bluuebunny/crossref_metadata_2025 huggingface dataset:
Posture-induced changes in intraocular pressure after ab externo XEN45 gel-stent implantation in patients with primary open-angle glaucoma
Authors: Jin Hyung Nam , Nam Jeong Woo , Zhang Haowei , Sung Mi Sun , Park Sang Woo
Published: December 2022

Background

To investigate posture-induced changes in intraocular pressure (IOP) after ab externo XEN45 Gel-Stent implantation in patients with medically uncontrolled primary open-angle glaucoma (POAG).

Methods

This prospective study included thirty-two eyes with POAG that underwent XEN45 Gel-Stent implantation as a standalone procedure using an ab externo approach at Chonnam National University Hospital. IOP was measured sequentially in the sitting position, supine position, and lateral decubitus position (LDP) before and at 1, 2, 3, and 6 months after surgery using an iCare IC200 rebound tonometer. In the LDP, the eye with XEN45 Gel-Stent implantation was in the dependent position.

Results

IOP at each position was significantly reduced after XEN45 Gel-Stent implantation. Posture-induced changes in IOP were maintained during the follow-up. The range of postural IOP changes was reduced at 1 month; however, no significant change was observed after that point compared with baseline levels.

Conclusions

A XEN45 Gel-Stent inserted using the ab externo approach can reduce IOP in various body positions, but seems to have limited effects on posture-induced changes in IOP in patients with POAG.
Osteosclerotic change as a therapeutic response to gefitinib in symptomatic non-small cell lung cancer bone metastasis
Authors: Miyagi Michihito , Katagiri Hirohisa , Murata Hideki , Wasa Junji , Takahashi Toshiaki , Murakami Haruyasu , Harada Hideyuki , Mori Keita , Takahashi Mitsuru
Published: December 2022

Background

Despite improvement in the overall survival of patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation, the effects of EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment on bone metastasis remain unclear. This study investigated radiological responses to gefitinib regarding bone metastasis in patients.

Methods

We treated 260 patients with NSCLC and symptomatic bone metastasis. Thirty-seven patients harboring EGFR mutation were treated with gefitinib for more than 30 days and followed up for more than 3 months (GEF group). We performed a retrospective observational study by selecting 36 cases without EGFR-TKI treatment, at least 3 months of follow-up, and at least two radiological evaluations as the control group. We assessed the best overall radiological response, interval from treatment initiation to appearance of a radiological response, and the local response maintenance rate.

Results

The best effect in the GEF group was 98% partial response or better, which was significantly higher than the 57% observed in the control group (p < 0.001). The GEF and control groups maintained 83% and 42% local response maintenance rates at one year, respectively (p < 0.001). In the GEF with radiotherapy group, the local response maintenance rate was maintained at 92% at 1 year, while in the GEF without RT group, there was a decrease in the local response maintenance rate from 270 days.

Conclusion

Gefitinib treatment for bone metastases in patients harboring EGFR mutation resulted in a beneficial osteosclerotic change in most patients. Combined gefitinib and radiotherapy provide long-lasting local control of bone metastases.
A systematic review and meta-analysis of neoadjuvant chemoimmunotherapy in stage III non-small cell lung cancer
Authors: Liu Wei , Zhang Tiantian , Zhang Qian , Li Li , Xu Chunhua
Published: December 2022

Background

Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease with different subtypes, multidisciplinary teams-led management, and a poor prognosis. Currently, the clinical benefits of stage III NSCLC in the neoadjuvant setting are still unclear. We performed a meta-analysis of published data on neoadjuvant chemoimmunotherapy in stage III NSCLC to systematically evaluate its efficacy and safety.

Methods

We searched the databases to identify eligible studies of neoadjuvant chemoimmunotherapy for stage III NSCLC. The primary outcomes mainly included pathological and radiological response outcomes, the feasibility of surgery, and the safety of the regimen. The pathological and radiological response included the rate of major pathologic response (MPR), complete pathologic response (pCR), radiological response outcomes, and R0 resection; The feasibility included the rate of surgical resection, conversion to thoracotomy, surgical complications, pathological downstaging of clinical disease stage. The safety included the incidence of treatment-related adverse events (TRAEs) and severe adverse events (SAEs). R 4.1.3 software was conducted for data analysis, and p < 0.05 was considered statistically significant.

