bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of anti-tumor approaches on the outcomes of cancer patients with COVID-19: a meta-analysis based on 52 cohorts incorporating 9231 participants
Authors: Wu Qing , Luo Shuimei , Xie Xianhe
Published: March 2022

Background

This study was designed to investigate the impact of anti-tumor approaches (including chemotherapy, targeted therapy, endocrine therapy, immunotherapy, surgery and radiotherapy) on the outcomes of cancer patients with COVID-19.

Methods

Electronic databases were searched to identify relevant trials. The primary endpoints were severe disease and death of cancer patients treated with anti-tumor therapy before COVID-19 diagnosis. In addition, stratified analyses were implemented towards various types of anti-tumor therapy and other prognostic factors. Furthermore, odds ratios (ORs) were hereby adopted to measure the outcomes with the corresponding 95% confidence intervals (CIs).

Results

As indicated in the study consisting of 9231 individuals from 52 cohorts in total, anti-tumor therapy before COVID-19 diagnosis could elevate the risk of death in cancer patients (OR: 1.21, 95%CI: 1.07–1.36,P = 0.0026) and the incidence of severe COVID-19 (OR: 1.19, 95%CI: 1.01–1.40,P = 0.0412). Among various anti-tumor approaches, chemotherapy distinguished to increase the incidence of death (OR = 1.22, 95%CI: 1.08–1.38,P = 0.0013) and severe COVID-19 (OR = 1.10, 95%CI: 1.02–1.18,P = 0.0165) as to cancer patients with COVID-19. Moreover, for cancer patients with COVID-19, surgery and targeted therapy could add to the risk of death (OR = 1.27, 95%CI: 1.00–1.61,P = 0.0472), and the incidence of severe COVID-19 (OR = 1.14, 95%CI: 1.01–1.30,P = 0.0357) respectively. In the subgroup analysis, the incidence of death (OR = 1.17, 95%CI: 1.03–1.34,P = 0.0158) raised in case of chemotherapy adopted for solid tumor with COVID-19. Besides, age, gender, hypertension, COPD, smoking and lung cancer all served as potential prognostic factors for both death and severe disease of cancer patients with COVID-19.

Conclusions

Anti-tumor therapy, especially chemotherapy, augmented the risk of severe disease and death for cancer patients with COVID-19, so did surgery for the risk of death and targeted therapy for the incidence of severe COVID-19.
Opioid agonist treatment (OAT) experiences and release plans among federally incarcerated individuals with opioid use disorder (OUD) in Ontario, Canada: a mixed-methods study
Authors: Russell Cayley , Nafeh Frishta , Pang Michelle , MacDonald Shanna Farrell , Derkzen Dena , Rehm Jürgen , Fischer Benedikt
Published: March 2022

Background

Incarcerated populations experience an elevated prevalence of opioid use disorder (OUD). Federal correctional institutions in Canada have increasingly treated OUD among correctional populations via opioid agonist treatment (OAT) – an evidence based pharmacotherapy that works to reduce drug use and related health harms. However, there is limited evidence regarding incarcerated individuals’ experiences with institutional-based OAT, as well potential OAT-related community release prospects. This information is important for optimal treatment retention and improved health. To address this knowledge gap, we conducted a longitudinal follow-up study examining OAT-related experiences among federally incarcerated individuals before and after community release. This article focuses on the baseline (pre-release) data.

Methods

This mixed-methods study examined OAT-related experiences and release prospects among n = 46 individuals scheduled for community release, recruited from seven federal prisons located in Ontario, Canada. Participants underwent a comprehensive interviewer-administered on-site assessment, including quantitative and qualitative items. Assessment data was furthermore linked to administrative correctional data. Data were analyzed using thematic qualitative and descriptive quantitative approaches.

Results

Participants had complex histories with opioid use including related negative health outcomes. Experiences with institutional OAT were divergent and provision was not standardized; those with OAT engagement pre-admission did not experience many challenges, whereas those initiating OAT during incarceration experienced barriers such as treatment waitlists and adverse process experiences. Most participants expressed a preference for buprenorphine-naloxone over methadone, but described difficulties accessing it. Participants were keen to transition into community-based treatment, yet envisaged prospective barriers and facilitators concerning successful reintegration and treatment continuity.

Conclusions

Major barriers towards the current administration of OAT in federal correctional systems in Canada exist, including extensive waitlists, non-standardized practices, and challenges accessing preferred OAT formulations; this contributes to sub-optimal treatment. Eliminating waitlists, standardizing OAT provision, providing additional OAT options, and more comprehensive release planning may be essential for treatment retention and positive outcomes.
The surgical outcomes and perioperative complications of bowel resection as part of debulking surgery of advanced ovarian cancer patients
Authors: Ye Shuang , Wang Yiyong , Chen Lei , Wu Xiaohua , Yang Huijuan , Xiang Libing
Published: March 2022

Background

To review the utilization of bowel resection in ovarian cancer surgery in our institution.

Methods

All ovarian cancer patients who received bowel resection between 2006/01 and 2018/12 were identified. Postoperative morbidities were assessed according to the Clavien–Dindo classification (CDC).

