of hepatitis B virus (HBV) infection who are receiving immunosuppressive therapy are at risk of HBV reactivation and disease. Therefore, HBV screening is required prior to administering antirheumatic drugs with immunosuppressive effects. This study aimed to determine the status of hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and hepatitis B surface antibody (HBsAb) screening prior to the initiation of drug therapy, including new antirheumatic drugs, in patients with rheumatoid arthritis.

Methods

This retrospective cross-sectional study used data from April 2014 to August 2022 from the Japanese hospital-based administrative claims database. The inclusion criteria were rheumatoid arthritis and first prescription date of antirheumatic drugs.

Results

A total of 82,282 patients with rheumatoid arthritis who were first prescribed antirheumatic drugs between April 2016 and August 2022 were included. Of the eligible patients, 9.7% (n=7,959) were screened for all HBV (HBsAg, HBsAb, and HbcAb) within 12 months prior to the date of initial prescription. The HBsAg test was performed in 30.0% (n=24,700), HBsAb test in 11.8% (n=9,717), and HBcAb test in 13.1% (n=10,824) of patients. The proportion of patients screened for HBV infection has been increasing since 2018; however, the proportion of patients screened for rheumatoid arthritis remains low.

Conclusions

Our findings suggest that HBV screening may be insufficient in patients who received antirheumatic drugs. With the increasing use of new immunosuppressive antirheumatic drugs, including biological agents, healthcare providers should understand the risk of HBV reactivation and conduct appropriate screening.
Fatal pulmonary embolism after surgery for small intestinal necrosis caused by idiopathic portal vein thrombosis: a case report
Authors: Iwasaki Hitoshi , Uehara Hideo , Fujimoto Yugo , Hasuda Hirofumi , Kusumoto Eiji , Hisamatsu Yuichi , Yoshida Rintaro , Sakaguchi Yoshihisa , Kusumoto Tetsuya
Published: April 2024

Background

Portal vein thrombosis (PVT) and venous thromboembolism (VTE) both result from partial or complete occlusion of a blood vessel by a blood clot. The prognosis of PVT is generally good; however, PVT with VTE, including pulmonary embolism (PE), has a high mortality rate. We report here a case of PE after surgery for small intestinal necrosis caused by idiopathic PVT.

Case presentation

A 69-year-old female attended our hospital with a chief complaint of upper abdominal discomfort, and was diagnosed with necrosis of the small intestine as a result of unexplained PVT. She underwent partial resection of the small intestine. On the second postoperative day, she suffered from respiratory distress and went into cardiopulmonary arrest. The patient recovered following cardiopulmonary resuscitation, but PE was detected. Extracorporeal veno-arterial cardiopulmonary resuscitation and anticoagulation therapy were initiated immediately and the thrombus was aspirated as much as possible. Two days later, extracorporeal veno-arterial cardiopulmonary resuscitation was withdrawn and anticoagulation therapy was continued. The patient subsequently recovered with no neurological damage and was discharged on day 26 after the above procedure.

Conclusions

Idiopathic PVT is often associated with VTE, and a prompt diagnosis and intervention may result in a good prognosis.
The impact of using ovarian-adnexal reporting data system magnetic resonance imaging (O-RADS MRI) score on risk stratification of sonographically indeterminate adnexal masses
Authors: Hassan Rania Mostafa A. , Ebrahim Saeed Abdel Monem , Kamal Marwa Rashad Ahmad , Tantawy Heba Fathy Ahmad
Published: April 2024

Background

Adnexal masses (AMs) are prevalent, leading to a substantial clinical effort including imaging for diagnosis, surgery, and pathology.

Aim of the study

The goal of this research was to evaluate the reliability of the Ovarian-Adnexal Reporting Data System Magnetic Resonance Imaging (O-RADS MRI) scale for diagnosing the sonographically indeterminate adnexal masses and to discriminate between malignant and benign ones using the O-RADS MRI scoring system.

Methods

This study included 72 cases with indeterminate adnexal masses in any age group. We excluded patients with previous history of operated adnexal lesion and patients who had contraindications for MRI as pacemakers or iron clips.

