bluuebunny/crossref_metadata_2025 huggingface dataset:
Astrocytic APOE4 removal confers cerebrovascular protection despite increased cerebral amyloid angiopathy
Authors: Xiong Monica , Wang Chao , Gratuze Maud , Saadi Fareeha , Bao Xin , Bosch Megan E. , Lee Choonghee , Jiang Hong , Serrano Javier Remolina , Gonzales Ernesto R. , Kipnis Michal , Holtzman David M.
Published: March 2023

Background

Alzheimer Disease (AD) and cerebral amyloid angiopathy (CAA) are both characterized by amyloid-β (Aβ) accumulation in the brain, although Aβ deposits mostly in the brain parenchyma in AD and in the cerebrovasculature in CAA. The presence of CAA can exacerbate clinical outcomes of AD patients by promoting spontaneous intracerebral hemorrhage and ischemia leading to CAA-associated cognitive decline. Genetically, AD and CAA share the ε4 allele of the apolipoprotein E (APOE) gene as the strongest genetic risk factor. Although tremendous efforts have focused on uncovering the role of APOE4 on parenchymal plaque pathogenesis in AD, mechanistic studies investigating the role of APOE4 on CAA are still lacking. Here, we addressed whether abolishing APOE4 generated by astrocytes, the major producers of APOE, is sufficient to ameliorate CAA and CAA-associated vessel damage.

Methods

We generated transgenic mice that deposited both CAA and plaques in which APOE4 expression can be selectively suppressed in astrocytes. At 2-months-of-age, a timepoint preceding CAA and plaque formation, APOE4 was removed from astrocytes of 5XFAD APOE4 knock-in mice. Mice were assessed at 10-months-of-age for Aβ plaque and CAA pathology, gliosis, and vascular integrity.

Results

Reducing the levels of APOE4 in astrocytes shifted the deposition of fibrillar Aβ from the brain parenchyma to the cerebrovasculature. However, despite increased CAA, astrocytic APOE4 removal reduced overall Aβ-mediated gliosis and also led to increased cerebrovascular integrity and function in vessels containing CAA.

Conclusion

In a mouse model of CAA, the reduction of  APOE4 derived specifically from astrocytes, despite increased fibrillar Aβ deposition in the vasculature, is sufficient to reduce Aβ-mediated gliosis and cerebrovascular dysfunction.
Sustainability of health services in refugee hosting districts: a qualitative study of health services in three west Nile refugee hosting districts, Uganda
Authors: Komakech Henry , Orach Christopher Garimoi , Atuyambe Lynn M.
Published: March 2023

Background

Humanitarian health assistance programmes have expanded from temporary approaches addressing short-term needs to providing long-term interventions in emergency settings. Measuring sustainability of humanitarian health services is important towards improving the quality of health services in refugee settings.

Objective

To explore the sustainability of health services following the repatriation of refugees from the west Nile districts of Arua, Adjumani and Moyo.

Methods

This was a qualitative comparative case study conducted in three west Nile refugee-hosting districts of Arua, Adjumani, and Moyo. In-depth interviews were conducted with 28 purposefully selected respondents in each of the three districts. Respondents included health workers and managers, district civic leaders, planners, chief administrative officers, district health officers, project staff of aid agencies, refugee health focal persons and community development officers.

Results

The study shows that in terms of organization capacity, the District Health Teams provided health services to both refugee and host communities with minimal support from aid agencies. Health services were available in most former refugee hosting areas in Adjumani, Arua and Moyo districts. However, there were several disruptions notably reduction and inadequate services due to shortage of drugs and essential supplies, lack of health workers, and closure or relocation of health facilities in around former settlements. To minimize disruptions the district health office reorganized health services. In restructuring health services, the district local governments closed or upgraded health facilities to address reduced capacity and catchment population. Health workers employed by aid agencies were recruited into government services while others who were deemed excess or unqualified were laid off. Equipment and machinery including machines and vehicles were transferred to the district health office in specific health facilities. Funding for health services was mainly provided by the Government of Uganda through the Primary Health Care Grant. Aid agencies, however, continued to provide minimal support health services for refugees who remained in Adjumani district.

Conclusion

Our study showed that while humanitarian health services are not designed for sustainability, several interventions continued at the end of the refugee emergency in the three districts. The embeddedness of the refugee health services in the district health systems ensured health services continued through public service delivery structures. It is important to strengthen the capacity of the local service delivery structures and ensure health assistance programmes are integrated into local health systems to promote sustainability.
Prognostic landscape of mitochondrial genome in myelodysplastic syndrome after stem-cell transplantation
Authors: Dong Jing , Buradagunta Christopher Staffi , Zhang Tao , Spellman Stephen , Bolon Yung-Tsi , DeZern Amy E. , Gadalla Shahinaz M. , Deeg H. Joachim , Nazha Aziz , Cutler Corey , Cheng Chao , Urrutia Raul , Auer Paul , Saber Wael
Published: March 2023

