bluuebunny/crossref_metadata_2025 huggingface dataset:
Portable medical orders and end-of-life measures in acute myeloid leukemia and myelodysplastic syndromes
Authors: LoCastro Marissa , Baran Andrea M. , Liesveld Jane L. , Huselton Eric , Becker Michael W. , O’Dwyer Kristen Marie , Aljitawi Omar S. , Baumgart Megan , Snyder Eric , Kluger Benzi , Loh Kah Poh , Mendler Jason H.
Published: September 2021

Patients with acute myeloid leukemia (AML) or a myelodysplastic syndrome (MDS) experience high rates of hospitalization, intensive care unit (ICU) admission, and in-hospital death at the end of life. Early goals-of-care (GOC) discussions may reduce the intensity of end-of-life (EOL) care. Portable Medical Order forms, known as Medical Orders for Life-Sustaining Treatment (MOLST) forms in New York state, assist patients in translating GOC discussions into specific medical orders that communicate their wishes during a medical emergency. To determine whether the timing of completion of a MOLST form is associated with EOL care in patients with AML or MDS, we conducted a retrospective study of 358 adult patients with AML or MDS treated at a single academic center and its affiliated sites, who died during a 5-year period. One-third of patients completed at least 1 MOLST form >30 days before death. Compared with patients who completed a MOLST form within 30 days of death or never, those who completed a MOLST form >30 days before death were less likely to receive transfusion (adjusted odds ratio [AOR], 0.39; P < .01), chemotherapy (AOR, 0.24; P < .01), or life-sustaining treatments (AOR, 0.21; P < .01) or to be admitted to the ICU (AOR, 0.21; P < .01) at EOL. They were also more likely to use hospice services (AOR, 2.72; P < .01). Earlier MOLST form completion was associated with lower intensity of care near EOL in patients with MDS or AML.
Platelets: a potential role in chronic respiratory diseases?
Authors: Chebbo Mohamad , Duez Catherine , Alessi Marie C. , Chanez Pascal , Gras Delphine
Published: September 2021

Platelets are small anucleate cells known for their role in haemostasis and thrombosis. In recent years, an increasing number of observations have suggested that platelets are also immune cells and key modulators of immunity. They express different receptors and molecules that allow them to respond to pathogens, and to interact with other immune cells. Platelets were linked to the pathogenesis of some inflammatory disorders including respiratory diseases such as asthma and idiopathic pulmonary fibrosis. Here, we discuss the involvement of platelets in different immune responses, and we focus on their potential role in various chronic lung diseases.
Minute ventilation/carbon dioxide production in congenital heart disease
Authors: Hager Alfred
Published: September 2021

This review summarises various applications of how ventilatory equivalent (ventilatory efficiency or better still ventilatory inefficiency) and the minute ventilation (VʹE)/carbon dioxide production (VʹCO2) slope obtained from cardiopulmonary exercise testing (CPET) can be used in the diagnostic or prognostic workup of patients with congenital heart disease.

The field of congenital heart disease comprises not only a very heterogeneous patient group with various heart diseases, but also various conditions in different stages of repair, as well as the different residuals seen in long-term follow-up. As such, various physiologic disarrangements must be considered in the analysis of increasedVʹE/VʹCO2slope from CPET in patients with congenital heart disease. In addition to congestive heart failure (CHF), cyanosis, unilateral pulmonary stenosis and pulmonary hypertension (PH) provide the background for this finding. The predictive value of increasedVʹE/VʹCO2slope on prognosis seems to be more important in conditions where circulatory failure is associated with failure of the systemic ventricle. In cyanotic patients, those with Fontan circulation, or those with substantial mortality from arrhythmia, the impact ofVʹE/VʹCO2on prognosis is not that important.
Postmortem diagnosis of pulmonary tumor thrombotic microangiopathy with rapid exacerbation in a patient with gastric cancer: a case report
Authors: Kamidani Ryo , Kumada Keisuke , Okada Hideshi , Yoshimura Genki , Kanayama Tomohiro , Tomita Hiroyuki , Miura Tomotaka , Oiwa Hideaki , Mizuno Yosuke , Kitagawa Yuichiro , Yasuda Ryu , Fukuta Tetsuya , Miyake Takahito , Doi Tomoaki , Yoshida Takahiro , Yoshida Shozo , Hara Akira , Ogura Shinji
Published: September 2021

Background

Pulmonary tumor thrombotic microangiopathy (PTTM) is a condition that involves the development of pulmonary hypertension due to the presence of microscopic tumor emboli of the peripheral pulmonary arteries. Here, we report a case of rapidly exacerbating PTTM associated with gastric cancer that was identified postmortem through pathological autopsy.

