bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of osteopontin and osteocyte-derived factors in secondary hyperparathyroidism-induced myopathy
Authors: Duque Eduardo J , Crispilho Shirley F , Oliveira Ivone B , Dominguez Wagner V , Silva Cleonice , Furukawa Luzia , Teng André K , Avesani Carla M , Shinjo Samuel K , Elias Rosilene M , Jorgetti Vanda , Moysés Rosa M A
Published: June 2024

Muscle weakness is a common symptom in CKD patients, and the pathway by which secondary hyperparathyroidism (SHPT) affects muscle function is unknown. Osteopontin (OPN), a bone matrix protein stimulated by PTH and phosphate, has been associated with inflammatory muscle diseases. In this observational and prospective cohort study, we evaluated 30 patients with severe SHPT (39 ± 12 yr; 18 women), before and 6 mo after parathyroidectomy (PTx). We examined the relationships among CKD–mineral and bone disorder parameters; myokine and inflammatory cytokine levels; and changes in resting energy expenditure (REE), muscle function, BMD, and muscle-related proteins. At baseline, the patients showed low gene expression of muscle turnover markers and irisin, as well as high protein expression of OPN, transforming growth factor beta (TGF-β), and fibroblast growth factor 21. Six months after PTx, REE and muscle mass had not changed, but physical performance, muscle strength, and bone mass improved, more so in patients undergoing total PTx. Also, there were reductions in the protein expression of OPN (11 vs 3%, p=.01) and TGF-β (21 vs 7%, p=.002) in muscle, together with a significant increase in irisin muscular levels (30 vs 35 pg/mg, p=.02). The gain in bone mass and the increase in irisin levels correlated with a reduction in PTH. The levels of interleukin (IL)-1β, tumor necrosis factor alpha, and IL-17 (markers of myositis) were also lower after PTx. Our data suggest that SHPT plays a role in CKD-induced muscle dysfunction, indirectly, via release of bone-specific proteins, which is partially reverted with PTx.
Protocol digest of a randomized phase III trial comparing S-1-based chemoradiotherapy with/without nivolumab for unresectable locally advanced or borderline resectable pancreatic cancer: JCOG1908E (PENETRATE)
Authors: Sano Yusuke , Kanai Masashi , Morizane Chigusa , Sasaki Keita , Yoshimura Michio , Ito Yoshinori , Furuse Junji , Ozaka Masato , Fukuda Haruhiko , Ueno Makoto ,   on behalf of the Hepatobiliary and Pancreatic Oncology Group in Japan Clinical Oncology Group
Published: June 2024

Pancreatic cancer remains a highly lethal disease with a 5-year survival proportion of <10%. Chemoradiotherapy is a treatment option for unresectable locally advanced (UR-LA) or borderline resectable (BR) pancreatic cancer, but its efficacy is not sufficient. Induction of the synergistic effect of irradiation and immune checkpoint inhibitors can be an attractive strategy. An open-label randomized phase III trial has been conducted since October 2020 to confirm the superiority of nivolumab plus S-1-based chemoradiotherapy over S-1-based chemoradiotherapy alone in patients with UR-LA or BR pancreatic cancer. A total of 216 patients will be enrolled in 14 institutions within 3.5 years. The primary endpoint of the safety run-in part is dose-limiting toxicity, and that of the phase III part is overall survival. This trial was registered at the Japan Registry of Clinical Trials as jRCT2080225361 (https://jrct.niph.go.jp/latest-detail/jRCT2080225361).
The relevance of eosinophils in chronic obstructive pulmonary disease: inflammation, microbiome, and clinical outcomes
Authors: Higham Andrew , Beech Augusta , Singh Dave
Published: June 2024

Chronic obstructive pulmonary disease is caused by the inhalation of noxious particles such as cigarette smoke. The pathophysiological features include airway inflammation, alveolar destruction, and poorly reversible airflow obstruction. A subgroup of patients with chronic obstructive pulmonary disease has higher blood eosinophil counts, associated with an increased response to inhaled corticosteroids and increased biomarkers of pulmonary type 2 inflammation. Emerging evidence shows that patients with chronic obstructive pulmonary disease with increased pulmonary eosinophil counts have an altered airway microbiome. Higher blood eosinophil counts are also associated with increased lung function decline, implicating type 2 inflammation in progressive pathophysiology in chronic obstructive pulmonary disease. We provide a narrative review of the role of eosinophils and type 2 inflammation in the pathophysiology of chronic obstructive pulmonary disease, encompassing the lung microbiome, pharmacological targeting of type 2 pathways in chronic obstructive pulmonary disease, and the clinical use of blood eosinophil count as a chronic obstructive pulmonary disease biomarker.
Incidence of peritoneal cancer after oophorectomy among BRCA1 and BRCA2 mutation carriers
Authors: Narod Steven A , Gronwald Jacek , Karlan Beth , Moller Pal , Huzarski Tomasz , Tung Nadine , Aeilts Amber , Eisen Andrea , Armel Susan Randall , Singer Christian F , Foulkes William D , Neuhausen Susan L , Olopade Olufunmilayo , Pal Tuya , Fruscio Robert , Metcalfe Kelly , Raj Rebecca , Jacobson Michelle , Sun Ping , Lubinski Jan , Kotsopoulos Joanne
Published: June 2024

Background

To estimate the incidence of primary peritoneal cancer after preventive bilateral oophorectomy in women with a BRCA1 or BRCA2 mutation.