Despite mitochondrial DNA (mtDNA) mutations are common events in cancer, their global frequency and clinical impact have not been comprehensively characterized in patients with myelodysplastic neoplasia (also known as myelodysplastic syndromes, MDS). Here we performed whole-genome sequencing (WGS) on samples obtained before allogenic hematopoietic cell transplantation (allo-HCT) from 494 patients with MDS who were enrolled in the Center for International Blood and Marrow Transplant Research. We evaluated the impact of mtDNA mutations on transplantation outcomes, including overall survival (OS), relapse, relapse-free survival (RFS), and transplant-related mortality (TRM). A random survival forest algorithm was applied to evaluate the prognostic performance of models that include mtDNA mutations alone and combined with MDS- and HCT-related clinical factors. A total of 2666 mtDNA mutations were identified, including 411 potential pathogenic variants. We found that overall, an increased number of mtDNA mutations was associated with inferior transplantation outcomes. Mutations in several frequently mutated mtDNA genes (e.g., MT-CYB and MT-ND5) were identified as independent predictors of OS, RFS, relapse and/or TRM after allo-HCT. Integration of mtDNA mutations into the models based on the Revised International Prognostic Scores (IPSS-R) and clinical factors related to MDS and allo-HCT could capture more prognostic information and significantly improve the prognostic stratification efforts. Our study represents the first WGS effort in MDS receiving allo-HCT and shows that there may be clinical utility of mtDNA variants to predict allo-HCT outcomes in combination with more standard clinical parameters.
CD46 targeted 212Pb alpha particle radioimmunotherapy for prostate cancer treatment
Authors: Li Jun , Huang Tao , Hua Jun , Wang Qiong , Su Yang , Chen Ping , Bidlingmaier Scott , Li Allan , Xie Zhongqiu , Bidkar Anil P. , Shen Sui , Shi Weibin , Seo Youngho , Flavell Robert R. , Gioeli Daniel , Dreicer Robert , Li Hui , Liu Bin , He Jiang
Published: March 2023

We recently identified CD46 as a novel prostate cancer cell surface antigen that shows lineage independent expression in both adenocarcinoma and small cell neuroendocrine subtypes of metastatic castration resistant prostate cancer (mCRPC), discovered an internalizing human monoclonal antibody YS5 that binds to a tumor selective CD46 epitope, and developed a microtubule inhibitor-based antibody drug conjugate that is in a multi-center phase I trial for mCRPC (NCT03575819). Here we report the development of a novel CD46-targeted alpha therapy based on YS5. We conjugated 212Pb, an in vivo generator of alpha-emitting 212Bi and 212Po, to YS5 through the chelator TCMC to create the radioimmunoconjugate, 212Pb-TCMC-YS5. We characterized 212Pb-TCMC-YS5 in vitro and established a safe dose in vivo. We next studied therapeutic efficacy of a single dose of 212Pb-TCMC-YS5 using three prostate cancer small animal models: a subcutaneous mCRPC cell line-derived xenograft (CDX) model (subcu-CDX), an orthotopically grafted mCRPC CDX model (ortho-CDX), and a prostate cancer patient-derived xenograft model (PDX). In all three models, a single dose of 0.74 MBq (20 µCi) 212Pb-TCMC-YS5 was well tolerated and caused potent and sustained inhibition of established tumors, with significant increases of survival in treated animals. A lower dose (0.37 MBq or 10 µCi 212Pb-TCMC-YS5) was also studied on the PDX model, which also showed a significant effect on tumor growth inhibition and prolongation of animal survival. These results demonstrate that 212Pb-TCMC-YS5 has an excellent therapeutic window in preclinical models including PDXs, opening a direct path for clinical translation of this novel CD46-targeted alpha radioimmunotherapy for mCRPC treatment.
Investigating the potential role of swertiamarin on insulin resistant and non-insulin resistant granulosa cells of poly cystic ovarian syndrome patients
Authors: Belani Muskaan A. , Shah Preeti , Banker Manish , Gupta Sarita S.
Published: March 2023

Background and aim

Conventional drugs have limitations due to prevalence of contraindications in PCOS patients. To explore the potential effects of swertiamarin, on abrupted insulin and steroidogenic signaling in human luteinized granulosa cells from PCOS patients with or without insulin resistance.

Experimental procedure

hLGCs from 8 controls and 16 PCOS patients were classified for insulin resistance based on down regulation of protein expression of insulin receptor-β (INSR- β) as shown in our previous paper. Cells were grouped as control, PCOS-IR and PCOS-NIR, treated with swertiamarin (66 µM) and metformin (1 mM). Expression of key molecules involved in insulin signaling, fat metabolism, IGF system and steroidogenesis were compared between groups.

Results

Swertiamarin significantly (P < 0.05) reversed the expression of INSR-β, PI(3)K, p-Akt, PKC-ζ, PPARγ, (P < 0.01) IRS (Ser 307) and IGF system in PCOS-IR group and was equally potent to metformin. In the same group, candidate genes viz SREBP1c, FAS, ACC-1 and CPT-1 were down regulated by swertiamarin (P < 0.001) and metformin (P < 0.001). Significant upregulation was demonstrated in expression of StAR, CYP19A1, 17β-HSD and 3β-HSD when treated with swertiamarin (P < 0.01) and metformin (P < 0.01) in PCOS-IR followed by increase in 17β-HSD and 3β-HSD enzyme activity along with estradiol and progesterone secretions. However, swertiamarin did not reveal any effect on PCOS-NIR group as compared to metformin that significantly (P < 0.01) reversed all the parameters related to steroidogenesis and down regulated basal expression of insulin signaling genes.