Results

Based on O-RADS MRI score, 44.4% of masses were diagnosed as O-RADS II indicating that they were almost certainly benign, 11.1% as O-RADS III indicating low risk malignancy, 8.3% as O-RADS IV indicating intermediate risk malignancy and 36.1% were diagnosed as O-RADS V indicating high risk malignancy. O-RADS MRI score for malignancy gave sensitivity of 92.31% (95%CI 63.97–99.81), specificity of 82.61% (95%CI 61.22–95.05), PPV of 75% (95%CI 54.84–88.11) and NPV of 95% (95%CI 74.12–99.21) with an overall accuracy of 86.11% (95%CI 70.50–95.33).

Conclusions

The O-RADS MRI score has excellent accuracy and validity in determining whether an AM is malignant or benign. Using this score in clinical practice may enable a tailored, patient-centered approach for masses that are sonographically indeterminate, avoiding unnecessary surgery, and in certain cases allows less extensive surgery, or even fertility preservation when appropriate.
Seasonal forecasting of
Bactrocera dorsalis
Hendel, 1912 (Diptera: Tephritidae) in bioclimatic zones of Sri Lanka using the SARIMA model
Authors: Wijekoon W. M. C. D. , Ganehiarachchi G. A. S. M. , Wegiriya H. C. E. , Vidanage S. P.
Published: April 2024

Bactrocera dorsalis
Hendel is a severe fruit pest that causes significant economic losses globally. Despite
B. dorsalis
having been distributed mostly across Asia, studies on its current and future density variation in Sri Lanka are sparse to date. The present study was thus carried out to assess the contemporary density variation (2020–2022) and future density fluctuation (2023–2025) of
B. dorsalis
in bioclimatic zones of Sri Lanka. The density was assessed using the monthly-based fruit fly trap collection method from randomly selected 40 locations in all bioclimatic zones (wet, intermediate, dry, and arid). The SARIMA modelling technique was applied for delineating the best-fit model and for density forecasting in each bioclimatic zone. The density variations were depicted for the year and for the bioclimatic zone (2020–2025) by colour intensity maps using QGIS. According to the findings,
B. dorsalis
shows a seasonal component to its year-round density variation and an ascending trend in its density from 2020 to 2025. Density forecasting records a 20%, 30%, 26%, and 37% density increase in the wet, intermediate, dry, and arid zones, respectively, in 2025. In 2025, the highest predicted
B. dorsalis
density from the arid zone and the lowest predicted density from the wet zone were recorded. This study contains the first forecasting attempt for
B. dorsalis
density using the SARIMA approach as well as the application of colour-intensity depiction for its density variation in Sri Lanka, which leads decision makers and stakeholders in economic agriculture to plan the scientific management of
B. dorsalis
to avoid its current and potential future threat to the country’s fruit industry.
Territorial heritage gentrification in Abdali in Amman, Jordan
Authors: Al Rabady Rama
Published: April 2024

Having established itself as a heritage discourse, planetary gentrification is being studied in terms of how it operates in the Global South. This study focuses on the case of Abdali Amman, a significant mixed-use neighbourhood in Jordan that has experienced numerous mega-gentrification initiatives. According to Bourdieu’s theories of the state and dispositional practices, this study critically evaluates urban gentrification practices. In terms of gentrification governance, which takes place in two adjacent ‘state’ and ‘civic’ zones inside the Abdali district, this study analyses the interactions between transnational and state actors and the intragovernmental (state-municipality) governance system. Gentrification in Amman is connected to the revitalisation of historic sites, is a matter of urban governance, and operates from the transnational sphere along national and local lines. Furthermore, gentrification is caught in a desire/resistance paradox with calls for legitimacy and recognition. As a country in the Global South, Jordan has welcomed capitalist urbanisation. Gentrification is articulated within a flux between deterritorialisation/reterritorialisation, producing a form of ‘heritage gentrification’ in which history and national heritage are sacrificed through a process of satellite gentrification that is rooted in generative cultural transformation and governed by decentralised power structures. Introducing a Western blueprint of planetary gentrification through narrow gates into non-Western environments is a prevailing challenge.
Clonal Hematopoiesis and Therapy-Related Myeloid Neoplasms After Autologous Transplant for Hodgkin Lymphoma
Authors: Yan Chengcheng , Richard Melissa A. , Gibson Christopher J. , He Jianbo , Bosworth Alysia , Crossman David K. , Singh Purnima , Hageman Lindsey , Kalra Rashi , Armenian Saro H. , Vose Julie , Weisdorf Daniel J. , Ebert Benjamin L. , Yasui Yutaka , Forman Stephen J. , Bhatia Ravi , Bhatia Smita
Published: April 2024