Methods

A total of 6310 women with a BRCA1 or BRCA2 mutation who underwent a preventive bilateral oophorectomy were followed for a mean of 7.8 years from oophorectomy. The 20-year cumulative incidence of peritoneal cancer post-oophorectomy was estimated using the Kaplan-Meier method. A left-truncated Cox proportional hazards analysis was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) associated with the age at oophorectomy, year of oophorectomy, and family history of ovarian cancer as well as hormonal and reproductive risk factors.

Results

Fifty-five women developed primary peritoneal cancer (n = 45 in BRCA1, 8 in BRCA2, and 2 in women with a mutation in both genes). Their mean age at oophorectomy was 48.9 years. The annual risk of peritoneal cancer was 0.14% for women with a BRCA1 mutation and 0.06% for women with a BRCA2 mutation. The 20-year cumulative risk of peritoneal cancer from the date of oophorectomy was 2.7% for BRCA1 carriers and 0.9% for BRCA2 mutation carriers. There were no peritoneal cancers in BRCA1 carriers who had the operation before age 35 or in BRCA2 carriers who had the operation before age 45.

Conclusions

For BRCA1 mutation carriers, the annual risk of peritoneal cancer for 20 years post-oophorectomy is 0.14% per year. The risk is lower for BRCA2 carriers (0.06% per year).
The Compact Root Architecture 2 systemic pathway is required for the repression of cytokinins and miR399 accumulation in Medicago truncatula N-limited plants
Authors: Argirò Luca , Laffont Carole , Moreau Corentin , Moreau Carol , Su Yangyang , Pervent Marjorie , Parrinello Hugues , Blein Thomas , Kohlen Wouter , Lepetit Marc , Frugier Florian
Published: June 2024

Legume plants can acquire mineral nitrogen (N) either through their roots or via a symbiotic interaction with N-fixing rhizobia bacteria housed in root nodules. To identify shoot-to-root systemic signals acting in Medicago truncatula plants at N deficit or N satiety, plants were grown in a split-root experimental design in which either high or low N was provided to half of the root system, allowing the analysis of systemic pathways independently of any local N response. Among the plant hormone families analyzed, the cytokinin trans-zeatin accumulated in plants at N satiety. Cytokinin application by petiole feeding led to inhibition of both root growth and nodulation. In addition, an exhaustive analysis of miRNAs revealed that miR2111 accumulates systemically under N deficit in both shoots and non-treated distant roots, whereas a miRNA related to inorganic phosphate (Pi) acquisition, miR399, accumulates in plants grown under N satiety. These two accumulation patterns are dependent on Compact Root Architecture 2 (CRA2), a receptor required for C-terminally Encoded Peptide (CEP) signaling. Constitutive ectopic expression of miR399 reduced nodule numbers and root biomass depending on Pi availability, suggesting that the miR399-dependent Pi-acquisition regulatory module controlled by N availability affects the development of the whole legume plant root system.
Hospital Burden of All-Cause Pneumonia and Nonbacteremic Pneumococcal Pneumonia in Adults in France Between 2013 and 2019
Authors: Sabra Ayman , Bourgeois Marie , Blanc Emmanuelle , Fievez Stephane , Moïsi Jennifer , Goussiaume Gwenaël , Lemaitre Magali , Watier Laurence , Coulombel Nicolas , Tréhony Julien , Tricotel Aurore , Baghdadi Yasmine , Fartoukh Muriel S
Published: June 2024

Background

Community-acquired pneumonia (CAP) is associated with significant morbidity and mortality. The study objective was to describe the hospital burden of pneumonia in the adult population in France.

Methods

This retrospective study was conducted from the National Health Insurance Database. All hospitalizations for pneumonia (all-cause) between 2013 and 2019 were included. Different risk categories for patients were established based on pneumococcal vaccine recommendations by French health authorities.

Results

A total of 2 199 240 episodes of CAP were registered over the study period (annual mean, 314 177 [standard deviation, 17 818.6]); 75% occurred in patients aged ≥65 years, among whom 47% were not classified in the moderate- or high-risk categories recommended for French pneumococcal vaccination. The incidence of CAP increased with age (117.9, 395.3, and 1916.7 per 100 000 for the age groups 18–49, 50–64, and ≥65 years, respectively, in 2019). Furthermore, being at risk of pneumococcal disease resulted in more severe outcomes, including longer episode duration (mean, 14 days in low-risk vs 17 days in high-risk patients) and higher risk of referral to critical care units (from 20% to 27%), of rehospitalization up to 180 days (from 39% to 67%), of in-hospital death (from 12% to 19%), and of 1-year mortality (from 26% to 49%).

