bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumour site is a risk factor for hepatocellular carcinoma after hepatectomy: a 1:2 propensity score matching analysis
Authors: Li Lian , Xu Liangliang , Zhou Siqi , Wang Peng , Zhang Ming , Li Bo
Published: March 2022

Background

The effect of the anatomic location of HCC on the prognosis of patients after hepatectomy is currently unclear.

Methods

Patients who underwent hepatectomy were retrospectively enrolled and divided into the right tumour resection group (R group) and the left tumour resection group (L group) according to the tumour anatomic location. To avoid bias, 1:2 propensity score matching (PSM) analysis was used. Based on the survival data, disease-free survival (DFS) and overall survival (OS) were evaluated by the Kaplan–Meier method, and long-term survival analysis was performed. Cox proportional hazards regression was used to analyse the risk factors associated with postoperative prognosis.

Results

A total of 700 patients were enrolled in our study. After 1:2 PSM, 354 and 177 patients were enrolled in the R group and the L group, respectively, with comparable baseline characteristics. Survival analysis showed that patients in the L group had a significantly higher recurrence rate than patients in the R group (P = 0.036), but there was no significant difference in the survival rate (P = 0.99). Long-term survival analysis showed that the survival rate of the L group was lower than that of the R group (P < 0.01). Multivariate analysis showed that tumour location in the left liver was an independent risk factor for tumour recurrence (hazard ratio, 1.263; 95% CI, 1.005–1.587) and long-term survival (hazard ratio, 3.232; 95% CI, 1.284–8.134).

Conclusion

For HCC patients, the recurrence rate and long-term survival rate of left liver tumours were significantly higher than those of right liver tumours, indicating that the anatomical location of the tumour has a significant effect on the survival of HCC patients.

Trial registration Chinese Clinical Trial Registry, ChiCTR2100052407. Registered 25 October 2021, http://www.chictr.org.cn/showproj.aspx?proj=135500.
Mirabegron for overactive bladder in frail patients 80 years or over (HOKUTO study)
Authors: Nakagomi Hiroshi , Mitsui Takahiko , Shimura Hiroshi , Ihara Tatsuya , Kira Satoru , Sawada Norifumi , Takeda Masayuki
Published: March 2022

Background

We assessed the efficacy and safety of mirabegron, a β3-adrenoceptor agonist, in older adults (≥ 80 years old) with overactive bladder (OAB).

Methods

OAB patients aged ≥ 80 years were enrolled in this prospective, single-arm observational study. OAB was diagnosed based on the OAB symptom score (OABSS); i.e., a total score of ≥ 3 points and an urgency score of ≥ 2 points. Patients who received 50 mg mirabegron once daily were evaluated at the baseline and at 4, 8, and 12 weeks. The changes from the baseline in the OABSS, International Prostate Symptom Score (IPSS), OAB questionnaire (OAB-q) score, and Vulnerable Elders Survey (VES-13) score were determined. Adverse events, laboratory tests, 12-lead electrocardiography, the QT interval according to Fridericia’s formula (QTcF), uroflowmetry, the post-void residual urine volume (PVR), and the Mini-Mental State Examination (MMSE) score were used to assess safety.

Results

Forty-three patients (median age: 84 years, range: 80–96 years) were examined. They had high rates of comorbidities and polypharmacy. Mirabegron significantly improved in total score of the OABSS, including urgency and urge incontinence. The total IPSS, IPSS quality-of-life (QOL) index, and OAB-q scores also significantly improved. Mirabegron improved in the VES-13 score. There were no significant changes in laboratory test values, uroflowmetry findings, PVR, the QTcF, or MMSE score. Two patients (4.7%) withdrew from the study after experiencing adverse events.

Conclusions

Mirabegron was well tolerated and significantly improved in OAB symptoms, and QOL in older patients.

Trial registration The present clinical study was approved by University of Yamanashi Institutional Review Board prior to study initiation (ID1447) and was retrospectively registered with the UMIN Clinical Trials Registry (UMIN-CTR), Japan (UMIN000045996) on Nov 6, 2021.
Women with polycystic ovary syndrome (PCOS) have reduced melatonin concentrations in their follicles and have mild sleep disturbances
Authors: Li Hongwanyu , Liu Mei , Zhang Cong
Published: March 2022

Background

Polycystic ovary syndrome (PCOS) is a common gynecologic disorder related to abnormal circadian rhythm. Therefore, we aimed to find whether the level of melatonin, a rhythm regulating hormone changed in the ovarian microenvironment in this disease.

Methods

The melatonin concentrations in follicular fluid (FF) were measured in 35 PCOS and 36 non-PCOS women undergoing in vitro fertilization (IVF) treatment.

Results

The FF melatonin concentration was significantly lower in PCOS women than non-PCOS women (p = 0.045) and it was found positively correlated with serum basal FSH level (r = 0.308, p = 0.013). In IVF procedures, there was no significant difference in the fertilization rate of oocytes between the two groups, but the high-quality embryogenesis rate on the third day of the PCOS group was significantly lower than that of the control group (p = 0.042), which showed a weak positive correlation with the FF melatonin concentration (rs = 0.240, p = 0.044). Furthermore, there was no significant difference in overall pregnancy outcome. The PSQI questionnaire showed that sleep disorders were more likely to exist in the PCOS group, though there was no significant difference.