Results

There were 182 patients in the anastomosis group and 100 patients in the ostomy group, yielding a total of 282 patients. The median age was 57 years, and most patients had high-grade serous histology (88.7%). Forty-nine (17.3%) patients received neoadjuvant chemotherapy. During the operation, 78.7% of patients had ascites, and the median volume was 800 mL. Extensive bowel resection (at least two-segment) and upper abdominal operation were performed in 29 (10.2%) and 69 (24.4%) patients, respectively. The rectosigmoid colon was the most commonly resected (83.8%) followed by right hemicolectomy (5.9%) and small bowel resection (2.8%). No macroscopic residual disease was observed in 42.9% of the patients, whereas 87.9% had residual disease ≤ 1 cm. Among the entire cohort, 23.0% (65/282) experienced different complications. Severe complications (CDC 3–5) accounted for 9.2% of complications and were mostly categorized as pleural effusion requiring drainage (3.5%) followed by wound dehiscence requiring delayed repair in the operating room (1.8%). Nine patients experienced anastomotic leakage (AL): one in the ostomy group with extensive bowel resection and eight in the anastomosis group. The overall AL rate was 4.2% (9/212) per anastomosis.

Conclusions

The execution of bowel resection as part of debulking surgery in patients with newly diagnosed ovarian cancer resulted in a severe morbidity rate of 9.2%.
Effect of fluocinolone acetonide (0.1%) treatment in oral lichen planus patients on salivary lactoferrin levels and Candida colonization: a prospective study
Authors: Saengprasittichok Nuttapong , Sucharitakul Jeerus , Matangkasombut Oranart , Prapinjumrune Chanwit
Published: March 2022

Background

Although topical steroids are an effective treatment for oral lichen planus, they can have suppressive effects on oral immunity and predispose the patients to Candida overgrowth. Lactoferrin is a crucial local immunity protein in the oral cavity with important antimicrobial activity. The aim of this study was to prospectively investigate salivary lactoferrin secretion levels and Candida colonization in oral lichen planus patients treated with fluocinolone acetonide 0.1% in orabase.

Methods

Saliva samples were collected from 15 oral lichen planus subjects who had never received topical steroid treatment prior to this study and 15 healthy volunteers to determine their salivary lactoferrin levels using an enzyme-linked immunosorbent assay and to investigate the presence of oral Candida species at baseline and 3 months after treatment with fluocinolone acetonide 0.1% in orabase. Statistical analysis was performed to compare lactoferrin secretion and Candida colonization levels between the groups using the Mann–Whitney U test for independent data or the Wilcoxon Signed-Rank test for paired data.

Results

The salivary lactoferrin secretion level was not significantly different between the control group and oral lichen planus patients or between before and after treatment with fluocinolone acetonide 0.1% in orabase (P > 0.05). Candida was detected in 11 (73.33%) healthy volunteers, 8 (53.33%) oral lichen planus patients before treatment, and 9 (60%) oral lichen planus patients after treatment with fluocinolone acetonide 0.1% in orabase. There was no significant difference in Candida counts between the groups (P > 0.05).

Conclusion

Our study indicates that using fluocinolone acetonide 0.1% in orabase to treat oral lichen planus for 3 months did not affect salivary lactoferrin protein secretion or Candida carriage.

Trial registration The trial was registered at the Thai Clinical Trials Registry (TCTR identifier: TCTR20200723002).
Assessing the relationship between body image and quality of life among rural and urban breast cancer survivors in China
Authors: An Jinghua , Zhou Kaina , Li Minjie , Li Xiaomei
Published: March 2022

Background

Breast cancer survivors experience altered body image and quality of life (QoL) due to the disease and its treatment. The multidimensional nature of body image and QoL makes their relationships complex. This study aimed to examine the associations between the two concepts in Chinese breast cancer survivors and test whether these associations are moderated by rural–urban residence.

Methods

A cross-sectional design was adopted. Breast cancer survivors were recruited via a convenience sampling method. Two validated questionnaires (the Body Image Self-Rating Questionnaire for Breast Cancer and 36-item Short-Form Health Survey) and questions assessing demographic and clinical covariates were administered. Multiple linear regressions were used to assess the relationship between body image and QoL domains and to examine the moderating effect of rural–urban residence.

Results

In our sample of 354 breast cancer survivors, half (50.28%) lived in rural areas. After adjusting for demographic and clinical variables, better perception of body image-related sexual activity change, role change, and psychological change was significantly associated with better physical (β ranged from − 0.15 to − 0.11, p < 0.05) and mental (β ranged from − 0.46 to − 0.34, p < 0.001) well-being. Better perception of body image-related social and behavior change was significantly associated only with better mental well-being (β ranged from − 0.40 to − 0.33, p < 0.001). The association between body image and mental well-being was much stronger in urban subjects (b = − 0.38, p < 0.001) than in rural subjects (b = − 0.20, p < 0.001).