Conclusions

This study establishes the incidence of CAP in adults in France, describes the significant burden of disease, and highlights the need for better prevention policies.
Recent advances in drug delivery applications of aqueous two-phase systems
Authors: Baghbanbashi Mojhdeh , Shiran Hadi Shaker , Kakkar Ashok , Pazuki Gholamreza , Ristroph Kurt
Published: June 2024

Aqueous two-phase systems (ATPSs) are liquid–liquid equilibria between two aqueous phases that usually contain over 70% water content each, which results in a nontoxic organic solvent-free environment for biological compounds and biomolecules. ATPSs have attracted significant interest in applications for formulating carriers (microparticles, nanoparticles, hydrogels, and polymersomes) which can be prepared using the spontaneous phase separation of ATPSs as a driving force, and loaded with a wide range of bioactive materials, including small molecule drugs, proteins, and cells, for delivery applications. This review provides a detailed analysis of various ATPSs, including strategies employed for particle formation, polymerization of droplets in ATPSs, phase-guided block copolymer assemblies, and stimulus-responsive carriers. Processes for loading various bioactive payloads are discussed, and applications of these systems for drug delivery are summarized and discussed.
Followers do not dictate the virality of news outlets on social media
Authors: Sangiorgio Emanuele , Cinelli Matteo , Cerqueti Roy , Quattrociocchi Walter
Published: June 2024

Initially conceived for entertainment, social media platforms have profoundly transformed the dissemination of information and consequently reshaped the dynamics of agenda-setting. In this scenario, understanding the factors that capture audience attention and drive viral content is crucial. Employing Gibrat’s Law, which posits that an entity’s growth rate is unrelated to its size, we examine the engagement growth dynamics of news outlets on social media. Our analysis includes the Facebook historical data of over a thousand news outlets, encompassing approximately 57 million posts in four European languages from 2008 to the end of 2022. We discover universal growth dynamics according to which news virality is independent of the traditional size of the outlet. Moreover, our analysis reveals a significant long-term impact of news source reliability on engagement growth, with engagement induced by unreliable sources decreasing over time. We conclude the article by presenting a statistical model replicating the observed growth dynamics.
Quantifying the vulnerabilities of the online public square to adversarial manipulation tactics
Authors: Truong Bao Tran , Lou Xiaodan , Flammini Alessandro , Menczer Filippo
Published: June 2024

Social media, seen by some as the modern public square, is vulnerable to manipulation. By controlling inauthentic accounts impersonating humans, malicious actors can amplify disinformation within target communities. The consequences of such operations are difficult to evaluate due to the challenges posed by collecting data and carrying out ethical experiments that would influence online communities. Here we use a social media model that simulates information diffusion in an empirical network to quantify the impacts of adversarial manipulation tactics on the quality of content. We find that the presence of hub accounts, a hallmark of social media, exacerbates the vulnerabilities of online communities to manipulation. Among the explored tactics that bad actors can employ, infiltrating a community is the most likely to make low-quality content go viral. Such harm can be further compounded by inauthentic agents flooding the network with low-quality, yet appealing content, but is mitigated when bad actors focus on specific targets, such as influential or vulnerable individuals. These insights suggest countermeasures that platforms could employ to increase the resilience of social media users to manipulation.
The New Politics (and Political Science) of Workers’ Rights?: A Review Article
Authors: Brown Trevor E
Published: June 2024

In this article, I review Daniel J. Galvin's Alt-Labor and the New Politics of Workers' Rights and situate it within a renewed scholarly interest in the politics of work and labor in the American politics subfield. I argue the book highlights several strengths and weaknesses of the literature, including the book’s attention to how America's highly polarized and fragmented governing system structures the politics of workers’ rights. Galvin’s book, I argue, also helps push the literature forward by encouraging scholars to think more deeply about the shifting institutional location of worker power, new and varying forms of worker organizations, and a set of co-constitutive problems faced by marginalized workers on and off the job. I conclude by suggesting the new wave of labor literature in the American politics subfield has underexplored implications for the growing research on democratic backsliding in the United States.
Price elasticity of demand and risk-bearing capacity in sovereign bond auctions
Authors: Albuquerque Rui , Cardoso-Costa José Miguel , Faias José Afonso
Published: June 2024

The paper uses bids submitted by primary dealer banks at auctions of sovereign bonds to quantify the price elasticity of demand. The price elasticity of demand correlates strongly with the volatility of returns of the same bonds traded in the secondary market but only weakly with their bid-ask spread. It predicts same-bond post-auction returns in the secondary market, even after controlling for pre-auction volatility. The evidence suggests that the price elasticity of demand is associated with the magnitude of price pressure in the secondary market around auction days and proxies for primary dealer risk-bearing capacity.
Microwave ablation of synovial hypertrophy in recurrent monoarthritis: the results of extended cohort and long-term follow-up
Authors: Deniz Rabia , Güzelbey Tevfik , Mutlu İlhan Nahit , Erdim Çağrı , Karaalioğlu Bilgin , Özgür Duygu Sevinç , Akkuzu Gamze , Kalkan Kübra , Kılıçkesmez Özgür , Bes Cemal
Published: June 2024

Objectives

Recurrent monoarthritis (RM) is a major challenge of many rheumatic diseases. Ablation is a well-known technique in the treatment of benign or malign lesions of different aetiologies. We aimed to investigate the success and safety of microwave ablation (MWA) as an adjunctive therapy in a cohort of medical treatment-resistant RM.

Methods

Patients with RM associated with different inflammatory diseases were included. MWA was performed after measuring the size of synovial hypertrophy with 15 or 20 W power and different durations until microbubbles were shown, indicating necrosis. Both clinical and radiologic data were recorded.

