bluuebunny/crossref_metadata_2025 huggingface dataset:
Scabies-induced lichen simplex chronicus misdiagnosed as psychogenic pruritus: a case report
Authors: Emmanuel Ozzy M. , Karovska Ana V. , Ikedilo Okey
Published: February 2021

Introduction

Lichen simplex chronicus has been defined as a localized skin condition characterized by thickening, hyperpigmentation and accentuated skin markings from chronic itching and from repeated scratching. The affected skin area is usually described as demarcated, and often circumscribed. It has even been defined as a “psychogenic pruritic disorder”. The idea of a neurological component has also been suggested, hence the term 'neurodermatitis circumscripta'. However, the pathophysiology of this condition remains unclear. Several associations and etiologies have been reported in literature, including strong links with mental disorders—anxiety and obsessive compulsive disorder to be specific. We report this case, most importantly, to highlight the value of an open-minded approach to patients and the 'old-fashioned' physician character of empathy, the skill of detailed history taking and physical examination, and lastly to suggest that lichen simplex chronicus may not always present as a localized, 'circumscripta' or demarcated area of skin.

Case description

When a sixty-five year-old Caucasian female presented to our clinic agitated, intensely scratching her entire body and complaining of severe pruritus, an open-minded detailed approach during history taking and physical examination led to the working diagnosis of diffuse lichenification from chronic scratching secondary to a “possible” cutaneous disorder. Her medical history was unremarkable, but her psychiatric history was significant for Anxiety disorder. She remained on her anxiolytic medication. Her presenting symptom was reported to have persisted for more than 9 months. Review of previous unremarkable lab results and a remarkable findings on detailed skin inspection led to an empiric, trial regimen consisting of three topical preparations: an anti-pruritic—to break the itch-scratch cycle, anti-inflammatory—to curb any inflammatory/immune response and a 'last-ditch' scabicidal application. Follow-up was scheduled, but the patient called the office requesting an earlier follow up appointment. The lesions had significantly improved and the hyper-pigmented, indurated and escoriated skin appearance had resolved; and most importantly, the pruritus.

Conclusion

Thus we conclude that lichen simplex chronicus may not always present as circumscribed or localized area of skin as currently noted in literature. Also, in patients with psychiatric conditions including anxiety and obsessive-compulsive disorder in particular, effort should be made to avoid stereotyping their presentation as part of their mental disorder spectrum. The value of detailed history and physical examination, mixed with empathy is highlighted. We make our recommendation considering the profound turnaround in the patient's condition and quality of life after several months of emotional and psychological suffering.
Bronchial mucosal ablation for bronchial stump closure in right pneumonectomy: a case report
Authors: Makidono Kimitaka , Miyata Yoshihiro , Ikeda Takuhiro , Tsutani Yasuhiro , Kai Yuichiro , Kushitani Kei , Takeshima Yukio , Okada Morihito
Published: February 2021

Background

Bronchial fistula is a severe complication of pneumonectomy with a high mortality rate. We previously reported a technique for bronchial closure to prevent bronchial fistula in a canine model. We described that mucosal ablation could result in primary wound healing and involve mucosal tight adhesions histologically. In this paper, the pathologic findings of one patient, who underwent autopsy 4 years after surgery, were reviewed.

Case presentation

A 70-year-old Japanese man was diagnosed with malignant pleural mesothelioma and underwent right extra-pleural pneumonectomy. The right main bronchus was cut using a scalpel. When closing the bronchial stump, the bronchial mucosa was ablated by electric cautery and sutured manually using 3-0 absorbable sutures. The bronchial fistula was not found after pneumonectomy. Four years after surgery, the patient died of recurrent malignant pleural mesothelioma and underwent autopsy. Macroscopic evaluation showed tight adhesions and white scars on the bronchial stump. Microscopic findings showed few inflammatory cells and α-smooth muscle actin (α-SMA)-positive cells.

Conclusions

The results from this case suggested that bronchial mucosal ablation leads to robust agglutination of bronchial stump over years. This technique is not only simple but also reliable to prevent bronchial fistula.
Retiform hemangioendothelioma: a case series and review of the literature
Authors: Chundriger Qurratulain , Tariq Muhammad Usman , Rahim Shabina , Abdul-Ghafar Jamshid , Din Nasir Ud
Published: February 2021

Background

Retiform Hemangioendothelioma (RH) is an extremely rare vascular tumor of intermediate biological behavior, which is prone to local recurrence but rarely shows metastasis to distant sites. It may harbor areas resembling Dabska tumor in some cases and angiosarcoma, which in its well differentiated form may exhibit similar pathological appearance in some areas, making it problematic to rule out a possibility of a malignant diagnosis on a core biopsy. Therefore, complete surgical resection with negative margins is essential for accurate diagnosis and local control.

Results

In our series, two of the three Pakistani cases were in females, with an age range between 18 and 50 years. Our first patient presented with symptoms of cardiac compromise and pulmonary hypertension. Her computed tomography scan showed multiple tumor masses within the mediastinum. The second patient presented with an ulcerated lesion on his scalp, at right temple. The third patient presented with a hard growth on her left 4th toe which was amputated. Histologically, all cases exhibited retiform arborizing vascular spaces lined by bland endothelial cells with hobnail nuclei, characteristic of retiform hemangioendothelioma. Immunohistochemical markers CD31, CD34 and ERG confirmed the vascular nature of the tumor. The first and the second patient are alive and healthy at 4 and 7 months follow up respectively, while the third patient is lost to follow up.

