bluuebunny/crossref_metadata_2025 huggingface dataset:
Achieving More Rapid Door-to-Needle Times and Improved Outcomes in Acute Ischemic Stroke in a Nationwide Quality Improvement Intervention
Authors: Xian Ying , Xu Haolin , Smith Eric E. , Saver Jeffrey L. , Reeves Mathew J. , Bhatt Deepak L. , Hernandez Adrian F. , Peterson Eric D. , Schwamm Lee H. , Fonarow Gregg C.
Published: November 2021

Background:

The benefits of tPA (tissue-type plasminogen activator) in acute ischemic stroke are time-dependent. However, delivery of thrombolytic therapy rapidly after hospital arrival was initially occurring infrequently in hospitals in the United States, discrepant with national guidelines.

Methods:

We evaluated door-to-needle (DTN) times and clinical outcomes among patients with acute ischemic stroke receiving tPA before and after initiation of 2 successive nationwide quality improvement initiatives: Target: Stroke Phase I (2010–2013) and Target: Stroke Phase II (2014–2018) from 913 Get With The Guidelines-Stroke hospitals in the United States between April 2003 and September 2018.

Results:

Among 154 221 patients receiving tPA within 3 hours of stroke symptom onset (median age 72 years, 50.1% female), median DTN times decreased from 78 minutes (interquartile range, 60–98) preintervention, to 66 minutes (51–87) during Phase I, and 50 minutes (37–66) during Phase II (
P
<0.001). Proportions of patients with DTN ≤60 minutes increased from 26.4% to 42.7% to 68.6% (
P
<0.001). Proportions of patients with DTN ≤45 minutes increased from 10.1% to 17.7% to 41.4% (
P
<0.001). By the end of the second intervention, 75.4% and 51.7% patients achieved 60-minute and 45-minute DTN goals. Compared with the preintervention period, hospitals during the second intervention period (2014–2018) achieved higher rates of tPA use (11.7% versus 5.6%; adjusted odds ratio, 2.43 [95% CI, 2.31–2.56]), lower in-hospital mortality (6.0% versus 10.0%; adjusted odds ratio, 0.69 [0.64–0.73]), fewer bleeding complication (3.4% versus 5.5%; adjusted odds ratio, 0.68 [0.62–0.74]), and higher rates of discharge to home (49.6% versus 35.7%; adjusted odds ratio, 1.43 [1.38–1.50]). Similar findings were found in sensitivity analyses of 185 501 patients receiving tPA within 4.5 hours of symptom onset.

Conclusions:

A nationwide quality improvement program for acute ischemic stroke was associated with substantial improvement in the timeliness of thrombolytic therapy start, increased thrombolytic treatment, and improved clinical outcomes.
Coming to the Rescue: Regulatory T Cells for Promoting Recovery After Ischemic Stroke
Authors: Zhang Yueman , Liesz Arthur , Li Peiying
Published: November 2021

Immune cell infiltration to the injured brain is a key component of the neuroinflammatory response after ischemic stroke. In contrast to the large amount of proinflammatory immune cells, regulatory T cells, are an important subgroup of T cells that are involved in maintaining immune homeostasis and suppress an overshooting immune reaction after stroke. Numerous previous reports have consistently demonstrated the beneficial role of this immunosuppressive immune cell population during the acute phase after experimental stroke by limiting inflammatory lesion progression. Two recent studies expanded now this concept and demonstrate that regulatory T cells-mediated effects also promote chronic recovery after stroke by promoting a proregenerative tissue environment. These recent findings suggest that boosting regulatory T cells could be beneficial beyond modulating the immediate neuroinflammatory response and improve chronic functional recovery.
Detecting Vicious Cycles in Urban Problem Knowledge Graph using
Inference Rules
Authors: Egami Shusaku , Kawamura Takahiro , Kozaki Kouji , Ohsuga Akihiko
Published: November 2021

Urban areas have many problems, including homelessness, graffiti, and littering. These problems are influenced by various factors and are linked to each other; thus, an understanding of the problem structure is required in order to detect and solve the root problems that generate vicious cycles. Moreover, before implementing action plans to solve these problems, local governments need to estimate cost-effectiveness when the plans are carried out. Therefore, this paper proposed constructing an urban problem knowledge graph that would include urban problems' causality and the related cost information in budget sheets. In addition, this paper proposed a method for detecting vicious cycles of urban problems using SPARQL queries with inference rules from the knowledge graph. Finally, several root problems that led to vicious cycles were detected. Urban-problem experts evaluated the extracted causal relations.
A replacement name for the genus-group name NannaBirket-Smith, 1965 (Erebidae: Arctiinae: Syntomini)
Authors: DE PRINS WILLY
Published: November 2021

In the fly family Scathophagidae (Diptera), the genus Nanna Strobl, 1894 was introduced as “(D. Nanna Becker) flavipes Fall. Zett. 2059, 6332, SS.11! Becker!” (Strobl 1894: 78), with Cordylura flavipes Fallén, 1819 as its type species. See Michelsen (2001: 323–326) for correct authorship and validity of the name Nanna Strobl, 1894 as senior synonym of names proposed by Becker (1894) in the same year.
Accurate Absolute Measurements of Liquid Water Content (LWC) and Ice Water Content (IWC) of Clouds and Precipitation with Spectrometric Water Raman Lidar
Authors: Reichardt Jens , Knist Christine , Kouremeti Natalia , Kitchin William , Plakhotnik Taras
Published: November 2021