Results

We applied MWA in total of 24 knee joints of 10 female and 12 male patients aged between 22 and 71 years. Median IA aspiration (IAA) need in the last 6 months before MWA was 5 (0–15). The median follow-up was 10 (3–16) months. Overall IAA count in the last 6 months before MWA in total of 144 months was 129, and decreased to 7 in post-MWA in total of 226 months (0.89 vs 0.03 per month, P < 0.001). The second MWA session was needed for three patients and a third session for one. Functional disability and pain scores were improved significantly (median score from 9 to 1, P < 0.00001, in both). In MRI, follow-up significant regression in synovial hypertrophy size was shown especially after the 6th month. No complication was observed during the procedure or follow-up.

Conclusion

As a less invasive technique compared with the surgical approach, MWA of synovial hypertrophy showed significant clinical improvement in RM safely. MWA seems promising as a treatment option candidate in the management of RM.
Proceedings of PRINCETON IV: PDE5 inhibitors and cardiac health symposium
Authors: Rosen Raymond C , Miner Martin , Burnett Arthur L , Blaha Michael J , Ganz Peter , Goldstein Irwin , Kim Noel , Kohler Tobias , Lue Tom , McVary Kevin , Mulhall John , Parish Sharon J , Sadeghi-Nejad Hossein , Sadovsky Richard , Sharlip Ira , Kloner Robert A
Published: June 2024

Introduction

Prior consensus meetings have addressed the relationship between phosphodiesterase type 5 (PDE5) inhibition and cardiac health. Given significant accumulation of new data in the past decade, a fourth consensus conference on this topic was convened in Pasadena, California, on March 10 and 11, 2023.

Objectives

Our meeting aimed to update existing knowledge, assess current guidelines, and make recommendations for future research and practice in this area.

Methods

An expert panel reviewed existing research and clinical practice guidelines.

Results

Key findings and clinical recommendations are the following: First, erectile dysfunction (ED) is a risk marker and enhancer for cardiovascular (CV) disease. For men with ED and intermediate levels of CV risk, coronary artery calcium (CAC) computed tomography should be considered in addition to previous management algorithms. Second, sexual activity is generally safe for men with ED, although stress testing should still be considered for men with reduced exercise tolerance or ischemia. Third, the safety of PDE5 inhibitor use with concomitant medications was reviewed in depth, particularly concomitant use with nitrates or alpha-blockers. With rare exceptions, PDE5 inhibitors can be safely used in men being treated for hypertension, lower urinary tract symptoms and other common male disorders. Fourth, for men unresponsive to oral therapy or with absolute contraindications for PDE5 inhibitor administration, multiple treatment options can be selected. These were reviewed in depth with clinical recommendations. Fifth, evidence from retrospective studies points strongly toward cardioprotective effects of chronic PDE5-inhibitor use in men. Decreased rates of adverse cardiac outcomes in men taking PDE-5 inhibitors has been consistently reported from multiple studies. Sixth, recommendations were made regarding over-the-counter access and potential risks of dietary supplement adulteration. Seventh, although limited data exist in women, PDE5 inhibitors are generally safe and are being tested for use in multiple new indications.

Conclusion

Studies support the overall cardiovascular safety of the PDE5 inhibitors. New indications and applications were reviewed in depth.
The Influence of the Number of Tree Searches on Maximum Likelihood Inference in Phylogenomics
Authors: Liu Chao , Zhou Xiaofan , Li Yuanning , Hittinger Chris Todd , Pan Ronghui , Huang Jinyan , Chen Xue-xin , Rokas Antonis , Chen Yun , Shen Xing-Xing
Published: June 2024

Maximum likelihood (ML) phylogenetic inference is widely used in phylogenomics. As heuristic searches most likely find suboptimal trees, it is recommended to conduct multiple (e.g., 10) tree searches in phylogenetic analyses. However, beyond its positive role, how and to what extent multiple tree searches aid ML phylogenetic inference remains poorly explored. Here, we found that a random starting tree was not as effective as the BioNJ and parsimony starting trees in inferring the ML gene tree and that RAxML-NG and PhyML were less sensitive to different starting trees than IQ-TREE. We then examined the effect of the number of tree searches on ML tree inference with IQ-TREE and RAxML-NG, by running 100 tree searches on 19,414 gene alignments from 15 animal, plant, and fungal phylogenomic datasets. We found that the number of tree searches substantially impacted the recovery of the best-of-100 ML gene tree topology among 100 searches for a given ML program. In addition, all of the concatenation-based trees were topologically identical if the number of tree searches was ≥10. Quartet-based ASTRAL trees inferred from 1 to 80 tree searches differed topologically from those inferred from 100 tree searches for 6/15 phylogenomic datasets. Finally, our simulations showed that gene alignments with lower difficulty scores had a higher chance of finding the best-of-100 gene tree topology and were more likely to yield the correct trees.
Animal and human bites
Authors: Cottrell Damon B. , Martin Catherine “Katie” M.
Published: June 2024

Patients who have experienced animal or human bites may present for care in a number of settings with a variety of injuries requiring different approaches to treatment and management. Because animal and human bites range in severity and can result in a host of sequelae, their evaluation and management can be complex. In caring for patients with an animal or human bite, NPs must consider the many factors relevant to such an injury.
Percent Final Height Is a Novel Method That Identifies Differences Between the Rate of Development in American Children of Different Races
Authors: Taylor Tristen N. , Yang Ally A. , Lee Tiffany M. , Diejomaoh Rioke M. , Bridges Callie S. , Kan J. Herman , Smith Brian G. , Cooperman Daniel R.
Published: June 2024

Introduction:

The Greulich & Pyle (G&P) Radiographic Atlas of Skeletal Development uses hand x-rays obtained between 1926 and 1942 on children of Caucasian ancestry. Our study uses modern Caucasian, Black, Hispanic, and Asian children to investigate patterns of development as a function of percent final height (PFH).