Conclusions

Our findings suggest that multidimensional body image is associated with physical and mental well-being in Chinese breast cancer survivors. Body image appears to play a larger role in urban breast cancer survivors’ mental well-being. Our results indicate that incorporating interventions that address body image issues would be advantageous for survivorship care to enhance QoL in breast cancer survivors. Furthermore, rural–urban differences should be considered in the strategic design of survivorship care programs in rural and urban settings.
Medical students’ experiences when empathizing with patients’ emotional issues during a medical interview – a qualitative study
Authors: Brodahl Knut Ørnes , Storøy Hanne-Lise Eikeland , Finset Arnstein , Pedersen Reidar
Published: March 2022

Background

There is evidence that empathy decreases as medical students go through clinical training. However, there are few in-depth studies investigating the students’ own experiences when trying to empathize in concrete clinical encounters. We therefore wanted to explore medical students’ perceptions, experiences, and reflections when empathizing with patients expressing emotional issues.

Methods

A qualitative content analysis of semi-structured interviews with third year medical students (N = 11) was conducted using video-stimulated recall from their own medical interview with a simulated chronically ill patient. Students were led to believe that the patient was real.

Results

Five themes which may influence student empathy during history-taking were identified through analysis of interview data: (1) Giving priority to medical history taking, (2) Interpreting the patient’s worry as lack of medical information, (3) Conflict between perspectives, (4) Technical communication skill rather than authentic and heart-felt and (5) The distant professional role.

Conclusions

The participating students described conflicts between a medical agenda, rules and norms for professional conduct and the students’ own judgments when trying to empathize with the patient. To our knowledge, this is the first study ever to document the students’ own perspective in concrete situations as well as how these reported experiences and reflections affect their empathy towards patients. Since we now know more about what is likely to hinder medical students’ empathy, educators should actively encourage group reflection and discussion in order to avoid these negative effects of history taking both inside and outside of the clinical setting.
Creating a better learning environment: a qualitative study uncovering the experiences of Master Adaptive Learners in residency
Authors: Regan Linda , Hopson Laura R. , Gisondi Michael A. , Branzetti Jeremy
Published: March 2022

Background

Adaptive expertise is an important physician skill, and the Master Adaptive Learner (MAL) conceptual model describes learner skills and behaviors integral to the acquisition of adaptive expertise. The learning environment is postulated to significantly impact how MALs learn, but it is unclear how these successful learners experience and interact with it. This study sought to understand the authentic experience of MALs within the learning environment and translate those experiences into practical recommendations to improve the learning environment for all trainees.

Methods

Following a constructivist paradigm, we conducted a thematic analysis of transcripts from focus groups composed of MALs to identify commonalities in experiences and practices of successful postgraduate trainees in the learning environment. Saturation was achieved after seven focus groups, consisting of thirty-eight participants representing fourteen specialties from four institutions. Researchers coded transcripts using constant comparison analysis, which served as the foundation for our thematic analysis.

Results

We identified eight themes and situated them within a 4-component model of the learning environment. Four themes were identified within the personal component: (1) patients drive learning; (2) learning has no endpoint; (3) management of emotions is crucial for learning; (4) successful learning requires a structured approach. Two themes were identified in the social component: (5) positive social relationships are leveraged to maximize learning; (6) teaching facilitates personal learning. Two themes were identified in the organizational component: (7) transitions challenge learners to adapt; (8) the learning environment dictates goal setting strategy. No major themes were identified in the physical/virtual component, although participants frequently used technology when learning.

Conclusions

Master Adaptive Learners experience similar facilitators of, and barriers to, success in the learning environment. Overall, our data show that acquisition of many successful strategies and skills that support learning are relegated to the hidden curriculum of residency training. Educators could support a more effective learning environment for all trainees by: (1) highlighting patients as the focal point of learning, (2) building a professional ‘learner’ identity, (3) teaching learning skills, and (4) creating opportunities for collaborative learning.
The impact of COVID-19 on ophthalmology resident surgical experience: a retrospective cross-sectional analysis
Authors: Vongsachang Hursuong , Fliotsos Michael J. , Lorch Alice C. , Singman Eric L. , Woreta Fasika A. , Justin Grant A.
Published: March 2022

Background

The coronavirus disease 2019 (COVID-19) pandemic caused significant disruption to in-office and surgical procedures in the field of ophthalmology. The magnitude of the impact of the pandemic on surgical training among ophthalmology residents is not known. This study aims to quantify changes in average case logs among United States (U.S.) ophthalmology residency graduates prior to and during the COVID-19 pandemic.

Methods

Retrospective, cross-sectional analysis of aggregate, national data on case logs of U.S. ophthalmology residency graduates from 2012 to 2020. The yearly percent change in the average number of procedures performed in the Accreditation Council for Graduate Medical Education (ACGME) ophthalmology resident case logs were analyzed using linear regression on log-transformed dependent variables. The average percent change from 2019 to 2020 was compared to the average yearly percent change from 2012 to 2019 for procedures performed as the primary surgeon, and primary surgeon and surgical assistant (S + A), as well as procedures for which there are ACGME minimum graduating numbers.