Conclusion

Swertiamarin, presents itself as a potential fertility drug in hLGCs from PCOS-IR patients.
Homologous recombination deficiency status predicts response to platinum-based chemotherapy in Chinese patients with high-grade serous ovarian carcinoma
Authors: Feng Zheng , Shao Di , Cai Yuhang , Bi Rui , Ju Xingzhu , Chen Dongju , Song Chengcheng , Chen Xiaojun , Li Jin , An Na , Li Yunjin , Zhou Qing , Xiu Zhihui , Zhu Shida , Wu Xiaohua , Wen Hao
Published: March 2023

Background

Homologous Recombination Deficiency (HRD) is a predictive biomarker for ovarian cancer treated with PARP inhibitors or for breast cancer treated with first-line platinum-based chemotherapy. However, limited research is documented on platinum-based treatment prediction with HRD as a biomarker in ovarian cancer patients, especially in the Chinese population.

Methods

We investigated the association between HRD status and the response of platinum-based chemotherapy in 240 Chinese HGSOC patients.

Results

The Pt-sensitive patients showed higher HRD scores than Pt-resistant ones, but this was not significant(median: 42.6 vs. 31.6, p = 0.086). (Pt)-sensitive rate was higher in HRD + BRCAm tumors and in HRD + BRCAwt tumors (HRD + BRCAm: 97%, p = 0.004 and HRD + BRCAwt: 90%, p = 0.04) compared with 74% in the HRD-BRCAwt tumors. We also found Pt-sensitive patients tend to be enriched in patients with BRCA mutations or non-BRCA HRR pathway gene mutations (BRCA: 93.6% vs 75.4%, p < 0.001; non-BRCA HRR: 88.6% vs 75.4%, p = 0.062). Patients with HRD status positive had significantly improved PFS compared with those with HRD status negative (median PFS: 30.5 months vs. 16.8 months, Log-rank p = 0.001). Even for BRCAwt patients, positive HRD was also associated with better PFS than the HRD-negative group (median: 27.5 months vs 16.8 months, Log-rank p = 0.010). Further, we found patients with pathogenic mutations located in the DNA-binding domain (DBD) of BRCA1 had improved FPS, compared to those with mutations in other domains. (p = 0.03).

Conclusions

The HRD status can be identified as an independent significance in Chinese HGSOC patients treated with first-line platinum-based chemotherapy.
AMH producing purely cystic virilizing adult granulosa cell tumor in 17 years old girl: a case report and review of literatures
Authors: Kitajima Michio , Kajimura Itsuki , Kitajima Yuriko , Murakami Naoko , Matsumura Asako , Matsumoto Kanako , Harada Ayumi , Hasegawa Yuri , Miura Kiyonori
Published: March 2023

Background

Androgen-producing granulosa cell tumor in adolescent girl is rare condition and clinical characteristics are not fully elucidated.

Case presentation

Seventeen years old girl complained of secondary amenorrhea was referred to our out-patient consultation. Markedly elevated serum testosterone, LH, and AMH levels were noted. Mild hirsutism and clitoromegaly were presented. Transabdominal ultrasonography and MRI revealed cystic mass occupied pelvic cavity probably originated from left ovary. Right ovary showed polycystic appearance. Laparoscopic left ovarian cystectomy was performed. After the surgery, her menstruation resumed along with normalized hormonal parameters, and clinical hyperandrogenism were improved. Since the scarcity of cellular lining of inner cyst wall, definitive pathological diagnosis was difficult. After the consultation with gynecological pathologist, the tumor was diagnosed as sex cord stromal tumor, highly suspicious for adult granulosa cell tumor. Residual left salpingo-oophorectomy was performed by additional laparoscopic surgery. Her serum testosterone and AMH levels were remained low with regular menstrual cycles and no evidence of recurrence.

Conclusions

Androgen-producing cystic granulosa cell tumor is rare gynecological disorders, which need both gynecologic oncological and endocrinological approach. Its clinical manifestations may bring some clues to the pathogenesis of ovulatory dysfunctions, such as polycystic ovary syndrome.
An analysis of risk factors associated with recurrent wheezing in the pediatric population
Authors: Zhu Yibing , Chen Lumin , Miao Yecheng , Chen Jinying , Bai Meng , Gao Haiyan , Zhu Zhirong , Zhang Yuxuan , Zhang Jianzhong , Raza Hafiz Khuram , Liu Guanghua
Published: March 2023

Background

Recurrent wheezing is a common clinical problem in early childhood, which is associated with significant morbidity. There is no international consensus on the management and prevention of recurrent wheezing; therefore, identifying the risk factors associated with recurrent wheezing is crucial to prevent episodes of wheezing in young children.

Methods

In this retrospective study, we collected the data of 24,737 patients who were admitted to our hospital between 27th April 2012 and 11th September 2019. After screening for patients with wheezing, we identified 8572 patients with a primary diagnosis of pneumonia with wheezing. Patients’ clinical data were collected from the hospital medical records. Patients were stratified for age in the groups of < 6 months, 6–12 months, and > 12 months.