PURPOSE

Therapy-related myeloid neoplasm (t-MN) is a life-threatening complication of autologous peripheral blood stem cell transplantation (aPBSCT) for Hodgkin lymphoma (HL). Although previous studies have reported an association between clonal hematopoiesis (CH) in the infused PBSC product and subsequent post-aPBSCT risk of t-MN in patients with non-HL, information about patients with HL treated with aPBSCT is not available.

METHODS

We constructed a retrospective cohort of 321 patients with HL transplanted at a median age of 34 years (range, 18-71). Targeted DNA sequencing of PBSC products performed for CH-associated or myeloid malignancy-associated genes identified pathogenic mutations in these patients.

RESULTS

CH was identified in the PBSC product of 46 patients (14.3%) with most prominent representation of DNMT3A (n = 25), PPM1D (n = 7), TET2 (n = 7), and TP53 (n = 5) mutations. Presence of CH in the PBSC product was an independent predictor of t-MN (adjusted hazard ratio [aHR], 4.50 [95% CI, 1.54 to 13.19]). Notably all patients with TP53 mutations in the PBSC product developed t-MN, whereas none of the patients with DNMT3A mutations alone (without co-occurring TP53 or PPM1D mutations) did. Presence of TP53 and/or PPM1D mutations was associated with a 7.29-fold higher hazard of t-MN when compared with individuals carrying no CH mutations (95% CI, 1.72 to 30.94). The presence of TP53 and/or PPM1D mutations was also associated with a 4.17-fold higher hazard of nonrelapse mortality (95% CI, 1.25 to 13.87). There was no association between CH and relapse-related mortality.

CONCLUSION

The presence of TP53 and/or PPM1D mutations in the PBSC product increases the risk of post-aPBSCT t-MN and nonrelapse mortality among patients with HL and may support alternative therapeutic strategies.
Tumor Size Is Not Everything: Advancing Radiomics as a Precision Medicine Biomarker in Oncology Drug Development and Clinical Care. A Report of a Multidisciplinary Workshop Coordinated by the RECIST Working Group
Authors: Nakajima Erica C. , Simpson Amber , Bogaerts Jan , de Vries Elisabeth G.E. , Do Richard , Garralda Elena , Goldmacher Greg , Kinahan Paul E. , Lambin Philippe , LeStage Barbara , Li Qin , Lin Frank , Litière Saskia , Perez-Lopez Raquel , Petrick Nicholas , Schwartz Lawrence , Seymour Lesley , Shankar Lalitha , Laurie Scott A.
Published: April 2024

Radiomics, the science of extracting quantifiable data from routine medical images, is a powerful tool that has many potential applications in oncology. The Response Evaluation Criteria in Solid Tumors Working Group (RWG) held a workshop in May 2022, which brought together various stakeholders to discuss the potential role of radiomics in oncology drug development and clinical trials, particularly with respect to response assessment. This article summarizes the results of that workshop, reviewing radiomics for the practicing oncologist and highlighting the work that needs to be done to move forward the incorporation of radiomics into clinical trials.
Effects of Hypertriglyceridemia With or Without NEFA Elevation on β-cell Function and Insulin Clearance and Sensitivity
Authors: Tricò Domenico , Rebelos Eleni , Astiarraga Brenno , Baldi Simona , Scozzaro Tiziana , Sacchetta Luca , Chiriacò Martina , Mari Andrea , Ferrannini Ele , Muscelli Elza , Natali Andrea
Published: April 2024

Context

Hypertriglyceridemia is a risk factor for developing type 2 diabetes (T2D) and might contribute to its pathogenesis either directly or through elevation of nonesterified fatty acids (NEFAs).