Case presentation

A 52-year-old Asian woman who experienced anterior chest pain while coughing visited the orthopedic department of the Gifu University Hospital. She was diagnosed as having multiple osteolytic bone metastases throughout her body and was subsequently scheduled to undergo combined positron emission tomography and computed tomography (CT) to search for a primary lesion. However, 4 days after her visit to the orthopedic department, she was unable to stand up and thus visited the emergency department. At the time of admission, physical examination results revealed that she had a percutaneous oxygen saturation level of 90% (on room air) and cyanosis and that she was in a state of hemodynamic shock. Laboratory test results revealed elevated levels of fibrin degradation products and D-dimer in her blood. Chest CT results were normal. She was admitted to the hospital’s general ward for follow-up but soon entered a gradually worsening state of shock and respiratory failure. Electrocardiography revealed findings associated with right heart strain; however, contrast-enhanced CT did not reveal the presence of pulmonary embolism. She was admitted to the intensive care unit and was treated for pulmonary hypertension; however, 45 h after her arrival at the hospital, she died of respiratory failure. A pathological autopsy revealed the presence of gastric cancer, tumor microemboli, and fibrous intimal thickening of the peripheral arteries of both lungs; thus, a diagnosis of PTTM was made.

Conclusions

In patients with carcinoma of unknown primary site and pulmonary hypertension with pulmonary embolism ruled out by CT, emergency physicians and intensivists must consider the possibility of PTTM, which represents an oncologic emergency, and initiate chemotherapy administration as soon as possible.
How does driving license withdrawal affect subjective well-being? A Swedish comparative survey study of visual field loss
Authors: Nyberg Jonna , Björklund Gunilla , Aretun Åsa , Berg Hans-Yngve , Strandberg Thomas
Published: September 2021

Research has found strong relationships between access to transport, accessibility of activities, and subjective well-being (SWB), and society is said to be car dependent. Accordingly, this study investigates, in a Swedish context, whether and how withdrawal of a driving license for a private car due to visual field loss (VFL) affects SWB. A web survey was used for statistical comparisons of three respondent groups (n = 436): people with a driving license, people with a driving license and VFL, and people whose driving license was withdrawn due to VFL. The inclusion criterion for all participants was that they should have a diagnosis that could cause VFL. The no-license group had lower overall SWB than did respondents with driving licenses. The no-license group also perceived less access to transport means in order to live a life to be satisfied with than did the other groups. The most used transport means in the no-license group was getting a lift in a car, though this group had a strong desire to drive a car. Few respondents in the license groups wanted to use specific transport means to a greater extent, car driving being the most used transport means. Some inter-group differences were seen regarding how access to activities (measured by frequency of actual trips) affected SWB. This study found a significant negative effect of driving license withdrawal on SWB. However, the results imply that qualitative aspects other than the relationship between the frequencies of trips and activities might also affect SWB, and more research on this subject is needed.
Vitrectomy for diabetic macular edema and the relevance of external limiting membrane
Authors: Ivastinovic Domagoj , Haas Anton , Weger Martin , Seidel Gerald , Mayer-Xanthaki Christoph , Lindner Ewald , Guttmann Andreas , Wedrich Andreas
Published: September 2021

Purpose

To evaluate the relevance of external limiting membrane (ELM) on the visual and morphological results in eyes with diabetic macular edema (DME) that underwent pars plana vitrectomy (PPV) with epiretinal membrane (ERM) and internal limiting membrane (ILM) peeling.

Methods

Medical records of patients with DME who underwent PPV at our unit between January 2017 and December 2019 were reviewed. We assessed preoperative and postoperative best-corrected visual acuity (BCVA), central macular thickness (CMT) using spectral domain OCT (optical coherence tomography). Exclusion criteria were previous PPV; incomplete data; concomitant diseases including retinal vein occlusion, age-related macular degeneration, uveitis; and a follow-up of less than 12 months. The surgeries were performed using 23- or 27-gauge vitrectomy. The ELM was graded depending on its configuration (grade 0 = intact, grade 1 to 3: disruption of varying extent).

Results

Ninety-nine eyes were enrolled. The postoperative follow up averaged 23.7 months. The preoperative and final BCVA averaged 0.71 ± 0.28 and 0.52 ± 0.3 logMAR, respectively (p = 0.002). The CMT averaged 515.2 ± 209.1 μm preoperatively and 327 ± 66.1 μm postoperatively (p = 0.001). Eyes with intact ELM (n = 8) had a significantly better BCVA compared to those with ELM disruption (0.28 ± 0.14 vs. 0.7 ± 0.25 logMAR, p = 0.01). The final CMT was similar among the groups (intact ELM: 317 ± 54.6 μm; ELM disruption: 334 ± 75.2, p = 0.31).

Conclusions

PPV with ERM and ILM peeling is an effective treatment of DME. Eyes with intact ELM preoperatively had a significantly better final visual outcome. To maximize the benefit for patients with DME we recommend early PPV as long as ELM is intact.
Comparisons of disease cluster patterns, prevalence and health factors in the USA, Canada, England and Ireland
Authors: Hernández Belinda , Voll Stacey , Lewis Nathan A. , McCrory Cathal , White Arthur , Stirland Lucy , Kenny Rose Anne , Reilly Richard , Hutton Craig P. , Griffith Lauren E. , Kirkland Susan A. , Terrera Graciela Muniz , Hofer Scott M.
Published: September 2021

Background

Identification of those who are most at risk of developing specific patterns of disease across different populations is required for directing public health policy. Here, we contrast prevalence and patterns of cross-national disease incidence, co-occurrence and related risk factors across population samples from the U.S., Canada, England and Ireland.