Methods:

A retrospective review, at a single institution, was conducted using children who received a hand x-ray, a height measurement taken within 60 days of that x-ray, and a final height. BA and CA were compared between races. PFH was calculated by dividing height at the time of the x-ray by their final height. To further evaluate differences between races in CA or BA, PFH was then modeled as a function of CA or BA using a fifth-degree polynomial regression, and mean ages at the 85th PFH were compared. Patients were then divided into Sanders stages 1, 2-4, and 5-8 and the mean PFH, CA, and BA of the Asian, Black, and Hispanic children were compared with the White children using Student t test. P values less than 0.05 were considered significant.

Results:

We studied 498 patients, including 53 Asian, 83 Black, 190 Hispanic, and 172 White patients. Mean BA was significantly greater than CA in Black males (1.27 y) and females (1.36 y), Hispanic males (1.12 y) and females (1.29 y), and White females (0.74 y). Hispanic and Black patients were significantly more advanced in BA than White patients (P<0.001). At the 85th PFH, White and Hispanic males were older than Black males by at least 7 months (P<0.001), and White females were significantly older than Hispanic females by 6.4 months (P<0.001). At 85th PFH for males, Hispanic and Black males had greater BA than White males by at least 5 months (P<0.001), and Asian females had a greater BA than Black females by at least 5 months (P<0.001). Compared with White children, Hispanic children were significantly younger at Sanders 2-4 than White children, and Black children were skeletally older at Sanders 5-8.

Conclusions:

BA was greater than CA by ≥1 year in Black and Hispanic children, and that these children had a significantly greater BA than their White counterparts. Black males and Hispanic females reached their 85th PFH at younger ages, and Hispanic males and Asian females were the most skeletally mature at their 85th PFH. Our results suggest that BA and CA may vary as a function of race, and further studies evaluating growth via the 85th PFH may be necessary.

Level of Evidence:

Therapeutic Study – Level IV
Study on the therapeutic effect of sintilimab combined with modified DCF regimen on advanced gastric cancer and its impact on Th1/Th2 immune balance
Authors: Cai Lili , Qu Lan , Cheng Yanjie , Zhang Jinfeng , Li Shiying , Wu Shenghong
Published: June 2024

The aim of this study was to observe the therapeutic effect of sintilimab combined with a modified docetaxel + cisplatin + fluorouracil (DCF) regimen on advanced gastric cancer and its effect on Th1/Th2 immune balance. Ninety-eight cases of advanced gastric cancer patients who visited our hospital from April 2020 to May 2022 were selected and divided into 48 cases each in the conventional group and the research group by random number table method; the DCF regimen was adopted in the conventional group, and sintilimab combined with modified DCF regimen was adopted in the research group, and the therapeutic effects of the patients in the two groups and the changes of Th1/Th2 immune indexes were compared. CEA, CA199, CA242, CD168 AQ3, and IL-4 in the study group were lower than those in the conventional group at the end of three cycles of treatment, and the difference was statistically significant (P < 0.001). The levels of IFN-γ and IL-4 in the study group at the end of three cycles of treatment were higher than those in the conventional group (P < 0.001). The incidence of adverse reactions during treatment in the study group was lower than that in the conventional group (P < 0.001), and the grading of adverse reactions in the study group was milder than that in the conventional group. Sintilimab combined with a modified DCF regimen in the treatment of advanced gastric cancer not only improves the therapeutic effect but also positively affects the Th1/Th2 immune balance, which provides better immune regulation for patients with advanced gastric cancer.
Hyper-late major response after 5 years of nivolumab: role of treatment beyond progression in head and neck cancer
Authors: Cabezas-Camarero Santiago , Cabrera-Martín María Nieves , Iglesias-Moreno María Cruz , Pérez-Segura Pedro
Published: June 2024

Patients with recurrent/metastatic (R/M) platinum-refractory squamous cell carcinoma of the head and neck (SCCHN) have fewer treatment options and harbor an especially poor prognosis. Maintaining treatment with anti-PD1 agents beyond response evaluation criteria in solid tumors-defined disease progression (TBP) has been shown to be efficacious in several solid tumors, including head and neck cancer. We present the case of a platinum-refractory locally recurrent, PD-L1-negative hypopharyngeal carcinoma, that received second-line nivolumab which was then maintained beyond progression under the following criteria: no Eastern Cooperative Oncology Group performance status deterioration, no rapidly progressive disease, no severe toxicity, and evidence of overall treatment benefit. The patient achieved a partial response 8 months after starting second-line nivolumab, with progressive disease at 26 months, then followed by the first TBP with nivolumab lasting for 15 months due to a new tumor progression. A second TBP with nivolumab lasting for 7 months, was followed by a third TBP with nivolumab for 12 months and achieving a major tumor response. Treatment is still ongoing 60 months after starting nivolumab, with excellent tolerance to therapy. Maintaining anti-PD1 agents beyond progression is an efficacious treatment option for patients with R/M SCCHN, that may achieve very durable disease control and even late major responses.
The Association Between Elevated Myocardial Injury-Related Biomarker (TnI) and Increased Mortality in Patients With Severe Fever With Thrombocytopenia Syndrome*
Authors: Liang Boyun , Xu Ling , Li Mingyue , Wang Hua , Lu Sihong , Fan Lei , Wang Tong , Li Junyuan , Zhu Bin , Wang Junzhong , Wang Baoju , Peng Cheng , Shen Shu , Zheng Xin
Published: June 2024

OBJECTIVES:

The objective of this study was to investigate the dynamic profiles of myocardial injury biomarkers and their association with mortality in patients with severe fever with thrombocytopenia syndrome (SFTS).

