bluuebunny/crossref_metadata_2025 huggingface dataset:
Different types of uncertainty distinguished by monkey prefrontal neurons
Authors: Matsumoto Madoka , Abe Hiroshi , Tanaka Keiji , Matsumoto Kenji
Published: January 2022

To adapt one’s behavior, in a timely manner, to an environment that changes in many different aspects, one must be sensitive to uncertainty about each aspect of the environment. Although the medial prefrontal cortex has been implicated in the representation and reduction of a variety of uncertainties, it is unknown whether different types of uncertainty are distinguished by distinct neuronal populations. To investigate how the prefrontal cortex distinguishes between different types of uncertainty, we recorded neuronal activities from the medial and lateral prefrontal cortices of monkeys performing a visual feedback-based action-learning task in which uncertainty of coming feedback and that of context change varied asynchronously. We found that the activities of two groups of prefrontal cells represented the two different types of uncertainty. These results suggest that different types of uncertainty are represented by distinct neural populations in the prefrontal cortex.
A Multicenter Cohort Study of Falls Among Patients Admitted to the ICU*
Authors: Wu Guosong , Soo Andrea , Ronksley Paul , Holroyd-Leduc Jayna , Bagshaw Sean M. , Wu Qunhong , Quan Hude , Stelfox Henry T.
Published: January 2022

OBJECTIVES:

To determine the incidence of falls, risk factors, and adverse outcomes, among patients admitted to the ICU.

DESIGN:

Retrospective cohort study.

SETTING:

Seventeen ICUs in Alberta, Canada.

PATIENTS:

Seventy-three thousand four hundred ninety-five consecutive adult patient admissions between January 1, 2014, and December 31, 2019.

MEASUREMENTS AND MAIN RESULTS:

A mixed-effects negative binomial regression model was used to examine risk factors associated with falls. Linear and logistic regression models were used to evaluate adverse outcomes. Six hundred forty patients experienced 710 falls over 398,223 patient days (incidence rate of 1.78 falls per 1,000 patient days [95% CI, 1.65–1.91]). The daily incidence of falls increased during the ICU stay (e.g., day 1 vs day 7; 0.51 vs 2.43 falls per 1,000 patient days) and varied significantly between ICUs (range, 0.37–4.64 falls per 1,000 patient days). Male sex (incidence rate ratio [IRR], 1.37; 95% CI, 1.15–1.63), previous invasive mechanical ventilation (IRR, 1.82; 95% CI, 1.40–2.38), previous sedative and analgesic medication infusions (IRR, 1.60; 95% CI, 1.15–2.24), delirium (IRR, 3.85; 95% CI, 3.23–4.58), and patient mobilization (IRR, 1.26; 95% CI, 1.21–1.30) were risk factors for falling. Falls were associated with longer ICU (ratio of means [RM], 3.10; 95% CI, 2.86–3.36) and hospital (RM, 2.21; 95% CI, 2.01–2.42) stays, but lower odds of death in the ICU (odds ratio [OR], 0.09; 95% CI, 0.05–0.17) and hospital (OR, 0.21; 95% CI, 0.14–0.30).

CONCLUSIONS:

We observed that among ICU patients, falls occur frequently, vary substantially between ICUs, and are associated with modifiable risk factors, longer ICU and hospital stays, and lower risk of death. Our study suggests that fall prevention strategies should be considered for critically ill patients admitted to ICU.
Early Neuromuscular Blockade in Moderate-to-Severe Pediatric Acute Respiratory Distress Syndrome
Authors: Rudolph Michelle W. , Kneyber Martin C. J. , Asaro Lisa A. , Cheifetz Ira M. , Wypij David , Curley Martha A. Q.
Published: January 2022

OBJECTIVES:

The use of neuromuscular blocking agents (NMBAs) in pediatric acute respiratory distress syndrome (PARDS) is common but unsupported by efficacy data. We sought to compare the outcomes between patients with moderate-to-severe PARDS receiving continuous NMBA during the first 48 hours of endotracheal intubation (early NMBA) and those without.

DESIGN:

Secondary analysis of data from the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) clinical trial, a pediatric multicenter cluster randomized trial of sedation.

SETTING:

Thirty-one PICUs in the United States.

PATIENTS:

Children 2 weeks to 17 years receiving invasive mechanical ventilation (MV) for moderate-to-severe PARDS (i.e., oxygenation index ≥ 8 and bilateral infiltrates on chest radiograph on days 0–1 of endotracheal intubation).

INTERVENTIONS:

NMBA for the entire duration of days 1 and 2 after intubation.

MEASUREMENTS AND MAIN RESULTS:

Among 1,182 RESTORE patients with moderate-to-severe PARDS, 196 (17%) received early NMBA for a median of 50.0% ventilator days (interquartile range, 33.3–60.7%). The propensity score model predicting the probability of receiving early NMBA included high-frequency oscillatory ventilation on days 0–2 (odds ratio [OR], 7.61; 95% CI, 4.75–12.21) and severe PARDS on days 0–1 (OR, 2.16; 95% CI, 1.50–3.12). After adjusting for risk category, early use of NMBA was associated with a longer duration of MV (hazard ratio, 0.57; 95% CI, 0.48–0.68; p < 0.0001), but not with mortality (OR, 1.62; 95% CI, 0.92–2.85; p = 0.096) compared with no early use of NMBA. Other outcomes including cognitive, functional, and physical impairment at 6 months post-PICU discharge were similar. Outcomes did not differ when comparing high versus low NMBA usage sites or when patients were stratified by baseline Pao
2/Fio
2 less than 150.