Conclusion

Owing to the rate of local recurrence, RH should always be considered in the differential diagnosis of vascular tumors showing arborizing blood vessels, as it may have an atypical presentation and it should be carefully differentiated from Dabska tumor and an angiosarcoma.
The value of a simple method to decrease diagnostic errors in Turner syndrome: a case report
Authors: Mousavi Seyedetahere , Amiri Batool , Beigi Saidee , Farzaneh Mohammadreza
Published: February 2021

Introduction

Turner syndrome is a genetic disorder in females and is the result of complete or partial loss of an X chromosome during fertilization. The missing X chromosome is originally either from the mother's ovum or the father's sperm cell. Approximately 45% of patients have the 45,X karyotype and the rest have other variants of Turner syndrome, which are either mosaicism patterns or structural abnormalities of the X chromosome. Here, we report a case of Turner syndrome that is the fifth case of Turner syndrome with balanced Robertsonian translocation of (13;14)(q10;q10), and the sixth case with 44,X chromosomes, reported in the literature thus far.

Case presentation

A 10.3-year-old Persian girl was brought to our clinic by her parents, with the complaint of failure to thrive and short height. She had been examined and investigated by endocrinologists since the age of 4 years, but no definite diagnosis was made. At the time of presentation, she had been through three provocative growth hormone tests and had been on no medications for about a year. Her physical examination revealed mild retrognathia and micrognathia. Initially, she was started on somatropin treatment which, after 12 months, did not appropriately improve her height velocity. Therefore, a more thorough physical examination was performed, in which high arched palate and low posterior hairline were observed. There was also a difference between target height and patient height standard deviation scores. Karyotype study was requested, and Turner syndrome was confirmed.

Conclusion

The diagnosis of this case was not straightforward, both because the somatic presentations were not obvious, and because the physicians had not looked for them when performing the physical examinations. This case report introduces a rare 44,X chromosome karyotype of Turner syndrome and highlights the value in using the difference between target height and patient height standard deviation scores as a simple and inexpensive tool for diagnosis of this syndrome.
Yttrium-90 radioembolization of isolated hepatic adrenocortical carcinoma metastases with negative surgical pathology
Authors: Lu Sen , Dhillon Jasreman , Johnson Julie Hallanger , El-Haddad Ghassan
Published: February 2021

Background

Adrenocortical carcinoma (ACC) is an uncommon malignancy with an estimated 15,400 new cases annually across the globe. The prognosis is generally poor as the disease is often already advanced at initial diagnosis due to non-specific symptoms. Even for local disease, recurrence after surgical resection is high. Treatment choices for advanced disease include mitotane, chemotherapy, ablation, chemoembolization, radioembolization, and external beam radiotherapy, with varying degrees of efficacy. To the best of our knowledge, there have only been two prior case studies of complete clinical and radiological response of stage 4 disease at 1 year and 2 years after yttrium-90 (90Y) microsphere selective internal radiation therapy (SIRT) of isolated hepatic metastases post-surgery and chemotherapy.

Case presentation

We present a case of a 58-year-old man with metastatic ACC who was treated with 90Y resin microsphere (SIR-spheres) for local control of liver metastases leading to a surgically proven negative pathology after partial hepatectomy 7 months after SIRT. The patient was initially diagnosed with stage 1 ACC that progressed 6 years later to stage 4 disease with new liver metastases that were deemed unresectable at an outside institution. After review of the case at multidisciplinary tumor board, he was referred for liver directed therapy for local tumor control. Angiographic workup demonstrated partial extrahepatic supply to the tumors from the right inferior phrenic artery, which was successfully embolized on the day of SIRT for flow redistribution. As the patient was being treated with mitotane that suppresses steroid production, he developed post-SIRT adrenal crisis, which was successfully controlled with steroids, highlighting the need for pre SIRT stress dose steroids.

Conclusions

This case continues to add to the literature supporting 90Y radioembolization as an effective treatment for isolated hepatic ACC metastases. Our case is the first to demonstrate surgically proven negative pathology after radioembolization. Further prospective study is warranted to better establish efficacy as well as safety of SIRT for ACC liver metastases.
Clinical results of fibroblast activation protein (FAP) specific PET for non-malignant indications: systematic review
Authors: Windisch Paul , Zwahlen Daniel R. , Giesel Frederik L. , Scholz Eberhard , Lugenbiel Patrick , Debus Jürgen , Haberkorn Uwe , Adeberg Sebastian
Published: February 2021

Purpose

Small molecules targeting fibroblast activation protein (FAP) have emerged as a new group of tracers for positron emission tomography (PET) in 2018. While most of the existing literature has been focussed on the application of FAP-specific PET in various kinds of cancers, some researchers have, both intentionally or unintentionally, used FAP-specific PET in patients with non-cancerous diseases. The purpose of this systematic review is therefore to summarize the available evidence of FAP-specific PET for non-malignant indications.