Conclusion

The obtained results suggested PCOS women had lower melatonin concentrations in the ovarian microenvironment.
Physical activity and health-related quality of life among high-risk women for type 2 diabetes in the early years after pregnancy
Authors: Sahrakorpi Niina , Engberg Elina , Stach-Lempinen Beata , Tammelin Tuija H. , Kulmala Janne , Roine Risto P. , Koivusalo Saila B.
Published: March 2022

Background

Previous studies have shown that physical activity (PA) correlates positively with health-related quality of life (HRQoL) in the general population. Few studies have investigated associations between device-measured PA and HRQoL among premenopausal women at risk for type 2 diabetes (T2D). In addition to physical well-being, general well-being improved by PA has been suggested to strengthen PA’s benefits in reducing metabolic diseases. The aim of this study was to examine the associations between PA and HRQoL (general and dimensions) among high-risk women in the early post-pregnancy years when T2D risk is highest and to estimate whether current obesity or prior gestational diabetes (GDM) modified these associations.

Methods

This cross-sectional study of high-risk women [body mass index (BMI) ≥ 30 kg/m2 and/or prior GDM)]4–6 years after delivery measured sleep, sedentary time, daily steps, and light (LPA), moderate-to-vigorous (MVPA), and vigorous PA (VPA) with the SenseWear ArmbandTM accelerometer for seven days and HRQoL with the 15D instrument.

Results

The analyses included 204 women with a median (IQR) age of 39 (6.0) years and a median BMI of 31.1 kg/m2 (10.9). 54% were currently obese (BMI ≥ 30 kg/m2), and 70% had prior gestational diabetes (GDM+). Women with obesity had lower PA levels than women with normal weight or overweight (p < 0.001) but there was no difference between the GDM+ or GDM− women. Women with both current obesity and GDM+ had highest sedentary time and lowest PA levels. The whole sample’s median 15D score was 0.934 (IQR 0.092), lower among women with obesity compared to the others (p < 0.001), but not different between GDM+ or GDM−. There was a positive correlation between VPA (adjusted rs = 0.262 p = 0.001) and the 15D score. After grouping according to BMI (< and ≥ 30 kg/m2), the associations remained significant only in women without obesity. Among them, sleep, total steps, MVPA, and VPA were positively associated with 15D.

Conclusions

Higher PA levels are associated with better HRQoL among high-risk women with normal weight and overweight but no differences were found among women affected by obesity in the early years after pregnancy.

Trial registration Ethics committees of Helsinki University Hospital (Dnro 300/e9/06) and South Karelian Central Hospital (Dnro 06/08).
Indicators and criteria of consciousness: ethical implications for the care of behaviourally unresponsive patients
Authors: Farisco Michele , Pennartz Cyriel , Annen Jitka , Cecconi Benedetta , Evers Kathinka
Published: March 2022

Background

Assessing consciousness in other subjects, particularly in non-verbal and behaviourally disabled subjects (e.g., patients with disorders of consciousness), is notoriously challenging but increasingly urgent. The high rate of misdiagnosis among disorders of consciousness raises the need for new perspectives in order to inspire new technical and clinical approaches.

Main body

We take as a starting point a recently introduced list of operational indicators of consciousness that facilitates its recognition in challenging cases like non-human animals and Artificial Intelligence to explore their relevance to disorders of consciousness and their potential ethical impact on the diagnosis and healthcare of relevant patients. Indicators of consciousness mean particular capacities that can be deduced from observing the behaviour or cognitive performance of the subject in question (or from neural correlates of such performance) and that do not define a hard threshold in deciding about the presence of consciousness, but can be used to infer a graded measure based on the consistency amongst the different indicators. The indicators of consciousness under consideration offer a potential useful strategy for identifying and assessing residual consciousness in patients with disorders of consciousness, setting the theoretical stage for an operationalization and quantification of relevant brain activity.

Conclusions

Our heuristic analysis supports the conclusion that the application of the identified indicators of consciousness to its disorders will likely inspire new strategies for assessing three very urgent issues: the misdiagnosis of disorders of consciousness; the need for a gold standard in detecting consciousness and diagnosing its disorders; and the need for a refined taxonomy of disorders of consciousness.
Safety and efficacy of G2-S16 dendrimer as microbicide in healthy human vaginal tissue explants
Authors: Rodríguez-Izquierdo I. , Serramía M. J. , Gómez R. , Espinosa G. , Genebat M. , Leal M. , Muñoz-Fernandez M. A.
Published: March 2022

Background

The absence of an effective treatment and vaccine in HIV-1 pandemic place preventive strategies such as safety and effective microbicide development as a central therapeutic approach to control HIV-1 pandemic nowadays.

Results

Studies of cytotoxicity, immune population status, inflammation or tissue damage and mainly prophylactic inhibition of HIV-1 infection in vaginal human explants demonstrate the biosafety and effectivity of G2-S16 dendrimer. Human explants treated with G2-S16 dendrimer or treated and HIV-1 infected do not presented signs of irritation, inflammation, immune activation or T cell populations deregulation.

Conclusions

Herein we conclude that G2-S16 dendrimer has demonstrated sufficient efficacy, biosafety, effectivity and behavior in the closest to the real-life condition model represented by the human healthy donor vaginal tissue explants, to raise G2-S16 dendrimer as a promising candidate to clinical trials to develop an effective microbicide against HIV-1 infection.