CONCLUSIONS:

Early NMBA use was associated with a longer duration of MV. This propensity score analysis underscores the need for a randomized controlled trial in pediatrics.
Monitoring Spinal Cord Tissue Oxygen in Patients With Acute, Severe Traumatic Spinal Cord Injuries
Authors: Visagan Ravindran , Hogg Florence R. A. , Gallagher Mathew J. , Kearney Siobhan , Zoumprouli Argyro , Papadopoulos Marios C. , Saadoun Samira
Published: January 2022

OBJECTIVES:

To determine the feasibility of monitoring tissue oxygen tension from the injury site (psct
o
2) in patients with acute, severe traumatic spinal cord injuries.

DESIGN:

We inserted at the injury site a pressure probe, a microdialysis catheter, and an oxygen electrode to monitor for up to a week intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), tissue glucose, lactate/pyruvate ratio (LPR), and psct
o
2. We analyzed 2,213 hours of such data. Follow-up was 6–28 months postinjury.

SETTING:

Single-center neurosurgical and neurocritical care units.

SUBJECTS:

Twenty-six patients with traumatic spinal cord injuries, American spinal injury association Impairment Scale A–C. Probes were inserted within 72 hours of injury.

INTERVENTIONS:

Insertion of subarachnoid oxygen electrode (Licox; Integra LifeSciences, Sophia-Antipolis, France), pressure probe, and microdialysis catheter.

MEASUREMENTS AND MAIN RESULTS:

psct
o
2 was significantly influenced by ISP (psct
o
2 26.7 ± 0.3 mm Hg at ISP > 10 mmHg vs psct
o
2 22.7 ± 0.8 mm Hg at ISP ≤ 10 mm Hg), SCPP (psct
o
2 26.8 ± 0.3 mm Hg at SCPP < 90 mm Hg vs psct
o
2 32.1 ± 0.7 mm Hg at SCPP ≥ 90 mm Hg), tissue glucose (psct
o
2 26.8 ± 0.4 mm Hg at glucose < 6 mM vs 32.9 ± 0.5 mm Hg at glucose ≥ 6 mM), tissue LPR (psct
o
2 25.3 ± 0.4 mm Hg at LPR > 30 vs psct
o
2 31.3 ± 0.3 mm Hg at LPR ≤ 30), and fever (psct
o
2 28.8 ± 0.5 mm Hg at cord temperature 37–38°C vs psct
o
2 28.7 ± 0.8 mm Hg at cord temperature ≥ 39°C). Tissue hypoxia also occurred independent of these factors. Increasing the Fio
2 by 0.48 increases psct
o
2 by 71.8% above baseline within 8.4 minutes. In patients with motor-incomplete injuries, fluctuations in psct
o
2 correlated with fluctuations in limb motor score. The injured cord spent 11% (39%) hours at psct
o
2 less than 5 mm Hg (< 20 mm Hg) in patients with motor-complete outcomes, compared with 1% (30%) hours at psct
o
2 less than 5 mm Hg (< 20 mm Hg) in patients with motor-incomplete outcomes. Complications were cerebrospinal fluid leak (5/26) and wound infection (1/26).

CONCLUSIONS:

This study lays the foundation for measuring and altering spinal cord oxygen at the injury site. Future studies are required to investigate whether this is an effective new therapy.
The incidence of second primary cancer in male and female patients with initial colorectal cancer: a SEER population-based study
Authors: Chen Yanyan , Han Chao , Huang Yadi , Liu Chao , Sheng Siqi , Ji Linlin , Zhu Jialong , Fu Gongbo , Mao Xiaobei , Huang Mengxi , Lei Zengjie , Chu Xiaoyuan
Published: January 2022

Background

Second primary cancer (SPC) after primary colorectal cancer (CRC), emerges as a novel challenge for cancer prevention with pronounced differences between female and male patients.

Methods

This was a retrospective study of 140 907 CRC survivors from the surveillance, epidemiology, and end results program database. Competing risk models and nomograms were constructed to predict the risk of SPCs, which were assessed with the C-Index, calibration and decision curve analysis.

Results

The 10-year cumulative incidence of SPC was higher in male than in female CRC survivors. The top five common SPCs in female CRC survivors were colorectal, breast, lung and bronchus, corpus and uterus and pancreatic cancers, while in male were prostate, colorectal, lung and bronchus, urinary cancer and melanoma of the skin. Breast and prostate were the most common sites for the development of SPCs after CRC. Older age, stage I and surgery were common risk factors for SPCs in both female and male. The nomogram for predicting the risk of developing SPC-breast cancer in female patients included age, race, site, histology grade, surgery, chemotherapy and stage. However, the model of predicting SPC-prostate cancer in male patients included age, race, site, size, surgery, chemotherapy, radiation and stage. Notably, the nomograms were validated to have a precise discriminative ability, accuracy and clinical effectiveness.

Conclusions

The study surveyed the characteristics of CRC survivors with a particular focus on the incidence of SPC. The models could help supervise the development of a second breast or prostate cancer in female or male CRC survivors.
Primary Cutaneous Alveolar Rhabdomyosarcoma in an Elderly Adult: A Rare Potential Mimic of Merkel Cell Carcinoma
Authors: Lindsey Miki S. , Bridge Julia A. , Douglas Donald S. , Foster Jennifer T. , Shalin Sara C. , Gardner Jerad M.
Published: January 2022