Results

Nine trials containing a total of 382 populations were eligible for the meta-analysis, with the pooled surgical resection rate of 90%. Owing to the large heterogeneity of the single-rate meta-analysis, the random effect model was adopted. The estimated pooled prevalence of MPR was 56% (95%CI 0.39–0.72) and of pCR was 39% (95%CI 0.28–0.51). The pooled rate of TRAEs was 65% (95%CI 0.17–0.99) and SAEs was 24% (95%CI 0.05–0.49).

Conclusion

Compared to neoadjuvant chemotherapy or immunotherapy, neoadjuvant chemoimmunotherapy achieved more pathological and radiological relief, and has a high surgical resection rate and low risk of conversion to thoracotomy and surgical complications, with poor tolerance of toxicity but rarely developing life-threatening adverse events. In conclusion, neoadjuvant chemoimmunotherapy is suggested to be beneficial for stage III NSCLC.
Using External Joint Stabilizer – Elbow (EJS-E) for treating elbow instability—biomechanical assessment and clinical outcomes
Authors: Ma Ching-Hou , Wu Chin-Hsien , Chiu Yen-Chun , Tsai Kun-Ling , Jou I-Ming , Tu Yuan-Kun
Published: December 2022

Background

This study aimed to evaluate the outcome of using an External Joint Stabilizer – Elbow (EJS-E) for persistent elbow instability based on biomechanical experiments and analysis of clinical results.

Methods

An EJS-E was used in 17 elbow instability patients. The median follow-up was 26 months (range, 12–42 months). We evaluated the flexion–extension and pronation-supination movement arcs, visual analog scale (VAS) score, Mayo Elbow Performance Score (MEPS), Broberg and Morrey classification system, and occurrence of complications in these patients. Moreover, construct stiffness and maximum strength tests were performed to evaluate the strength of the fixation techniques.

Results

The final median range of the extension-to-flexion and pronation-to-supination arc of the elbow was 135° (range, 110°–150°) and 165° (range, 125°–180°), respectively. The VAS pain scores were > 3 in two patients. The median MEPS was 90 (range, 80–100 points). Five patients showed signs of grade I post-traumatic osteoarthritis according to the Broberg and Morrey radiographic classification system, while grade II changes were observed in three patients. Complications included axis pin loosening with pin-tract infection in two patients, transient ulnar nerve symptoms in two patients, heterotopic ossification in two patients, and suture anchors infection in one patient. Based on the biomechanical testing results, the EJS-E exhibited higher stiffness and resisting force in varus loading. It was 0.5 (N/mm) stiffer and 1.8 (N·m) stronger than the internal joint stabilizer (IJS) by difference of medians (p < 0.05).

Conclusions

Biomechanical and clinical outcomes show that EJS-E via the posterior approach can restore mobility and stability in all patients, thus serving as a valuable alternative option for the treatment of persistent instability of the elbow.
Association between hospital acquired disability and post-discharge mortality in patients after living donor liver transplantation
Authors: Hanada Masatoshi , Hidaka Masaaki , Soyama Akihiko , Tanaka Takayuki , Hara Takanobu , Matsushima Hajime , Haraguchi Masafumi , Kitamura Mineaki , Sekino Motohiro , Oikawa Masato , Nagura Hiroki , Takeuchi Rina , Sato Shuntaro , Takahata Hideaki , Eguchi Susumu , Kozu Ryo
Published: December 2022

Background

Hospital-acquired disability (HAD) in patients who undergo living donor liver transplantation (LDLT) is expected to worsen physical functions due to inactivity during hospitalization. The aim of this study was to explore whether a decline in activities of daily living from hospital admission to discharge is associated with prognosis in LDLT patients, who once discharged from a hospital.

Methods

We retrospectively examined the relationship between HAD and prognosis in 135 patients who underwent LDLT from June 2008 to June 2018, and discharged from hospital once. HAD was defined as a decline of over 5 points in the Barthel Index as an activity of daily living assessment. Additionally, LDLT patients were classified into four groups: low or high skeletal muscle index (SMI) and HAD or non-HAD. Univariate and multivariate Cox proportional hazard models were used to evaluate the association between HAD and survival.