Graphical Abstract
A four-stage model for murine natural killer cell development in vivo
Authors: Ma Shoubao , Caligiuri Michael A. , Yu Jianhua
Published: March 2022

Natural killer (NK) cells are the predominant innate lymphoid cells that mediate anti-viral and anti-tumor immunity. NK cells arise from hematopoietic stem cells in the bone marrow (BM) and undergo lineage specification and maturation. Despite the importance of NK cells for innate immunity and the development of innovative cancer therapy, the detailed steps linking NK progenitor (NKP) cell development through immature NK (iNK) cells to mature NK (mNK) cells are poorly defined. In this study, we found that CD49b, NK1.1, and NKp46 are sequentially acquired during the development of murine Lin−CD122+ NKP cells. Introducing NKp46 allows us to propose a four-stage developmental model, wherein CD122+NK1.1−CD49b−NKp46− defines an NKP population, CD122+NK1.1−CD49b+NKp46− and CD122+NK1.1+CD49b−/+ NKp46− define iNK-a and iNK-b populations, respectively, and CD122+NK1.1+CD49b+NKp46+ defines an mNK population. These four NK cell populations are phenotypically distinct based on their expression of cell surface markers, transcription factors, and effector molecules. Using a differentiation assay ex vivo and adoptive transfer model in vivo, we confirmed that NK cell development follows our predicted four-stage model. Taken together, our findings establish two distinct populations of immature NK cells and define a model for mouse NK cell development.
Solamargine induces hepatocellular carcinoma cell apoptosis and autophagy via inhibiting LIF/miR-192-5p/CYR61/Akt signaling pathways and eliciting immunostimulatory tumor microenvironment
Authors: Yin Shuangshuang , Jin Wenke , Qiu Yuling , Fu Leilei , Wang Tao , Yu Haiyang
Published: March 2022

Hepatocellular carcinoma (HCC) is well-known to be a highly prevalent malignant tumor, but the treatment of this pathological state has been still challenging. Solamargine (SM), a traditional Chinese herb-derived compound, has been widely reported to possess multiple antitumor properties. However, whether SM plays a vital role in HCC therapy and how it exerts an antitumor effect remains unclear. Thus, in this study, we demonstrated that SM inhibited the proliferation of HCC and effectively induced HCC cell apoptosis and autophagy in vitro and in vivo. Mechanistically, the oncogenic factor LIF was aberrantly elevated in HCC tissues and down-regulated by SM in HCC cells, as well as subsequently the overexpression of LIF could restore the anti-HCC effects of SM via miR-192-5p/CYR61/Akt signaling pathways. Additionally, SM could repolarize tumor associated macrophages by LIF/p-Stat3 to inhibit the growth and epithelial-mesenchymal transition of HCC, and simultaneously affected other immune cell populations in the immune (tumor) microenvironment by regulating macrophages, such as MDSCs, DCs and T cell populations. Together, these findings exploit the potential use of SM against HCC and shed light on exploring SM as a potent candidate drug for the future HCC therapeutics.
Diabetes‐related foot disease research in Aotearoa New Zealand: a bibliometric analysis (1970–2020)
Authors: Carroll Matthew , Al‐Busaidi Ibrahim Saleh , Coppell Kirsten J. , Garrett Michele , Ihaka Belinda , O'Shea Claire , Wu Justina , York Steve
Published: March 2022

Background

The aim of this bibliometric study was to examine trends in the quality and quantity of published diabetes‐related foot disease (DRFD) research in Aotearoa/New Zealand (NZ) over the past five decades.

Method

In July 2021, the Scopus® database was searched for DRFD‐related publications (1970–2020) using predetermined search and inclusion criteria. Bibliometric data were extracted from Scopus® and Journal Citation Reports. Retrieved bibliometric indicators were analysed in Biblioshiny, an R Statistical Software interface and reported using descriptive statistics.

Results

Forty‐seven DRFD‐related articles were identified. The annual number of publications showed a significant upward trend increasing from one in 1988 to a peak of six in 2018 (P < 0.001). The majority of identified articles (n = 31, 66%) were published in the last decade (2011–2020). Basic/clinical research accounted for 87% (n = 41) of publications and 14 (30%) investigated the screening and/or prevention of DRFD. The average citation per article was 20.23 (range: 0–209) and the median impact factor was 4.31 (range, 1.82–79.32). Over a third of articles (36%) had an international authorship network. Funding was reported in 15 (32%) articles; 12 (26%) were supported by public national grants vs. three (6%) reporting industry‐sponsorship.

Conclusion

DRFD articles authored by NZ researchers have increased over the past five decades. Despite NZ researchers having increased their global impact through collaborative networks, most of the research was classified as low‐level evidence, with limited focus on Indigenous Māori and limited financial support and funding. Increased funding for interventional research is required to enable a higher level of evidence‐based and practice‐changing research to occur. With rates of diabetes‐related amputations higher in Māori future research must focus on reducing inequalities in diabetes‐related outcomes for Māori by specifically targeting the prevention and screening of DRFD in primary care settings in NZ.
Associations between the size of individual plantar intrinsic and extrinsic foot muscles and toe flexor strength
Authors: Kusagawa Yuki , Kurihara Toshiyuki , Maeo Sumiaki , Sugiyama Takashi , Kanehisa Hiroaki , Isaka Tadao
Published: March 2022

Background

The size of the plantar intrinsic and extrinsic foot muscles has been shown to be associated with toe flexor strength (TFS). Previous studies adopted the size of limited plantar intrinsic foot muscles or a compartment containing several muscles as an independent variable for TFS. Among the plantar intrinsic and extrinsic foot muscles, therefore, it is unclear which muscle(s) primarily contributes to TFS production. The present study aimed to clarify this subject.