Rhabdomyosarcoma (RMS) rarely arises as a primary skin tumor. It is also very rare in older adults, especially the alveolar type. We report an 80-year-old White woman who presented with a painful, erythematous, raised lesion (2 × 3.5 cm) above the left knee that was fixed within the skin, yet mobile about underlying soft tissue. A punch biopsy showed monotonous malignant round blue cells involving the dermis. Immunostains showed diffuse expression of CD56, focal chromogranin, focal dot-like pancytokeratin, CK7, and neurofilament, but negative for synaptophysin, CK20, SOX-10, MUM-1, CD43, TTF-1, and CD99. A CK20-negative variant of Merkel cell carcinoma was initially favored, but given the unusual immunophenotype and the presence of cellular dyscohesion, desmin and myogenin stains were performed, both of which were diffusely positive. Molecular testing revealed rearrangement of PAX3 and FOXO1 loci, confirming the diagnosis of alveolar RMS. PET/CT showed a probable 1.9-cm left inguinal lymph node metastasis; no internal or deep soft tissue primary tumor mass was identified, supporting a true primary cutaneous origin. Alveolar RMS may express keratins and neuroendocrine markers, making it easy to confuse with Merkel cell carcinoma on those exceptionally rare instances, when it arises in the skin of older adults.
A COVID-19 Patient Discharged According to Strict Discharge Standards: Viral Negativity in Both Nasopharynx and Feces
Authors: Chen Enqiang , Wang Lichun , Tang Guangming , Wang Menglan , Tao Yachao , Feng Ping , Tang Hong
Published: January 2022

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) currently has spread all over the world. However, the dynamic characteristics of SARS-CoV-2 infections have not previously been described in detail. Here, we report a cured patient in West China Hospital, and describe the dynamic detection of SARS-CoV-2-RNA in different specimens and viral specific IgM and IgG antibodies in blood. The findings suggest that the fecal SARS-CoV-2-RNA negativity may be considered as a new standard for de isolation. Serum IgM and IgG antibodies detection were helpful for early diagnosis of SARS-CoV-2 infection and judgment of patients in recovery stage, respectively.
Research Progress on the Pathogenesis of Hemorrhagic Fever with Renal Syndrome
Authors: Du Hong , Wang Pingzhong , Bai Xuefan , Li Jing , Wang Xiaoyan , Hu Haifeng , Zhang Ying , Jiang Hong , Shen Huanjun , Zhan Jiayi , Lian Jianqi
Published: January 2022

Hemorrhagic fever with renal syndrome (HFRS) is an acute natural focus epidemic disease characterized by fever, shock, hemorrhage and kidney injury caused by hantavirus infection. Hantavirus mainly infects human vascular endothelial cells, and induces extensive damage to small blood vessels and capillaries. Increased vascular permeability is the pathological basis for clinical manifestations of HFRS. Although domestic and foreign scholars have carried out many studies on the hantavirus pathogenesis, such as the immune pathological response induced by hantavirus, host genetics and apoptosis, thrombocytopenia, coagulation and fibrinolysis dysfunction, and the vascular endothelial damage, the pathogenesis of HFRS has not been fully elucidated and there is no effective drug yet. In-depth discussion of the molecular mechanism of HFRS and finding effective therapeutic drugs are still the research hotspots on the field of hantavirus/HFRS. This review will elaborate the research progress on the pathogenesis of HFRS in recent years.
Efficacy of Wen-Dan Decoction in the treatment of patients with coronary heart disease
Authors: Zhang Xiaoyu , Wang Yingwei , Liu Lufei , Jiang Hui , Wang Jing , Xiao Yang , Wang Jianwei
Published: January 2022

Background:

Coronary heart disease (CHD) is a heart disease caused by myocardial ischemia, hypoxia or necrosis due to stenosis or occlusion of lumen caused by coronary atherosclerosis. It belongs to ischemic cardiomyopathy and is more common in clinic. Previous studies have shown that Wen-Dan Decoction (WDD) is safe and effective, but there is a lack of systematic reviews. The purpose of this study is to systematically study the efficacy of WDD in the treatment of patients with CHD.

Methods:

We will search the following databases: PubMed, EMBASE, Web of Science, Central, Chinese databases China Biomedical Literature, Wanfang Chinese digital periodical and conference database (Wanfang Database), China National Knowledge Infrastructure database, and VIP Chinese Science and Technique Journals Database (VIP) from inception to August 2021. All published randomized controlled trials related to this study will be included. The ongoing or unpublished trials will be searched from National Institutes of Health clinical registry Clinical Trials, International Clinical Trials Registry Platform and the Chinese clinical trial registration platform. Two researchers separately screened the literature and extracted data. The primary outcome is total effective rate. The RevMan V5.3 will be used to evaluate literature and data analysis synthesis.

Results:

This study will provide a reliable evidence-based basis for the clinical application of WDD in the treatment of patients with CHD.

Conclusion:

The effectiveness of WDD for CHD will be evaluated.

Unique INPLASY number:

2021110001
Biomechanical comparison between double-plate fixation and posterior plate fixation for comminuted olecranon fracture using two triceps screws in synthetic bone model
Authors: Lee Yohan , Cho Bong Wan , Kim Min Bom , Lee Young Ho
Published: January 2022

Background:

Although preventing triceps fragment displacement is essential for treating an olecranon fracture, we frequently encounter situations in which only a few screws can be fixed to the triceps fragment. The aim of this study was to compare the stability of double-plate fixation and posterior plate fixation for olecranon fractures when the triceps fragment was small and only 2 screws could be inserted.

Methods:

A composite ulna model was used to simulate olecranon fracture. Four groups were formed consisting of double-plate and posterior plates with cortical and locking screws. The cyclic loading test was conducted for 500 cyclic loads of 5 to 50 N on a specimen to measure micromotion and displacement of the gap caused by light exercise. The load-to-failure test was performed by applying a load until fixation loss, defined as when the fracture gap increased by 2 mm or more or catastrophic failure occurred, to measure the maximum load.