Results

Across all procedures and roles, average case logs in 2020 were lower than the averages in 2019. While average total cases logged as primary surgeon increased yearly by 3.2% (95% CI: 2.7, 3.8%, p < 0.001) from 2012 to 2019, total primary surgeon case logs decreased by 11.2% from 2019 to 2020. Cataract (-22.0%) and keratorefractive (-21.1%) surgery experienced the greatest percent decrease in average primary surgeon cases logged from 2019 to 2020. Average total cases logged as S + A experienced an average yearly increase by 1.2% (95% CI: 0.9,1.6%, p < 0.001) prior to 2020, but decreased by 9.6% from 2019 to 2020. For ACGME minimum requirements, similar changes were observed. Specifically, the average case logs in YAG, SLT, filtering (glaucoma), and intravitreal injections had been increasing significantly prior to 2020 (p < 0.05 for all) but decreased in 2020.

Conclusions

These findings demonstrate the vulnerability of ophthalmology residency programs to a significant interruption in surgical volume. There is a critical need for development of competency-based, rather than volume-based, requirements to evaluate readiness for independent practice.
Chinese physicians’ perceptions of palliative care integration for advanced cancer patients: a qualitative analysis at a tertiary hospital in Changsha, China
Authors: Hahne Jessica , Wang Xiaomin , Liu Rui , Zhong Yuqiong , Chen Xin , Liu Xing , Khoshnood Kaveh , Li Xin
Published: March 2022

Background

Little previous research has been conducted outside of major cities in China to examine how physicians currently perceive palliative care, and to identify specific goals for training as palliative care access expands. This study explored physicians’ perceptions of palliative care integration for advanced cancer patients in Changsha, China.

Methods

We conducted semi-structured qualitative interviews with physicians (n = 24) specializing in hematology or oncology at a tertiary hospital.

Results

Most physicians viewed palliative care as equivalent to end-of-life care, while a minority considered it possible to integrate palliative care with active treatment. Almost all physicians maintained separate conversations about palliative care with family members and patients, communicating more directly with family members than with patients about prognosis and goals of care. Physicians described experiencing ethical tension between the desire of family members to protect the patient from knowing they have advanced cancer, and the patient’s “right to decide” about palliative treatment. Physicians varied overall regarding perceptions of the role they should have in discussions about goals of care.

Conclusions

As palliative care access expands in China, medical training should encourage earlier integration of palliative care for advanced cancer, address ethical issues faced by physicians communicating about palliative care, and establish guidance on the role of the physician in discussions about goals of care.
Shifting to a model of donor conception that entails a communication agreement among the parents, donor, and offspring
Authors: Ishii Tetsuya , de Miguel Beriain Iñigo
Published: March 2022

Background

Some persons conceived with donor gametes react negatively when they found their birth via donor conception. They request access to information about and seek to communicate with the donor. However, some countries mandate donor anonymity. Other countries allow donor-conceived persons to access donor information, but they can only use this access if their parents have disclosed donor conception to them. We investigated a thorny issue of donor conception: whether donor conception should be shifted from an anonymous basis to a non-anonymous basis.

Methods

We review the issues and concerns regarding donor conception. We then consider the impact of direct-to-consumer genetic testing on donor conception, as well as the influence of donor conception on offspring’s identity and the potential of different types of donors. To discuss the future policy of donor conception, the policies on the anonymity of gamete donors were investigated using publicly-available documents in 15 countries.

Results

The aim of mandating donor anonymity is to protect the privacy of the donor and intended parents. However, the diffusion of direct-to-consumer genetic testing may make it impossible to maintain anonymity. Birth via donor conception shapes the offspring’s identity, and the donor may further influence the development of offspring’s identity through communications. It remains important to disclose donor conception to donor-conceived offspring and to provide them with donor information. However, that information might be insufficient for some donor-conceived persons. Here are benefits to having open-identity donors and known donors. Such donors can make an agreement with the parents regarding future communication with the offspring, although both sides should respect privacy. Subsequent counseling for all parties involved can result in better tripartite communication agreements.

Conclusions

In sum, ethical and practical issues that complicate donor anonymity are driving a shift to non-anonymous donor conception, in which all parties come to a communication agreement. To pave the way for such a donor conception system, transitional measures can be put into place. For countries that already adopted non-anonymous donor conception, ensuring the communication agreements is important to protect the rights of parents, donor, and offspring.
Trust and digital privacy in healthcare: a cross-sectional descriptive study of trust and attitudes towards uses of electronic health data among the general public in Sweden
Authors: Belfrage Sara , Helgesson Gert , Lynøe Niels
Published: March 2022

Background

The ability of healthcare to protect sensitive personal data in medical records and registers might influence public trust, which in turn might influence willingness to allow healthcare to use such data. The aim of this study was to examine how the general public’s trust relates to their attitudes towards uses of health data.

Methods

A stratified sample from the general Swedish population received a questionnaire about their willingness to share health data. Respondents were also asked about their trust in the management and protection of electronic health data.

Results

A large majority (81.9%) of respondents revealed high levels of trust in the ability of healthcare to protect electronic patient data. Good health was associated with significantly higher levels of trust compared to bad health. Respondents with low levels of trust were significantly less willing to allow personal data to be used for different purposes and were more inclined to insist on being asked for permission beforehand. Those with low levels of trust also perceived risks of unauthorized access to personal data to be higher and the likely damage of such unauthorized access worse, compared to those with high levels of trust.