Methods

In 17 young adult men, a series of anatomical cross‐sectional area of individual plantar intrinsic and extrinsic foot muscles was obtained along the foot length and the lower leg length, respectively, using magnetic resonance imaging. Maximal anatomical cross‐sectional area (ACSAmax) and muscle volume (MV) for each constituent muscle of the plantar intrinsic foot muscles (flexor hallucis brevis; flexor digitorum brevis, FDB; abductor hallucis; adductor hallucis oblique head, ADDH‐OH; adductor hallucis transverse head, ADDH‐TH; abductor digiti minimi; quadratus plantae) and extrinsic foot muscles (flexor hallucis longus; flexor digitorum longus) were measured. TFS was measured with a toe grip dynamometry.

Results

TFS was significantly associated with the ACSAmax for each of the ADDH‐OH (r = 0.674, p = 0.003), ADDH‐TH (r = 0.523, p = 0.031), and FDB (r = 0.492, p = 0.045), and the MV of the ADDH‐OH (r = 0.582, p = 0.014). As for the ADDH‐OH, the correlation coefficient with TFS was not statistically different between ACSAmax and MV (p = 0.189). Stepwise multiple linear regression analysis indicated that ACSAmax and MV of the ADDH‐OH alone explained 42 and 29%, respectively, of the variance in TFS.

Conclusion

The ADDH‐OH is the primary contributor to TFS production among the plantar intrinsic and extrinsic foot muscles as the result of the stepwise multiple linear regression analysis.
Digital PCR applications for the diagnosis and management of infection in critical care medicine
Authors: Merino Irene , de la Fuente Amanda , Domínguez-Gil Marta , Eiros José María , Tedim Ana P. , Bermejo-Martín Jesús F.
Published: March 2022

Infection (either community acquired or nosocomial) is a major cause of morbidity and mortality in critical care medicine. Sepsis is present in up to 30% of all ICU patients. A large fraction of sepsis cases is driven by severe community acquired pneumonia (sCAP), which incidence has dramatically increased during COVID-19 pandemics. A frequent complication of ICU patients is ventilator associated pneumonia (VAP), which affects 10–25% of all ventilated patients, and bloodstream infections (BSIs), affecting about 10% of patients. Management of these severe infections poses several challenges, including early diagnosis, severity stratification, prognosis assessment or treatment guidance. Digital PCR (dPCR) is a next-generation PCR method that offers a number of technical advantages to face these challenges: it is less affected than real time PCR by the presence of PCR inhibitors leading to higher sensitivity. In addition, dPCR offers high reproducibility, and provides absolute quantification without the need for a standard curve. In this article we reviewed the existing evidence on the applications of dPCR to the management of infection in critical care medicine. We included thirty-two articles involving critically ill patients. Twenty-three articles focused on the amplification of microbial genes: (1) four articles approached bacterial identification in blood or plasma; (2) one article used dPCR for fungal identification in blood; (3) another article focused on bacterial and fungal identification in other clinical samples; (4) three articles used dPCR for viral identification; (5) twelve articles quantified microbial burden by dPCR to assess severity, prognosis and treatment guidance; (6) two articles used dPCR to determine microbial ecology in ICU patients. The remaining nine articles used dPCR to profile host responses to infection, two of them for severity stratification in sepsis, four focused to improve diagnosis of this disease, one for detecting sCAP, one for detecting VAP, and finally one aimed to predict progression of COVID-19. This review evidences the potential of dPCR as a useful tool that could contribute to improve the detection and clinical management of infection in critical care medicine.
Clinical significance of HER2-low expression in early breast cancer: a nationwide study from the Korean Breast Cancer Society
Authors: Won Hye Sung , Ahn Juneyoung , Kim Yongseon , Kim Jin Sung , Song Jeong-Yoon , Kim Hong-Kyu , Lee Jeeyeon , Park Heung Kyu , Kim Yong-Seok
Published: March 2022

Background

There is an increasing interest in HER2-low breast cancer with promising data from clinical trials using novel anti-HER2 antibody–drug conjugates. We explored the differences in clinicopathological characteristics and survival outcomes between HER2-low and HER2-IHC 0 breast cancer.

Methods

Using nationwide data from the Korean Breast Cancer Registry between 2006 and 2011, 30,491 patients with stages I to III breast cancer were included in the analysis: 9,506 (31.2%) in the HER2-low group and 20,985 (68.8%) in the HER2-IHC 0 group. Kaplan–Meier and Cox proportional hazards regression survival analysis were used to compare breast cancer-specific survival between the two groups.

Results

HER2-low breast cancer was more frequent in patients with hormone receptor-positive breast cancer than in those with triple-negative breast cancer. In patients with hormone receptor-positive breast cancer, HER2-low breast cancer was associated with fewer T4 tumors, higher histological grade, and a negative lymphatic invasion. In patients with triple-negative breast cancer, HER2-low breast cancer was associated with a high lymph node ratio and positive lymphatic invasion. HER2-low breast cancer was significantly associated with a lower Ki-67 labeling index. No significant difference was observed in overall survival between the two groups. HER2-low breast cancer showed significantly better breast cancer-specific survival than HER2-IHC 0 breast cancer, regardless of the hormone receptor status. In multivariate analysis, the impact of low HER2 expression on breast cancer-specific survival was significant only in triple-negative breast cancer (HRs, 0.68; 95% CI, 0.49–0.93; P = 0.019).