Results

Among the 8569 pediatric pneumonia patients with wheezing, there were 343 patients with recurrent wheezing. Most enrolled patients were under 6 months of age (45.17%) and had a normal birth weight (86.95%). Winter was the most common onset season for the first episode of wheezing, while spring was the most common season for the second episode of wheezing for those with recurrent wheezing. The univariate and multivariate logistic regression analysis for the risk factor associated with recurrent wheezing showed that male gender, past history of respiratory and cardiovascular diseases, low birth weight, development of severe pneumonia, and PICU admission were significantly associated with recurrent wheezing.

Conclusion

Male gender, past history of respiratory and cardiovascular diseases, low birth weight, severe pneumonia, and PICU admission are independent risk factors of recurrent wheezing in the pediatric population.
Paraneoplastic pemphigus and Castleman’s disease: a case report and a revision of the literature
Authors: Irrera Mariangela , Bozzola Elena , Cardoni Antonello , DeVito Rita , Diociaiuti Andrea , El Hachem Maya , Girardi Katia , Marchesi Alessandra , Villani Alberto
Published: March 2023

Background

In literature, a few reports described an association between paraneoplastic pemphigus (PNP) and Castelman’s disease (CD), but no consensus have been proposed for the diagnostic-therapeutical approach. Aim of this study is to present a case report and explore the relationship between PNP and CD in pediatric patients, focusing on clinical manifestations, histopathological findings, treatment and outcome to find elements for an early diagnosis.

Case presentation

We present the clinical case of a 13 years old girl with a challenging diagnosis of PNP and CD who underwent therapy at first with Rituximab and then with Siltuximab, for the control of symptoms.

Conclusions

Reviewing literature, 20 clinical cases have been described in the pediatric age. Diagnosis may be challenging, requiring an average of 3 months (range from 3 weeks to 2 years). In all cases, the initial manifestations were mucocutaneous lesions, especially oral lesions with poor response to conventional treatment. Systemic symptoms may be present as well. Therapeutical approach is still discussed with no consensus. Almost all patients received corticosteroids with poor response. Other drugs including azathioprine, methotrexate, cyclosporine and monoclonal antibodies have been evaluated for the control of the disease. Further studies and experimental trials urge to define the diagnostic criteria and therapy protocol.
Positive end-expiratory pressure induced changes in airway driving pressure in mechanically ventilated COVID-19 Acute Respiratory Distress Syndrome patients
Authors: da Cruz Mônica Rodrigues , Camilo Luciana Moisés , da Costa Xavier Tiago Batista , da Motta Ribeiro Gabriel Casulari , Medeiros Denise Machado , da Fonseca Reis Luís Felipe , da Silva Guimarães Bruno Leonardo , Japiassú André Miguel , Carvalho Alysson Roncally Silva
Published: March 2023

Background

The profile of changes in airway driving pressure (dPaw) induced by positive-end expiratory pressure (PEEP) might aid for individualized protective ventilation. Our aim was to describe the dPaw versus PEEP curves behavior in ARDS from COVID-19 patients.

Methods

Patients admitted in three hospitals were ventilated with fraction of inspired oxygen (FiO2) and PEEP initially adjusted by oxygenation-based table. Thereafter, PEEP was reduced from 20 until 6 cmH2O while dPaw was stepwise recorded and the lowest PEEP that minimized dPaw (PEEPmin_dPaw) was assessed. Each dPaw vs PEEP curve was classified as J-shaped, inverted-J-shaped, or U-shaped according to the difference between the minimum dPaw and the dPaw at the lowest and highest PEEP. In one hospital, hyperdistention and collapse at each PEEP were assessed by electrical impedance tomography (EIT).

Results

184 patients (41 including EIT) were studied. 126 patients (68%) exhibited a J-shaped dPaw vs PEEP profile (PEEPmin_dPaw of 7.5 ± 1.9 cmH2O). 40 patients (22%) presented a U (PEEPmin_dPaw of 12.2 ± 2.6 cmH2O) and 18 (10%) an inverted-J profile (PEEPmin_dPaw of 14,6 ± 2.3 cmH2O). Patients with inverted-J profiles had significant higher body mass index (BMI) and lower baseline partial pressure of arterial oxygen/FiO2 ratio. PEEPmin_dPaw was associated with lower fractions of both alveolar collapse and hyperinflation.

Conclusions

A PEEP adjustment procedure based on PEEP-induced changes in dPaw is feasible and may aid in individualized PEEP for protective ventilation. The PEEP required to minimize driving pressure was influenced by BMI and was low in the majority of patients.
The Role of Transcriptomics in Redefining Critical Illness
Authors: Pelaia Tiana M. , Shojaei Maryam , McLean Anthony S.
Published: March 2023

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2023. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901.
Interrogating the sepsis host immune response using cytomics
Authors: Lindell Robert B. , Meyer Nuala J.
Published: March 2023

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online athttps://www.biomedcentral.com/collections/annualupdate2023. Further information about the Annual Update in Intensive Care and Emergency Medicine is available fromhttps://link.springer.com/bookseries/8901.
Hemodynamic Implications of Prone Positioning in Patients with ARDS
Authors: Lai Christopher , Monnet Xavier , Teboul Jean-Louis
Published: March 2023