Results:

Eight samples per group were tested through the pilot study. All groups were stable with a micromotion of <0.5 mm. However, the mean micromotion showed significant differences between the 4 groups (P < .001, Table 1

). In the mean micromotion during exercise, posterior plating with cortical screws was the most stable (0.09 ± 0.02 mm) while double-plating with cortical screws was the most unstable (0.42 ± 0.11 mm). At the maximum load, posterior plating with locking screws was the strongest (205.3 ± 2.8 N) while double-plating with cortical screws was the weakest (143.3 ± 27.1 N). There was no significant difference in displacement after light exercise between the groups.

Conclusions:

This study showed that when 2 triceps screws were used, both groups were stable during light exercise, but posterior-plating was stronger than double-plating.
Primary liposarcoma of the omentum
Authors: Gao Ying , Qin Yujie , Wang Yingchao , Quan Xiaoling , Wei Xiaoyi , Yao Jiaxi
Published: January 2022

Rationale:

Omental liposarcoma is extremely rare, and only a few reports have been published in the literature. Due to the rarity of the disease, establishing a clear diagnosis and formulating a treatment plan may be challenging for clinicians.

Patient concerns:

The patient was a 51-year-old woman who presented with a protruding mass and pain in the lower abdomen.

Diagnosis:

Magnetic resonance imaging revealed a tumor measuring 15 cm in diameter in the pelvis. Ovarian cancer was suspected based on pre-operative imaging findings.

Interventions:

An exploratory laparotomy was performed. Intra-operative analysis of the frozen section suggested a benign tumor.

Outcomes:

Postoperative histopathological analysis confirmed the diagnosis of omental liposarcoma. The patient recovered well after surgery.

Lesson:

This case report helps clinical oncologists to develop a comprehensive understanding of this disease and treat it accordingly.
The analysis of root canal curvature and direction of maxillary lateral incisors by using cone-beam computed tomography
Authors: Wang Linlin , Wang Zhensong , Wang Qiang , Han Jingchao , Tian Hongsheng
Published: January 2022

The aim of this study was to investigate root canal curvature and direction of maxillary lateral incisors in Shandong, China.

Cone beam computed tomography (CBCT) images of 176 maxillary lateral incisors of 88 patients were collected in Shandong Province, China. Software included with CBCT was used to measure the angle of root canal curvature of maxillary lateral incisors on the maximum bending plane. In addition, the direction of each root canal was recorded. The data were statistically analyzed by SPSS 17.0 software package.

The results showed that all the samples had a single canal (Vertucci's type I). The incidence of straight root canals, curved root canals, and S-type root canals was 39.2%, 58%, and 2.8%, respectively. The difference in the mean angle of root canal curvature failed to identify any differences between the left and right side (P > .05). The most curved root canal of maxillary lateral incisors oriented in the palato-distal direction.

The maxillary lateral incisors were mainly curved root canals of which the proportion of moderate curvature was the largest. Software included with CBCT would provide some valuable information for root canal instrumentation of maxillary lateral incisors.
Late-infantile GM1 gangliosidosis
Authors: Noh Eu Seon , Park Hye Mi , Kim Min Sun , Park Hyung-Doo , Cho Sung Yoon , Jin Dong-Kyu
Published: January 2022

Rationale:

Monosialotetrahexosylganglioside (GM1) gangliosidosis is a rare lysosomal storage disorder caused by the deficiency of ß-galactosidase. Because clinical symptoms of GM1 gangliosidosis overlap with other neurodevelopmental disorders, the diagnosis of this disease is not easy, specifically in late infantile GM1 gangliosidosis. This report described a case of late-infantile GM1 gangliosidosis mistaken for juvenile idiopathic arthritis.

Patient concerns:

A 16-year-old girl was referred to our hospital due to persistent multiple joint deformities and mental retardation, which could not be explained by juvenile idiopathic arthritis.

Diagnosis:

We made a diagnosis of late infantile GM1 gangliosidosis through enzyme assays and genetic testing after a skeletal survey.

Interventions:

The patient underwent cervical domeplasty and laminectomy for cord compression and received rehabilitation treatment.

Outcomes:

The patient is receiving multidisciplinary care at a tertiary center for variable skeletal disease and conditions associated with GM1 gangliosidosis.

Lessons:

Late infantile GM1 gangliosidosis should be considered in the differential diagnosis of progressive neurologic decline and skeletal dysostosis.
Mechanistic insights into the use of rhubarb in diabetic kidney disease treatment using network pharmacology
Authors: Gao Yingyuan , Nan Zheng
Published: January 2022

In this study, we predicted the core active compounds of rhubarb used in the treatment of diabetic kidney disease (DKD) and the related core gene targets and pathways using network pharmacological approaches.

The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to identify active compounds of rhubarb. PharmMapper was used to predict the gene targets of active compounds, which were subsequently provided a standard nomenclature using the UniProt database. In addition, DKD-related target genes were predicted using GeneCards, Online Mendelian Inheritance in Man, and Therapeutic Target Database. The genes that were targeted both by rhubarb active compounds and implicated in DKD (hereafter referred to as overlapping target genes) were identified using Venny 2.1. A drug–target–disease network diagram was obtained using Cytoscape and a protein–protein interaction network diagram was constructed using the STRING database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of overlapping target proteins were performed using the Database for Annotation, Visualization and Integrated Discovery Bioinformatics Resources 6.8.