Results

HAD was identified in 47 LDLT patients (34.8%). The HAD group had a significantly higher all-cause mortality than the non-HAD group (log-rank: p < 0.001), and in the HAD/low SMI group, all-cause mortality was highest between the groups (log-rank: p < 0.001). In multivariable analysis, HAD was an independent risk factor for all-cause mortality (hazard ratio [HR]: 16.54; P < 0.001) and HAD/low SMI group (HR: 16.82; P = 0.002).

Conclusion

HAD was identified as an independent risk factor for all-cause mortality suggesting that it could be a key component in determining prognosis after LDLT. Future larger-scale studies are needed to consider the overall new strategy of perioperative rehabilitation, including enhancement of preoperative physiotherapy programs to improve physical function.
Oral manifestations of delusional infestation: a case series
Authors: Alsafwani Zahra , Aljishi Morooj , Shiboski Caroline , Jordan Richard , Villa Alessandro
Published: December 2022

Background

Delusional infestation (DI) is a rare psychotic disorder characterized by a patient’s false belief that the body is infested with living or non-living organisms in the absence of clinical evidence of disease. Based on the underlying etiology, DI can be classified into primary and secondary forms based on the presence or absence of an underlying condition or previously diagnosed psychiatric disorder. This paper discusses a condition that is not commonly reported in the literature.

Case presentation

Here, we describe four patients diagnosed with DI of the oral cavity. In each case, the patients’ intraoral examinations revealed either traumatic lesions or no signs of mucosal disease. Management involved symptom management, medical therapy, and/or a referral to the primary care provider.

Conclusion

Because oral health care providers may encounter patients with DI, they should familiarize themselves with this unusual condition in order to recognize the condition and initiate prompt referral to a psychiatrist.
The use of digital escape rooms in nursing education
Authors: Rodríguez-Ferrer J. M. , Manzano-León A. , Fernández-Jiménez C. , Aguilar-Parra J. M. , Cangas A. J. , Luque de la Rosa A.
Published: December 2022

Negative attitudes and prejudices towards people with a mental disorder are common across cultures and societies. The stigma associated with mental illness leads to a lower quality of life, given the discrimination and social exclusion suffered by people with this type of disorder. In the field of health, research has shown that doctors and nurses also manifest these types of stigmatizing behaviors and attitudes. The present study aims to create and apply an educational escape room for the purpose of training nursing students in mental health, promoting positive attitudes towards people who have a mental disorder. To do so, a pre-post study was conducted with an experimental group and a control group to determine whether the escape room was effective for the modification of stigmatizing behaviors compared to transmissive lecture class, and a third measurement was made at 6 months only to the experimental group to evaluate whether the changes produced by the escape room were maintained in the long term. The results indicate that the students participating in the study obtained better scores in sensitization and these remain better over time. It is concluded that the escape room used is suitable for the training and sensitization of future nursing professionals in the field of mental health, facilitating the learning of knowledge and positive attitudes towards severe mental disorder.
Baseline representativeness of patients in clinics enrolled in the PRimary care Opioid Use Disorders treatment (PROUD) trial: comparison of trial and non-trial clinics in the same health systems
Authors: Wartko Paige D , Qiu Hongxiang , Idu Abisola E. , Yu Onchee , McCormack Jennifer , Matthews Abigail G. , Bobb Jennifer F. , Saxon Andrew J. , Campbell Cynthia I. , Liu David , Braciszewski Jordan M. , Murphy Sean M. , Burganowski Rachael P. , Murphy Mark T. , Horigian Viviana E. , Hamilton Leah K. , Lee Amy K. , Boudreau Denise M. , Bradley Katharine A.
Published: December 2022

Background

Pragmatic primary care trials aim to test interventions in “real world” health care settings, but clinics willing and able to participate in trials may not be representative of typical clinics. This analysis compared patients in participating and non-participating clinics from the same health systems at baseline in the PRimary care Opioid Use Disorders treatment (PROUD) trial.

Methods

This observational analysis relied on secondary electronic health record and administrative claims data in 5 of 6 health systems in the PROUD trial. The sample included patients 16–90 years at an eligible primary care visit in the 3 years before randomization. Each system contributed 2 randomized PROUD trial clinics and 4 similarly sized non-trial clinics. We summarized patient characteristics in trial and non-trial clinics in the 2 years before randomization (“baseline”). Using mixed-effect regression models, we compared trial and non-trial clinics on a baseline measure of the primary trial outcome (clinic-level patient-years of opioid use disorder (OUD) treatment, scaled per 10,000 primary care patients seen) and a baseline measure of the secondary trial outcome (patient-level days of acute care utilization among patients with OUD).