Methods

Participants (n = 62,111) were drawn from the US Health and Retirement Study (n = 10,858); the Canadian Longitudinal Study on Ageing (n = 36,647); the English Longitudinal Study of Ageing (n = 7938) and The Irish Longitudinal Study on Ageing (n = 6668). Self-reported lifetime prevalence of 10 medical conditions, predominant clusters of multimorbidity and their specific risk factors were compared across countries using latent class analysis.

Results

The U.S. had significantly higher prevalence of multimorbid disease patterns and nearly all diseases when compared to the three other countries, even after adjusting for age, sex, BMI, income, employment status, education, alcohol consumption and smoking history. For the U.S. the most at-risk group were younger on average compared to Canada, England and Ireland. Socioeconomic gradients for specific disease combinations were more pronounced for the U.S., Canada and England than they were for Ireland. The rates of obesity trends over the last 50 years align with the prevalence of eight of the 10 diseases examined. While patterns of disease clusters and the risk factors related to each of the disease clusters were similar, the probabilities of the diseases within each cluster differed across countries.

Conclusions

This information can be used to better understand the complex nature of multimorbidity and identify appropriate prevention and management strategies for treating multimorbidity across countries.
Intra-articular therapy with methotrexate or tumor necrosis factor inhibitors in rheumatoid arthritis: a systematic review
Authors: Sullivan Megan M. , Pham Michael M. , Marks Lisa A. , Aslam Fawad
Published: September 2021

Background

Persistent monoarthritis in otherwise well-controlled rheumatoid arthritis presents a therapeutic challenge. Intra-articular (IA) steroids are a mainstay of treatment, though some have queried whether IA disease modifying anti-rheumatic drugs (DMARD) and biologics can be used in those who fail steroid injections.

Methods

A systematic literature review was conducted using four medical databases to identify randomized, controlled trials assessing IA therapies in RA patients. Included studies underwent Cochrane Risk of Bias 2 assessment for quality.

Results

Twelve studies were included, 6 of which examined intra-articular (IA) TNF inhibitors (TNFi), and 6 studies evaluating IA methotrexate. Of those evaluating IA TNFi, one study reported statistical improvement in TNFi therapy when compared with placebo. The remaining 5 studies compared IA TNFi therapy with steroid injections. IA TNFi had statistically improved symptom scores and clinical assessments comparable with IA steroid treatments.

In the 6 studies evaluating IA methotrexate, the addition of methotrexate to steroid intra-articular therapy was not found to be beneficial, and singular methotrexate injection was not superior to the control arms (saline or triamcinolone). Risk-of-bias (ROB) assessment with the Revised Cochrane ROB tool indicated that 2 of 6 TNFi studies were at some risk or high risk for bias, compared with 5 out of 6 methotrexate studies.

Conclusion

For persistent monoarthritis in rheumatoid arthritis, IA methotrexate was not found to have clinical utility. Intra-articular TNFi therapy appears to have equal efficacy to IA steroids, though the optimal dose and frequency of injections is yet unknown.
GLP-1 receptor agonists and cardiorenal outcomes in type 2 diabetes: an updated meta-analysis of eight CVOTs
Authors: Giugliano Dario , Scappaticcio Lorenzo , Longo Miriam , Caruso Paola , Maiorino Maria Ida , Bellastella Giuseppe , Ceriello Antonio , Chiodini Paolo , Esposito Katherine
Published: September 2021

Background

A meta-analysis is presented of cardiovascular outcome trials (CVOTs) comparing glucagon-like peptide-1 receptor agonists (GLP-1RA) versus placebo on cardiorenal outcomes in patients with type 2 diabetes mellitus (T2DM).

Methods

We did an electronic search up to June 30, 2021, for eligible trials. We did a meta-analysis of available trial data using a random-effects model to calculate overall hazard ratios (HRs) and 95% CI (confidence intervals). We included data from 8 CVOTs and 60,080 patients (72.4% with established cardiovascular disease).

Results

GLP-1RA reduced major cardiovascular events (MACE) by 14% (HR = 0.86, 95% CI 0.79–0.94, P = 0.006) with a non-significant heterogeneity between subgroups of patients with and without cardiovascular disease (P = 0.127). GLP-1RA also reduced the risk of cardiovascular death by 13% (P = 0.016), nonfatal stroke by 16% (P = 0.007), hospitalization for heart failure by 10% (P = 0.023), all-cause mortality by 12% (P = 0.012), and the broad composite kidney outcome by 17% (P = 0.012), which was driven by a reduction in macroalbuminuria only (HR = 0.74, 0.67–0.82, P < 0.001).

Conclusions

GLP-1RA have moderate benefits on MACE, and also reduce hospitalization for heart failure and all-cause mortality; they also have robust benefits on reducing the incidence of macroalbuminuria.
Regulatory T cells protect against brain damage by alleviating inflammatory response in neuromyelitis optica spectrum disorder
Authors: Ma Xue , Qin Chuan , Chen Man , Yu Hai-Han , Chu Yun-Hui , Chen Ting-Jun , Bosco Dale B. , Wu Long-Jun , Bu Bi-Tao , Wang Wei , Tian Dai-Shi
Published: September 2021

Background and purpose

Neuromyelitis optica spectrum disorder (NMOSD) is mainly an anti-aquaporin 4 (anti-AQP4) autoantibodies-mediated idiopathic inflammatory demyelinating disease of the central nervous system. Systemic and local inflammatory responses play a key role in the pathophysiology of NMOSD. However, the role of the crucial immunomodulators CD4+CD25+ forkhead box P3+ (Foxp3) regulatory T cells (Tregs) has not been investigated in NMOSD.