Eighteen core active compounds of rhubarb were extracted, and 136 target genes of rhubarb were identified. Some of the active compounds revealed by the network pharmacological analysis were catechin, aloe-emodin, rhein, and emodin; certain core target proteins suggested by the protein–protein interaction network analysis were AKT1, PIK3R1, and SRC. The overlapping target genes were primarily involved in apoptosis and proteolysis, with the PI3K/Akt signaling pathway identified as significantly enriched.

Network pharmacological strategies were used to identify core active compounds of rhubarb and their related pathways. We believe that our study will provide potential and effective novel targets to identify active compounds of rhubarb for treating DKD.
Procedural analgesia with nitrous oxide at home for epidermolysis bullosa
Authors: Murciano Manuel , Laterza Claudia , Attolini Ettore , Storelli Sonia , Dipietro Giovanni , Rubino Antonio , Annicchiarico Giuseppina
Published: January 2022

Rationale:

Epidermolysis bullosa (EB) is an inherited disease characterized by fragile skin with painful blistering, which requires lifelong skin and wound care. This case report describes the use of inhaled nitrous oxide (N2O) for procedural pain control at home during wound care in a young man with severe dystrophic EB. To our knowledge, only 1 case was reported by Ingelmo et al in 2017 regarding the use of N2O at home in a 4-year-old-child. To date, no such attempt has been made in adult patients.

Patient concerns:

Our patient was a 28-year-old man. Frequent blisters appear spontaneously, and are often preceded by erythema and itching. Patient required daily treatment daily consisting of lancing blisters with a needle and emptying them by compression.

Diagnoses:

Severe recessive dystrophic EB diagnosed at the time of delivery.

Interventions:

Procedural pain control was managed by the auto-administration of an inhaled N2O and air gas mixture.

Outcomes:

Conscious sedation with N2O leads to beneficial effects, such as reduction in dressing duration, acute procedural pain, local antibiotic needing, medication memory, anxiety, anticipatory pain, and fatigue after the dressing session.

Lessons:

N2O analgesia is safe and effective, resulting in a significant reduction in procedural pain and an improvement in the quality of life of patients and their caregivers.
Consensus recommendations on managing the selected comorbidities including cardiovascular disease, osteoporosis, and interstitial lung disease in rheumatoid arthritis
Authors: Yu Kuang-Hui , Chen Hsin-Hua , Cheng Tien-Tsai , Jan Yeong-Jian , Weng Meng-Yu , Lin Yeong-Jang , Chen Hung-An , Cheng Jui-Tseng , Huang Kuang-Yung , Li Ko-Jen , Su Yu-Jih , Leong Pui-Ying , Tsai Wen-Chan , Lan Joung-Liang , Chen Der-Yuan
Published: January 2022

Background:

Rheumatoid arthritis (RA)-related comorbidities, including cardiovascular disease (CVD), osteoporosis (OP), and interstitial lung disease (ILD), are sub-optimally managed. RA-related comorbidities affect disease control and lead to impairment in quality of life. We aimed to develop consensus recommendations for managing RA-related comorbidities.

Methods:

The consensus statements were formulated based on emerging evidence during a face-to-face meeting of Taiwan rheumatology experts and modified through three-round Delphi exercises. The quality of evidence and strength of recommendation of each statement were graded after a literature review, followed by voting for agreement. Through a review of English-language literature, we focused on the existing evidence of management of RA-related comorbidities.

Results:

Based on experts’ consensus, eleven recommendations were developed. CVD risk should be assessed in patients at RA diagnosis, once every 5 years, and at changes in DMARDs therapy. Considering the detrimental effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids on CVD risks, we recommend using the lowest possible dose of corticosteroids and prescribing NSAIDs cautiously. The OP/fragility fracture risk assessment includes dual-energy X-ray absorptiometry and fracture risk assessment (FRAX) in RA. The FRAX-based approach with intervention threshold is a useful strategy for managing OP. RA-ILD assessment includes risk factors, pulmonary function tests, HRCT imaging and a multidisciplinary decision approach to determine RA-ILD severity. A treat-to-target strategy would limit RA-related comorbidities.

Conclusions:

These consensus statements emphasize that adequate control of disease activity and the risk factors are needed for managing RA-related comorbidities, and may provide useful recommendations for rheumatologists on managing RA-related comorbidities.
Sphingomonas paucimobilis - a rare cause of splenic abscesses
Authors: Birlutiu Victoria , Dobritoiu Simona Elena , Ghibu Andreea Magdalena , Birlutiu Rares Mircea , Boicean Loredana Camelia
Published: January 2022

Rationale:

Infections with Sphingomonas paucimobilis are rarely described in the literature and can be community-acquired or associated with healthcare, especially in patients with chronic conditions (e.g., diabetes mellitus), malignancies, or other causes of immunosuppression, except in people without comorbidities. We present the case of a patient with diabetes mellitus and hypertension diagnosed during a routine evaluation, with splenic abscess caused by S paucimobilis. Our literature search revealed no other case report of splenic abscess caused only by S paucimobilis.

Patient concerns:

We present the case of a 55-year-old Caucasian man with type 2 diabetes mellitus and hypertension.

Diagnosis:

Thoraco-abdominal computed tomography revealed splenomegaly of 20X16X18 cm, with a homogeneous subcapsular hypodense collection, with a mass effect on the left hemidiaphragm.

Interventions:

The patient underwent surgical intervention and S paucimobilis was isolated on blood agar.

Outcome:

The patient received treatment with ciprofloxacin (500 mg twice daily) for 14 days, with favorable outcomes.