Conclusions

Trust in the ability of healthcare to protect electronic health is generally high in Sweden. Those with higher levels of trust are more willing to let their data be used, including without informed consent. It thus seems crucial to promote trust in order to be able to reap the benefits that digitalization makes possible through increased access and use of data in healthcare.
Provider perceptions of challenges to identifying women Veterans with hazardous substance use
Authors: Giannitrapani Karleen F. , Holliday Jesse R. , Dawson Andrew W. , Huynh Alexis K. , Hamilton Alison B. , Timko Christine , Hoggatt Katherine J.
Published: March 2022

Background

Approximately one-third of women Veterans Health Administration (VHA) users have substance use disorders (SUD). Early identification of hazardous substance use in this population is critical for the prevention and treatment of SUD. We aimed to understand challenges to identifying women Veterans with hazardous substance use to improve future referral, evaluation, and treatment efforts.

Methods

Design: We conducted a secondary analysis of semi-structured interviews conducted with VHA interdisciplinary women’s SUD providers at VA Greater Los Angeles Healthcare System. Participants: Using purposive and snowball sampling we interviewed 17 VHA providers from psychology, social work, women’s health, primary care, and psychiatry. Approach: Our analytic approach was content analysis of provider perceptions of identifying hazardous substance use in women Veterans.

Results

Providers noted limitations across an array of existing identification methodologies employed to identify women with hazardous substance use and believed these limitations were abated through trusting provider-patient communication. Providers emphasized the need to have a process in place to respond to hazardous use when identified. Provider level factors, including provider bias, and patient level factors such as how they self-identify, may impact identification of women Veterans with hazardous substance use. Tailoring language to be sensitive to patient identity may help with identification in women Veterans with hazardous substance use or SUD who are not getting care in VHA but are eligible as well as those who are not eligible for care in VHA.

Conclusions

To overcome limitations of existing screening tools and processes of identifying and referring women Veterans with hazardous substance use to appropriate care, future efforts should focus on minimizing provider bias, building trust in patient-provider relationships, and accommodating patient identities.
Activity and safety of SHR3680, a novel antiandrogen, in patients with metastatic castration-resistant prostate cancer: a phase I/II trial
Authors: Qin Xiaojian , Ji Dongmei , Gu Weijie , Han Weiqing , Luo Hong , Du Chuanjun , Zou Qing , Sun Zhongquan , He Chaohong , Zhu Shaoxing , Chong Tie , Yao Xin , Wan Ben , Yang Xinfeng , Bai Aobing , Jin Chunlei , Zou Jianjun , Ye Dingwei
Published: March 2022

Background

Antagonizing the androgen-receptor (AR) pathway is an effective treatment strategy for patients with metastatic castration-resistant prostate cancer (CRPC). Here, we report the results of a first-in-human phase 1/2 study which assessed the safety, pharmacokinetics, and activity of SHR3680 (a novel AR antagonist) in patients with metastatic CRPC.

Methods

This phase 1/2 study enrolled patients with progressive metastatic CRPC who had not been previously treated with novel AR-targeted agents. In the phase 1 dose-escalation portion, patients received oral SHR3680 at a starting daily dose of 40 mg, which was subsequently escalated to 80 mg, 160 mg, 240 mg, 360 mg, and 480 mg per day. In phase 2 dose-expansion portion, patients were randomized to receive daily dose of 80 mg, 160 mg, or 240 mg of SHR3680. The primary endpoint in phase 1 was safety and tolerability and in phase 2 was the proportion of patients with a prostate-specific antigen (PSA) response (≥ 50% decrease of PSA level) at week 12.

Results

A total of 197 eligible patients were enrolled and received SHR3680 treatment, including 18 patients in phase 1 and 179 patients in phase 2. No dose-limiting toxicities were reported and the maximum tolerated dose was not reached. Treatment-related adverse events (TRAEs) occurred in 116 (58.9%) patients, with the most common one being proteinuria (13.7%). TRAEs of grade ≥ 3 occurred in only 23 (11.7%) patients, and no treatment-related deaths occurred. Antitumor activities were evident at all doses, including PSA response at week 12 in 134 (68.0%; 95% CI, 61.0–74.5) patients, stabilized bone disease at week 12 in 174 (88.3%; 95% CI, 87.2–95.5) patients, and responses in soft tissue lesions in 21 (34.4%, 95% CI, 22.7–47.7) of 61 patients.

Conclusion

SHR3680 was well tolerated and safe, with promising anti-tumor activity across all doses tested in patients with metastatic CRPC. The dose of 240 mg daily was recommended for further phase 3 study.

Trial registration

Clinicaltrials.gov NCT02691975; registered February 25, 2016.
Left displacement of the third gastric compartment in an alpaca: the first case report in China
Authors: Song Yuxi , Wang Zheng , Li Ran , Hao Dandan , Wang Zhijie , Xia Cheng , Bai Yunlong
Published: March 2022

Background

Left displacement of the third gastric compartment (LDC3) in alpacas is an extremely rare condition and has not been reported thus far. Therefore, we describe the clinical diagnosis and treatment of LDC3 in an alpaca.