Methods

Twenty-five patients with anti-AQP4-postive NMOSD undergoing an attack and 21 healthy controls (HCs) were enrolled. Frequencies of T cell subsets and Tregs in the peripheral blood were assessed by flow cytometry. Additionally, a model of NMOSD using purified immunoglobulin G from anti-AQP4-antibodies-positive patients with NMOSD and human complement injected into brain of female adult C57BL/6J mice was established. Infiltrated Tregs into NMOSD mouse brain lesions were analyzed by flow cytometry, histological sections, and real-time quantitative Polymerase Chain Reaction. Astrocyte loss, demyelination, and inflammatory response were also evaluated in our NMOSD mouse model. Finally, we examined the effects of both depletion and adoptive transfer of Tregs.

Results

The percentage of Tregs, especially naïve Tregs, among total T cells in peripheral blood was significantly decreased in NMOSD patients at acute stage when compared to HCs. Within our animal model, the number and proportion of Tregs among CD4+ T cells were increased in the lesion of mice with NMOSD. Depletion of Tregs profoundly enhanced astrocyte loss and demyelination in these mice, while adoptive transfer of Tregs attenuated brain damage. Mechanistically, the absence of Tregs induced more macrophage infiltration, microglial activation, and T cells invasion, and modulated macrophages/microglia toward a classical activation phenotype, releasing more chemokines and pro-inflammatory cytokines. In contrast, Tregs transfer ameliorated immune cell infiltration in NMOSD mice, including macrophages, neutrophils, and T cells, and skewed macrophages and microglia towards an alternative activation phenotype, thereby decreasing the level of chemokines and pro-inflammatory cytokines.

Conclusion

Tregs may be key immunomodulators ameliorating brain damage via dampening inflammatory response after NMOSD.
Understanding Australian female chiropractors’ experiences of inappropriate patient sexual behaviour: a study using Interpretive Phenomenological Analysis
Authors: Innes Stanley , Maurice Laura , Lastella Michele , O’Mullan Catherine
Published: September 2021

Introduction

Female practitioners are often subjected to inappropriate patient sexual behaviour (IPSB). Adverse consequences of such sexual harassment include for the practitioner psychological stress effects and negative work-related consequences that contributes to career dissatisfaction and burnout. Confronting the issue within the healthcare context has been shown to be problematic because practitioners feel an obligation to protect the therapeutic relationship above their own personal discomfort. There is an absence of research on this topic with respect to female chiropractors and we proposed a qualitative study aimed to explore female chiropractors lived experiences of managing incidents of IPSB.

Method

An Interpretive Phenomenological Analysis methodology was chosen for this study. In June and July of 2018 female chiropractors in Western Australian were recruited via Facebook sites and invited to participate in face-to-face interviews for an Honours degree study exploring the lived experience of IPSB.

Results

Participants were seven female chiropractors currently practicing in Western Australia, who had experienced an incident of IPSB. Four super-ordinate themes emerged from the analysis; (1) familiar but inarticulable, (2) the cost of conflict, (3) I’m used to it, and (4) the element of surprise. Overall, the participants recognised the incidents as inappropriate but chose to ignore the situation as a means to avoid conflict in the treatment room. Recommendations are made to better manage IPSB including greater patient awareness of appropriate behaviour, specific curriculum content and assertiveness training in undergraduate programs and continuing professional education, as well as the creation of ethical guidelines for patient behaviour by regulatory bodies.

Conclusion

This is the first study to give a forum for female chiropractors to discuss their experiences of IPSB. The domain of private practice is not immune to incidents IPSB and although similar to day-to-day non-clinical life is nonetheless surprising and impactful.
Eyes wide shut: necessity and effect of adjunctive procedures after decompression surgery in patients with endocrine orbitopathy
Authors: Krause Matthias , Kamal Mohammad , Halama Dirk , Hierl Thomas , Sterker Ina , Zimmerer Rüdiger , Lethaus Bernd , Bartella Alexander K.
Published: September 2021

Background

Orbital decompression surgery is frequently the last therapeutic measure in the surgical treatment of endocrine orbitopathy (EO). Additional rehabilitative and corrective surgical treatments are often used to improve the resulting eyelid stigmata, such as an increased lid aperture and scleral show. The aim of the study was to evaluate the effect of adjunctive surgical procedures after orbital decompression surgery in patients with EO.

Methods

A total of 120 orbitae from 65 patients with EO from 2010 to 2020 at a tertiary care center in Germany were retrospectively evaluated. Ocular surface area (OSA) and vertical palpebral fissures were three-dimensionally analyzed at the following stages: presurgical decompression, postsurgical decompression, and post-adjunctive surgical procedures. For the analysis of vertical palpebral fissures, predefined vertical line distances were measured on the upper and lower lids in the central, medial, and lateral pupillary regions.

Results

The initial OSA was 2,98 ± 0.85 cm2, and it decreased significantly after decompression surgery to 2.52 ± 0.62 cm2. After adjunct surgical procedures, OSA further decreased to 2,31 ± 0,55 cm2. Furthermore, a statistically significant reduction in all pupillary parameters was noted after each treatment step. More lid-lengthening procedures were performed on the lower lid than on the upper lid. Canthoplasty (n = 13) was the most frequently performed procedure during rehabilitation.