Lessons:

S paucimobilis, a low-virulence bacterium, can cause community-acquired or nosocomial infections. Visceral localizations, usually symptomatic, can evolve rapidly, and the diagnosis is associated with complications or, as in our case, with careful investigation of some changes in laboratory investigations.
Analysis of factors predicting the application of chemical pleurodesis for pneumothorax
Authors: Shimoda Masafumi , Tanaka Yoshiaki , Hiramatsu Miyako , Morimoto Kozo , Arakawa Kenichi , Abe Taro , Ito Koki , Suga Miyuri , Shiraishi Yuji , Yoshimori Kozo , Ohta Ken
Published: January 2022

Chemical pleurodesis is performed in pneumothorax patients to treat nonresolving air leakage or prevent recurrence. However, factors that might predict the need for chemical pleurodesis remain unknown. Therefore, this study investigated predictive factors for the application of chemical pleurodesis for pneumothorax.

We retrospectively analyzed 401 adult pneumothorax patients who underwent chest tube drain insertion during hospitalization at Fukujuji Hospital from January 2016 to December 2020. The patients were divided into 3 groups: the pleurodesis group, comprising 89 patients treated with chemical pleurodesis; the nonpleurodesis group, comprising 206 patients treated without chemical pleurodesis; and the surgical group, comprising 106 patients treated surgically. Data for patients in the pleurodesis group were compared to those in the nonpleurodesis or surgical group, and a predictive score of the application of chemical pleurodesis for pneumothorax was developed.

Compared with the nonpleurodesis group, in the pleurodesis group, patient age was higher (P < .001), emphysema (n = 33 (37.1%) vs 70 (34.0%), P = .045), and interstitial pneumonitis (n = 19 (21.3%) vs 19 (9.2%), P = .022) were more common causes, and chest tube suction was more common (n = 78 (87.96%) vs n = 123 (59.7%), P < .001). Similar results were found between the pleurodesis and surgical groups. We developed a score for predicting the application of chemical pleurodesis for pneumothorax, including the following factors: age ≥55 years; presence of emphysema and/or interstitial pneumonitis; and use of chest tube suction. The score for the pleurodesis group showed a high area under the receiver operating characteristic curve compared with that for the nonpleurodesis group (0.776 [95% confidence interval]: 0.725–0.827). With a score of 2 as the cutoff value, the sensitivity was 91.0% and the specificity was 52.4%. In a comparison between the pleurodesis and surgical groups, the predicting score showed the high AUC of 0.904 (95% confidence interval: 0.863–0.945).

This study reveals predictive factors for the application of chemical pleurodesis and provides a predictive score including 3 factors.
Effect of calcium and magnesium on inflammatory cytokines in accidentally multiple fracture adults
Authors: Song Yongxing , Xu Long , Jin Xin , Chen Deqing , Jin Xiuhui , Xu Guangtao
Published: January 2022

Calcium (Ca) and magnesium (Mg), which play an important role in several cellular processes, is essential for normal development of the skeleton and maintenance of tissue homeostasis. Deficiency of these elements might delay bone fracture recovery or accelerates bone loss. We aimed to examine whether supplementation of trace element (TE) promotes fracture healing in accidentally fracturing adults by involvement of inflammatory mechanism.

A short-term follow-up in clinic was performed. Totally, 117 subjects diagnosed with multiple fractures by traffic accidents were recruited in this study. Serum Ca and Mg levels were measured by inductively coupled plasma atomic emission spectrophotometry. Short-term changes such as serum C-reactive protein, interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha in normal treatment and TE supplement groups were detected by enzyme-linked immunosorbent assay. Student t test and the Spearman correlation were performed to analyze the data.

Significantly negative correlations between Ca (r = 0.7032; P < .001) and Mg (r = 0.2719; P < .05) and injury severity score were observed. Serum Ca and Mg were significantly increased at Day 5, 7, and 9 following TE supplements. After treatment, serum C-reactive protein, IL-1β, IL-6, and tumor necrosis factor alpha were significantly reduced whereas cytokine levels of the TE supplement group were found to be lower than that of the normal treatment group after Day 3.

These findings suggest that Ca and Mg levels are associated with the injury severity of multiple fractures, and the supplement could reduce the inflammation, which may be beneficial for the bone recovery and disease process.
Genomic Landscape of Lymphatic Malformations: A Case Series and Response to the PI3Kα Inhibitor Alpelisib in an N-of-One Clinical Trial
Authors: Shaheen Montaser F. , Tse Julie Y. , Sokol Ethan S. , Masterson Margaret , Bansal Pranshu , Rabinowitz Ian , Tarleton Christy A. , Dobroff Andrey S. , Smith Tracey L. , Bocklage Thèrése J. , Mannakee Brian K. , Gutenkunst Ryan N. , Bischoff Joyce E. , Ness Scott A. , Riedlinger Gregory M. , Groisberg Roman , Pasqualini Renata , Ganesan Shridar , Arap Wadih
Published: January 2022

Background

Lymphatic malformations (LMs) often pose treatment challenges due to a large size or a critical location that could lead to disfigurement, and there are no standardized treatment approaches for either refractory or unresectable cases.

Methods

We examined the genomic landscape of a patient cohort of LMs (n=30 cases) that underwent comprehensive genomic profiling (CGP) using a large-panel next generation sequencing (NGS) assay. Immunohistochemical analyses were completed in parallel.

Results

These LMs had low mutational burden with hotspot PIK3CA mutations and NRAS mutations being most frequent, and mutually exclusive. All LM cases with Kaposi sarcoma-like (kaposiform) histology had NRAS mutations. One index patient presented with subacute abdominal pain and was diagnosed with a large retroperitoneal lymphatic malformation harboring a somatic PIK3CA gain-of-function mutation (H1047R). The patient achieved a rapid and durable complete response to the PI3Kα inhibitor alpelisib within the context of a personalized N-of-1 clinical trial (NCT03941782). In translational correlative studies, canonical PI3Kα pathway activation was confirmed by immunohistochemistry and human LM-derived lymphatic endothelial cells carrying an allele with an activating mutation at the same locus were sensitive in vitro to alpelisib in a concentration-dependent manner.