A detailed description is given of how the liquid water content (LWC) and the ice water content (IWC) can be determined accurately and absolutely from the measured water Raman spectra of clouds. All instrumental and spectroscopic parameters that affect the accuracy of the water-content measurement are discussed and quantified; specifically, these are the effective absolute differential Raman backscattering cross section of water vapor , and the molecular Raman backscattering efficiencies ηliq and ηice of liquid and frozen microparticles, respectively. The latter two are determined following rigorous theoretical approaches combined with Raman Lidar for Atmospheric Moisture Sensing (RAMSES) measurements. For ηice, this includes a new experimental method that assumes continuity of the number of water molecules across the vertical extent of the melting layer. Examples of water-content measurements are presented, including supercooled liquid-water clouds and melting layers. Error sources are discussed; one effect that stands out is interfering fluorescence by aerosols. Aerosol effects and calibration issues are the main reasons why spectral Raman measurements are required for quantitative measurements of LWC and IWC. The presented study lays the foundation for cloud microphysical investigations and for the evaluation of cloud models or the cloud data products of other instruments. As a first application, IWC retrieval methods are evaluated that are based on either lidar extinction or radar reflectivity measurements. While the lidar-based retrievals show unsatisfactory agreement with the RAMSES IWC measurements, the radar-based IWC retrieval which is used in the Cloudnet project performs reasonably well. On average, retrieved IWC agrees within 20% to 30% (dry bias) with measured IWC.
The Long-Term Value of Networking and Diverse Professional Experience in Online Communication Master’s Cohorts: Strategic Benefits of a Closed-Cohort Structure
Authors: Pendleton Shanetta M. , Gibson Rhonda
Published: November 2021

A survey of alumni from a 10-year-old cohort-based online master’s program in digital communication showed that respondents felt high levels of sense of community both during the program and after graduation. Respondents reported using Facebook and email to interact with members of their cohorts, and other cohorts, and highly valued the ability to network with industry professionals with a diversity of communication experience. However, respondents felt the need for more identity-based diversity among cohort members.
Deporting EU national offenders from the UK after Brexit: Moving from a system that recognises individuals, to one that sees only offenders
Authors: Collinson Jonathan
Published: November 2021

Deportation is a core state practice for the management and control of time-served foreign national offenders. Post-Brexit law changes mean that EU national offenders in the UK will become subject to the same deportation rules which apply to non-EU national offenders. This article argues that the law that applied to EU national offenders before Brexit, derived from the EU’s Citizens’ Rights Directive, was underpinned by a focus on the offender as an individual person. In contrast, UK deportation law that applies to third-country nationals, and to EU nationals after Brexit, sees only the label of ‘offender’. This argument is made by examining two important elements of the contrasting deportation laws: the permitted justifications for deportation and the importance of rehabilitation. On permitted justifications for deportation, the Citizens’ Rights Directive requires individualised rationales for deportation and prohibits justifications based solely on the fact of past offending. This future-orientation also encouraged UK courts to focus on the foreign national offender as an individual who is capable of rehabilitation and reform, whereas the UK’s post-Brexit rules justify deportation on the basis of the status of offender: a status that is determined by prior conviction, is hard to lose and makes limited space for considering the potential for rehabilitation.
Scleroderma renal crisis in a patient with paraneoplastic systemic sclerosis
Authors: Frediani Marcella M , Mattedi Francisco Z , Cavalcante Livia B , Costa e Silva Verônica T , Caires Renato A , Burdmann Emmanuel A , Costalonga Elerson C
Published: November 2021

The incidence of malignancy is increased in systemic sclerosis (SS). Nevertheless, only a few cases of paraneoplastic SS (pSS) have been described. Scleroderma renal crisis is an uncommon but severe complication of SS, with acute kidney failure, abrupt onset of hypertension and microangiopathy. We present the case of a previously healthy patient who was diagnosed with ovarian carcinoma and underwent chemotherapy with carboplatin and paclitaxel. In association with the cancer, she developed SS and scleroderma renal crisis. She received initial supportive treatment, but her renal function worsened, and she started on hemodialysis. Furthermore, she received adjuvant surgical treatment for the cancer. Eighty-four days after cytoreductive surgery, her renal function recovered, and her SS manifestations improved.
Morbidities and mortality in patients with hereditary thrombotic thrombocytopenic purpura
Authors: Borogovac Azra , Reese Jessica A. , Gupta Samiksha , George James N.
Published: November 2021

Hereditary thrombotic thrombocytopenic purpura (hTTP) is a rare disorder caused by severe ADAMTS13 deficiency. Major morbidities and death at a young age are common. Although replacement of ADAMTS13 can prevent morbidities and death, current regimens of plasma prophylaxis are insufficient. We identified 226 patients with hTTP in 96 reports published from 2001 through 2020. Age at diagnosis was reported for 202 patients; 117 were female and 85 were male. The difference was caused by diagnosis of 34 women during pregnancy, suggesting that many men and nulliparous women are not diagnosed. Eighty-three patients had severe jaundice at birth; hTTP was suspected and effectively treated in only 3 infants. Of the 217 patients who survived infancy, 73 (34%) had major morbidities defined as stroke, kidney injury, or cardiac injury that occurred at a median age of 21 years. Sixty-two patients had stroke; 13 strokes occurred in children age 10 years or younger. Of the 54 patients who survived their initial major morbidity and were subsequently observed, 37 (69%) had sustained or subsequent major morbidities. Of the 39 patients who were observed after age 40 years, 20 (51%) had experienced a major morbidity. Compared with an age- and sex-matched US population, probability of survival was lower at all ages beginning at birth. Prophylaxis was initiated in 45 patients with a major morbidity; in 11 (28%), a major morbidity recurred after prophylaxis had begun. Increased recognition of hTTP and more effective prophylaxis started at a younger age are required to improve health outcomes.
Impact of enhanced recovery after surgery protocol compliance on patients’ outcome in benign hysterectomy and establishment of a predictive nomogram model
Authors: Shen Yiwei , Lv Feng , Min Su , Wu Gangming , Jin Juying , Gong Yao , Yu Jian , Qin Peipei , Zhang Ying
Published: November 2021