Conclusion

Surgical decompression surgery improves OSA and leads to a significant reduction in lid aperture. Adjunctive surgical procedures, addressing the upper and lower lid, have a significant influence on the ongoing clinical course and contribute to a reduction in OSA.
Association of prenatal medical risk with breastfeeding outcomes up to 12 months in the All Our Families community-based birth cohort
Authors: Scime Natalie V. , Metcalfe Amy , Nettel-Aguirre Alberto , Tough Suzanne C. , Chaput Kathleen H.
Published: September 2021

Background

Prenatal medical risk describes physical health issues or biological factors that predate or arise during pregnancy which heighten the risk of adverse outcomes, and often warrant specialized obstetric care. The influence of the nature and magnitude of prenatal risk on breastfeeding outcomes remains poorly understood. The objective of this study was to determine the association between prenatal medical risk and breastfeeding initiation and duration up to 1 year postpartum.

Methods

We analysed a subset of data from the All Our Families longitudinal cohort (n = 2706) of women in Calgary, Canada who delivered a liveborn infant between 2008 and 2010. Data were collected from self-report questionnaires and medical records. Women with complete data on prenatal medical risk factors and breastfeeding outcomes were included in this analysis. Prenatal medical risk was operationalized as one integer score of risk severity and four binary risk types capturing pre-pregnancy characteristics, past obstetric problems, current obstetric problems, and substance use. Outcomes were breastfeeding initiation defined as the infant ever receiving breast milk, and duration operationalized as still breastfeeding at 4 months, at 12 months, and time to breastfeeding cessation in weeks. We used logistic regression and Cox regression with right censoring at 52 weeks or attrition to calculate odds ratios (OR) and hazard ratios (HR), respectively, adjusting for sociodemographic vulnerability, parity, mode of delivery, and gestational age.

Results

Prenatal medical risk severity and type were not significantly associated with breastfeeding initiation, with the exception of pre-pregnancy risk type (OR 0.45; 95% CI 0.26, 0.77). Risk severity was associated with lower odds of breastfeeding to 4 months (OR 0.94; 95% CI 0.90, 0.99), 12 months (OR 0.93; 95% CI 0.87, 0.98), and earlier breastfeeding cessation (HR 1.05; 95% CI 1.02, 1.08). Associations with shorter breastfeeding length across the first postpartum year were observed for pre-pregnancy, current obstetric, and substance use risk types, but not past obstetric problems.

Conclusion

Prenatal medical risk is associated with shortened duration of breastfeeding. Women with prenatal medical risk may benefit from the proactive arrangement of lactation support before and following delivery to promote continued breastfeeding.
Sintilimab, stereotactic body radiotherapy and granulocyte–macrophage colony stimulating factor as second-line therapy for advanced non-small cell lung cancer: safety run-in results of a multicenter, single-arm, phase II trial
Authors: Ni Jianjiao , Zhou Yue , Wu Lin , Ai Xinghao , Dong Xiaorong , Chu Qian , Han Chengbo , Wang Xiaofei , Zhu Zhengfei
Published: September 2021

Objectives

The SWORD trial is the first multicenter, single arm, phase II study assessing the safety and efficacy of a PD-1 inhibitor (Sintilimab), stereotactic body radiotherapy (SBRT) and granulocyte–macrophage colony stimulating factor (GM-CSF) in advanced non-small cell lung cancer (NSCLC) without sensitizing driver mutations. A safety run-in phase was conducted to determine the tolerability of the experimental treatment.

Materials and methods

Twenty metastatic NSCLC patients who failed first-line chemotherapy were enrolled, and they received SBRT (8 Gy × 3) to one lesion, followed by Sintilimab (200 mg d1, every 3 weeks, until disease progression, unacceptable toxicity, or up to 35 cycles) and GM-CSF (125 μg/m2 d1-d14, cycle 1) within 2 weeks after SBRT. In addition, blood and tissue samples were serially collected for translational research.

Results

Median age of the patients was 61 and all of them had more than 5 lesions at baseline. The sites of SBRT included lung (n = 11), mediastinal lymph node (n = 5), liver (n = 1), abdominal lymph node (n = 1), pleural nodule (n = 1) and vertebra (n = 1). No patients had dose-limiting toxicities (DLTs) and 18 patients experienced treatment-related adverse event (TRAE). The most common TRAEs were fatigue (50%), fever (30%), and ostealgia (20%), and they all were grade 1. Only 2 grade 3 TRAEs were observed, including elevation of liver enzymes in one and transient acute heart failure in another. No grade 4 or 5 AE was observed.

Conclusion

Sintilimab, SBRT and GM-CSF for advanced NSCLC is safe with manageable TRAEs and the trial continues to recruit participants.