Methods

The MEDLINE database was searched for studies presenting the clinical use of FAP-specific PET, the records were screened according to PRISMA guidelines and articles containing patients suffering from non-malignant diseases were included.

Results

Sixteen studies with 303 patients were included. FAP-specific PET has been used in cardiac imaging, IgG4-related disease, benign tumors as well as various kinds of inflammation. Two prospective studies on FAP-specific PET for IgG4-related disease show its potential to differentiate inflammatory from fibrotic lesions, which could be used to determine the management of these patients.

Conclusion

While publications on FAP-specific PET for non-malignant indications are mostly limited to case reports and incidental findings, the first retrospective and prospective studies present promising results for IgG4-related as well as cardiovascular disease that warrant further research. Several currently recruiting trials will add to the body evidence in the next few years.
What drives different treatment choices? Investigation of hospital ownership, system membership and competition
Authors: Bayindir Esra Eren , Schreyögg Jonas
Published: February 2021

Background

Differences in ownership types have attracted considerable interest because of policy implications. Moreover, competition in hospital markets is promoted to reduce health care spending. However, the effects of system membership and competition on treatment choices of hospitals have not been considered in studying hospital ownership types. We examine the treatment choices of hospitals considering ownership types (not-for-profit, for-profit, and government), system membership, patient insurance status (insured, and uninsured) and hospital competition in the United States.

Methods

We estimate the probability of according the procedure as the treatment employing logistic regression. We consider all procedures accorded at hospitals, controlling for procedure type and diagnosis as well as relevant patient and hospital characteristics. Competition faced by hospitals is measured using a distance-weighted approach separately for procedural groups. Patient records are obtained from State Inpatient Databases for 11 states and hospital characteristics come from American Hospital Association Annual Survey.

Results

Not-for-profit hospitals facing low for-profit competition that are nonmembers of hospital systems, act like government hospitals, whereas not-for-profits facing high for-profit competition and system member not-for-profits facing low for-profit competition are not statistically significantly different from their for-profit counterparts in terms of treatment choices. Uninsured patients are on average 7% less likely to be accorded the procedure as the treatment at system member not-for-profit hospitals facing high for-profit competition than insured patients. System member not-for-profit hospitals, which account for over half of the observations in the analysis, are on average 16% more likely to accord the procedure as the treatment when facing high for-profit competition than low-for-profit competition.

Conclusions

We show that treatment choices of hospitals differ by system membership and the level of for-profit competition faced by the hospitals in addition to hospital ownership type and health insurance status of patients. Our results support that hospital system member not-for-profits and not-for-profits facing high for-profit competition are for-profits in disguise. Therefore, system membership is an important characteristic to consider in addition to market competitiveness when tax exemption of not-for-profits are revisited. Moreover, higher competition may lead to increasing health care costs due to more aggressive treatment choices, which should be taken into account while regulating hospital markets.
Classification of acetic acid bacteria and their acid resistant mechanism
Authors: Qiu Xiaoman , Zhang Yao , Hong Housheng
Published: February 2021

Acetic acid bacteria (AAB) are obligate aerobic Gram-negative bacteria that are commonly used in vinegar fermentation because of their strong capacity for ethanol oxidation and acetic acid synthesis as well as their acid resistance. However, low biomass and low production rate due to acid stress are still major challenges that must be overcome in industrial processes. Although acid resistance in AAB is important to the production of high acidity vinegar, the acid resistance mechanisms of AAB have yet to be fully elucidated. In this study, we discuss the classification of AAB species and their metabolic processes and review potential acid resistance factors and acid resistance mechanisms in various strains. In addition, we analyze the quorum sensing systems ofKomagataeibacterandGluconacetobacterto provide new ideas for investigation of acid resistance mechanisms in AAB in the form of signaling pathways. The results presented herein will serve as an important reference for selective breeding of high acid resistance AAB and optimization of acetic acid fermentation processes.
The rollout of the COVID-19 vaccination: what can Canada learn from Israel?
Authors: Marchildon Gregory P.
Published: February 2021

This commentary compares Israel’s COVID-10 vaccination response to the much slower and less successful vaccination campaign in Canada. Although Canada did start with some structural disadvantages relative to Israel including less centralized and coherent emergency planning and a more complex demographic geography, there are, nonetheless, some important policy lessons Canada can draw from Israel. These include a more strategic use of national leadership in the vaccination campaign and the greater use of primary care resources and providers.
Intensive care management of patients with COVID-19: a practical approach
Authors: Hajjar Ludhmila Abrahão , Costa Isabela Bispo Santos da Silva , Rizk Stephanie Itala , Biselli Bruno , Gomes Brenno Rizerio , Bittar Cristina Salvadori , de Oliveira Gisele Queiroz , de Almeida Juliano Pinheiro , de Oliveira Bello Mariana Vieira , Garzillo Cibele , Leme Alcino Costa , Elena Moizo , Val Fernando , de Almeida Lopes Marcela , Lacerda Marcus Vinícius Guimarães , Ramires José Antonio Franchini , Kalil Filho Roberto , Teboul Jean-Louis , Landoni Giovanni
Published: February 2021

SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), is responsible for the largest pandemic facing humanity since the Spanish flu pandemic in the early twentieth century. Since there is no specific antiviral treatment, optimized support is the most relevant factor in the patient's prognosis. In the hospital setting, the identification of high-risk patients for clinical deterioration is essential to ensure access to intensive treatment of severe conditions in a timely manner. The initial management of hypoxemia includes conventional oxygen therapy, high-flow nasal canula oxygen, and non-invasive ventilation. For patients requiring invasive mechanical ventilation, lung-protective ventilation with low tidal volumes and plateau pressure is recommended. Cardiovascular complications are frequent and include myocardial injury, thrombotic events, myocarditis, and cardiogenic shock. Acute renal failure is a common complication and is a marker of poor prognosis, with significant impact in costs and resources allocation. Regarding promising therapies for COVID-19, the most promising drugs until now are remdesivir and corticosteroids although further studies may be needed to confirm their effectiveness. Other therapies such as, tocilizumab, anakinra, other anti-cytokine drugs, and heparin are being tested in clinical trials. Thousands of physicians are living a scenario that none of us have ever seen: demand for hospital exceed capacity in most countries. Until now, the certainty we have is that we should try to decrease the number of infected patients and that an optimized critical care support is the best strategy to improve patient’s survival.
Obstructed labor and its association with adverse feto-maternal outcome in Ethiopia: a protocol for a systematic review and meta-analysis
Authors: Yeshitila Yordanos Gizachew , Desta Melaku , Kebede Abraham
Published: February 2021

Background

Obstructed labor accounted for 22% of obstetrical complications and 9% of all maternal deaths in low- and middle-income countries. Even though there are separate studies regarding obstructed labor and its complication in Ethiopia, their results are inconsistent. The objectives of this review will be to estimate the pooled the prevalence of obstructed labor and to identify adverse feto-maternal outcomes associated with obstructed labor in Ethiopia.

Methods

Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline will be followed to conduct this systematic review and meta-analysis. The databases we will search will be PubMed, Cochrane Library, Google Scholar, CINAHL, African Journals Online, Dimensions, and Summon per country online databases. To search the relevant literature, we will use the following key search terms: “prevalence,” “adverse outcome,” “obstructed labour,” “maternal near miss,” “neonatal near miss,” “perinatal outcome,” “cesarean section,” “obstetric fistula,” “uterine rupture,” and “Ethiopia.” Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument will be used for evaluating the quality of the studies. Appropriate statistical tests will be conducted to quantify the between studies heterogeneity and for the assessment of publication bias. We will check individual study influence analysis and also do subgroup analysis. The STATA version 15 will be used for statistical analysis.

Discussion

Our systematic review and meta-analysis will provide the pooled prevalence of obstructed labor and its association with adverse feto-maternal outcomes in Ethiopia. The finding of this study will be helpful to design appropriate preventive and promotive strategies for reducing of obstructed labor-related maternal mortality.

Systematic review registration

PROSPEROCRD42020196153.
The effects of weight fluctuation on the components of metabolic syndrome: a 16-year prospective cohort study in South Korea
Authors: Chin Young Ran , So Eun Sun
Published: February 2021

Background

Weight fluctuation (WF) is highly prevalent in parallel with the high prevalence of intentional or unintentional dieting. The health risks of frequent WF for metabolic syndrome (MS) have become a public health concern, especially for health care providers who supervise dieting as an intervention to prevent obesity-related morbidity or to improve health, as well as for the general population for whom dieting is of interest. The aim of this study was to investigate the long-term effect of WF on the risk of MS in Koreans.

Methods

This study analyzed secondary data from the Korean Genome and Epidemiology Study, a 16-year prospective cohort study, on 8150 individuals using time-dependent Cox regression.

Results

WF did not increase the risk of MS in either normal-weight or obese subjects. In an analysis of the components of MS, greater WF significantly increased the risk of abdominal obesity (HR = 1.05, 95% CI = 1.02–1.07, p < 0.001) in normal-weight individuals. However, WF did not increase the risk of hyperglycemia, low high-density lipoprotein cholesterol levels, elevated blood pressure, or raised fasting glucose in normal-weight individuals, and it did not influence any of the components of MS in obese individuals.

Conclusion

Since WF was found to be a risk factor for abdominal obesity, which is the most reliable predictor of MS, it should be considered when addressing weight control. Further studies on cut-off points for the degree of weight loss in a certain period need to be conducted to help clinicians provide guidance on appropriate weight control.
Competing socio-technical narratives in times of grid capacity challenges: the representative case of Sweden
Authors: Libertson Frans
Published: February 2021

Background

Around the globe the electricity sector is strikingly similar, as regardless of nation it is structured around centralized large-scale power production. However, these centralized systems are currently experiencing operational problems related to climate change, energy security and aging grid infrastructures. In Sweden, the lack of investment and maintenance of the grid have created bottlenecks in certain regions, which are now facing an electricity shortage. This capacity crisis has received the attention of the media and generated a debate around the future trajectory of the electricity system.