Background

Enhanced recovery after surgery (ERAS) pathways have been shown to improve clinical outcomes after surgery. Considering the importance of patient experience for patients with benign surgery, this study evaluated whether improved compliance with ERAS protocol modified for gynecological surgery which recommended by the ERAS Society is associated with better clinical outcomes and patient experience, and to determine the influence of compliance with each ERAS element on patients’ outcome after benign hysterectomy.

Methods

A prospective observational study was performed on the women who underwent hysterectomy between 2019 and 2020. A total of 475 women greater 18 years old were classified into three groups according to their per cent compliance with ERAS protocols: Group I: < 60% (148 cases); Group II:≥60 and < 80% (160 cases); Group III: ≥80% (167 cases). Primary outcome was the 30-day postoperative complications. Second outcomes included QoR-15 questionnaire scores, patient satisfaction on a scale from 1 to 7, and length of stay after operation. After multivariable binary logistic regression analyse, a nomogram model was established to predict the incidence of having a postoperative complication with individual ERAS element compliance.

Results

The study enrolled 585 patients, and 475 completed the follow-up assessment. Patients with compliance over 80% had a significant reduction in postoperative complications (20.4% vs 41.2% vs 38.1%, P < 0.001) and length of stay after surgery (4 vs 5 vs 4, P < 0.001). Increased compliance was also associated with higher patient satisfaction and QoR-15 scores (P < 0.001),. Among the five dimensions of the QoR-15, physical comfort (P < 0.05), physical independence (P < 0.05), and pain dimension (P < 0.05) were better in the higher compliance groups. Minimally invasive surgery (MIS) (P < 0.001), postoperative nausea and vomiting (PONV) prophylaxis (P < 0.001), early mobilization (P = 0.031), early oral nutrition (P = 0.012), and early removal of urinary drainage (P < 0.001) were significantly associated with less complications. Having a postoperative complication was better predicted by the proposed nomogram model with high AUC value (0.906) and sensitivity (0.948) in the cohort.

Conclusions

Improved compliance with the ERAS protocol was associated with improved recovery and better patient experience undergoing hysterectomy. MIS, PONV prophylaxis, early mobilization, early oral intake, and early removal of urinary drainage were of concern in reducing postoperative complications.

Trial registration

Chinese Clinical Trial Registry, ChiCTR1800019178. Registered on 30/10/2018.
The receipt of information by family physicians about their patient’s emergency department visits: a record linkage study of electronic medical records to health administrative data
Authors: Jaakkimainen Liisa , Chung Hannah , Lu Hong , Pinzaru Bogdan , Candido Elisa
Published: November 2021

Background

Canadians are known to be frequent users of emergency department (ED) care. However, the exchange of information from ED visits to family physicians (FPs) is not well known. Our objectives were to determine whether Canadian FPs received information about their patient’s ED visit and the patient characteristics related to the receipt of ED information.

Methods

This study was a descriptive record linkage study of FP Electronic Medical Record (EMR) data linked to health administrative data. Our study cohort included patients who had at least one ED visit in 2010 or 2015 in Ontario, Canada. An ED visit could include a transfer to or from another ED. The receipt of information from an ED note was examined in relation to patient age, sex, neighbourhood income quintiles, rurality and comorbidity.

Results

There were 26,609 patients in 2010 and 50,541 patients in 2015 with at least one ED visit. In 2010, 53.3% of FPs received an ED note for patients having a single ED visit compared to 41.0% in 2015. For patients with multiple ED visits, 58.2% of FPs received an ED note in 2010 compared to 45.7% in 2015. FPs were more likely to receive an ED note for patients not living in low income neighbourhoods, older patients, patients living in small urban areas and for patients having moderate comorbidity. FPs were less likely to receive a note for patients living in rural areas.

Conclusions

Community-based FPs are more likely to get information after an ED visit for their older and sicker patients. However, FPs do not receive any information from EDs for over half their patients. Electronic health record technologies and their adoption by ED providers need to improve the seamless transfer of information about the care provided in EDs to FPs in the community.
Diagnosis of orthostatic tremor using smartphone accelerometry
Authors: Calvo Nicholas E. , Ferrara Joseph M.
Published: November 2021

Background

Primary orthostatic tremor (OT) is a rare movement disorder characterized by a 13–18 Hz leg tremor, which arises when standing and is relieved by walking/sitting. Those affected generally do not fall, but experience fear of falling, lessened by ambulation. Because of its low amplitude, the tremor is not readily visible, and diagnosis requires confirmation with surface electromyography (sEMG). Recently, applications using the accelerometer feature of smartphones have been used to detect and quantify tremors, including OT, though the accuracy of smartphone accelerometry (SPA) in diagnosing OT is unknown.