Trial registration ClinicalTrials.gov, NCT04106180. Registered 26 September 2019, SBRT in Combination With Sintilimab and GM-CSF for the Treatment of Advanced NSCLC-Tabular View-ClinicalTrials.gov.
Improving the continuity and coordination of ambulatory care through feedback and facilitated dialogue—a study protocol for a cluster-randomised trial to evaluate the ACD study (Accountable Care in Germany)
Authors: Sundmacher Leonie , Flemming Ronja , Leve Verena , Geiger Isabel , Franke Sebastian , Czihal Thomas , Krause Clemens , Wiese Birgitt , Meyer Frank , Brittner Matthias , Pollmanns Johannes , Martin Johannes , Brandenburg Paul , Schultz Annemarie , Brua Emmanuelle , Schneider Udo , Dortmann Olga , Rupprecht Christoph , Wilm Stefan , Schüttig Wiebke
Published: September 2021

Background

Patients in Germany are free to seek care from any office-based physician and can always ask for multiple opinions on a diagnosis or treatment. The high density of physicians and the freedom to choose among them without referrals have led to a need for better coordination between the multiple health professionals treating any given patient. The objectives of this study are to (1) identify informal networks of physicians who treat the same patient population, (2) provide these physicians with feedback on their network and patients, using routine data and (3) give the physicians the opportunity to meet one another in facilitated network meetings.

Methods

The Accountable Care Deutschland (ACD) study is a prospective, non-blinded, cluster-randomised trial comprising a process and economic evaluation of informal networks among 12,525 GPs and office-based specialists and their 1.9 million patients. The units of allocation are the informal networks, which will be randomised either to the intervention (feedback and facilitated meetings) or control group (usual care). The informal networks will be generated by identifying connections between office-based physicians using complete datasets from the Regional Associations of Statutory Health Insurance (SHI) Physicians in Hamburg, Schleswig Holstein, North Rhine and Westphalia Lip, as well as data from three large statutory health insurers in Germany. The physicians will (a) receive feedback on selected indicators of their own treatment activity and that of the colleagues in their network and (b) will be invited to voluntary, facilitated network meetings by their Regional Association of SHI physicians. The primary outcome will be ambulatory-care-sensitive hospitalisations at baseline, at the end of the 2-year intervention period, and at six months and at 12 months after the end of the intervention period. Data will be analysed using the intention-to-treat principle. A pilot study preceded the ACD study.

Discussion

Cochrane reviews show that feedback can improve everyday medical practice by shedding light on previously unknown relationships. Providing physicians with information on how they are connected with their colleagues and what the outcomes are of care delivered within their informal networks can help them make these improvements, as well as strengthen their awareness of possible discontinuities in the care they provide.

Trial registration

German Clinical Trials Register DRKS00020884. Registered on 25 March 2020—retrospectively registered.
Vaccine trials during a pandemic: potential approaches to ethical dilemmas
Authors: Alqahtani Manaf , Mallah Saad I. , Stevenson Nigel , Doherty Sally
Published: September 2021

Ever since the emergence of the coronavirus disease 2019 (COVID-19), global public health infrastructures and systems, along with community-wide collaboration and service, have risen to an unprecedented challenge. Vaccine development was immediately propelled to the centre of all our scientific, public health and community efforts. Despite the development of SARS-CoV-2 vaccines arguably being the greatest and most palpable achievements of the past 12 months, they have also been one of the most contentious and debated issues during the pandemic. However, what uniquely differentiates vaccine development is its intimate relationship with the community it seeks to serve; both in its clinical trial testing as an efficacious and safe prophylactic, and its post-developmental ‘roll-out’ success, as an effective public health tool. These relationships have birthed a myriad of complexities, from community-based mistrust, to academically contended ethical dilemmas. Indeed, the accelerated advances in the COVID-19 vaccine race have further exacerbated this phenomenon, bringing with it new ethical dilemmas that need to be examined to ensure the continued clinical success of these therapeutics and a renewed societal trust in clinical medicine.

In this paper, we discuss two major ethical dilemmas: (1) the equipoise of continuing new vaccine trials in the advent of successful candidates and (2) the maleficence of blinded placebo arms. Accordingly, we discuss six different potential approaches to these ethical dilemmas: (1) continuing with placebo-controlled trials, (2) transitioning from placebo-controlled to open-label, (3) unblinding at-risk priority groups only, (4) transitioning to a blinded stepped-wedge cross-over design, (5) progressing to a blinded active-controlled stepped-wedge cross-over trial, and (6) conducting randomised stepped-wedge community trials. We also propose a decision-making algorithm for relevant stakeholders in advanced stages of vaccine trials.

It is important to remember that the emergent nature of the COVID-19 situation does not justify a compromise on core ethical values. In fact, the discourse surrounding this topic and the decisions made will remain a potent case study and a continuously referenced example for all such future scenarios.
Presence of a cryptic Onchocerca species in black flies of northern California, USA
Authors: Kulpa Matthew , Nelson Kimberly J. , Morales Alana M. , Ryan Bonnie M. , Koschik Michelle L. , Scott Jamesina J. , Verocai Guilherme G.
Published: September 2021

Background

Black flies (Diptera: Simuliidae) serve as arthropod vectors for various species ofOnchocerca(Nematoda: Onchocercidae) that may be associated with disease in humans, domestic animals, and wildlife. The emergence of zoonoticOnchocerca lupiin North America and reports of cervid-associated zoonotic onchocerciasis byOnchocerca jakutensishighlight the need for increased entomological surveillance. In addition, there is mounting evidence thatOnchocercadiversity in North America is far greater than previously thought, currently regarded asOnchocerca cervipedisspecies complex. This study reports new geographic records and black fly vector associations of an uncharacterizedOnchocercaspecies.