Conclusions

These findings suggest that the biology and clinical impact of low HER2 expression can differ according to the hormone receptor status and support the need for further investigation on the understanding of the biology of HER2-low breast cancer.
Pooled safety results across phase 3 randomized trials of intravenous golimumab in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis
Authors: Husni M. Elaine , Deodhar Atul , Schwartzman Sergio , Chakravarty Soumya D. , Hsia Elizabeth C. , Leu Jocelyn H. , Zhou Yiying , Lo Kim H. , Kavanaugh Arthur
Published: March 2022

Background

Intravenous (IV) golimumab, a TNFi, is approved for treating rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). We analyzed pooled safety results from three phase 3 IV golimumab trials in these rheumatologic diseases and hypothesized that the safety profile of IV golimumab would be similar to that established for other TNFi, including subcutaneous golimumab.

Methods

Data from three double-blind, randomized trials of IV golimumab in patients with RA, PsA, and AS, each with a placebo-controlled period and an extension of active treatment, were included. Golimumab 2 mg/kg was administered at weeks 0 and 4, then every 8 weeks through week 100 (RA) or week 52 (PsA, AS). Concomitant low-dose, oral corticosteroids were permitted. Concomitant methotrexate was required in the RA trial and permitted in the PsA and AS trials; placebo patients crossed over to golimumab at weeks 24 (RA, PsA) and 16 (AS), respectively. Adverse events (AEs), including infections, serious infections, malignancies, and major adverse cardiovascular events (MACE), were assessed through week 112 (RA) or week 60 (PsA, AS).

Results

In total, 539 patients were randomized to placebo, and 740 patients were randomized to golimumab; 1248 patients received ≥ 1 golimumab administration. Among the placebo and golimumab patients, respectively, during the placebo-controlled periods, 40.6% and 50.3% had an AE, 2.4% and 3.8% had a serious AE, and 0.4% and 0.8% had a serious infection. Among all golimumab-treated patients, the numbers of events/100 patient-years (95% CI) were as follows: AEs, 175.2 (169.0, 181.6); serious AEs, 12.7 (11.0, 14.5); serious infections, 3.4 (2.5, 4.4); active tuberculosis, 0.4 (0.1, 0.8); opportunistic infection, 0.2 (0.1, 0.6); malignancies, 0.4 (0.2, 0.9), and MACE, 0.5 (0.2, 1.0). There were no cases of lymphoma. Three (0.6%) placebo-treated patients and 6 (0.5%) golimumab-treated patients died during the studies. Concomitant methotrexate was associated with increased occurrence of elevated alanine transaminase levels and lower incidence of antibodies to golimumab. During the placebo-controlled periods, serious infections in the placebo and golimumab groups were more common in patients receiving concomitant low-dose oral corticosteroids vs. those not receiving corticosteroids.

Conclusions

IV golimumab demonstrated a safety profile that was broadly consistent across these rheumatologic indications and with other TNFi, including subcutaneous golimumab. Concomitant methotrexate or corticosteroids were associated with an increase in specific AEs.

Trial registrations

ClinicalTrials.gov, NCT00973479. Registered on September 9, 2009. ClinicalTrials.gov, NCT02181673. Registered on July 4, 2014. ClinicalTrials.gov, NCT02186873. Registered on July 10, 2014.
Single-centre survival analysis over 10 years after MR-guided radiofrequency ablation of liver metastases from different tumour entities
Authors: Olthof Susann-Cathrin , Wessling Daniel , Winkelmann Moritz T. , Rempp Hansjörg , Nikolaou Konstantin , Hoffmann Rüdiger , Clasen Stephan
Published: March 2022

Background

Radiofrequency ablation (RFA) is a minimal-invasive, local therapy in patients with circumscribed metastatic disease. Although widely used, long time survival analysis of treated liver metastases is still pending while also analysing the patients’ experience of MR-based radiofrequency.

Methods

Monocentric, retrospective analysis of long-time overall and progression free survival (OS; PFS) of 109 patients, treated with MRI-guided hepatic RFA between 1997 and 2010, focusing on colorectal cancer patients (CRC). Complimentary therapies were evaluated and Kaplan Meier-curves were calculated. Patients’ experience of RFA was retrospectively assessed in 28 patients.

Results

1-, 3-, 5-, 10-year OS rates of 109 patients with different tumour entities were 83.4%, 53.4%, 31.0% and 22.9%, median 39.2 months, with decreasing survival rates for larger metastases size. For 72 CRC patients 1-, 3-, 5-, 10-year OS rates of 90.2%, 57.1%, 36.1% and 26.5% were documented (median 39.5 months). Thereof, beneficial outcome was detected for patients with prior surgery of the CRC including chemotherapy (median 53.0 months), and for liver metastases up to 19 mm (28.5% after 145 months). Hepatic PFS was significantly higher in patients with liver lesions up to 29 mm compared to larger ones (p = 0.035). 15/28 patients remembered RFA less incriminatory than other applied therapies.

Conclusions

This is the first single-centre, long-time OS and PFS analysis of MRI-guided hepatic RFA of liver metastases from different tumour entities, serving as basis for further comparison studies. Patients’ experience of MR based RFA should be analysed simultaneously to the performed RFA in the future.
Anti-PD-L1 monoclonal antibody for the management of chronic disseminated intravascular coagulation secondary to a urothelial carcinoma: a case report
Authors: Maiorano Silvia , Gulden-Sala Wiebke , Gerber Bernhard , Ghilardi Guido
Published: March 2022

Background

Thrombocytopenia is often considered a risk factor for bleeding, but conversely may be associated with an increased thrombotic risk in several clinical situations. Here we present a patient with arterial thrombosis and chronic disseminated intravascular coagulation caused by metastatic urothelial carcinoma. As the treatment for a disseminated intravascular coagulation caused by a neoplasia is the treatment of the underlying disease itself, our case highlights a new therapeutic approach—immunotherapy—in a patient prone to hematological complications due to conventional chemotherapy.