Results

Patients were generally similar between the 10 trial clinics (n = 248,436) and 20 non-trial clinics (n = 341,130), although trial clinics’ patients were slightly younger, more likely to be Hispanic/Latinx, less likely to be white, more likely to have Medicaid/subsidized insurance, and lived in less wealthy neighborhoods. Baseline outcomes did not differ between trial and non-trial clinics: trial clinics had 1.0 more patient-year of OUD treatment per 10,000 patients (95% CI: − 2.9, 5.0) and a 4% higher rate of days of acute care utilization than non-trial clinics (rate ratio: 1.04; 95% CI: 0.76, 1.42).

Conclusions

trial clinics and non-trial clinics were similar regarding most measured patient characteristics, and no differences were observed in baseline measures of trial primary and secondary outcomes. These findings suggest trial clinics were representative of comparably sized clinics within the same health systems. Although results do not reflect generalizability more broadly, this study illustrates an approach to assess representativeness of clinics in future pragmatic primary care trials.
Systematic surveillance of patient-reported symptoms of viral respiratory tract infectious Syndromes in diverse populations
Authors: Gander Jennifer C. , Chrenka Ella , Cromwell Lee , Truitt Anjali R. , Sesay Musu , Segall Marni , Amouzou Sandra A. , Hudgins Alexander F. , Kodthala Prasanthi , Roblin Douglas , Deneal Adrienne N. , Whiting Thomas , Powers John H. , Martinson Brian C.
Published: December 2022

Background

Patient reported outcome measures (PROM) can improve patient care and be crucial for symptom tracking especially during disease outbreaks. FLU-PRO Plus is a validated PROM used to track viral respiratory symptoms. Our study aimed to evaluate the feasibility of using FLU-PRO© Plus, to track symptoms across three healthcare systems.

Methods

The prospective, longitudinal study recruited adults between February-May 2021 from HealthPartners Institute (HP), Kaiser Permanente Georgia (KPGA), and Kaiser Permanente Mid-Atlantic States (KPMAS). Adult members were eligible if they had a positive lab or diagnosis for either COVID-19 or influenza-like illness (ILI) or exhibited 2 + viral respiratory symptoms. Descriptive statistics were calculated to describe the patient characteristics for participants that were eligible for FLU-PRO Plus, successfully contacted, attempted to log in to the FLU-PRO Plus website, and participants who completed FLU-PRO Plus Day 1. Bivariable and multivariable logistic regression using PROC GLIMMIXX investigated the patient characteristics associated with (1) successful contact and (2) FLU-PRO Plus Day 1 completion.

Results

We identified a total of 15,650 eligible participants during the enrollment period: 9,582 from HP, 1,740 from KPGA, and 4,328 from KPMAS. Among the total of 409 eligible adults who attempted to participate in FLU-PRO Plus, 317 completed FLU-PRO Plus Day 1. Among the 317 individuals that completed FLU-PRO Plus Day 1, 205 (67.5%) were diagnosed with COVID-19; 112 adults diagnosed with COVID-19 completed FLU-PRO Plus Day 14. Among adults successfully contacted, adults aged 35–64 (OR = 1.40, 95% CI 1.05, 1.87), females (OR = 1.77, 95% CI 1.38, 2.27), and adults diagnosed with COVID-19 (OR = 1.66, 95% CI 1.27, 2.17) had higher odds of completing FLU-PRO Plus Day 1; Asian adults (OR = 0.38, 95% CI 0.19, 0.76) and Black and African American adults (OR = 0.33, 95% CI 0.19, 0.76) had lower odds compared to White adults.

Conclusion

Our study reports on the feasibility of patients across three integrated healthcare systems utilizing FLU-PRO Plus to monitor their respiratory symptoms. Patient reported outcome measures (PROM) can improve patient care, quality of life, and reduce the strain of limited resources on healthcare systems. Future FLU-PRO Plus studies should develop an implementation strategy to fully integrate FLU-PRO Plus within clinical care and patient management.
Determinants of utilization of malaria preventive measures during pregnancy among women aged 15 to 49 years in Kenya: an analysis of the Malaria Indicator Survey 2020
Authors: Mkubwa Beatrice , Kagura Juliana , Chirwa Tobias , Ibisomi Latifat , Kinyanjui Samson
Published: December 2022

Background

Malaria is a significant cause of morbidity and mortality. Malaria infection in pregnancy can have severe consequences for the fetus and the mother. To fight against malaria infection in pregnancy, Kenya integrated the issuance of an insecticide-treated net (ITN) and intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTpSP) with antenatal care (ANC) for pregnant women. However, the uptake of the ITN and IPTpSP is still low. Individual, social, or structural factors may influence the low uptake. It is, therefore, important to identify the determinants associated with the uptake of ITN and IPTpSP during pregnancy in Kenya.