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2023. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901.
Update on the management of acute respiratory failure using non-invasive ventilation and pulse oximetry
Authors: Abe Tatsuhiko , Takagi Toshishige , Fujii Tomoko
Published: March 2023

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2023. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901.
Managing the Physiologically Difficult Airway in Critically Ill Adults
Authors: Jabaley Craig Steven
Published: March 2023

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2023. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901.
Setting and Monitoring of Mechanical Ventilation During Venovenous ECMO
Authors: Assouline Benjamin , Combes Alain , Schmidt Matthieu
Published: March 2023

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2023. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901.
Neurological and respiratory effects of lung protective ventilation in acute brain injury patients without lung injury: brain vent, a single centre randomized interventional study
Authors: Beqiri Erta , Smielewski Peter , Guérin Claude , Czosnyka Marek , Robba Chiara , Bjertnæs Lars , Frisvold Shirin K.
Published: March 2023

Introduction

Lung protective ventilation (LPV) comprising low tidal volume (VT) and high positive end-expiratory pressure (PEEP) may compromise cerebral perfusion in acute brain injury (ABI). In patients with ABI, we investigated whether LPV is associated with increased intracranial pressure (ICP) and/or deranged cerebral autoregulation (CA), brain compensatory reserve and oxygenation.

Methods

In a prospective, crossover study, 30 intubated ABI patients with normal ICP and no lung injury were randomly assigned to receive low VT [6 ml/kg/predicted (pbw)]/at either low (5 cmH2O) or high PEEP (12 cmH2O). Between each intervention, baseline ventilation (VT 9 ml/kg/pbw and PEEP 5 cmH2O) were resumed. The safety limit for interruption of the intervention was ICP above 22 mmHg for more than 5 min. Airway and transpulmonary pressures were continuously monitored to assess respiratory mechanics. We recorded ICP by using external ventricular drainage or a parenchymal probe. CA and brain compensatory reserve were derived from ICP waveform analysis.

Results

We included 27 patients (intracerebral haemorrhage, traumatic brain injury, subarachnoid haemorrhage), of whom 6 reached the safety limit, which required interruption of at least one intervention. For those without intervention interruption, the ICP change from baseline to “low VT/low PEEP” and “low VT/high PEEP” were 2.2 mmHg and 2.3 mmHg, respectively, and considered clinically non-relevant. None of the interventions affected CA or oxygenation significantly. Interrupted events were associated with high baseline ICP (p < 0.001), low brain compensatory reserve (p < 0.01) and mechanical power (p < 0.05).

The transpulmonary driving pressure was 5 ± 2 cmH2O in both interventions. Partial arterial pressure of carbon dioxide was kept in the range 34–36 mmHg by adjusting the respiratory rate, hence, changes in carbon dioxide were not associated with the increase in ICP.

Conclusions

The present study found that most patients did not experience any adverse effects of LPV, neither on ICP nor CA. However, in almost a quarter of patients, the ICP rose above the safety limit for interrupting the interventions. Baseline ICP, brain compensatory reserve, and mechanical power can predict a potentially deleterious effect of LPV and can be used to personalize ventilator settings.

Trial registrationNCT03278769. Registered September 12, 2017.

Graphical Abstract
Novel serum biomarkers for predicting neurological outcomes in postcardiac arrest patients treated with targeted temperature management
Authors: Song Hwan , Bang Hyo Jin , You Yeonho , Park Jung Soo , Kang Changshin , Kim Hyo Joon , Park Kyu Nam , Oh Sang Hoon , Youn Chun Song
Published: March 2023

Objective

To determine the clinical feasibility of novel serum biomarkers in out-of-hospital cardiac arrest (OHCA) patients treated with target temperature management (TTM).

Methods

This study was a prospective observational study conducted on OHCA patients who underwent TTM. We measured conventional biomarkers, neuron‑specific enolase and S100 calcium-binding protein (S-100B), as well as novel biomarkers, including tau protein, neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and ubiquitin C-terminal hydrolase-L1 (UCH-L1), at 0, 24, 48, and 72 h after the return of spontaneous circulation identified by SIMOA immunoassay. The primary outcome was poor neurological outcome at 6 months after OHCA.

Results

A total of 100 patients were included in this study from August 2018 to May 2020. Among the included patients, 46 patients had good neurologic outcomes at 6 months after OHCA. All conventional and novel serum biomarkers had the ability to discriminate between the good and poor neurological outcome groups (p < 0.001). The area under the curves of the novel serum biomarkers were highest at 72 h after cardiac arrest (CA) (0.906 for Tau, 0.946 for NFL, 0.875 for GFAP, and 0.935 for UCH-L1). The NFL at 72 h after CA had the highest sensitivity (77.1%, 95% CI 59.9–89.6) in predicting poor neurological outcomes while maintaining 100% specificity.