DESIGN:

A retrospective cohort study.

SETTINGS:

Union Hospital in Wuhan, China.

PATIENTS:

A total of 580 patients with SFTS, observed between May 2014 and December 2021, were included in the final analysis.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

In total, 580 patients with SFTS were enrolled in the study, comprised of 469 survivors and 111 nonsurvivors, with a 21-day fatality rate of 19.1%. The elevation of troponin I (TnI) was observed in 61.6% patients (357/580) with SFTS upon admission, and 68.4% patients (397/580) developed an abnormal TnI level during hospitalization. Multivariate logistic regression identified age, viral load, platelet count, creatinine level, and TnI level as potential risk factors for mortality in patients with SFTS. The results of restricted cubic splines revealed that when the TnI level (baseline TnI: 1.55 [lg (ng/L+1)], peak value: TnI 1.90 [lg (ng/L+1)]) exceeded a certain threshold, the predicted mortality of patients with SFTS increased alongside the rise in TnI levels. Mortality rate surpassed 40% among patients with SFTS with TnI greater than or equal to 10 times the upper limit of normal at admission (43.8%) or during hospitalization (41.7%). Older age, a history of cardiovascular disease, and higher d-dimer levels were potential risk factors for elevated TnI levels in patients with SFTS.

CONCLUSIONS:

Elevated TnI levels were prevalent among patients with SFTS and were strongly associated with an increased risk of mortality.
Sclerosing Dermatofibrosarcoma Protuberans: A Possible Diagnosis When a Small Biopsy Shows Sclerotic Fibroma-Like Features
Authors: Kurimoto Toru , Mitsui Yasuhiro , Nakanishi Takashi , Morita Kohei , Ishida Eiwa , Ogawa Kohei , Koga Kaori , Fukumoto Takaya , Asada Hideo
Published: June 2024

Dermatofibrosarcoma protuberans (DFSP) is a neoplasm of intermediate malignancy with high local recurrence rates. The sclerosing variant is characterized by the presence of sclerotic areas in more than 50% of tumors and is rarely reported. In this report, we describe a case of sclerosing DFSP with areas histopathologically resembling sclerotic fibroma, where the initial biopsy tissue presented a diagnostic challenge. A 77-year-old man presented with a 2-cm firm, erythematous nodule on the chest. A punch biopsy revealed plywood-like sclerosis and spindle cells with a vaguely storiform pattern. The tumor cells were positive for CD34. Sclerotic fibroma and DFSP were considered differential diagnoses. Subsequent excisional biopsy revealed that the tumor comprised 3 different histopathological areas: classic DFSP, sclerotic fibroma-like, and giant cell fibroblastoma-like. This report highlights the importance of reevaluating the clinical context and excision for further characterization.
Validity of the 1984 Interim Guidelines on Airborne Ultrasound and Gaps in the Current Knowledge
Authors:   International Commission on Non-Ionizing Radiation Protection
Published: June 2024

Airborne ultrasound is used for various purposes both in industrial and public settings, as well as being produced as a by-product by a range of sources. The International Radiation Protection Association (IRPA) published interim guidelines on limiting human exposure to airborne ultrasound in 1984, based on the limited scientific evidence that was available at that time. In order to investigate whether research since 1984 requires the development of revised exposure guidelines we considered (a) within the context of ultrasound exposure the relevance to health of the biological endpoints/mechanisms listed in the IRPA guidelines, (b) the validity of the exposure limits, and (c) whether there are biological endpoints/mechanisms not covered in the guidelines. The analysis of the available evidence showed that the biological endpoints that form the basis of the guidelines are relevant to health and the guidelines provide limits of exposure based on the evidence that was available at the time. However, the IRPA limits and their associated dosimetry were based on limited evidence, which may not be considered as scientifically substantiated. Further, there is no substantiated evidence of biological endpoints/mechanisms not covered by the IRPA guidelines. These two observations could mean that IRPA’s limits are too low or too high. Research since the IRPA guidelines has made some improvements in the knowledge base, but there are still significant data gaps that need to be resolved before a formal revision of the guidelines can be made by ICNIRP, including research needs related to health outcomes and improved dosimetry. This statement makes a number of recommendations for future research on airborne ultrasound.
HAZMAT Technician-level Emergency Response: A Mental Model Framework for Radiological Dispersal Device (RDD) Incidents
Authors: Leek Angela E. , Keren Nir , Blumenthal Daniel , Irwin William , Musolino Stephen
Published: June 2024