Objective

This study aimed at comparing the glucometabolic effects of acute hypertriglyceridemia alone or combined with NEFA elevation in subjects without diabetes.

Methods

Twenty-two healthy lean volunteers underwent 5-hour intravenous infusions of either saline or Intralipid, without (n = 12) or with heparin (I + H; n = 10) to activate the release of NEFAs. Oral glucose tolerance tests (OGTTs) were performed during the last 3 hours of infusion. Insulin sensitivity, insulin secretion rate (ISR), model-derived β-cell function, and insulin clearance were measured after 2 hours of lipid infusion and during the OGTTs.

Results

In fasting conditions, both lipid infusions increased plasma insulin and ISR and reduced insulin clearance without affecting plasma glucose and insulin sensitivity. These effects on insulin and ISR were more pronounced for I + H than Intralipid alone. During the OGTT, the lipid infusions markedly impaired glucose tolerance, increased plasma insulin and ISR, and decreased insulin sensitivity and clearance, without significant group differences. Intralipid alone inhibited glucose-stimulated insulin secretion (ie, β-cell glucose sensitivity) and increased β-cell potentiation, whereas I + H had neutral effects on these β-cell functions.

Conclusion

In healthy nonobese subjects, mild acute hypertriglyceridemia directly reduces glucose tolerance and insulin sensitivity and clearance, and has selective and opposite effects on β-cell function that are neutralized by NEFAs. These findings provide new insight into plausible biological signals that generate and sustain insulin resistance and chronic hyperinsulinemia in the development of T2D.
A Case of Cribriform-Morular Thyroid Carcinoma Presenting Without Thyroid Nodule
Authors: Rao Angela , Needleman Leor , Lalakea M Lauren , Hsu Emory
Published: April 2024

Cribriform-morular thyroid carcinoma is a rare type of thyroid cancer. It has a strong association with familial adenomatous polyposis (FAP), a hereditary genetic disorder that predisposes individuals to the development of numerous polyps in the colon and rectum. We describe the case of a young female patient who presented with an enlarging goiter, notably without detectable thyroid nodules or masses on ultrasound, who after total thyroidectomy was found to have cribriform-morular thyroid carcinoma. This diagnosis led to genetic testing and diagnosis of FAP syndrome. We demonstrate that this rare thyroid carcinoma may present with nonsuspicious findings on sonographic evaluation while being a valuable harbinger in the diagnosis of FAP syndrome.
Cervicomediastinal Hematoma: Atypical Presentation of a Parathyroid Carcinoma
Authors: Cicia Martina , Papi Giampaolo , Scillitani Alfredo , Corrado Stefania , Locantore Pietro , Pontecorvi Alfredo
Published: April 2024

Parathyroid carcinoma (PC) is a rare endocrine neoplasm that typically presents with osteopenia/osteoporosis, nephrolithiasis, asthenia, and neuropsychiatric symptoms. We describe the case of a 48-year-old woman, presenting with a large painful hematoma in the cervicomediastinal area. The neck ultrasound (US) demonstrated a solid lesion measuring 40 × 80 × 55 mm, markedly hypoechoic, which extended from the right thyroid lobe to the mediastinum. The blood tests showed elevated serum calcium and parathyroid hormone (PTH) concentrations, consistent with hypercalcemic primary hyperparathyroidism. The patient was rehydrated and treated with furosemide, cholecalciferol, and bisphosphonate, and underwent right lower parathyroidectomy, right hemithyroidectomy, and lymphadenectomy of the right VI cervical level. Histological examination was diagnostic for nonangioinvasive or neuroinvasive PC, and the thyroid lobe was the site of lymphocytic thyroiditis; all removed lymph nodes were benign. The postoperative course was regular. Postoperative neck US showed a hypoechoic left thyroid lobe without evidence of residual neoplasm in the right thyroid bed. Levothyroxine therapy of 50 mcg/day was started because of serum thyrotropin concentrations elevated at 18 mcIU/mL (normal reference range, 0.35-4.0 mIU/mL). Eight years after diagnosis, the patient is in good general condition, with no clinical, biochemical, or imaging evidence of disease persistence/recurrence.
A Palestinian Woman’s Writings
Authors: Kamal Noura
Published: April 2024