Clinical case

A 74-year-old Caucasian male patient with a history of urothelial carcinoma of the bladder and moderate thrombocytopenia had multiple arterial thrombotic events despite antiplatelet therapy and anticoagulation. A diagnosis of chronic disseminated intravascular coagulation in the setting of a metastatic bladder urothelial carcinoma was made. The patient was treated with an anti-PD-L1 monoclonal antibody, and achieved a rapid response with subsequent reversal of the disseminated intravascular coagulation.

Conclusion

Unexplained arterial or venous thrombosis despite adequate thromboprophylaxis should be investigated, especially in the setting of thrombocytopenia. Chronic disseminated intravascular coagulation is a possible, life-threatening reason for this clinical picture, and should prompt rapid identification of the underlying disease. To the best of our knowledge, this is the second case of chronic disseminated intravascular coagulation due to neoplastic disease treated with immunotherapy.
Dendritic epidermal T cells secreting exosomes promote the proliferation of epidermal stem cells to enhance wound re-epithelialization
Authors: Liu Mian , Liu Zhihui , Chen Yunxia , Peng Shiya , Yang Jiacai , Chen Cheng , Wang Jue , Shang Ruoyu , Tang Yuanyang , Huang Yong , Zhang Xiaorong , Hu Xiaohong , Liou Yih-Cherng , Luo Gaoxing , He Weifeng
Published: March 2022

Background

Efficient re-epithelialization is important for successful skin wound healing. The proportion of epidermal stem cells (EpSCs) and dendritic epidermal T cells (DETCs) determines the extent of wound re-epithelialization, especially in large areas of skin tissue loss. However, it remains unknown whether and how DETCs regulate the status of EpSCs to impact wound re-epithelialization.

Methods

To investigate how DETCs regulate EpSCs in skin re-epithelialization, we utilized normal or full-thickness skin deficient wide type (WT) mice and Tcrσ knockout (Tcrσ−/−) mice with DETCs or DETCs-derived exosomes (Exos) treatment. Flow cytometry analysis (FCAS), BrdU labelled experiments, immunofluorescence and immunohistochemical assays were performed to detect the proportion of EpSCs in the epidermis. Wound closure rate and re-epithelialization were assayed by a macroscopical view and hematoxylin–eosin (H&E) staining. EpSCs in vitro were co-cultured with DETCs in a transwell-dependent or -independent manner, or supplement with GW4869 or Exos (5 µg/mL, 15 µg/mL and 45 µg/mL), and the proliferation of EpSCs was detected by means of FCAS and CFSE.

Results

Our data showed that the proportion of CD49fbriCD71dim cells, K15+ cells and BrdU+ cells in the normal epidermis of Tcrδ−/− mice had no significant difference compared to WT mice. For wounded Tcrδ−/− mice, DETCs treatment increase the proportion of CD49fbriCD71dim cells, K15+ cells and BrdU+ cells in the epidermis around the wound in comparison to PBS treatment. DETCs significantly increased the number of CD49fbriCD7dim cells and K15+ cells through transwell-dependent or -independent manners relative to control group. Furthermore, Exos stimuli remarkedly promote the proliferation of EpSCs compared to control group, while the increasement was suppressed when DETCs were interfered with GW4869. Gross observation and H&E staining showed that Exos significantly accelerated wound closure and increased re-epithelialization length in Tcrδ−/− mice when compared to control mice. Additionally, we found in vivo that Exos observably facilitated the proliferation of CD49fbriCD7dim cells and K15+ cells.

Conclusions

We revealed that DETCs enhanced the proliferation of EpSCs in the epidermis around the wounds to accelerate re-epithelialization in which Exos played important roles in the remote regulation of EpSCs proliferation. Together, these findings suggest a mechanistic link among DETC-derived exosomes, the proliferation of EpSCs, and wound re-epithelialization in the skin.
Efficacy and safety of mesenchymal stem cells in the treatment of systemic sclerosis: a systematic review and meta-analysis
Authors: Cui Jiehan , Jin Lu , Ding Meng , He Jingjing , Yang Lin , Cui Shaoxin , Wang Xiaoping , Ma Jun , Liu Aijing
Published: March 2022

Background

Systemic sclerosis (SSc) is an autoimmune disease with high morbidity and mortality characterized by fibrosis of the skin and internal organs. Some studies have investigated the use of stem cells to treat SSc. Herein, a systematic review and meta-analysis was conducted to determine the efficacy and safety of mesenchymal stem cells (MSCs) in the treatment of SSc.

Methods

PubMed, Embase, Cochrane Library, Web of Science, OVID, China National Knowledge Infrastructure and Wanfang databases were searched up to February 1, 2021. Literature screening, data extraction and quality assessment were conducted independently by two researchers in according to the inclusion and exclusion criteria. The discrepancies were resolved by a third researcher.