This research examines the cognitive frameworks used by HAZMAT technicians when responding to incidents involving Radiological Dispersal Devices (RDDs), which are conventional explosive devices with radioactive materials incorporated. The objective is to introduce the Expected Mental Model State (EMMS) as a comprehensive evaluation tool for assessing and enhancing the expertise and situational awareness of emergency responders dealing with radiation crises. Through a series of expert focus group sessions using the well-established qualitative methodology of grounded theory, an Expected Mental Model State (EMMS) was developed. The methodology used an influence diagram architecture to conceptually capture and codify key areas relevant to effective emergency response. The research identifies fourteen EMMS key conceptual domains, further elaborated into 301 subtopics, providing a multi-dimensional structure for the proposed mental model framework. Three pivotal notions of mental model emerged within the EMMS framework: Knowledge Topology, Envisioning (Belief), and Response and Operability. These notions were found to align with previous theories of mental models and are vital for understanding how HAZMAT technicians conceptualize and respond to RDD incidents. The study emphasizes the critical role of mental models in enhancing preparedness and effective response strategies during radiation emergencies. The EMMS framework offers a versatile methodology that can be adapted across various kinds of emergency responders and high-risk situations, including the broader Chemical, Biological, Radiological, and Nuclear (CBRN) spectrum. Using this EMMS framework to develop an EMMS Diagnostic Matrix can provide a roadmap for identifying areas for the development of specialized training modules that have the potential to significantly elevate both the quality and efficacy of responder training and preparation.
Emerging alternatives to keratoplasty for corneal endothelial cell dysfunction
Authors: Kaufman Ron , Jun Albert S.
Published: June 2024

Purpose of review

While effective for treating endothelial dysfunction, keratoplasty has shortcomings including limited access to donor tissue for much of the world. Thus, alternative strategies are under development. This review explores the main advancements achieved in this field during 2022–2023.

Recent findings

Recent publications further support the validity of intracameral cultivated allogeneic endothelial cell injection and Descemet stripping only, while emphasizing the benefits of adjunctive Rho-associated kinase inhibitor (ROCKi) therapy. New donor-independent artificial implants, such as EndoArt, show favorable results. Multiple pharmacologic agents, especially ROCKi, show promise as monotherapies, yet none are currently approved for human treatment. Multiple regenerative and genetic therapies are being investigated but all are still in preclinical stages.

A plethora of innovative alternatives to keratoplasty for endothelial disease is in development. Among these, surgical methods are still the mainstay of treatment and closest to clinical application, though further studies to establish their benefits over keratoplasty are needed. Albeit promising, pharmacologic, regenerative, and genetic approaches require validation and are farther from clinical application.
Neuromuscular electrical stimulation, muscle mass, and physical function decline in the early phase after living donor liver transplantation
Authors: Yoshioka Yuji , Oshima Yohei , Sato Susumu , Tamaki Akira , Hamada Ryota , Miyasaka Junsuke , Hata Koichiro , Ito Takashi , Ikeguchi Ryosuke , Hatano Etsuro , Matsuda Shuichi
Published: June 2024

This study aims to investigate the effects of neuromuscular electrical stimulation (NMES) in addition to conventional early mobilization in the early postoperative period after living donor liver transplantation (LTx) on body composition and physical function. This was a retrospective single-center cohort study. Adult subjects who were admitted for living donor LTx from 2018 to 2023 were included in the analysis. After April 2020, patients underwent 4 weeks of NMES in addition to conventional rehabilitation. The skeletal muscle mass index, body cell mass, and physical function, including the 6-minute walking distance, were assessed before surgery and at discharge, and changes in these outcomes were compared before and after the introduction of NMES. Sixty-one patients were in the NMES group, and 53 patients before the introduction of NMES were in the control group. ANCOVA with etiology, obstructive ventilatory impairment, Child-Pugh classification, and initial body composition value as covariates demonstrated that there was a significantly smaller decline of body cell mass (−2.9±2.7 kg vs. −4.4±2.7 kg, p = 0.01), as well as of the skeletal muscle mass index (−0.78±0.73 kg/m2 vs. −1.29±1.21 kg/m2, p = 0.04), from baseline to discharge in the NMES group than in the control group; thus, the decline after surgery was suppressed in the NMES group. Four weeks of NMES, in addition to conventional rehabilitation in the early period after LTx, may attenuate the deterioration of muscle mass. It is suggested that NMES is an option for developing optimized rehabilitation programs in the acute postoperative period after LTx.
Anti-BCMA CAR-T therapy for multiple myeloma with extramedullary disease: A case report and review of the literature
Authors: Shi Huihui , Zhang Man , Su Yajing , Liu Jingwen , Guo Jiayuan , Liu Mingxin , Ma Qiuling
Published: June 2024

Introduction:

Multiple myeloma (MM) with extramedullary disease (EMD) is rare in clinical practice, and B cell maturation antigen (BCMA) CAR-T cell therapy is a novel therapy for hematologic malignancies. Very few reports have been published on the effect of CAR-T-cell therapy in MM with EMD. Here, we report a case of MM with extramedullary lesions treated with BCMA CAR-T therapy.

Case presentation:

A 66-year-old female patient presented to our hospital with an enlarged left maxillary gingiva.

Diagnosis:

Diagnosis of indolent MM stage III (DS staging) and stage III (ISS and R ISS) with extramedullary lesions.

Intervention:

The patient underwent a clinical trial of humanized anti-BCMA CAR T cell therapy.

Results:

Symptoms improved; left gingival hyperplasia and swelling resolved; left buccal mass resolved; and neck and submandibular masses resolved. Pathological examination of the exfoliated masses showed necrotic tissue.