Despite their success as agents in social, political, economic, and cultural spheres, Palestinian women face tremendous hardships due to Israeli occupation and the patriarchal social and political structure. One issue that the literature has not sufficiently explored is how women use various forms of art to make sense of these obstacles and navigate the struggles of daily life. By narrating the story of one Palestinian woman and her relationship with writing, this article explores Palestine women’s attempts to redefine public space and discourse while reflecting on broader questions of the relationships between art, agency, gender, and power. The article sheds light on how art can be mobilized both to navigate daily obstacles and challenge the hegemonic power of official institutions and to induce paradigm shifts within the genre of writing itself. The article argues that writing can be considered a tool both for managing everyday life and for confronting larger questions of power imbalance and enforced suffering.
Association of Postoperative Hypoglycemia With Mortality After Elective Craniotomy
Authors: He Jialing , Zhang Yu , Cheng Xin , Tian Yixin , Hao Pengfei , Li Tiangui , Xiao Yangchun , Peng Liyuan , Feng Yuning , Deng Haidong , Wang Peng , Chong Weelic , Hai Yang , Chen Lvlin , You Chao , Jia Lu , Fang Fang
Published: April 2024

BACKGROUND AND OBJECTIVES:

Hypoglycemia is a known risk of intensive postoperative glucose control in neurosurgical patients. However, the impact of postoperative hypoglycemia after craniotomy remains unexplored. This study aimed to determine the association between postoperative hypoglycemia and mortality in patients undergoing elective craniotomy.

METHODS:

This study involved adult patients who underwent elective craniotomy at the West China Hospital, Sichuan University, between January 2011 and March 2021. We defined moderate hypoglycemia as blood glucose levels below 3.9 mmol/L (70 mg/dL) and severe hypoglycemia as blood glucose levels below 2.2 mmol/L (40 mg/dL). The primary outcome was postoperative 90-day mortality.

RESULTS:

This study involved 15 040 patients undergoing an elective craniotomy. Overall, 504 (3.4%) patients experienced moderate hypoglycemia, whereas 125 (0.8%) patients experienced severe hypoglycemia. Multivariable analysis revealed that both moderate hypoglycemia (adjusted odds ratio [aOR] 1.86, 95% CI 1.24-2.78) and severe (aOR 2.94, 95% CI 1.46-5.92) hypoglycemia were associated with increased 90-day mortality compared with patients without hypoglycemia. Moreover, patients with moderate (aOR 2.78, 95% CI 2.28-3.39) or severe (aOR 16.70, 95% CI 10.63-26.23) hypoglycemia demonstrated a significantly higher OR for major morbidity after adjustment, compared with those without hypoglycemia. Patients experiencing moderate (aOR 3.20, 95% CI 2.65-3.88) or severe (aOR 14.03, 95% CI 8.78-22.43) hypoglycemia had significantly longer hospital stays than those without hypoglycemia. The risk of mortality and morbidity showed a tendency to increase with the number of hypoglycemia episodes in patients undergoing elective craniotomy (P for trend = .01, <.001).