Methods

We completed SPA in consecutive adults (18+ years), who presented to our neurology clinic with either subjective leg shakiness upon standing or unsteadiness when standing that lessened with ambulation, which comprised 59 of 2578 patients. We assessed tremor using the StudyMyTremor application on an iPhone 6 s adhered with tape to the patient’s tibialis anterior. Surface electromyography was completed on the same muscle. The primary outcome of this study was to determine SPA’s sensitivity and specificity in detecting OT compared with surface electromyography.

Results

Fifty-nine patients with the following diagnoses were included: OT (6), Parkinson’s disease, Hereditary Spastic Paraplegia, orthostatic hypotension, essential tremor, spinal cerebellar ataxia, sensory ataxia and functional movement disorder. Smartphone accelerometry detected a 13–18 Hz tremor in 5 of 6 patients diagnosed with OT by sEMG with no false positives in other conditions, yielding a sensitivity of 83%, specificity of 100% in the cohort we studied.

Conclusions

Though a larger sample size is desirable, preliminary data suggest that smartphone accelerometry is an alternative to surface electromyography in diagnosing OT.
Nomogram based on autophagy related genes for predicting the survival in melanoma
Authors: Deng Guangtong , Wang Wenhua , Li Yayun , Sun Huiyan , Chen Xiang , Zeng Furong
Published: November 2021

Background

Autophagy, a highly conserved lysosomal degradation pathway, is associated with the prognosis of melanoma. However, prognostic prediction models based on autophagy related genes (ARGs) have never been recognized in melanoma. In the present study, we aimed to establish a novel nomogram to predict the prognosis of melanoma based on ARGs signature and clinical parameters.

Methods

Data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases were extracted to identify the differentially expressed ARGs. Univariate, least absolute shrinkage and selection operator (LASSO) and multivariate analysis were used to select the prognostic ARGs. ARGs signature, age and stage were then enrolled to establish a nomogram to predict the survival probabilities of melanoma. The nomogram was evaluated by concordance index (C-index), receiver operating characteristic (ROC) curve and calibration curve. Decision curve analysis (DCA) was performed to assess the clinical benefits of the nomogram and TNM stage model. The nomogram was validated in GEO cohorts.

Results

Five prognostic ARGs were selected to construct ARGs signature model and validated in the GEO cohort. Kaplan-Meier survival analysis suggested that patients in high-risk group had significantly worse overall survival than those in low-risk group in TCGA cohort (P = 5.859 × 10–9) and GEO cohort (P = 3.075 × 10–9). We then established and validated a novel promising prognostic nomogram through combining ARGs signature and clinical parameters. The C-index of the nomogram was 0.717 in TCGA training cohort and 0.738 in GEO validation cohort. TCGA/GEO-based ROC curve and decision curve analysis (DCA) demonstrated that the nomogram was better than traditional TNM staging system for melanoma prognosis.

Conclusion

We firstly developed and validated an ARGs signature based-nomogram for individualized prognosis prediction in melanoma patients, which could assist with decision making for clinicians.
What protects us against the COVID-19 threat? Cultural tightness matters
Authors: Dong Dan , Chen Zhipeng , Zong Min , Zhang Peng , Gu Wen , Feng Yi , Qiao Zhihong
Published: November 2021

Background

The only previous studies that formulated a theoretical model of epidemics for psychological response relative to cultural perspectives have focused on the role of individualism–collectivism and have omitted analysis of tightness–looseness. This study explored the role of cultural tightness in relation to psychological disorders during the outbreak of the COVID-19 pandemic.

Methods

We recruited 1827 Chinese adolescents (Mage = 18.16 ± 2.23 years, 53.3% female) to participate a cross-sectional survey. Participants completed a series of questionnaires, including the scales of cultural tightness, risk perception of COVID-19 pandemic, perceived protection efficacy, anxiety and depression. A latent moderated structural equations model was used to analyse the mediating and moderating effects of risk perception regarding COVID-19, cultural tightness and perceived protection efficacy on psychological disorders.

Results

The results showed that greater risk perception of COVID-19 predicted greater psychological disorders, however cultural tightness moderated this positive relationship. The increase in psychological disorders with risk perception regarding COVID-19 was less pronounced among people who lived in tighter cultural areas. In addition, this moderating effect of cultural tightness was further mediated by perceived protection efficacy; that is, tight culture protects against psychological disorders by enhancing perceived protection efficacy.

Conclusion

This study enriched the theoretical framework of cultural tightness and indicated its importance in the field of mental health and health policies. It also emphasized the importance of tight culture as a protective factor against psychological disorders in case of COVID-19 outbreaks, providing valuable practical insight into psychological prevention for COVID-19 outbreaks.
m6A regulator expression profile predicts the prognosis, benefit of adjuvant chemotherapy, and response to anti-PD-1 immunotherapy in patients with small-cell lung cancer
Authors: Zhang Zhihui , Zhang Chaoqi , Luo Yuejun , Wu Peng , Zhang Guochao , Zeng Qingpeng , Wang Lide , Yang Zhaoyang , Xue Liyan , Zheng Bo , Zeng Hua , Tan Fengwei , Xue Qi , Gao Shugeng , Sun Nan , He Jie
Published: November 2021

Background

Small cell lung cancer (SCLC) is lethal and possesses limited therapeutic options. Platinum-based chemotherapy—with or without immune checkpoint inhibitors (anti-PDs)—is the current first-line therapy for SCLCs; however, its associated outcomes are heterogeneous. N6-methyladenosine (m6A) is a novel and decisive factor in tumour progression, chemotherapy resistance, and immunotherapy response. However, m6A modification in SCLC remains poorly understood.