Conclusion:

MM with extramedullary lesions often has limited treatment options, and traditional chemotherapy methods are ineffective; however, BCMA CAR-T cell therapy can significantly improve the symptoms of extramedullary lesions in MM.
Bibliometric and visual analyses of advancements in chronic kidney disease management
Authors: Dong Li , Tan Lian
Published: June 2024

Chronic kidney disease (CKD) is characterized by high incidence, prolonged course, significant health damage, and a heavy societal burden. Understanding the history and content of CKD research is crucial to further its recognition and management, in addition to reducing its individual and societal burdens. This study aimed to assess the management history of CKD to provide a foundation for clinical medical staff to systematically understand its evolution. The Web of Science Core Collection database was screened for CKD management studies published between January 1, 1948, and December 31, 2021. From the search results, we performed statistical descriptions of the publication date, volume, and type. Using VOS-viewer 1.6.19, variables from the included articles were obtained for keyword co-occurrence clustering and sequence analyses to determine research themes, segment phases based on publication volumes over varied timeframes, assess the dynamic progression of CKD management, and anticipate future research trends. In total, 26,133 articles met the inclusion criteria. The analysis revealed 3 stages of CKD management research: the slow development stage (1948–1998), which was initiated by epidemiological studies without ideal clustering; the steady growth stage (1999–2010), which was focused on CKD complication management and quality-of-life research; and the rapid development stage (2011–2022), which was dominated by 7 major clusters, mainly regarding the treatment and management of severe conditions and management patterns. The CKD research journey is comprised of 3 stages, the contents of which form an interconnected research model. Future research should focus on the establishment of management models and the application of intelligent management tools. Furthermore, this work can serve as a reference for the further expansion of research in this field and in improving its management.
AST/ALT ratio is an independent risk factor for diabetic retinopathy: A cross-sectional study
Authors: Luo Jian , Yu Fang , Zhou Haifeng , Wu Xueyan , Zhou Quan , Liu Qin , Gan Shenglian
Published: June 2024

The aspartate to alanine transaminase (AST/ALT) ratio indicates oxidative stress and inflammatory reactions related to the occurrence of diabetic retinopathy (DR). Currently, there are no reports on the correlation between AST/ALT ratio and DR. Hence, this study aimed to explore the relationship between AST/ALT ratio and DR. This cross-sectional study utilized data from the Metabolic Management Center of the First People’s Hospital in City. In total, 1365 patients with type 2 diabetes mellitus (T2DM) participated in the study, including 244 patients with DR and 1121 patients without DR. We collected the results of fundus photography, liver function, and other research data and grouped them according to tertiles of AST/ALT ratios. DR prevalence was the highest in the group with the highest AST/ALT ratio (22.12%, P = .004). Both univariate (OR = 2.25, 95% CI: 1.51–3.34, P < .001) and multivariable logistic regression analyses (adjusted for confounding factors) showed that the risk of DR increased by 36% when the AST/ALT ratio increased by 1 standard deviation (SD) (OR = 1.36, 95% CI: 1.16–1.59, P < .001), and 29.3% was mediated by the duration of diabetes. A sensitivity analysis confirmed the stability of the results. This study showed that an increase in AST/ALT ratio is an independent risk factor for DR.
Clinical and economic burden of medicare beneficiaries with multiple myeloma and renal impairment: An observational study
Authors: Hari Parameswaran , Latremouille-Viau Dominick , Lin Peggy , Guerin Annie , Sasane Medha
Published: June 2024

Evidence on real-world clinical and economic outcomes in patients with multiple myeloma (MM) and renal impairment (RI) is limited in the United States. This retrospective study aimed to generate an updated comprehensive assessment of the clinical and economic outcomes of MM patients with RI using the Medicare research identifiable files data with Part D linkage, which might assist in assessing the total clinical and socioeconomic burden of these high-risk and challenging-to-treat patients. Treatment patterns and clinical and economic outcomes in first line (1L) to fourth line (4L) therapy were described in Medicare beneficiaries (2012 to 2018) for MM patients with RI (RI MM cohort). For reference purposes, information on a general cohort of MM patients was generated and reported to highlight the clinical and economic burden of RI. Since the goal was to describe the burden of these patients, this study was not designed as a comparison between the 2 cohorts. Compared with the general MM cohort (n = 13,573), RI MM patients (24.9%) presented high MM-associated comorbidities. In the RI MM cohort, bortezomib–dexamethasone (45.7%), bortezomib–lenalidomide (18.6%), lenalidomide (12.3%), and bortezomib–cyclophosphamide (12.1%) were the most prevalent regimens in 1L; carfilzomib and pomalidomide were mostly received in 3L to 4L; and daratumumab in 4L. Across 1L to 4L, the RI MM cohort presented shorter median real-world progression-free survival (1L: 12.9 and 16.4 months) and overall survival (1L: 31.1 and 46.8 months) and higher all-cause healthcare resource utilization (1L incidence rate of inpatient days: 12.1 and 7.8 per person per year) than the general MM cohort. In the RI MM cohort, the mean all-cause total cost increased from 1L to 4L ($14,549–$18,667 per person per month) and was higher than that of the general MM cohort. RI MM patients presented higher clinical and economic burdens across 1L to 4L than the general MM patients in real-world clinical practice.