Methods

To better understand the biodiversity and geographic distribution ofOnchocerca, 485 female black flies (2015: 150, 2016: 335) were collected using CO2-baited traps from February to October 2015–2016 in Lake County, northern California, USA. Individual flies were morphologically identified and pooled (≤ 10 individuals) by species, collection date, and trap location. Black fly pools were processed for DNA extraction, and subsequent PCR and sequencing targeting of the NADH dehydrogenase subunit 5 gene of filarioids.

Results

Among the pools of black flies, there were 158 individuals ofSimulium tescorum(2015: 57, 2016: 101), 302 individuals ofSimulium vittatum(sensu lato[s.l.]) (2015: 82, 2016: 220), 16 individuals ofSimulium clarum“black” phenotype (2015: 5, 2016: 11), and 13 individuals ofS. clarum“orange” phenotype (2015: 6, 2016: 7). PCR analysis revealed the percentage of filarioid-positive pools were 7.50% (n = 3) forS. tescorum, 3.75% (n = 3) forS. vittatum(s.l., likelyS. tribulatum), 7.69% (n = 1) forS. clarum“black” phenotype, and no positives forS. clarum“orange” phenotype. Genetic distance and phylogenetic analyses suggest that the northern CaliforniaOnchocercaisolates belong to the same species reported in black flies from southern California (average pairwise comparison: 0.32%), and seem closely related toOnchocercaisolates of white-tailed deer from upstate New York (average pairwise comparison: 2.31%).

Conclusion

A crypticOnchocercaspecies was found in Lake County, California, and may be a part of a larger, continentally distributed species complex rather than a single described species of North America. In addition, there are at least three putative vectors of black flies (S. clarum,S. tescorum,S. vittatum) associated with this crypticOnchocercaspecies. A comprehensive reassessment of North AmericanOnchocercabiodiversity, host, and geographic range is necessary.

Graphical abstract
Advances in GLP-1 treatment: focus on oral semaglutide
Authors: Eliaschewitz Freddy G. , Canani Luis Henrique
Published: September 2021

Background

There is currently a large arsenal of antidiabetic drugs available to treat type 2 diabetes (T2D). However, this is a serious chronic disease that affects millions of adults worldwide and is responsible for severe complications, comorbidities, and low quality of life when uncontrolled due mainly to delays in initiating treatment or inadequate therapy. This review article aims to clarify the therapeutic role of the oral formulation of the glucagon-like peptide 1 receptor agonist (GLP-1 RA) semaglutide in treating typical T2D patients. The discussion focused on metabolic, glycemic, and weight alteration effects and the safety of the therapy with this drug.

Main text

Therapy with glucagon-like peptide 1 receptor agonist (GLP-1 RA) promotes strategic changes in the pathophysiological pathway of T2D and improves the secretion of glucagon and insulin, which results in a reduction in blood glucose levels and the promotion of weight loss. Until recently, the only route for semaglutide administration was parenteral. However, an oral formulation of GLP-1 RA was recently developed and approved by the Brazilian Health Regulatory Agency (ANVISA) and the Food and Drug Administration (FDA) based on the Peptide Innovation for Early Diabetes Treatment (PIONEER) program results. A sequence of 10 clinical studies compared oral semaglutide with placebo or active standard-of-care medications (empagliflozin 25 mg, sitagliptin 100 mg, or liraglutide 1.8 mg) in different T2D populations.

Conclusions

Oral semaglutide effectively reduces glycated hemoglobin (HbA1c) levels and body weight in a broad spectrum of patients with T2D and shows cardiovascular safety. Oral semaglutide broadens therapy options and facilitates the adoption of earlier GLP-1 RA treatment once T2D patients present low rates of treatment discontinuation. The main adverse events reported were related to the gastrointestinal tract, common to GLP-1 RA class drugs.
Serum albumin was negatively associated with diabetic peripheral neuropathy in Chinese population: a cross-sectional study
Authors: Yan Pijun , Tang Qian , Wu Yuru , Wan Qin , Zhang Zhihong , Xu Yong , Zhu Jianhua , Miao Ying
Published: September 2021

Background

Previous studies that explored the relationship of serum albumin with diabetic peripheral neuropathy (DPN) have indicated inconsistent results. Thus, the present study aimed to evaluated the association between serum albumin and DPN, defined as vibration perception threshold (VPT) values ≥ 25 V and/or inability to feel the monofilament, in Chinese patients with type 2 diabetes mellitus (T2DM).

Methods

1465 T2DM patients aged ≥ 16 years, who completed the measurement of serum albumin and DPN screening between 2012 and 2015, were included in the cross-sectional study. Correlation and multivariate logistic regression analysis models were used to evaluate the possible relationship between serum albumin and DPN.