Methods

We systematically explored the molecular features and clinical significance of m6A regulators in SCLC. We then constructed an m6A regulator-based prognostic signature (m6A score) based on our examination of 256 cases with limited-stage SCLC (LS-SCLC) from three different cohorts—including an independent cohort that contained 150 cases with qPCR data. We additionally evaluated the relationships between the m6A score and adjuvant chemotherapy (ACT) benefits and the patients’ responses to anti-PD-1 treatment. Immunohistochemical (IHC) staining and the HALO digital pathological platform were used to calculate CD8+ T cell density.

Results

We observed abnormal somatic mutations and expressions of m6A regulators. Using the LASSO Cox model, a five-regulator-based (G3BP1, METTL5, ALKBH5, IGF2BP3, and RBM15B) m6A score was generated from the significant regulators to classify patients into high- and low-score groups. In the training cohort, patients with high scores had shorter overall survival (HR, 5.19; 2.75–9.77; P < 0.001). The prognostic accuracy of the m6A score was well validated in two independent cohorts (HR 4.6, P = 0.006 and HR 3.07, P < 0.001). Time-dependent ROC and C-index analyses found the m6A score to possess superior predictive power than other clinicopathological parameters. A multicentre multivariate analysis revealed the m6A score to be an independent prognostic indicator. Additionally, patients with low scores received a greater survival benefit from ACT, exhibited more CD8+ T cell infiltration, and were more responsive to cancer immunotherapy.

Conclusions

Our results, for the first time, affirm the significance of m6A regulators in LS-SCLC. Our multicentre analysis found that the m6A score was a reliable prognostic tool for guiding chemotherapy and immunotherapy selections for patients with SCLC.
Macrophage-biomimetic porous Se@SiO2 nanocomposites for dual modal immunotherapy against inflammatory osteolysis
Authors: Ding Cheng , Yang Chuang , Cheng Tao , Wang Xingyan , Wang Qiaojie , He Renke , Sang Shang , Zhu Kechao , Xu Dongdong , Wang Jiaxing , Liu Xijian , Zhang Xianlong
Published: November 2021

Background

Inflammatory osteolysis, a major complication of total joint replacement surgery, can cause prosthesis failure and necessitate revision surgery. Macrophages are key effector immune cells in inflammatory responses, but excessive M1-polarization of dysfunctional macrophages leads to the secretion of proinflammatory cytokines and severe loss of bone tissue. Here, we report the development of macrophage-biomimetic porous SiO2-coated ultrasmall Se particles (porous Se@SiO2 nanospheres) to manage inflammatory osteolysis.

Results

Macrophage membrane-coated porous Se@SiO2 nanospheres(M-Se@SiO2) attenuated lipopolysaccharide (LPS)-induced inflammatory osteolysis via a dual-immunomodulatory effect. As macrophage membrane decoys, these nanoparticles reduced endotoxin levels and neutralized proinflammatory cytokines. Moreover, the release of Se could induce macrophage polarization toward the anti-inflammatory M2-phenotype. These effects were mediated via the inhibition of p65, p38, and extracellular signal-regulated kinase (ERK) signaling. Additionally, the immune environment created by M-Se@SiO2 reduced the inhibition of osteogenic differentiation caused by proinflammation cytokines, as confirmed through in vitro and in vivo experiments.

Conclusion

Our findings suggest that M-Se@SiO2 have an immunomodulatory role in LPS-induced inflammation and bone remodeling, which demonstrates that M-Se@SiO2 are a promising engineered nanoplatform for the treatment of osteolysis occurring after arthroplasty.

Graphical Abstract
The health risks of dysphagia for patients with head and neck cancer: a multicentre prospective observational study
Authors: Cristofaro Maria Giulia , Barca Ida , Ferragina Francesco , Novembre Daniela , Ferro Yvelise , Pujia Roberta , Montalcini Tiziana
Published: November 2021

It is well known that malnutrition is a frequent co-morbidity in cancer patients, especially in those with head and neck neoplasms. This may be due both to the presence of dysphagia symptoms and to the appearance of adverse effects on chemotherapy and / or radiotherapy. The aim of this retrospective observational multicentric study is to evaluate the nutritional status between dysphagia cancer patients and non-dysphagia cancer patients. Data from 60 patients were analysed, 31 of which without dysphagia and 29 with dysphagia. Results highlight that patients with dysphagia had higher involuntary body weight loss than non-dysphagia ones (p < 0.001). By analysing the entire population, it stands out a weight loss rate of 12 ± 9% compared to the usual weight was observed and a prevalence of moderate / severe malnutrition diagnosis of 53%. Furthermore, 76% of the population who manifested the symptom of dysphagia presented severe malnutrition already at the first visit, compared to 32% of non-dysphagia subjects.
Evaluation of the therapeutic regimen in COVID-19 in transplant patients: where do immunomodulatory and antivirals stand?
Authors: Shafiekhani Mojtaba , Shahabinezhad Farbod , Niknam Tahmoores , Tara Seyed Ahmad , Haem Elham , Mardani Parviz , Zare Zahra , Jafarian Sedigheh , Mirzad Jahromi Khatereh , Arabsheybani Sara , Moeini Yalda Sadat , Alavi Jalile , Jalali Seyed Soroush , Salimi Maryam , Shahriarirad Reza , Malekhosseini Seyed Ali
Published: November 2021

Background

The management of COVID-19 in organ transplant recipients is among the most imperative, yet less discussed, issues based on their immunocompromised status along with their vast post-transplant medication regimens. No conclusive study has been published to evaluate proper anti-viral and immunomodulator medications effect in treating COVID-19 patients to this date.