Results

The purpose of this study is to analyze the ongoing media discourse in Sweden to determine whether there is a dominant narrative in the debate and its potential implications. The findings indicate that the government is unanimously held accountable for the electricity shortage and that there is a strong inclination toward a centralized electricity system as a solution.

Conclusion

The results indicate that the dominating centralized narrative, should it receive too much traction, might create a technological lock-in and result in overlooking the many advantages of a decentralized electricity system. Ultimately, this might give rise to an outdated electricity system that stalls its transformation toward a more sustainable path.
Management of a hospital-wide vancomycin-resistant Enterococcus faecium outbreak in a Dutch general hospital, 2014–2017: successful control using a restrictive screening strategy
Authors: Weterings Veronica , van Oosten Anita , Nieuwkoop Ellen , Nelson Jolande , Voss Andreas , Wintermans Bas , van Lieshout Joris , Kluytmans Jan , Veenemans Jacobien
Published: February 2021

Background

The emergence of vancomycin resistant enterococci poses a major problem in healthcare settings. Here we describe a hospital-wide outbreak of vancomycin-resistant Enterococcus faecium in a general hospital in The Netherlands in the period December 2014–February 2017. Due to late detection of the outbreak, a large cohort of approximately 25,000 (discharged) patients was classified as ‘VRE suspected’. Hereupon a mitigated screening and isolation policy, as compared with the national guideline, was implemented to control the outbreak.

Methods

After the outbreak was identified, a screening policy consisting of a single rectal swab culture (with enrichment broth) to discontinue isolation and removing ‘VRE suspected’ label in the electronic patient files for readmitted VRE suspected patients, was implemented. In addition to the on admission screening, periodic hospital-wide point prevalence screening, measures to improve compliance with standard infection control precautions and enhanced environmental cleaning were implemented to control the outbreak.

Results

Between September 2014 and February 2017, 140 patients were identified to be colonised by vanA mediated vancomycin-resistant Enterococcus faecium (VREfm). Two of these patients developed bacteraemia. AFLP typing showed that the outbreak was caused by a single clone. Extensive environmental contamination was found in multiple wards. Within nine months after the detection of the outbreak no new VRE cases were detected.

Conclusion

We implemented a control strategy based on targeted screening and isolation in combination with implementation of general precautions and environmental cleaning. The strategy was less stringent than the Dutch national guideline for VRE control. This strategy successfully controlled the outbreak, while it was associated with a reduction in the number of isolation days and the number of cultures taken.
Post-peak Behaviour of Composite Column Using a Ductile Lightweight Aggregate Concrete
Authors: Hamidian Mohammad Reza , Shafigh Payam
Published: February 2021

Oil palm shell (OPS) concrete filled steel tube (CFT) columns are acknowledged to be a new type of sustainable composite column. In this type of column, the conventional coarse aggregate was partially replaced with OPS lightweight aggregate to provide a green composite column. This type of CFT column showed higher energy absorption and flexibility compared to CFT columns with normal weight concrete. This research studied the effect of the strength of OPS concrete on the axial compressive behaviour of CFT columns for two grades of OPS concretes. The behaviour was comparable to that of CFT columns with two grades of normal concrete. The results showed that the CFT columns with OPS concrete achieved a new post-peak behaviour. The experimental results of the axial compressive load were compared with the estimation of two international standards. EC4-1994 and ACI318-14 showed a reliable and conservative estimation of the axial load capacity of CFT columns, respectively.
Lactobacillus reuteri-derived extracellular vesicles maintain intestinal immune homeostasis against lipopolysaccharide-induced inflammatory responses in broilers
Authors: Hu Rujiu , Lin Hua , Wang Mimi , Zhao Yuezhen , Liu Haojing , Min Yuna , Yang Xiaojun , Gao Yupeng , Yang Mingming
Published: February 2021

Background

Lactobacillus reuteri strains are widely used as probiotics to prevent and treat inflammatory bowel disease by modulating the host’s immune system. However, the underlying mechanisms by which they communicate with the host have not been clearly understood. Bacterial extracellular vesicles (EVs) have been considered as important mediators of host-pathogen interactions, but their potential role in commensals-host crosstalk has not been widely studied. Here, we investigated the regulatory actions of EVs produced by L. reuteri BBC3, a gut-associated commensal bacterium of Black-Bone chicken, in the development of lipopolysaccharide (LPS)-induced intestinal inflammation in a chicken model using both in vivo and in vitro experiments.