CONCLUSION:

Among patients undergoing an elective craniotomy, moderate hypoglycemia and severe hypoglycemia are associated with increased mortality, major morbidity, and prolonged hospital stays. In addition, the risk of mortality and major morbidity increases with the number of hypoglycemia episodes.
The Impact of Preprocedural Platelet Function Testing on Periprocedural Complication Rates Associated With Pipeline Flow Diversion: An International Multicenter Study
Authors: Vranic Justin E. , Dmytriw Adam A. , Berglar Inka K. , Alotaibi Naif M. , Cancelliere Nicole M. , Stapleton Christopher J. , Rabinov James D. , Harker Pablo , Gupta Rajiv , Bernstock Joshua D. , Koch Matthew J. , Raymond Scott B. , Mascitelli Justin R. , Patterson T. Tyler , Seinfeld Joshua , White Andrew , Case David , Roark Christopher , Gandhi Chirag D. , Al-Mufti Fawaz , Cooper Jared , Matouk Charles , Sujijantarat Nanthiya , Devia Diego A. , Ocampo-Navia Maria I. , Villamizar-Torres Daniel E. , Puentes Juan C. , Salem Mohamed M. , Baig Ammad , El Namaani Kareem , Kühn Anna Luisa , Pukenas Bryan , Jankowitz Brian T. , Burkhardt Jan Karl , Siddiqui Adnan , Jabbour Pascal , Singh Jasmeet , Puri Ajit S. , Regenhardt Robert W. , Mendes Pereira Vitor , Patel Aman B.
Published: April 2024

BACKGROUND AND OBJECTIVES:

Dual antiplatelet therapy (DAPT) is necessary to minimize the risk of periprocedural thromboembolic complications associated with aneurysm embolization using pipeline embolization device (PED). We aimed to assess the impact of platelet function testing (PFT) on reducing periprocedural thromboembolic complications associated with PED flow diversion in patients receiving aspirin and clopidogrel.

METHODS:

Patients with unruptured intracranial aneurysms requiring PED flow diversion were identified from 13 centers for retrospective evaluation. Clinical variables including the results of PFT before treatment, periprocedural DAPT regimen, and intracranial complications occurring within 72 h of embolization were identified. Complication rates were compared between PFT and non-PFT groups. Differences between groups were tested for statistical significance using the Wilcoxon rank sum, Fisher exact, or χ2 tests. A P-value <.05 was statistically significant.

RESULTS:

580 patients underwent PED embolization with 262 patients dichotomized to the PFT group and 318 patients to the non-PFT group. 13.7% of PFT group patients were clopidogrel nonresponders requiring changes in their pre-embolization DAPT regimen. Five percentage of PFT group [2.8%, 8.5%] patients experienced thromboembolic complications vs 1.6% of patients in the non-PFT group [0.6%, 3.8%] (P = .019). Two (15.4%) PFT group patients with thromboembolic complications experienced permanent neurological disability vs 4 (80%) non-PFT group patients. 3.7% of PFT group patients [1.5%, 8.2%] and 3.5% [1.8%, 6.3%] of non-PFT group patients experienced hemorrhagic intracranial complications (P > .9).

CONCLUSION:

Preprocedural PFT before PED treatment of intracranial aneurysms in patients premedicated with an aspirin and clopidogrel DAPT regimen may not be necessary to significantly reduce the risk of procedure-related intracranial complications.
Sealing the deal – Antarctic fur seals' active hunting tactics to capture small evasive prey revealed by miniature sonar tags
Authors: Chevallay Mathilde , Guinet Christophe , Goulet-Tran Didier , Jeanniard du Dot Tiphaine
Published: April 2024