Method

This retrospective study was conducted in Shiraz Transplant Hospital, Iran from March 2020 to May 2021 and included COVID-19 diagnosed patients based on SARS-CoV-2 RT-PCR positive test who had been hospitalized for at least 48 h before enrolling in the study. Clinical and demographic information of patients, along with their treatment course and the medication used were evaluated and analyzed using multiple regression analysis.

Results

A total of 245 patients with a mean age of 49.59 years were included with a mortality rate of 8.16%. The administration of Remdesivir as an anti-viral drug (P value < 0.001) and Tocilizumab as an immunomodulator drug (P value < 0.001) could reduce the hospitalization period in the hospital and the intensive care unit, as well as the mortality rates significantly. Meanwhile, the patients treated with Lopinavir/Ritonavir experienced a lower chance of survival (OR < 1, P value = 0.04). No significant difference was observed between various therapeutic regimens in clinical complications such as bacterial coinfections, cardiovascular and gastrointestinal adverse reactions, and liver or kidney dysfunctions.

Conclusion

The administration of Remdesivir as an anti-viral and Tocilizumab as an immunomodulatory drug in solid-organ transplant
recipients could be promising treatments of choice to manage COVID-19.
Physical exercise and goal attainment after shunt surgery in idiopathic normal pressure hydrocephalus: a randomised clinical trial
Authors: Rydja Johanna , Kollén Lena , Hellström Per , Owen Katarina , Lundgren Nilsson Åsa , Wikkelsø Carsten , Tullberg Mats , Lundin Fredrik
Published: November 2021

Background

Rehabilitation in iNPH is suggested to be an important factor to improve patients’ functions but there are lack of clinical trials evaluating the effect of rehabilitation interventions after shunt surgery in iNPH. The objective of this study was to evaluate the effect of a physical exercise programme and goal attainment for patients with idiopathic normal pressure hydrocephalus (iNPH) after surgery compared to a control group.

Methods

This was a dual centre randomised controlled trial with assessor blinding, intention-to-treat (ITT) and per protocol (PP) analysis. Individuals diagnosed with iNPH scheduled to undergo shunt surgery at the Linköping University Hospital in Linköping and Sahlgrenska University Hospital in Gothenburg, Sweden were consecutively eligible for inclusion. Inclusion was conducted between January 2016 and June 2018. The patients were randomised 1:1 using sequentially numbered sealed envelopes to receive either written exercise information (control group) or written information and an additional supervised high-intensity, functional exercise programme (HIFE) executed twice weekly over 12 weeks (exercise group). Preoperatively, the patients set individual goals. The primary outcome was change from baseline in the total iNPH scale score at the post-intervention follow-up. Secondary outcomes were goal attainment, and change in the separate scores of gait, balance, neuropsychology and continence and in the total score after 6 months.

Results

In total, 127 participants were randomised to the exercise group (n = 62) and to the control group (n = 65). In the ITT population (exercise group, n = 50; control group, n = 59), there were no between-group differences in the primary outcome, but the attrition rate in the exercise group was high. The exercise group improved more than the control group in the balance domain scores after 6 months. Post-intervention, the PP exercise population achieved their set goals to a greater extent than the controls.

Conclusions

An additional effect of the 12-week HIFE-programme on the overall improvement according to the iNPH-scale after shunt surgery in iNPH was not shown. This could be due to high attrition rate. However, the long-term effect on balance and higher goal achievement indicate beneficial influences of supervised physical exercise.

Trial registrationclinicaltrials.gov, NCT02659111. Registered 20 January 2016,https://clinicaltrials.gov/ct2/show/NCT02659111
Compositional and structural analysis of engineered stones and inorganic particles in silicotic nodules of exposed workers
Authors: León-Jiménez Antonio , Mánuel José M. , García-Rojo Marcial , Pintado-Herrera Marina G. , López-López José Antonio , Hidalgo-Molina Antonio , García Rafael , Muriel-Cueto Pedro , Maira-González Nieves , Del Castillo-Otero Daniel , Morales Francisco M.
Published: November 2021

Background

Engineered stone silicosis is an emerging disease in many countries worldwide produced by the inhalation of respirable dust of engineered stone. This silicosis has a high incidence among young workers, with a short latency period and greater aggressiveness than silicosis caused by natural materials. Although the silica content is very high and this is the key factor, it has been postulated that other constituents in engineered stones can influence the aggressiveness of the disease. Different samples of engineered stone countertops (fabricated by workers during the years prior to their diagnoses), as well as seven lung samples from exposed patients, were analyzed by multiple techniques.