Results

L. reuteri BBC3 produced nano-scale membrane vesicles with the size range of 60–250 nm. Biochemical and proteomic analyses showed that L. reuteri BBC3-derived EVs (LrEVs) carried DNA, RNA and several bioactive proteins previously described as mediators of other probiotics’ beneficial effects such as glucosyltransferase, serine protease and elongation factor Tu. In vivo broiler experiments showed that administration of LrEVs exerted similar effects as L. reuteri BBC3 in attenuating LPS-induced inflammation by improving growth performance, reducing mortality and decreasing intestinal injury. LrEVs suppressed the LPS-induced expression of pro-inflammatory genes (TNF-α, IL-1β, IL-6, IL-17 and IL-8), and improved the expression of anti-inflammatory genes (IL-10 and TGF-β) in the jejunum. LrEVs could be internalized by chicken macrophages. In vitro pretreatment with LrEVs reduced the gene expression of TNF-α, IL-1β and IL-6 by suppressing the NF-κB activity, and enhanced the gene expression of IL-10 and TGF-β in LPS-activated chicken macrophages. Additionally, LrEVs could inhibit Th1- and Th17-mediated inflammatory responses and enhance the immunoregulatory cells-mediated immunosuppression in splenic lymphocytes of LPS-challenged chickens through the activation of macrophages. Finally, we revealed that the reduced content of both vesicular proteins and nucleic acids attenuated the suppression of LrEVs on LPS-induced inflammatory responses in ex vivo experiments, suggesting that they are essential for the LrEVs-mediated immunoregulation.

Conclusions

We revealed that LrEVs participated in maintaining intestinal immune homeostasis against LPS-induced inflammatory responses in a chicken model. Our findings provide mechanistic insight into how commensal and probiotic Lactobacillus species modulate the host’s immune system in pathogens-induced inflammation.
Belinostat in combination with standard cyclophosphamide, doxorubicin, vincristine and prednisone as first-line treatment for patients with newly diagnosed peripheral T-cell lymphoma
Authors: Johnston Patrick B. , Cashen Amanda F. , Nikolinakos Petros G. , Beaven Anne W. , Barta Stefan Klaus , Bhat Gajanan , Hasal Steven J. , De Vos Sven , Oki Yasuhiro , Deng Changchun , Foss Francine M.
Published: February 2021

Background

Belinostat is a histone deacetylase inhibitor approved for relapsed refractory peripheral T-cell lymphoma (PTCL). The primary objective of this study was to determine the maximum tolerated dose (MTD) of belinostat combined with CHOP (Bel-CHOP). Secondary objectives included safety/tolerability, overall response rate (ORR), and belinostat pharmacokinetics (PK).

Methods

Patients were ≥ 18 years with histologically confirmed, previously untreated PTCL. Patients received belinostat (1000 mg/m2 once daily) + standard CHOP for 6 cycles with varying schedules using a 3 + 3 design in Part A. Part B enrolled patients at MTD dose.

Results

Twenty-three patients were treated. One patient experienced DLT (Grade 3 non-hematologic toxicity) on Day 1–3 schedule, resulting in escalation to Day 1–5 schedule (n = 3). No DLTs were observed and Day 1–5 schedule with 1000 mg/m2 was declared as MTD. Twelve additional patients were enrolled in Part B using MTD. Median relative dose intensity was 98%. All patients experienced adverse events (AEs), including nausea (78%), fatigue (61%), and vomiting (57%). Serious AEs occurred in 43%, with febrile neutropenia (17%) and pyrexia (13%). Overall ORR was 86% with 71% reported CR at MTD. Belinostat PK parameters were similar to single-agent.

Conclusions

Bel-CHOP was well tolerated and MTD in CHOP combination was the same dose and schedule as single agent dosing.

Trial Registration: ClinicalTrials.gov Identifier: NCT01839097.
Characterization of the human skin resistome and identification of two microbiota cutotypes
Authors: Li Zhiming , Xia Jingjing , Jiang Liuyiqi , Tan Yimei , An Yitai , Zhu Xingyu , Ruan Jie , Chen Zhihua , Zhen Hefu , Ma Yanyun , Jie Zhuye , Xiao Liang , Yang Huanming , Wang Jian , Kristiansen Karsten , Xu Xun , Jin Li , Nie Chao , Krutmann Jean , Liu Xiao , Wang Jiucun
Published: February 2021

Background

The human skin microbiota is considered to be essential for skin homeostasis and barrier function. Comprehensive analyses of its function would substantially benefit from a catalog of reference genes derived from metagenomic sequencing. The existing catalog for the human skin microbiome is based on samples from limited individuals from a single cohort on reference genomes, which limits the coverage of global skin microbiome diversity.

Results

In the present study, we have used shotgun metagenomics to newly sequence 822 skin samples from Han Chinese, which were subsequently combined with 538 previously sequenced North American samples to construct an integrated Human Skin Microbial Gene Catalog (iHSMGC). The iHSMGC comprised 10,930,638 genes with the detection of 4,879,024 new genes. Characterization of the human skin resistome based on iHSMGC confirmed that skin commensals, such as Staphylococcus spp, are an important reservoir of antibiotic resistance genes (ARGs). Further analyses of skin microbial ARGs detected microbe-specific and skin site-specific ARG signatures. Of note, the abundance of ARGs was significantly higher in Chinese than Americans, while multidrug-resistant bacteria (“superbugs”) existed on the skin of both Americans and Chinese. A detailed analysis of microbial signatures identified Moraxella osloensis as a species specific for Chinese skin. Importantly, Moraxella osloensis proved to be a signature species for one of two robust patterns of microbial networks present on Chinese skin, with Cutibacterium acnes indicating the second one. Each of such “cutotypes” was associated with distinct patterns of data-driven marker genes, functional modules, and host skin properties. The two cutotypes markedly differed in functional modules related to their metabolic characteristics, indicating that host-dependent trophic chains might underlie their development.