Conclusion

Novel serum biomarkers reliably predicted poor neurological outcomes for patients with OHCA treated with TTM when life-sustaining therapy was not withdrawn. Cutoffs from two large existing studies (TTM and COMACARE substudy) were externally validated in our study. The predictive power of the novel biomarkers was the highest at 72 h after CA.
BEAT CF pulmonary exacerbations core protocol for evaluating the management of pulmonary exacerbations in people with cystic fibrosis
Authors: Schultz Andre , McLeod Charlie , Berry Scott , Marsh Julie , McKenzie Anne , Messer Mitch , Wood Jamie , Saville Ben , Jaffe Adam , Ranganathan Sarath , Stick Steve , Wark Peter , Webb Steve , Snelling Tom
Published: March 2023

Background

Cystic fibrosis (CF) is a rare, inherited, life-limiting condition predominantly affecting the lungs, for which there is no cure. The disease is characterized by recurrent pulmonary exacerbations (PEx), which are thought to drive progressive lung damage. Management of these episodes is complex and generally involves multiple interventions targeting different aspects of disease. The emergence of innovative trials and use of Bayesian statistical methods has created renewed opportunities for studying heterogeneous populations in rare diseases. Here, we present the protocol for the BEAT CF PEx cohort, a prospective, multi-site, perpetual, platform enrolling adults and children with CF. The BEAT CF PEx cohort will be used to evaluate the comparative effectiveness of interventions for the treatment of PEx requiring intensive therapy (PERITs), with a primary focus on short-term improvements in lung function. This will be achieved through the conduct of cohort-nested studies, including adaptive clinical trials, within the BEAT CF PEx cohort. This protocol will outline key features of the BEAT CF PEx cohort, including the design, implementation, data collection and management, governance and analysis, and dissemination of results.

Methods

This platform will be conducted across multiple sites, commencing with CF treatment centers in Australia. People of all ages with a clinical diagnosis of CF will be eligible to participate, except those who have previously received a lung transplant. Data including demographic and clinical information, treatment details, and outcomes (including safety, microbiology, and patient-reported outcome measures including quality of life scores) will be systematically collected and securely stored via a digital centralized trial management system (CTMS). The primary endpoint is the absolute change in the percentage predicted forced expiratory volume in 1 s (ppFEV1) from the commencement of intensive therapy to 7 to 10 days afterwards.

Discussion

The BEAT CF PEx cohort will report clinical, treatment, and outcome data for PEx among people with CF and is intended to serve as a core (master) protocol for future nested, interventional trials evaluating treatment(s) for these episodes. The protocols for nested sub-studies are beyond the scope of this document and will be reported separately.

Trial registration

ANZCTR BEAT CF Platform – ACTRN12621000638831. Registration date: Sept. 26, 2022.
PROphylaxis for paTiEnts at risk of COVID-19 infecTion (PROTECT-V)
Authors: Humphrey Toby J. L. , Dosanjh Davinder , Hiemstra Thomas F. , Richter Alex , Chen-Xu Michael , Qian Wendi , Jha Vivekanand , Gatley Katrina , Adhikari Rakshya , Dowling Francis , Smith Rona M.
Published: March 2023

Background

Despite the introduction of vaccination, there remains a need for pre-exposure prophylactic agents against SARS-CoV-2. Several patient groups are more vulnerable to SARS-CoV-2 infection by virtue of underlying health conditions, treatments received or suboptimal responses to vaccination.

Methods

PROTECT-V is a platform trial testing pre-exposure prophylactic interventions against SARS-CoV-2 infection in vulnerable patient populations (organ transplant recipients; individuals with oncological/haematological diagnoses, immune deficiency or autoimmune diseases requiring immunosuppression or on dialysis). Multiple agents can be evaluated across multiple vulnerable populations sharing placebo groups, with the option of adding additional treatments at later time points as these become available. The primary endpoint is symptomatic SARS-CoV-2 infection, and each agent will be independently evaluated in real time when the required number of events occurs. Presently, three agents are approved in the platform: intranasal niclosamide, nasal and inhaled ciclesonide and intravenous sotrovimab.

Discussion

Despite the introduction of vaccination, there remains a need for pre-exposure prophylactic agents against SARS-CoV-2. Several patient groups are more vulnerable to COVID-19 disease by virtue of underlying health conditions, treatments received or suboptimal responses to vaccination.

Trial registration

ClinicalTrials.gov NCT04870333. EudraCT 2020-004144-28
Overall morbidity after total minimally invasive keyhole oesophagectomy versus hybrid oesophagectomy (the MICkey trial): study protocol for a multicentre randomized controlled trial
Authors: Klotz Rosa , Diener Markus K. , Schmidt Thomas , Hackert Thilo , Graf Sandra , Fuchs Hans F. , Grimminger Peter , Egberts Jan-Hendrick , Gockel Ines , van der Sluis Pieter C. , Doerr-Harim Colette , Klose Christina , Feißt Manuel , Mihaljevic Andre L.
Published: March 2023

Background

Oesophageal cancer (EC) is the sixth leading cause of cancer death worldwide. Oesophageal resection is the only curative treatment option for EC which is frequently performed via an abdominal and right thoracic approach (Ivor-Lewis operation). This 2-cavity operation is associated with a high risk of major complications. To reduce postoperative morbidity, several minimally invasive techniques have been developed that can be broadly classified into either hybrid oesophagectomy (HYBRID-E) via laparoscopic/robotic abdominal and open thoracic surgery or total minimally invasive oesophagectomy (MIN-E). Both, HYBIRD-E and MIN-E, compare favourable to open oesophagectomy. However, there is still an evidence gap comparing HYBRID-E with MIN-E with regard to postoperative morbidity.