Conclusions

Our findings establish that LM patients with conventional or kaposiform histology have distinct, yet targetable, driver mutations.

Funding

R.P. and W.A. are supported by awards from the Levy-Longenbaugh Fund. S.G. is supported by awards from the Hugs for Brady Foundation. This work has been funded in part by the NCI Cancer Center Support Grants (CCSG; P30) to the University of Arizona Cancer Center (CA023074), the University of New Mexico Comprehensive Cancer Center (CA118100), and the Rutgers Cancer Institute of New Jersey (CA072720). B.K.M. was supported by National Science Foundation via Graduate Research Fellowship DGE-1143953.

Clinical trial number

NCT03941782
Reduced mesophyll conductance by cell wall thickening and chloroplasts decreasing driven the decline of photosynthesis under sole NH4+ supply
Authors: Cao Yiwen , Pan Yonghui , Liu Tianheng , Wang Min , Guo Shiwei
Published: January 2022

The relationship between nitrogen (N) sources and photosynthetic capacity of leaf differs between species. However, the leaf anatomical variabilities related to photosynthesis (A) of shrubs under different forms of N remain imperfectly known. Here, Lonicera Japonica (a shrub) was grown hydroponically in the presence of three forms of N (sole NH4+, 50%/50% NH4+/NO3− and sole NO3−). A and photosynthetic N use efficiency significantly decreased under sole NH4+ supply, in parallel with down-regulated stomatal conductance (gs), mesophyll conductance (gm), and electron transfer rate (J). Up to the total A decline of 41.28% in sole NH4+ supply (compare with sole NO3−), the gm attributed to 60.3% of the total limitations. Besides, the decreased internal air space explained the increase of gas-phase resistance, and the increased liquid-phase resistance in sole NH4+ supply was ascribed to the thicker cell wall thickness (Tcw) and decreased chloroplasts exposed surface area per unit leaf area (Sc/S). The discrepancy of Sc/S could be interpreted by the altered chloroplasts numbers and the distance between adjacent chloroplasts (Dchl-chl). These results indicate the alteration of Tcw and chloroplast numbers were the main causes of the difference in gm in coping with varied N sources.

Highlight

Cell wall and chloroplast variability determining the mesophyll conductance under different nitrogen forms
Maternal investment evolves with larger body size and higher diversification rate in sharks and rays
Authors: Mull Christopher G , Pennell Matthew W , Yopak Kara E , Dulvy Nicholas K
Published: January 2022

Across vertebrates, live-bearing has evolved at least 150 times from ancestral egg-laying into a diverse array of forms and degrees of prepartum maternal investment.1,2A key question is how this reproductive diversity arose and whether reproductive diversification underlies species diversification?3–11To test these questions, we evaluate the most basal jawed vertebrates, sharks, rays, chimaeras of Class Chondrichthyans, which have one of the greatest ranges of reproductive and ecological diversity among vertebrates.2,12We reconstructed the sequence of reproductive mode evolution across a time-calibrated molecular phylogeny of 610 chondrichthyans.13We find egg-laying is ancestral, and live-bearing evolved at least seven times. Matrotrophy (i.e. maternal contributions beyond the yolk) evolved at least 15 times, with evidence of one reversal. In sharks, transitions to live-bearing and matrotrophy are more prevalent in larger-bodied species in the tropics. Further, the evolution of live-bearing is associated with a near-doubling of the diversification rate, but, there is only a small increase in diversification associated with the appearance of matrotrophy and increased rates of speciation are associated with the colonization of novel habitats, contrary to what has been demonstrated in teleosts.3,4This highlights a potential key difference between chondrichthyans and other fishes, specifically a slower rate of reproductive isolation following speciation, suggesting different rate-limiting mechanisms for diversification between these clades.14The chondrichthyan diversification and radiation, particularly throughout the shallow tropical shelf seas and oceanic pelagic habitats, appears to be associated with the evolution of live-bearing and the proliferation of a wide range of maternal investment in developing offspring.
Genome characteristic of Bordetella parapertussis isolated from Iran
Authors: Safarchi Azadeh , Saedi Samaneh , Tay Chin Yen , Lamichhane Binit , Lotfi Masoumeh Nakhost , Shahcheraghi Fereshteh
Published: January 2022

Pertussis also known as whooping cough is a respiratory infection in humans particularly in infants and usually caused by Bordetella pertussis. However, Bordetella parapertussis can also cause a similar clinical syndrome. During 2012 to 2015, from nasal swabs sent from different provinces to the pertussis reference laboratory of Pasture Institute of Iran for pertussis confirmation, seven B. parapertussis isolates were identified by bacterial culture, biochemical tests, and the presence of IS1001 insertion in the genome by real-time PCR. Furthermore, the expression of pertactin (Prn) as one the major virulence factor for bacterial adhesion was investigated using western blot. Moreover, the genomic characteristic of one recently collected isolate, IRBP134, from a seven-month infant was investigated using Illumina NextSeq sequencing protocol. The results revealed the genome with G+C content 65% and genome size 4.7 Mbp. A total of 81 single nucleotide polymorphisms (SNPs) and 13 short insertion and deletions were found in the genome compared to the B. parapertussis 12822 as a reference genome showing ongoing evolutionary changes in our isolate. A phylogeny relationship of IRBP134 was also investigated using global B. parapertussis available genomes.
Age-Related Impairment of Innate and Adaptive Immune Responses Following Intranasal Herpes Simplex Infection
Authors: Srivastava Ruchi , Agrawal Anshu , Vahed Hawa , BenMohamed Lbachir
Published: January 2022