Conclusions

The development of the iHSMGC will facilitate further studies on the human skin microbiome. In the present study, it was used to further characterize the human skin resistome. It also allowed to discover the existence of two cutotypes on the human skin. The latter finding will contribute to a better understanding of the interpersonal complexity of the skin microbiome.
Expression of immune checkpoints on circulating tumor cells in men with metastatic prostate cancer
Authors: Zhang Tian , Agarwal Anika , Almquist R. Garland , Runyambo Daniella , Park Sally , Bronson Elizabeth , Boominathan Rengasamy , Rao Chandra , Anand Monika , Oyekunle Taofik , Healy Patrick , McNamara Megan A. , Ware Kathryn , Somarelli Jason A. , George Daniel J. , Armstrong Andrew J.
Published: February 2021

Background

A subset of men with metastatic prostate cancer (mPC) responds to immune checkpoint inhibitors, and there is an unmet need to predict those most likely to benefit. We characterized circulating tumor cells (CTCs) for expression of immune checkpoint ligands in men with mPC as a non-invasive biomarker of immune evasion and immunotherapy benefit.

Methods

Three cohorts of patients were enrolled: 1) men with mCRPC starting abiraterone acetate/prednisone or enzalutamide (pre-ARSI), 2) men with mCRPC who were progressing on enzalutamide or abiraterone acetate/prednisone (post-ARSI), and 3) men with newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) starting androgen deprivation therapy. CTCs were captured using the CellSearch® system and stained for PD-L1, PD-L2, B7-H3, and CTLA-4 at baseline, on treatment, and disease progression. Summary statistics on mean CTCs per cohort, as well as rates of ligand positivity were used to analyze CTCs by cohort and by timepoint.

Results

Men in all cohorts and timepoints had prevalent CTC B7-H3 expression (> 80%). We found evidence for CTC PD-L1 expression across disease states, in which > 1 positive CTC or > 50% of CTCs were positive for PD-L1 in 40 and 30% of men with mHSPC, respectively, 60 and 20% of men with mCRPC pre-ARSI, and 70 and 30% of men with mCRPC post-ARSI. CTC PD-L2 expression was present in 20–40% of men in each disease state, while CTC CTLA-4 expression was rare, present in 20% of men with mCRPC pre-ARSI and 10% of men with mCRPC post-ARSI or with mHSPC. CTC immune checkpoint expression was heterogeneous within/between men and across disease states.

Conclusions

We have identified that CTCs from men with mPC heterogeneously express immune checkpoints B7-H3, PD-L1, PD-L2, and CTLA-4, and the detection of these immune checkpoints may enable monitoring on immunotherapy.
5-year outcomes of salvage endoscopic nasopharyngectomy for recurrent nasopharyngeal carcinoma
Authors: Thamboo Andrew , Patel Vishal S. , Hwang Peter H.
Published: February 2021

Objective

Recurrent nasopharyngeal carcinoma (rNPC) can be salvaged with re-irradiation, open nasopharyngectomy, and more recently endoscopic nasopharyngectomy. However, long-term outcomes of endoscopic approaches are lacking. Thus, we report 5-year outcomes following endoscopic nasopharyngectomy for rNPC.

Methods

Patients who underwent endoscopic nasopharyngectomy for rNPC between January 2000 and January 2012 were retrospectively reviewed. Patients were included if they had their first endoscopic nasopharyngectomy at least 5 years prior to this study. Presenting (cTNM) status and recurrent (rTNM) status for each recurrence was determined. Outcomes included margin status, disease recurrence, death, and complication rates.

Results

Thirteen patients were included. Four patients had a prior open nasopharyngectomy. Mean time follow-up was 74.3 months (range = 56.4–96 months). Negative margins were achieved in 77% of initial cases. Positive margins were associated with higher rT stages. Re-recurrence was seen in 6 patients, which was also associated with a higher cStage and rStage. All patients with positive margins had re-recurrence. Four patients required repeat endoscopic nasopharyngectomy and two received chemoradiation. All four with a second endoscopic procedure had further disease recurrence. Five-year local disease-free and overall survival rates were 53.9 and 84.6%, respectively. The minor complication rate was 52.6%, major operative complication rate was 0.0%, and late complication rate was 23.1%.

Conclusion

Endoscopic nasopharyngectomy demonstrates promising 5-year overall survival rate for rT1 and rT2 cases of rNPC with favorable complication rates. Lower rStages were associated with a higher disease-free rate, and lower cStages were associated with improved overall prognosis. Close surveillance and prompt management of recurrences can be associated with favorable long-term tumor control.

Level of evidence

4

Graphical Abstract
Interdisciplinary conversations in STEM education: can faculty understand each other better than their students do?
Authors: Rabin Jeffrey M. , Burgasser Adam , Bussey Thomas J. , Eggers John , Lo Stanley M. , Seethaler Sherry , Stevens Laura , Weizman Haim
Published: February 2021

Rate of change concepts from calculus are presented and applied rather differently in college mathematics, physics, biology, and chemistry classes. This is not simply a matter of pedagogical style but reflects real cultural differences between these disciplines. We describe the efforts of our interdisciplinary collaboration to understand and reconcile these differences as we designed and discussed instructional videos for students. We summarize our conversations about terminology, notation, functions, rates, units, and sign conventions across the disciplines. We present some strategies that enabled us to communicate effectively, resolve confusions, and reach shared understandings. Our work has implications for others involved in collaborative interdisciplinary projects and for STEM educators.