Case presentation

A 2-year-old brown female alpaca (Vicugna pacos) was presented to evaluate a 3-day history of abdominal distension causing loss of both appetite and thirst, along with oliguria and low to no defecation. Clinical examination, X-ray examination, surgical exploration, and determination of gastric pH (pH ~ 2.35) confirmed that LDC3 resulted in abdominal distension. The gastric wall of the displaced third gastric compartment was incised for the expulsion of pneumatosis, and a medical-grade silicone tube was inserted into the incision to remove the effusion by siphoning. Surgical treatment proved to effectively alleviate the abdominal distension caused by LDC3 without apparent side effects.

Conclusions

To our knowledge, this case is the first known report of LDC3 in an alpaca in China. A similar condition, left displaced abomasum, has previously been described in cattle and sheep.
Acceleration of the DNA methylation clock among lynch syndrome-associated mutation carriers
Authors: Cuadros Marta , Cano Carlos , Garcia-Rodriguez Sonia , Martín José Luis , Poyatos-Andujar Antonio , Ruiz-Cabello Francisco , Pedrinaci Susana , Durán Gema , Benavides Manuel , Bautista-Ojeda María Dolores , Pereda Teresa , Benitez-Cantos Maria Soledad , Medina Pedro , Blanco Armando , Gonzalez Antonio , Lizardi Paul
Published: March 2022

Background

DNA methylation (DNAm) age metrics have been widely accepted as an epigenetic biomarker for biological aging and disease. The purpose of this study is to assess whether or not individuals carrying Lynch Syndrome-associated mutations are affected in their rate of biological aging, as measured by the epigenetic clock.

Methods

Genome-wide bisulfite DNA sequencing data were generated using DNA from CD4 + T-cells obtained from peripheral blood using 27 patient samples from Lynch syndrome families. Horvath’s DNAm age model based on penalized linear regression was applied to estimate DNAm age from patient samples with distinct clinical and genetic characteristics to investigate cancer mutation-related aging effects.

Results

Both Lynch mutation carriers and controls exhibited high variability in their estimated DNAm age, but regression analysis showed steeper slope for the Lynch mutation carriers. Remarkably, six Lynch Syndrome-associated mutation carriers showed a strong correlation to the control group, and two sisters carrying Lynch Syndrome-associated mutations, with no significant difference in lifestyle and similar chronological age, were assigned very different DNAm age.

Conclusions

Future studies will be required to explore, in larger patient populations, whether specific epigenetic age acceleration is predictive of time-to-cancer development, treatment response, and survival. Epigenetic clock DNAm metrics may be affected by the presence of cancer mutations in the germline, and thus show promise of potential clinical utility for stratified surveillance strategies based on the relative risk for imminent emergence of tumor lesions in otherwise healthy Lynch Syndrome-associated mutation carriers.
A novel bi-alleleic DDX41 mutations in B-cell lymphoblastic leukemia: case report
Authors: Shin Woo Yong , Yoon Seug Yun , Park Rojin , Kim Jung-Ah , Song Ho Hyun , Bang Hae In , Won Jong-Ho , Kim Jieun
Published: March 2022

Background

The germline mutations of DDX41, also known as DEAD box RNA helicase 41, have been found in about 1.5% of myeloid neoplasms (MNs). Development of MDS/AML is relatively common in germline DDX41 mutations. However, a variety of hematological malignancies (HMs) have been reported.

Case presentation

We report a novel case of bi-alleleic DDX41 mutations in B-cell lymphoblastic leukemia (B-ALL), with unusual location of DDX41 mutations. The gene expression profile (GEP) of Ph + B-ALL with bi-alleleic DDX41 mutations showed heterogeneously transitional GEP and altered gene expression levels of genes involved in the process essential for red blood cells and myeloid cell differentiation were noted.

Conclusions

We report that DDX41 mutations are unusual but can be an underlying event in Ph + B-ALL and screening DDX41 mutations can be also informative for patients awaiting for haploidentical stem cell transplantation and choosing the therapy.
Development of methodology for assessing steroid-tapering in clinical trials for biologics in asthma
Authors: Korn Stephanie , Howarth Peter , Smith Steven G. , Price Robert G. , Yancey Steven W. , Prazma Charlene M. , Bel Elisabeth H.
Published: March 2022

Background

Long-term use of oral corticosteroids (OCS) is associated with a risk of adverse events and comorbidities. As such, a goal in assessing the efficacy of biologics in severe asthma is often to monitor reduction in OCS usage. Importantly, however, OCS dose reductions must be conducted without loss of disease control.

Main body

Herein, we describe the development of OCS-sparing study methodologies for biologic therapies in patients with asthma. In particular, we focus on four randomized, placebo-controlled, parallel-group studies of varying sizes (key single-center study [n = 20], SIRIUS [n = 135], ZONDA [n = 220], VENTURE [n = 210]) and one open-label study (PONENTE [n = 598]), which assessed the effect of asthma biologics (mepolizumab, benralizumab or dupilumab) on OCS use using predefined OCS-tapering schedules. In particular, we discuss the evolution of study design elements in these studies, including patient eligibility criteria, the use of tailored OCS dose reduction schedules, monitoring of outcomes, the use of biomarkers and use of repetitive assessments of adrenal function during OCS tapering.