Results

A total of 9 studies encompassing 133 SSc patients were included in the study. Compared to the baseline after treatment with MSCs: 1. The modified Rodnan skin score (mRSS) was significantly reduced in patients with SSc (P < 0.00001). 2. MSCs decreased the number of digital ulcer, mouth handicap scale, and visual analog scale of hand pain in SSc patients (P = 0.0007 and P = 0.03, respectively). 3. No statistical differences were detected in Raynaud's condition score and Cochin hand function scale score at 6 months of MSCs therapy (P = 0.5 and P = 0.62). 4. After 12 months of follow-up, MSCs improve carbon monoxide diffusing capacity and forced vital capacity of SSc patients (P < 0.05). 5. Overall, MSCs application was safe; a few cases exhibited swelling at the injection site, diarrhea and arthralgia, which had self-recovery, and no severe adverse events occurred in the included trials.

Conclusions

MSC therapy improves the degree of skin thickening, lung function, and mouth opening and relieves finger ulcers and pain in patients with SSc without severe adverse events. Thus, MSCs or MSCs combined with plasma and traditional medicine might be an effective and promising treatment of SSc patients.

PROSPERO registration number: CRD42020200350
Development of off-the-shelf hematopoietic stem cell-engineered invariant natural killer T cells for COVID-19 therapeutic intervention
Authors: Li Yan-Ruide , Dunn Zachary Spencer , Garcia Gustavo , Carmona Camille , Zhou Yang , Lee Derek , Yu Jiaji , Huang Jie , Kim Jocelyn T. , Arumugaswami Vaithilingaraja , Wang Pin , Yang Lili
Published: March 2022

Background

New COVID-19 treatments are desperately needed as case numbers continue to rise and emergent strains threaten vaccine efficacy. Cell therapy has revolutionized cancer treatment and holds much promise in combatting infectious disease, including COVID-19. Invariant natural killer T (iNKT) cells are a rare subset of T cells with potent antiviral and immunoregulatory functions and an excellent safety profile. Current iNKT cell strategies are hindered by the extremely low presence of iNKT cells, and we have developed a platform to overcome this critical limitation.

Methods

We produced allogeneic HSC-engineered iNKT (AlloHSC-iNKT) cells through TCR engineering of human cord blood CD34+ hematopoietic stem cells (HSCs) and differentiation of these HSCs into iNKT cells in an Ex Vivo HSC-Derived iNKT Cell Culture. We then established in vitro SARS-CoV-2 infection assays to assess AlloHSC-iNKT cell antiviral and anti-hyperinflammation functions. Lastly, using in vitro and in vivo preclinical models, we evaluated AlloHSC-iNKT cell safety and immunogenicity for off-the-shelf application.

Results

We reliably generated AlloHSC-iNKT cells at high-yield and of high-purity; these resulting cells closely resembled endogenous human iNKT cells in phenotypes and functionalities. In cell culture, AlloHSC-iNKT cells directly killed SARS-CoV-2 infected cells and also selectively eliminated SARS-CoV-2 infection-stimulated inflammatory monocytes. In an in vitro mixed lymphocyte reaction (MLR) assay and an NSG mouse xenograft model, AlloHSC-iNKT cells were resistant to T cell-mediated alloreaction and did not cause GvHD.

Conclusions

Here, we report a method to robustly produce therapeutic levels of AlloHSC-iNKT cells. Preclinical studies showed that these AlloHSC-iNKT cells closely resembled endogenous human iNKT cells, could reduce SARS-CoV-2 virus infection load and mitigate virus infection-induced hyperinflammation, and meanwhile were free of GvHD-risk and resistant to T cell-mediated allorejection. These results support the development of AlloHSC-iNKT cells as a promising off-the-shelf cell product for treating COVID-19; such a cell product has the potential to target the new emerging SARS-CoV-2 variants as well as the future new emerging viruses.
Assessment of automated assays for serum amyloid A, haptoglobin (PIT54) and basic biochemistry in broiler breeders experimentally infected with Escherichia coli
Authors: Kromann Sofie , Olsen Rikke Heidemann , Bojesen Anders Miki , Jensen Henrik Elvang , Thøfner Ida
Published: March 2022

Biomarkers of inflammation are valuable tools for health status evaluation in numerous species. However, in poultry, methods for measuring acute phase proteins (APP) are sparse and rely on manual laboratory labour reserving these parameters mainly for research studies with APP as a focus point. To extend the use of APP beyond tightly focused research studies, blood from experimentally infected and control hens was analysed using equipment available in many veterinary clinics in order to identify easily accessible biomarkers of infection. Blood samples from broiler breeders (n = 30) inoculated intratracheally with either Escherichia coli or sterile vehicle were randomly selected at 2, 4 and 7 days post-infection (dpi) and subjected to biochemical analysis. Samples for bacteriological testing were collected, and all animals were subjected to a full necropsy for disease confirmation. Significantly higher levels of serum amyloid A were evident in the infected birds at 2 and 4 dpi (p < 0.01) compared to the controls. Likewise, haptoglobin (PIT54) levels were significantly elevated at 4 dpi (p < 0.01) in the infected animal, whilst at 2 dpi magnesium and calcium were significantly lower in the infected group (p < 0.05). Gross pathology and bacteriology confirmed the presence of infection in the E. coli inoculated birds. In conclusion, equipment routinely used in other species for rapid analysis of blood samples, successfully differentiated between sick and healthy birds, hereby, showing great potential as an easily added parameter of evaluation in research studies, and as a valuable decision-making tool for poultry veterinarians.
Acute rhabdomyolysis in hepatitis-associated aplastic anemia patient undergoing allogeneic hematopoietic stem-cell transplantation: case report and literature review
Authors: Li Yuzhu , Hong Yilei , Shen Yingying , Liu Qi , Chen Ying , Shao Keding , Shen Yiping , Ye Baodong , Wu Dijiong
Published: March 2022

Background

Hepatitis-associated aplastic anemia (HAAA) is a specific type of aplastic anemia, and hematopoietic stem-cell transplantation (HSCT) is recommended as the first-line. Acute rhabdomyolysis (AR) during hematopoietic stem-cell transplantation (HSCT) is a rare, serious complication, with only 10 cases reported in the world so far.