In theory, there’s no difference between theory and practice. But in practice, there is.

– Benjamin Brewster. Also attributed to Yogi Berra.
Geomagnetic Virtual Observatories: monitoring geomagnetic secular variation with the Swarm satellites
Authors: Hammer Magnus D. , Cox Grace A. , Brown William J. , Beggan Ciarán D. , Finlay Christopher C.
Published: February 2021

We present geomagnetic main field and secular variation time series, at 300 equal-area distributed locations and at 490 km altitude, derived from magnetic field measurements collected by the three Swarm satellites. These Geomagnetic Virtual Observatory (GVO) series provide a convenient means to globally monitor and analyze long-term variations of the geomagnetic field from low-Earth orbit. The series are obtained by robust fits of local Cartesian potential field models to along-track and East–West sums and differences of Swarm satellite data collected within a radius of 700 km of the GVO locations during either 1-monthly or 4-monthly time windows. We describe two GVO data products: (1) ‘Observed Field’ GVO time series, where all observed sources contribute to the estimated values, without any data selection or correction, and (2) ‘Core Field’ GVO time series, where additional data selection is carried out, then de-noising schemes and epoch-by-epoch spherical harmonic analysis are applied to reduce contamination by magnetospheric and ionospheric signals. Secular variation series are provided as annual differences of the Core Field GVOs. We present examples of the resulting Swarm GVO series, assessing their quality through comparisons with ground observatories and geomagnetic field models. In benchmark comparisons with six high-quality mid-to-low latitude ground observatories we find the secular variation of the Core Field GVO field intensities, calculated using annual differences, agrees to an rms of 1.8 nT/yr and 1.2 nT/yr for the 1-monthly and 4-monthly versions, respectively. Regular sampling in space and time, and the availability of data error estimates, makes the GVO series well suited for users wishing to perform data assimilation studies of core dynamics, or to study long-period magnetospheric and ionospheric signals and their induced counterparts. The Swarm GVO time series will be regularly updated, approximately every four months, allowing ready access to the latest secular variation data from the Swarm satellites.
Correction to: ICU-outcomes in CAR-T patients—A single centre experience
Authors: Materski T. , John M. , Pirani T. , Benjamin R. , Kuhnl A. , Potter V. , Sanderson R. , Metaxa V.
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Feasibility of ABLE 1.0—a program aiming at enhancing the ability to perform activities of daily living in persons with chronic conditions
Authors: Nielsen Kristina Tomra , Guidetti Susanne , von Bülow Cecilie , Klokker Louise , Wæhrens Eva Ejlersen
Published: February 2021

Background

The “A Better everyday LifE” (ABLE) intervention was developed to accommodate the need of a program addressing ability to perform activities of daily living (ADL) in persons with chronic conditions living at home. During intervention development, it is necessary to evaluate relevant aspects of the feasibility of a program. Thus, the aim was to evaluate the feasibility of content and delivery of ABLE version 1.0.

Methods

A one group pre- and post-test design was applied. Thirty persons with chronic conditions, two occupational therapists (OTs), and five occupational therapy students (OTSs) participated. ABLE 1.0 is an 8-week program consisting of ADL evaluation (session 1); goal setting and reasons for ADL problems (session 2); intervention (sessions 3–7); and re-evaluation (final session), conducted in the clients’ home-setting and local area. Sessions 1–4 and the final session was mandatory.

To evaluate the feasibility of content and delivery, the OTs, after each session, reported on applied intervention component(s), time-use, needed equipment, adjustments, meaningfulness, confidence, progress toward goal attainment, and side effects using registration forms. The clients reported on progress toward goal attainment, meaningfulness, and satisfaction. Clinically relevant improvements in ADL ability were identified using the ADL-Interview (ADL-I) and the Assessment of Motor and Process Skills (AMPS). Goal attainment was evaluated using the Goal Attainment Scaling (GAS).

Results

Twenty clients (67%) completed ABLE 1.0 and received four sessions (median = 4, range 4–7) each lasting between 30 and 94 min. Most frequently applied component was “Changing habits related to task performance”. Generally, OTs reported having the needed equipment. Deviations from the manual were made by omission of GAS and AMPS and less than mandatory number of sessions per client. The OTs reported confidence in delivering the program and the clients perceived the program as meaningful and satisfying, and experienced progress toward goal attainment. Goal attainment was found in 52% of the goals. Sixteen (80%) clients obtained clinically relevant improvements in self-reported or observed ADL ability.

Conclusions

The content and delivery of ABLE 1.0 was feasible. However, the study revealed a need to adjust the recruitment procedure and make minor changes in the intervention manual. A pilot randomized controlled trial (RCT) study is recommended.

Trial registration

The study was registered at ClinicalTrials.gov with registration no. NCT03335709 on November 8, 2017.