Methods

The MICkey trial is a multicentre randomized controlled superiority trial with two parallel study groups. A total of 152 patients with oesophageal cancer scheduled for elective oesophagectomy will be randomly assigned 1:1 to the control group (HYBRID-E) or to the intervention group (MIN-E). The primary endpoint will be overall postoperative morbidity assessed via the comprehensive complication index (CCI) within 30 days after surgery. Specific perioperative parameters, as well as patient-reported and oncological outcomes, will be analysed as secondary outcomes.

Discussion

The MICkey trial will address the yet unanswered question whether the total minimally invasive oesophagectomy (MIN-E) is superior to the HYBRID-E procedure regarding overall postoperative morbidity.

Trial registration

DRKS00027927 U1111-1277-0214. Registered on 4th July 2022
The Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) for serious mental illness in community mental health part 1: study protocol for a hybrid type 2 effectiveness-implementation cluster-randomized trial
Authors: Sarfan Laurel D. , Agnew Emma R. , Diaz Marlen , Dong Lu , Fisher Krista , Spencer Julia M. , Howlett Shayna A. , Hache Rafael Esteva , Callaway Catherine A. , Kilbourne Amy M. , Buysse Daniel J. , Harvey Allison G.
Published: March 2023

Background

Serious mental illness (SMI) can have devastating consequences. Unfortunately, many patients with SMI do not receive evidence-based psychological treatment (EBPTs) in routine practice settings. One barrier is poor “fit” between EBPTs and contexts in which they are implemented. The present study will evaluate implementation and effectiveness outcomes of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) implemented in community mental health centers (CMHCs). TranS-C was designed to target a range of SMI diagnoses by addressing a probable mechanism and predictor of SMI: sleep and circadian problems. We will investigate whether adapting TranS-C to fit CMHC contexts improves providers’ perceptions of fit and patient outcomes.

Methods

TranS-C will be implemented in at least ten counties in California, USA (N = 96 providers; N = 576 clients), via facilitation. CMHC sites are cluster-randomized by county to Adapted TranS-C or Standard TranS-C. Within each county, patients are randomized to immediate TranS-C or usual care followed by delayed treatment with TranS-C (UC-DT). Aim 1 will compare TranS-C (combined Adapted and Standard) with UC-DT on improvements in sleep and circadian problems, functional impairment, and psychiatric symptoms. Sleep and circadian problems will also be tested as a mediator between treatment condition (combined TranS-C versus UC-DT) and functional impairment/psychiatric symptoms. Aim 2 will evaluate whether Adapted TranS-C is superior to Standard TranS-C with respect to provider perceptions of fit. Aim 3 will evaluate whether the relation between TranS-C treatment condition (Adapted versus Standard) and patient outcomes is mediated by better provider perceptions of fit in the Adapted condition. Exploratory analyses will (1) compare Adapted versus Standard TranS-C on patient perceptions of credibility/improvement and select PhenX Toolkit outcomes and (2) evaluate possible moderators.

Discussion

This trial has the potential to (a) expand support for TranS-C, a promising transdiagnostic treatment delivered to patients with SMI in CMHCs; (b) take steps toward addressing challenges faced by providers in delivering EBPTs (i.e., high caseloads, complex patients, poor fit); and (c) advance evidence on causal strategies (i.e., adapting treatments to fit context) in implementation science.

Trial registration

Clinicaltrials.gov NCT04154631. Registered on 6 November 2019. https://clinicaltrials.gov/ct2/show/NCT04154631
Comparing the clinical and cost-effectiveness of remote (telehealth and online) cognitive behavioral therapy-based treatments for high-impact chronic pain relative to usual care: study protocol for the RESOLVE multisite randomized control trial
Authors: Mayhew Meghan , Balderson Benjamin H. , Cook Andrea J. , Dickerson John F. , Elder Charles R. , Firemark Alison J. , Haller Irina V. , Justice Morgan , Keefe Francis J. , McMullen Carmit K. , O’Keeffe-Rosetti Maureen C. , Owen-Smith Ashli A. , Rini Christine , Schneider Jennifer L. , Von Korff Michael , Wandner Laura D. , DeBar Lynn L.
Published: March 2023

Background

Cognitive behavioral therapy for chronic pain (CBT-CP) is an effective but underused treatment for high-impact chronic pain. Increased access to CBT-CP services for pain is of critical public health importance, particularly for rural and medically underserved populations who have limited access due to these services being concentrated in urban and high income areas. Making CBT-CP widely available and more affordable could reduce barriers to CBT-CP use.