Results

Patients with higher quartiles of serum albumin had significantly lower VPT values and prevalence of DPN compared with those with lower quartiles (P for trend < 0.01), and there was an inverse relationship between serum albumin and VPT values and prevalence of DPN (all P < 0.01). Multivariate logistic regression analysis demonstrated that the risk of DPN was progressively decreased across serum albumin quartiles (P for trend < 0.01), and participants in the highest quartile of serum albumin were at a significantly decreased risk of DPN compared to those in the lowest quartile (odds rate: 0.311, 95% confidence intervals 0.134–0.724, P < 0.01). ROC analysis revealed that the optimal cutoff point of serum albumin for the prevalence of DPN was 39.95 g/L in patients with T2DM, with a sensitivity of 65.88% and a specificity of 66.7%.

Conclusions

Decreased levels of serum albumin might be correlated with increased risk of DPN in Chinese patients with T2DM. Future longitudinal studies with large samples are warranted to confirm our findings, and elucidate putative mechanisms for the association.
Adequacy of setting standards for kick impact in the Taekwondo electronic scoring system: comparison of a reference group model based on empirical data
Authors: Choi Chang-Hwan , Oh Hyeri , Jeon Minsoo
Published: September 2021

Background

In Taekwondo competitions, the rule is that points are scored when the impact of the kick reaches a predetermined threshold of strength. This study aimed to explore the adequacy of the protector and scoring system (PSS) designed to determine taekwondo body scoring based on a reference group model (RGM). Specifically, the kicking impact of the PSS was calculated using data from 188 matches fought during of 2018 Jakarta Asian Games. The RGM was designed based on empirical data by classifying the victory and defeat groups by gender and weight class, and the scoring method was set according to these criteria.

Result

The result of this study are as follows. First, there was no difference in the average impact of kicks of taekwondo players by weight class. Second, result of setting up the kick scoring impact standards of taekwondo PSS by classifying the winning and non-winning groups, the kick scoring impact set by the WT was found to be high in all weight classes except 58 kg. Lastly, result of comparing the settings of impact to score according to weight classes, the kick scoring impact standard set by the WT was higher in heavyweight (men's: under 80 kg, + 80 kg, women's: under 67 kg, over 67 kg) than in the lightweight (men's: under 58 kg, under 63 kg, under 68 kg, women's: under 49 kg, under 53 kg, under 57 kg).

Conclusion

The kick scoring impact set by the WT was found to be high in all weight classes except for the under 58 kg class defining kick scoring impact based on the standards of WT-certified PSS by classifying the matches into winning and non-winning groups. Finally, as a result of comparing the scoring impact settings according to weight class, the kick scoring impact standard set by the WT was higher for the heavier weight classes than for the lighter weight classes.
Insulin-like growth factor-2 does not improve behavioral deficits in mouse and rat models of Angelman Syndrome
Authors: Berg Elizabeth L. , Petkova Stela P. , Born Heather A. , Adhikari Anna , Anderson Anne E. , Silverman Jill L.
Published: September 2021

Background

Angelman Syndrome (AS) is a rare neurodevelopmental disorder for which there is currently no cure or effective therapeutic. Since the genetic cause of AS is known to be dysfunctional expression of the maternal allele of ubiquitin protein ligase E3A (UBE3A), several genetic animal models of AS have been developed. Both theUbe3amaternal deletion mouse and rat models of AS reliably demonstrate behavioral phenotypes of relevance to AS and therefore offer suitable in vivo systems in which to test potential therapeutics. One promising candidate treatment is insulin-like growth factor-2 (IGF-2), which has recently been shown to ameliorate behavioral deficits in the mouse model of AS and improve cognitive abilities across model systems.

Methods

We used both theUbe3amaternal deletion mouse and rat models of AS to evaluate the ability of IGF-2 to improve electrophysiological and behavioral outcomes.

Results

Acute systemic administration of IGF-2 had an effect on electrophysiological activity in the brain and on a metric of motor ability; however the effects were not enduring or extensive. Additional metrics of motor behavior, learning, ambulation, and coordination were unaffected and IGF-2 did not improve social communication, seizure threshold, or cognition.

Limitations

The generalizability of these results to humans is difficult to predict and it remains possible that dosing schemes (i.e., chronic or subchronic dosing), routes, and/or post-treatment intervals other than that used herein may show more efficacy.

Conclusions

Despite a few observed effects of IGF-2, our results taken together indicate that IGF-2 treatment does not profoundly improve behavioral deficits in mouse or rat models of AS. These findings shed cautionary light on the potential utility of acute systemic IGF-2 administration in the treatment of AS.
Isolated pancreatic injury in an adolescent treated with Roux-en-Y pancreatojejunostomy: a case report and review of the literature
Authors: Naiem Mohamed Eltayeb Abdelrahman , Arabi Nassir Alhaboob
Published: September 2021

Background

Pancreatic injury presented as isolated injury in the pediatric population is exceptionally rare, with a conveyed incidence of less than 2% of all abdominal trauma injuries cases and a very controversial management approach for grade III injuries.

Case presentation

A 16-year-old adolescent Sudanese boy was referred to our emergency department with a 5-day history of upper and left hypochondrial pain after blunt abdominal trauma to the epigastric region with a solid object. Grade III pancreatic body trauma with major duct involvement can be successfully treated operatively. The boy was discharged home on day 10 with regular oral intake and diet. A follow-up for 6 months continued by phone, and it was uneventful with no further complications.

Conclusions

Roux-en-Y pancreatojejunostomy reconstruction can be a safe and valuable surgical option when the surgical approach is considered for grade III pancreatic injury.