Case presentation

Herein, we present a case of AR developing during HLA-haploidentical HSCT in a 55-year-old man who suffered from HAAA. On day 7 after stem cell transfusion, the patient reported a muscle pull in thigh and complained of muscle swelling, pain and change in urine color. Despite the timely diagnosis (based on the levels of myoglobin and creatine kinase, and muscle MRI findings, etc.) and rapid hydration and alkalization, the situation progressed dramatically, and the patient died of multi-organ failure during the preparation for continuous renal replacement therapy (CRRT). Five days after his death, the whole-exome sequencing result confirmed that the patient had a germline missense mutation in SCN4A I 1545 V and ACTN3 R577X.

Conclusion

AR is a rare but threatening complication during HSCT, especially in cases with kidney dysfunction. The creatine kinase level may not truly and completely reflect the severity and prognosis for cases with localized lesion. We suggest that genetic analysis should be performed for better understanding the pathological changes of AR during HSCT, especially for patients with bone marrow failure.
Anaerobic RSH-dependent tellurite reduction contributes to Escherichia coli tolerance against tellurite
Authors: Muñoz-Diaz P. , Jiménez K. , Luraschi R. , Cornejo F. , Figueroa M. , Vera C. , Rivas-Pardo A. , Sandoval J. M. , Vásquez C. , Arenas F.
Published: March 2022

Background

Tellurium is a rare metalloid that exerts high toxicity on cells, especially on bacteria, partly due to reactive oxygen species (ROS) generation. Moreover, it has also been observed that tellurite can target free cell thiols groups (RSH) (i.e. reduced glutathione (GSH)), enhancing the cellular redox imbalance. Additionally, in vitro experiments have suggested that several enzymes can reduce tellurite (IV) to its elemental form (0); where RSH present on their active sites may be responsible for the process. Nevertheless, the mechanisms implemented by bacteria for tellurite reduction and its role in resistance have not been evaluated in vivo.

Results

This work shows that tellurite reduction to elemental tellurium is increased under anaerobic conditions in E. coli cells. The in vivo tellurite reduction is related to the intracellular concentration of total RSH, in the presence and absence of oxygen. This metabolization of tellurite directly contributes to the resistance of the bacteria to the oxyanion.

Conclusions

We demonstrated that in vivo tellurite reduction is related to the intracellular thiol concentration, i.e. large availability of cellular RSH groups, results in a more significant reduction of tellurite. Furthermore, we observed that, when the bacterium exhibits less resistance to the oxyanion, a decreased tellurite reduction was seen, affecting the growth fitness. Together, these results let us propose that tellurite reduction and the intracellular RSH content are related to the oxyanion bacterial resistance, this tripartite mechanism in an oxygen-independent anaerobic process.
Communication with face masks during the COVID-19 pandemic for adults with hearing loss
Authors: Poon Brenda T. , Jenstad Lorienne M.
Published: March 2022

Face masks have become common protective measures in community and workplace environments to help reduce the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Face masks can make it difficult to hear and understand speech, particularly for people with hearing loss. An aim of our cross-sectional survey was to investigate the extent that face masks as a health and safety protective measure against SARS-CoV-2 have affected understanding speech in the day-to-day lives of adults with deafness or hearing loss, and identify possible strategies to improve communication accessibility. We analyzed closed- and open-ended survey responses of 656 adults who self-identified as D/deaf or hard of hearing. Over 80% of respondents reported difficulty with understanding others who wore face masks. The proportion of those experiencing difficulty increased with increasing hearing loss severity. Recommended practical supports to facilitate communication and social interaction included more widespread use of clear face masks to aid lip-reading; improved clarity in policy guidance on face masks; and greater public awareness and understanding about ways to more clearly communicate with adults with hearing loss while wearing face masks.
Platform placemaking and the digital urban culture of Airbnbification
Authors: Törnberg Petter
Published: March 2022

This paper develops the notion of “platform placemaking”, describing how platforms mobilize user data to remake urban spatial imaginaries in their interests. Using Airbnb as a case, the paper studies the digital urban culture of “Airbnbification” – examining how Airbnb’s reviews and descriptions become part of reshaping urban place, while contributing to the place alienation of long-term residents. Airbnb feeds a surge in urban tourists on the hunt for “real urban experiences”: off-the-beaten-track, everyday and mundane urban life, seen as representing something “real” and “authentic”. This paper situates Airbnb in the literature on postmodern consumption, and examines the way hosts and guests on Airbnb stage, perform and construct cosmopolitanism and “authentic” urban place to cater to the values of new urban tourism. The paper introduces an approach to studying digital urban culture through platform data, using computational discourse analysis to examine Airbnb in New York City. By linking narratives in reviews and neighborhood descriptions to census data, we examine how authenticity and cosmopolitanism is staged and marketed. The paper argues that Airbnb serves to promote a value system that devalues the cultural and spatial capital of long-term residents, implying that the new tourists’ cosmopolitan longing to belong may thus come at the cost of the locals’ own sense of belonging. The platform placemaking of Airbnb thus emphasizes urban place as a consumption experience, while depressing other ways of experiencing the city.