Methods

As part of the National Institutes of Health Helping to End Addiction Long-term® (NIH HEAL) initiative, we designed and implemented a comparative effectiveness, 3-arm randomized control trial comparing remotely delivered telephonic/video and online CBT-CP-based services to usual care for patients with high-impact chronic pain. The RESOLVE trial is being conducted in 4 large integrated healthcare systems located in Minnesota, Georgia, Oregon, and Washington state and includes demographically diverse populations residing in urban and rural areas. The trial compares (1) an 8-session, one-on-one, professionally delivered telephonic/video CBT-CP program; and (2) a previously developed and tested 8-session online CBT-CP-based program (painTRAINER) to (3) usual care augmented by a written guide for chronic pain management. Participants are followed for 1 year post-allocation and are assessed at baseline, and 3, 6, and 12 months post-allocation. The primary outcome is minimal clinically important difference (MCID; ≥ 30% reduction) in pain severity (composite of pain intensity and pain-related interference) assessed by a modified 11-item version of the Brief Pain Inventory-Short Form at 3 months. Secondary outcomes include pain severity, pain intensity, and pain-related interference scores, quality of life measures, and patient global impression of change at 3, 6, and 12 months. Cost-effectiveness is assessed by incremental cost per additional patient with MCID in primary outcome and by cost per quality-adjusted life year achieved. Outcome assessment is blinded to group assignment.

Discussion

This large-scale trial provides a unique opportunity to rigorously evaluate and compare the clinical and cost-effectiveness of 2 relatively low-cost and scalable modalities for providing CBT-CP-based treatments to persons with high-impact chronic pain, including those residing in rural and other medically underserved areas with limited access to these services.

Trial registration

ClinicalTrials.gov NCT04523714. This trial was registered on 24 August 2020.
The effects of qigong intervention based on the Internet on quality of life and physical fitness in Chinese postoperative breast cancer patients: a protocol of randomized controlled trial
Authors: Li Chengxiang , Dong Xiaosheng , Yu Lina , Yuan Kai , Yi Xiangren , Shen Yuanlong , Niu Hu
Published: March 2023

Background

The purpose of this study is to verify the improvement of remote qigong intervention on the quality of life and physical fitness of breast cancer patients after surgery by means of a randomized controlled trial and to compare it with the conventional exercise combination of aerobic exercise and resistance training.

Methods/design

The research approach applied in this study is a randomized controlled trial. After completing the baseline questionnaire and physical fitness test, participants were randomly assigned to either the qigong group or the combined exercise rehabilitation group. Patients in the qigong group performed Qigong-Baduanjin twice a week for 30 min each time under remote guidance and practiced Baduanjin by themselves at other times. Patients in the combined exercise rehabilitation group were given resistance training twice a week for 30 min under remote guidance, and walking the rest of the time. At the end of the 12-week intervention, outcomes testing and data collection were carried out. The primary outcomes are quality of life, measured using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and the Functional Assessment of Cancer Therapy-Breast (FATC-B). The secondary outcomes include cardiopulmonary endurance, upper limb strength, lower limb strength, and skinfold thickness.

Discussion

The importance of postoperative exercise rehabilitation for breast cancer has been gradually accepted by more and more doctors and patients, but further research and development of simple and practical means of exercise rehabilitation are necessary. Remote qigong intervention for breast cancer patients via the Internet will be a great alternative.

Trial registration

Chinese Clinical Trial Registry ChiCTR1900027989. Registered on December 7, 2019.
Effectiveness of structured self-evaluation of video recorded performance on peripheral intravenous catheter insertion: a randomised control trial study protocol
Authors: Hernon Orlaith , McSharry Edel , Simpkin Andrew , MacLaren Iain , Carr Peter J.
Published: March 2023

Background

Clinical psychomotor skills training is a core component of undergraduate nursing education. Performing technical skills competently involves the use of cognitive and motor function. The training of these technical skills is typically carried out in clinical simulation laboratories. Peripheral intravenous catheter/cannula insertion is an example of a technical skill. It is the most common invasive procedure performed in the healthcare environment. Owing to unacceptable clinical risk and complications to patients, it is imperative that practitioners performing these skills are trained effectively to provide patients with best practice and high-quality care. Technologies identified as innovative teaching methods to help train students in this skill and in the skill of venepuncture include virtual reality, hypermedia and simulators. However, little high-quality evidence exists to confirm such educational approaches are effective.

Methods/design

This study is a single-centre, non-blinded, two-group, pre-test and post-test randomised control trial. The randomised control trial will investigate whether a formal structured self-evaluation of videoed performance (experimental group) has an impact on nursing students’ peripheral intravenous cannulation knowledge, performance and confidence. The control group will also be videoed performing the skill but they will not view or self-evaluate their videoed performance. The peripheral intravenous cannulation procedures will be carried out in a clinical simulation laboratory using a task trainer. The data collection tools will be completed online using survey forms. Students will be randomised into the experimental group or into the control group using simple random sampling. The primary outcome measures the nursing students’ knowledge level of the skill of peripheral intravenous cannulation insertion. Secondary outcomes evaluate procedural competence and self-reported confidence and practices in the clinical environment.

Discussion

This randomised control trial will investigate whether this pedagogical approach, using video modelling and self-evaluation, will positively influence students’ knowledge, confidence and performance in the skill of peripheral intravenous cannulation. Evaluating such teaching strategies using stringent methodologies may be impactful in influencing the training provided to healthcare practitioners.

Trial registration

The randomised control trial detailed in this article is an educational research study and so does not fall under the ICMJE definition of a clinical trial as “any research project that prospectively assigns people or a group of people to an intervention, with or without concurrent comparison or control groups, to study the relationship between a health-related intervention and a health outcome”.