The ability of predators to adopt hunting tactics that minimise escape reactions from prey is crucial for efficient foraging, and depends on detection capabilities and locomotor performance of both predators and prey. Here, we investigated the efficiency of a small pinniped, the Antarctic fur seal (Arctocephalus gazella) at exploiting their small prey by describing for the first time their fine-scale predator–prey interactions. We compared these with those from another diving predator, the southern elephant seal (Mirounga leonina) that forage on the same prey type. We used data recorded by a newly developed sonar tag that combines active acoustics with ultrahigh-resolution movement sensors to study simultaneously the fine-scale behaviour of both Antarctic fur seals and prey during predator–prey interactions in more than 1200 prey capture events for eight female Antarctic fur seals. Our results showed that Antarctic fur seals and their prey detect each other at the same time, i.e. 1–2 s before the strike, forcing Antarctic fur seals to display reactive fast-moving chases to capture their prey. In contrast, southern elephant seals detect their prey up to 10 s before the strike, allowing them to approach their prey stealthily without triggering an escape reaction. The active hunting tactics used by Antarctic fur seals is probably very energy consuming compared with the stalking tactics used by southern elephant seals but might be compensated for by the consumption of faster-moving larger prey. We suggest that differences in manoeuvrability, locomotor performance and detection capacities and in pace of life between Antarctic fur seals and southern elephant seals might explain these differences in hunting styles.
Refinement of a technique for collecting and evaluating the osmolality of haemolymph from Drosophila larvae
Authors: Kurio Misato , Tsukasa Yuma , Uemura Tadashi , Usui Tadao
Published: April 2024

Ex vivo physiological experiments using small insect models such as Drosophila larvae have become increasingly useful to address fundamental biological questions. To perform such experiments, various artificial saline solutions have been developed, but their osmolality varies significantly from one to the next. Such a variation of osmolality stems, in part, from the difficulty of determining the true value of haemolymph osmolality in Drosophila larvae. Thus, there is a pressing need to refine protocols for collecting and measuring the osmolality of the larval haemolymph. Two major obstacles are thought to impede the accurate analysis of haemolymph collected from small insects: melanin formation and gut-derived contamination. Here, we greatly refined existing haemolymph collection methods, evaluated the purity of the collected haemolymph under melanin-free conditions, and concluded that the true value of haemolymph osmolality is close to 306.0 mOsm kg–1 in Drosophila larvae.
Validation of Polar Elixir™ Pulse Oximeter against Arterial Blood Gases during Stepwise Steady-State Inspired Hypoxia
Authors: RUSSELL MONICA K. , HORTON JOHN F. , CLERMONT CHRISTIAN A. , DEMARTY JENNIFER M. , TRANSFIGURACION LEO C. , WOROBETS BREANN R. , PINEDA MARK E. , SANTANIEMI NUUTTI , STERGIOU PRO , ASMUSSEN MICHAEL J. , DAY TREVOR A.
Published: April 2024

Purpose

The purpose of this study was to evaluate the accuracy of peripheral oxygen saturation (SpO2) measurements from Polar Elixir™ pulse oximetry technology compared with arterial oxygen saturation (SaO2) measurements during acute stepwise steady-state inspired hypoxia at rest. A post hoc objective was to determine if SpO2 measurements could be improved by recalibrating the Polar Elixir™ algorithm with SaO2 values from a random subset of participants.

Methods

The International Organization for Standardization (ISO) protocol (ISO 80601-2-61:2017) for evaluating the SpO2 accuracy of pulse oximeter equipment was followed whereby five plateaus of SaO2 between 70% and 100% were achieved using stepwise reductions in inspired O2 during supine rest. Blood samples drawn through a radial arterial catheter from 25 participants were first used to compare SaO2 with SpO2 measurements from Polar Elixir™. Then the Polar Elixir™ algorithm was recalibrated using SaO2 data from 13 random participants, and SpO2 estimates were recalculated for the other 12 participants. For SaO2 values between 70% and 100%, root mean square error, intraclass correlation coefficients (ICC), Pearson correlations, and Bland–Altman plots were used to assess the accuracy, agreement, and strength of relationship between SaO2 values and SpO2 values from Polar Elixir™.

Results

The initial root mean square error for Polar Elixir™ was 4.13%. After recalibrating the algorithm, the RMSE was improved to 2.67%. The ICC revealed excellent levels of agreement between SaO2 and Polar Elixir™ SpO2 values both before (ICC(1,3) = 0.837, df = 574, P < 0.001) and after (ICC(1,3) = 0.942, df = 287, P < 0.001) recalibration.

Conclusions

Relative to ISO standards, Polar Elixir™ yielded accurate SpO2 measurements during stepwise inspired hypoxia at rest when compared with SaO2 values, which were improved by recalibrating the algorithm using a subset of the SaO2 data.