Immune function declines with age, leading to an increased vulnerability to respiratory viral infections. The mechanisms by which aging negatively impacts the innate and adaptive immune system leading to enhanced susceptibility to infections remain to be fully elucidated. In the present study, we used a mouse model of intranasal infection with herpes simplex virus type 1 (HSV-1), a virus that can enter the lungs through the nasal route causing pneumonia, a serious health concern in the elderly. Following intranasal inoculation of young (6 weeks), adult (36 weeks), and aged (68 weeks) with HSV-1 (KOS strain) we: (i) compared the local and systemic innate and adaptive immune response to infection; and (ii) correlated the level and type of immune response to protection against HSV-1 infection. Compared to young and adult mice, aged mice displayed: (i) increased basal level activation of epithelial cells with a decreased expression of TLR3; (ii) increased activation of dendritic cells with increased expression of MHC-1, MHC-II and CD80/86; and (iii) decreased production of type-I interferons upon stimulation; (iv) a delay in cytokines and chemokines production in the lungs; and (v) an impairment in function (CD107 and IFN-γ production) of HSV-specific CD8+T cells. These impairment in innate and adaptive immune responses in aged mice following intranasal HSV-1 inoculation was associated with symptomatic herpes infection. The findings suggest an age-related impairment of both innate and adaptive immune responses which may exacerbate herpes infection and disease in the elderly.

IMPORTANCE

Immune function declines with age, leading to an increased vulnerability of the elderly to respiratory viral infections. The mechanisms by which aging negatively impacts the innate and adaptive immune system leading to enhanced susceptibility to respiratory infections remain to be fully elucidated. The present study showed that, compared to young and adult mice, aged mice displayed increased basal level activation of epithelial cells with a decreased expression of TLR3 increased activation of dendritic cells associated with an impairment of HSV-specific CD8+T cell responses. These immune dysregulations were associated with to symptomatic herpes infection. The findings suggest an age-related impairment of both innate and adaptive immune responses which may exacerbate herpes infection and disease in the elderly.
Hantaan virus replication is promoted via AKT activated mitochondria OXPHOS
Authors: Dong Yuhang , Zhang Xiaoxiao , Li Mengyang , Ying Qikang , Feng Yunan , Li Zhoupeng , Wu Xingan , Wang Fang
Published: January 2022

Oxidative phosphorylation (OXPHOS) is a vital pathway provides ATP for intracellular activities. Here, we found that Hantaan virus (HTNV) exploited mitochondria OXPHOS to assist its replication in host cells and Protein Kinase B/AKT played a major function in this process. Inhibiting AKT activation by BEZ treatment can inhibit HTNV replication and prevent the increase of OXPHOS level caused by HTNV infection. We also found that HTNV infection can promote AKT translocation to mitochondria, where AKT phosphorylates Polynucleotide phosphorylase (PNPT). Taken together, our research demonstrates that HTNV replication exploits OXPHOS in host cells and it increases OXPHOS function by AKT-PNPT interaction in mitochondria.

IMPORTANCE

Virus depends on metabolic pathways in host cells to favor its replication. This is a vital process which needs complicated host-virus interaction and targeting this process is a new strategy for antiviral drug development. Hantaan virus (HTNV) is the major pathogen which causes Hemorrhagic Fever with Renal Syndrome (HFRS) in China. However, there are neither effective therapeutic drugs nor FDA-licensed vaccine against HFRS, a deeper understanding of HTNV infection characteristics is of great significance for global public health and safety. This research means to elucidate the major metabolic pathway exploited by HTNV during its replication in host cells and its underlying molecular mechanism, which can enrich our understanding about HTNV biological characteristics and pathogenesis, also provide a new view on anti-HTNV drug development.
Innate immune responses in patients treated with SBRT irradiation enhances prostate cancer remissions
Authors: Cheema Amrita K , Li Yaoxiang , Collins Sean , Suy Simeng , Ventimiglia Mary , Kowalczyk Keith , Hankins Ryan , Lynch John , Janowski Einsley-Marie , Grindrod Scott , Villagra Alejandro , Dritschilo Anatoly
Published: January 2022

Stereotactic body radiation therapy (SBRT) is a curative therapeutic modality employing large fractional doses of highly conformal radiation therapy for cancer treatment. To understand the mechanisms underlying clinical responses to radiation therapy, SBRT offers a unique window for high-throughput analysis of post-radiation molecular events to inform predictive biomarker discovery and strategies for multi-disciplinary therapeutics. We performed longitudinal analysis of plasma proteins and metabolites from patients treated with prostate SBRT, comparing cohorts of patients in clinical remission to cohorts experiencing PSA-determined cancer progression. We observed onset of post-SBRT DNA Damage Response (DDR), cell cycle arrest, and immune response signaling in patients within one hour of treatment and innate immune response signaling that persisted for up to three months following treatment. Furthermore, patients in remission experienced more robust immune responses and metabolite elevations consistent with a pro-inflammatory, M1-mediated innate immune activation in the short-term following SBRT, whereas patients with disease progression had less robust immune responses and M2-mediated metabolite elevations. We interpret these data to support a critical role for innate immune activation in the clinical outcomes of patients receiving radiation therapy for prostate cancer potentially improving future multidisciplinary therapeutic strategies.

One Sentence Summary

Following SBRT, proteomic and metabolomic profiles reveal a robust immune activation that correlates with prostate cancer remission