Results

The different countertops were composed of SiO2 in percentages between 87.9 and 99.6%, with variable relationships of quartz and cristobalite depending on the sample. The most abundant metals were Al, Na, Fe, Ca and Ti. The most frequent volatile organic compounds were styrene, toluene and m-xylene, and among the polycyclic aromatic hydrocarbons, phenanthrene and naphthalene were detected in all samples. Patients were all males, between 26 and 46 years-old (average age: 36) at the moment of the diagnosis. They were exposed to the engineered stone an average time of 14 years. At diagnosis, only one patient had progressive massive fibrosis. After a follow-up period of 8 ± 3 years, four patients presented progressive massive fibrosis. Samples obtained from lung biopsies most frequently showed well or ill-defined nodules, composed of histiocytic cells and fibroblasts without central hyalinization. All tissue samples showed high proportion of Si and Al at the center of the nodules, becoming sparser at the periphery. Al to Si content ratios turned out to be higher than 1 in two of the studied cases. Correlation between Si and Al was very high (r = 0.93).

Conclusion

Some of the volatile organic compounds, polycyclic aromatic hydrocarbons and metals detected in the studied countertop samples have been described as causative of lung inflammation and respiratory disease. Among inorganic constituents, aluminum has been a relevant component within the silicotic nodule, reaching atomic concentrations even higher than silicon in some cases. Such concentrations, both for silicon and aluminum showed a decreasing tendency from the center of the nodule towards its frontier.
A clinical predictive model for risk stratification of patients with severe acute lower gastrointestinal bleeding
Authors: Singh Manraj , Chiang Jayne , Seah Andre , Liu Nan , Mathew Ronnie , Mathur Sachin
Published: November 2021

Background

Lower gastrointestinal bleeding (LGIB) is a common presentation of surgical admissions, imposing a significant burden on healthcare costs and resources. There is a paucity of standardised clinical predictive tools available for the initial assessment and risk stratification of patients with LGIB. We propose a simple clinical scoring model to prognosticate patients at risk of severe LGIB and an algorithm to guide management of such patients.

Methods

A retrospective cohort study was conducted, identifying consecutive patients admitted to our institution for LGIB over a 1-year period. Baseline demographics, clinical parameters at initial presentation and treatment interventions were recorded. Multivariate logistic regression was performed to identify factors predictive of severe LGIB. A clinical management algorithm was developed to discriminate between patients requiring admission, and to guide endoscopic, angiographic and/or surgical intervention.

Results

226/649 (34.8%) patients had severe LGIB. Six variables were entered into a clinical predictive model for risk stratification of LGIB: Tachycardia (HR ≥ 100), hypotension (SBP < 90 mmHg), anaemia (Hb < 9 g/dL), metabolic acidosis, use of antiplatelet/anticoagulants, and active per-rectal bleeding. The optimum cut-off score of ≥ 1 had a sensitivity of 91.9%, specificity of 39.8%, and positive and negative predictive Values of 45% and 90.2%, respectively, for predicting severe LGIB. The area under curve (AUC) was 0.77.

Conclusion

Early diagnosis and management of severe LGIB remains a challenge for the acute care surgeon. The predictive model described comprises objective clinical parameters routinely obtained at initial triage to guide risk stratification, disposition and inpatient management of patients.
Is the combination of bilateral pulmonary nodules and mosaic attenuation on chest CT specific for DIPNECH?
Authors: Samhouri Bilal F. , Koo Chi Wan , Yi Eunhee S. , Ryu Jay H.
Published: November 2021

Background

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is characterized by multifocal proliferation of pulmonary neuroendocrine cells. On chest CT, DIPNECH exhibits bilateral pulmonary nodules and mosaic attenuation in most patients. We sought to: (1) assess the specificity of this pattern (i.e., bilateral pulmonary nodules together with mosaic attenuation) for DIPNECH; (2) describe its differential diagnosis; and (3) identify the clinico-radiologic features that may help prioritize DIPNECH over other diagnostic considerations.

Methods

We searched the Mayo Clinic records from 2015 to 2019 for patients with bilateral pulmonary nodules and mosaic attenuation on CT who had a diagnostic lung biopsy. A thoracic radiologist reviewed all CT scans. Chi-square test was used for categorical variables, and odds ratios were utilized to measure the association between certain variables and DIPNECH.

Results

Fifty-one patients met our inclusion criteria; 40 (78%) were females and 34 (67%) were never-smokers. Median age was 65 (interquartile range 55–73) years. Lung biopsy was surgical in 21 patients (41%), transbronchial in 17 (33%), and transthoracic in 12 (24%); explanted lungs were examined in 1 (2%). Metastatic/multifocal cancer was the most common diagnosis, and was found in 17 (33%) cases. Bronchiolitis was diagnosed in 12 patients (24%), interstitial lung disease in 10 (20%), and DIPNECH in 5 (10%). Previous diagnosis of an obstructive lung disease (odds ratio 15.8; P = 0.002), and peribronchial nodular distribution on CT (odds ratio 14.4; P = 0.006) were significantly correlated with DIPNECH. Although statistical significance was not reached, DIPNECH nodules were more likely to display solid attenuations (80% vs. 67%, P = 0.45), and were more numerous; > 10 nodules were seen in 80% of DIPNECH cases vs. 52% in others (P = 0.23). Because DIPNECH primarily affects women, we analyzed the women-only cohort and found similar results.

Conclusions

Various disorders can manifest the CT pattern of bilateral pulmonary nodules together with mosaic attenuation, and this combination is nonspecific for DIPNECH, which was found in only 10% of our cohort. Previous diagnosis of an obstructive lung disease, and peribronchial distribution of the nodules on CT increased the likelihood of DIPNECH vs. other diagnoses.
Undifferentiated laryngeal carcinoma with hyaline bodies in a cat
Authors: Torrigiani Filippo , Gelain Maria Elena , Cavicchioli Laura , Di Maggio Roberta , Banzato Tommaso , Bonsembiante Federico
Published: November 2021

Background

Primary laryngeal neoplasms are rare in cats, with lymphoma and squamous cell carcinoma being the most commonly diagnosed tumour types. These tumours are usually highly aggressive, difficult to treat, and have a poor prognosis. Here an undifferentiated laryngeal carcinoma with hyaline bodies in a cat is reported.