Conclusion

Taken together, these developments have improved OCS-sparing asthma studies in recent years and the lessons learned may help with optimization of further OCS-sparing studies, and potentially clinical practice in the future.
Lower miR-21/ROS/HNE levels associate with lower glycemia after habit-intervention: DIAPASON study 1-year later
Authors: La Sala Lucia , Tagliabue Elena , Mrakic-Sposta Simona , Uccellatore Anna Chiara , Senesi Pamela , Terruzzi Ileana , Trabucchi Emilio , Rossi-Bernardi Luigi , Luzi Livio
Published: March 2022

Background

The prevalence of prediabetes is increasing in the global population and its metabolic derangements may expose to a higher risk to develop type 2 diabetes (T2D) and its cardiovascular burden. Lifestyle modifications might have considerable benefits on ameliorating metabolic status. Alternative biomarkers, such as circulating miR-21, has been recently discovered associated with dysglycemia. Here we evaluated, in a longitudinal cohort of dysglycemic population the relation between the circulating miR-21/ROS/HNE levels and the habit-intervention (HI) after 1 year of follow-up.

Methods

1506 subjects from DIAPASON study were screened based on the Findrisc score. Of them, 531 subjects with Findrisc ≥ 9 were selected for dysglycemia (ADA criteria) and tested for circulating miR-21, ROS and HNE levels, as damaging-axis. 207 subjects with dysglycemia were re-evaluated after 1-year of habit intervention (HI). Repeated measures tests were used to evaluate changes from baseline to 1-year of follow-up. The associations between glycemic parameters and miR-21/ROS/HNE were implemented by linear regression and logistic regression models.

Results

After HI, we observed a significant reduction of miR-21/ROS/HNE axis in dysglycemic subjects, concomitantly with ameliorating of metabolic parameters, including insulin resistance, BMI, microalbuminuria, reactive hyperemia index and skin fluorescence. Significant positive interaction was observed between miR-21 axis with glycaemic parameters after HI. Lower miR-21 levels after HI, strongly associated with a reduction of glycemic damaging-axis, in particular, within-subjects with values of 2hPG < 200 mg/dL.

Conclusions

Our findings demonstrated that HI influenced the epigenetic changes related to miR-21 axis, and sustain the concept of reversibility from dysglycemia. These data support the usefulness of novel biological approaches for monitoring glycemia as well as provide a screening tool for preventive programmes.
Facile synthesis of near-infrared responsive on-demand oxygen releasing nanoplatform for precise MRI-guided theranostics of hypoxia-induced tumor chemoresistance and metastasis in triple negative breast cancer
Authors: Zhang Dong , You Yuanyuan , Xu Yuan , Cheng Qingqing , Xiao Zeyu , Chen Tianfeng , Shi Changzheng , Luo Liangping
Published: March 2022

Background

Hypoxia is an important factor that contributes to chemoresistance and metastasis in triple negative breast cancer (TNBC), and alleviating hypoxia microenvironment can enhance the anti-tumor efficacy and also inhibit tumor invasion.

Methods

A near-infrared (NIR) responsive on-demand oxygen releasing nanoplatform (O2-PPSiI) was successfully synthesized by a two-stage self-assembly process to overcome the hypoxia-induced tumor chemoresistance and metastasis. We embedded drug-loaded poly (lactic-co-glycolic acid) cores into an ultrathin silica shell attached with paramagnetic Gd-DTPA to develop a Magnetic Resonance Imaging (MRI)-guided NIR-responsive on-demand drug releasing nanosystem, where indocyanine green was used as a photothermal converter to trigger the oxygen and drug release under NIR irradiation.

Results

The near-infrared responsive on-demand oxygen releasing nanoplatform O2-PPSiI was chemically synthesized in this study by a two-stage self-assembly process, which could deliver oxygen and release it under NIR irradiation to relieve hypoxia, improving the therapeutic effect of chemotherapy and suppressed tumor metastasis. This smart design achieves the following advantages: (i) the O2 in this nanosystem can be precisely released by an NIR-responsive silica shell rupture; (ii) the dynamic biodistribution process of O2-PPSiI was monitored in real-time and quantitatively analyzed via sensitive MR imaging of the tumor; (iii) O2-PPSiI could alleviate tumor hypoxia by releasing O2 within the tumor upon NIR laser excitation; (iv) The migration and invasion abilities of the TNBC tumor were weakened by inhibiting the process of EMT as a result of the synergistic therapy of NIR-triggered O2-PPSiI.

Conclusions

Our work proposes a smart tactic guided by MRI and presents a valid approach for the reasonable design of NIR-responsive on-demand drug-releasing nanomedicine systems for precise theranostics in TNBC.