Case presentation

A 13-year-old cat was presented for progressive respiratory signs. Diagnostic procedures revealed a partially obstructive laryngeal mass. Cytology was compatible with a poorly differentiated malignant tumour, with neoplastic cells frequently containing large intracytoplasmic hyaline bodies. After 1 month the patient was euthanised due to a worsening clinical condition and submitted for post-mortem examination, which confirmed the presence of two laryngeal masses. Histopathology confirmed the presence of an undifferentiated neoplasm with marked features of malignancy. Strong immunolabelling for pancytokeratin led to a diagnosis of undifferentiated carcinoma, however, histochemical and immunohistochemical investigations could not elucidate the origin of the large intracytoplasmic hyaline bodies observed in tumour cells, which appeared as non-membrane bound deposits of electron-dense material on transmission electron microscopy.

Conclusion

This is the first report of primary undifferentiated laryngeal carcinoma in a cat. Our case confirms the clinical features and the short survival that have been reported in other studies describing feline laryngeal tumours. Moreover, for the first time in feline literature, we describe the presence of intracytoplasmic hyaline bodies in neoplastic cells that were compatible with the so-called hyaline granules reported in different human cancers and also in the dog.
STAT proteins: a kaleidoscope of canonical and non-canonical functions in immunity and cancer
Authors: Awasthi Nagendra , Liongue Clifford , Ward Alister C.
Published: November 2021

STAT proteins represent an important family of evolutionarily conserved transcription factors that play key roles in diverse biological processes, notably including blood and immune cell development and function. Classically, STAT proteins have been viewed as inducible activators of transcription that mediate cellular responses to extracellular signals, particularly cytokines. In this ‘canonical’ paradigm, latent STAT proteins become tyrosine phosphorylated following receptor activation, typically via downstream JAK proteins, facilitating their dimerization and translocation into the nucleus where they bind to specific sequences in the regulatory region of target genes to activate transcription. However, growing evidence has challenged this paradigm and identified alternate ‘non-canonical’ functions, such as transcriptional repression and roles outside the nucleus, with both phosphorylated and unphosphorylated STATs involved. This review provides a revised framework for understanding the diverse kaleidoscope of STAT protein functional modalities. It further discusses the implications of this framework for our understanding of STAT proteins in normal blood and immune cell biology and diseases such as cancer, and also provides an evolutionary context to place the origins of these alternative functional modalities.
TMPRSS4 promotes cancer stem–like properties in prostate cancer cells through upregulation of SOX2 by SLUG and TWIST1
Authors: Lee Yunhee , Yoon Junghwa , Ko Dongjoon , Yu Minyeong , Lee Soojin , Kim Semi
Published: November 2021

Background

Transmembrane serine protease 4 (TMPRSS4) is a cell surface–anchored serine protease. Elevated expression of TMPRSS4 correlates with poor prognosis in colorectal cancer, gastric cancer, prostate cancer, non–small cell lung cancer, and other cancers. Previously, we demonstrated that TMPRSS4 promotes invasion and proliferation of prostate cancer cells. Here, we investigated whether TMPRSS4 confers cancer stem–like properties to prostate cancer cells and characterized the underlying mechanisms.

Methods

Acquisition of cancer stem–like properties by TMPRSS4 was examined by monitoring anchorage-independent growth, tumorsphere formation, aldehyde dehydrogenase (ALDH) activation, and resistance to anoikis and drugs in vitro and in an early metastasis model in vivo. The underlying molecular mechanisms were evaluated, focusing on stemness-related factors regulated by epithelial–mesenchymal transition (EMT)-inducing transcription factors. Clinical expression and significance of TMPRSS4 and stemness-associated factors were explored by analyzing datasets from The Cancer Genome Atlas (TCGA).

Results

TMPRSS4 promoted anchorage-independent growth, ALDH activation, tumorsphere formation, and therapeutic resistance of prostate cancer cells. In addition, TMPRSS4 promoted resistance to anoikis, thereby increasing survival of circulating tumor cells and promoting early metastasis. These features were accompanied by upregulation of stemness-related factors such as SOX2, BMI1, and CD133. SLUG and TWIST1, master EMT-inducing transcription factors, made essential contributions to TMPRSS4-mediated cancer stem cell (CSC) features through upregulation of SOX2. SLUG stabilized SOX2 via preventing proteasomal degradation through its interaction with SOX2, while TWIST1 upregulated transcription of SOX2 by interacting with the proximal E-box element in the SOX2 promoter. Clinical data showed that TMPRSS4 expression correlated with the levels of SOX2, PROM1, SNAI2, and TWIST1. Expression of SOX2 was positively correlated with that of TWIST1, but not with other EMT-inducing transcription factors, in various cancer cell lines.

Conclusions

Together, these findings suggest that TMPRSS4 promotes CSC features in prostate cancer through upregulation of the SLUG- and TWIST1-induced stem cell factor SOX2 beyond EMT. Thus, TMPRSS4/SLUG–TWIST1/SOX2 axis may represent a novel mechanism involved in the control of tumor progression.