Graphical Abstract
Functionalizing silica sol–gel with entrapped plant virus-based immunosorbent nanoparticles
Authors: McNulty Matthew J. , Hamada Naomi , Delzio Jesse , McKee Liber , Nandi Somen , Longo Marjorie L. , McDonald Karen A.
Published: March 2022

Advancements in understanding and engineering of virus-based nanomaterials (VBNs) for biomedical applications motivate a need to explore the interfaces between VBNs and other biomedically-relevant chemistries and materials. While several strategies have been used to investigate some of these interfaces with promising initial results, including VBN-containing slow-release implants and VBN-activated bioceramic bone scaffolds, there remains a need to establish VBN-immobilized three dimensional materials that exhibit improved stability and diffusion characteristics for biosensing and other analyte-capture applications. Silica sol–gel chemistries have been researched for biomedical applications over several decades and are well understood; various cellular organisms and biomolecules (e.g., bacteria, algae, enzymes) have been immobilized in silica sol-gels to improve viability, activity, and form factor (i.e., ease of use). Here we present the immobilization of an antibody-binding VBN in silica sol–gel by pore confinement. We have shown that the resulting system is sufficiently diffuse to allow antibodies to migrate in and out of the matrix. We also show that the immobilized VBN is capable of antibody binding and elution functionality under different buffer conditions for multiple use cycles. The promising results of the VBN and silica sol–gel interface indicate a general applicability for VBN-based bioseparations and biosensing applications.

Graphical Abstract
Naloxone protection, social support, network characteristics, and overdose experiences among a cohort of people who use illicit opioids in New York City
Authors: Bennett Alex S. , Scheidell Joy , Bowles Jeanette M. , Khan Maria , Roth Alexis , Hoff Lee , Marini Christina , Elliott Luther
Published: March 2022

Background

Despite increased availability of take-home naloxone, many people who use opioids do so in unprotected contexts, with no other person who might administer naloxone present, increasing the likelihood that an overdose will result in death. Thus, there is a social nature to being “protected” from overdose mortality, which highlights the importance of identifying background factors that promote access to protective social networks among people who use opioids.

Methods

We used respondent-driven sampling to recruit adults residing in New York City who reported recent (past 3-day) nonmedical opioid use (n = 575). Participants completed a baseline assessment that included past 30-day measures of substance use, overdose experiences, and number of “protected” opioid use events, defined as involving naloxone and the presence of another person who could administer it, as well as measures of network characteristics and social support. We used modified Poisson regression with robust variance to estimate unadjusted and adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs).

Results

66% of participants had ever been trained to administer naloxone, 18% had used it in the past three months, and 32% had experienced a recent overdose (past 30 days). During recent opioid use events, 64% reported never having naloxone and a person to administer present. This was more common among those: aged ≥ 50 years (PR: 1.18 (CI 1.03, 1.34); who identified as non-Hispanic Black (PR: 1.27 (CI 1.05, 1.53); experienced higher levels of stigma consciousness (PR: 1.13 (CI 1.00, 1.28); and with small social networks (< 5 persons) (APR: 1.14 (CI 0.98, 1.31). Having a recent overdose experience was associated with severe opioid use disorder (PR: 2.45 (CI 1.49, 4.04), suicidality (PR: 1.72 (CI 1.19, 2.49), depression (PR: 1.54 (CI 1.20, 1.98) and positive urinalysis result for benzodiazepines (PR: 1.56 (CI 1.23, 1.96), but not with network size.

Conclusions

Results show considerable gaps in naloxone protection among people who use opioids, with more vulnerable and historically disadvantaged subpopulations less likely to be protected. Larger social networks of people who use opioids may be an important resource to curtail overdose mortality, but more effort is needed to harness the protective aspects of social networks.
Harm reduction in the Heartland: public knowledge and beliefs about naloxone in Nebraska, USA
Authors: Schlosser Allison , Habecker Patrick , Bevins Rick
Published: March 2022

Background

Opioid-related overdose deaths have been increasing in the United States (U.S.) in the last twenty years, creating a public health challenge. Take-home naloxone is an effective strategy for preventing opioid-related overdose death, but its widespread use is particularly challenging in smaller cities, towns, and rural areas where it may be stigmatized and/or poorly understood.

Methods

We analyzed data on knowledge and beliefs about drug use and naloxone among the general public in Nebraska, a largely rural state in the Great Plains region of the U.S., drawing on the 2020 Nebraska Annual Social Indicators Survey.

Results

Respondents reported negative beliefs about people who use drugs (PWUD) and little knowledge of naloxone. Over half reported that members of their community view PWUD as blameworthy, untrustworthy, and dangerous. Approximately 31% reported being unaware of naloxone. Only 15% reported knowing where to obtain naloxone and less than a quarter reported knowing how to use it. Knowing where to obtain naloxone is associated with access to opioids and knowing someone who has recently overdosed, but having ever used opioids or being close to someone who uses opioids is not associated with naloxone knowledge. Finally, almost a quarter of respondents endorsed the belief that people who use opioids will use more if they have access to naloxone.

Conclusion

Our findings highlight stigmatizing beliefs about PWUD and underscore the need for further education on naloxone as an effective strategy to reduce opioid-related overdose death. We highlight the implications of these findings for public education efforts tailored to non-urban communities.