Methods

Data were from the 2020 Kenya Malaria Indicator Survey (MIS). A total of 1779 women between the ages of 15 to 49 years who had a history of either being pregnant or having given birth within 5 years before the MIS survey were included. Survey-adjusted multinomial logistic regression was used in the analysis.

Results

During pregnancy, ITN use was more than half (54.9%). The use of at least one dose of IPTpSP was 43.5%, three or more doses of IPTpSP was 27.2%, and only 28.2% of the participants used both ITN and IPTpSP during pregnancy. The significant determinants of combined use of ITN and IPTpSP during pregnancy were maternal age (RR 3.57, CI 1.80–7.08; p=<0.001), maternal education (RRR 2.84, CI 1.33–6.06; p=0.007), wealth index (RR 2.14, CI 1.19–3.84; p=0.011) and living in the different malaria epidemiological zones: lake endemic (RRR 10.57 CI 5.65–19.76; p=<0.001), coastal endemic area (RRR 4.86 CI 1.86–12.67; p=0.001), seasonal (RRR 0.21 CI 0.10–0.39; p=<0.001) and low risk (RRR 0.07, CI 0.03–0.17; p=<0.001).

Conclusion

The uptake of malaria preventive measures is still below 80% for both ITN and IPTpSP during pregnancy in Kenya. The significant results on determinants of the use of ITN and IPTpSP could be considered in implementing malaria prevention programmes during pregnancy. For example, sensitizing the community on the importance of antenatal care visits will provide a platform to teach the importance of malaria prevention in pregnancy. Moreover, the pregnant mothers receive an ITN and IPTpSP during the ANC visit.
Characterization of a lipid droplet and endoplasmic reticulum stress related gene risk signature to evaluate the clinical and biological value in hepatocellular carcinoma
Authors: Guo Ziwei , Liang Jun
Published: December 2022

Introduction

Lipid metabolism and endoplasmic reticulum (ER) stress play an important role in the progression and metastasis of hepatocellular carcinoma (HCC). We aimed to establish lipid droplet (LD)-associated and ER stress-related gene risk signature as prognostic indicators.

Materials and methods

Literature searches for LD-associated proteins was screened and validated in The Cancer Genome Atlas (TCGA) and International Cancer Genome Collaboratory (ICGC) databases. A total of 371 samples were enrolled from the TCGA RNA-seq dataset (training cohort) and 240 samples from IGGC RNA-seq dataset (validation cohort). A 10-gene risk signature was established by the last absolute shrinkage and selection operator (LASSO) regression analysis. The prognostic value of the risk signature was evaluated by Cox regression, Kaplan–Meier and ROC Curve analyses. Biological features associated with LD and ER stress-related factors were explored by functional analysis and in vitro experiment.

Results

Based on the medical literatures, 124 lipid droplet-associated proteins were retrieved, and three genes failed to establish a valid prognostic model. ER stress was considered as an important component by functional analysis. A 10-gene risk signature compared the clinicopathology characteristics, immunosuppressive events and a nomogram in HCC patients.

Conclusion

LD-associated and ER stress-related gene risk signatures highlighted poor prognosis for clinicopathological features, positively correlate with macrophages and T cell immunoglobulin and mucin-3 (TIM-3) expression in the tumor microenvironment, and might act as independent prognostic factors.
Validation and reliability of the Dutch version of the EORTC QLQ-BLM30 module for assessing the health-related quality of life of patients with muscle invasive bladder cancer
Authors: Ripping T. M. , Rammant E. , Witjes J. A. , Aaronson N. K. , van Hemelrijck M. , van Hoogstraten L. M. C. ,   BlaZIB study group, Boormans J. , Goossens C. A. , van der Heijden A. G. , Hulshof M. C. C. M. , van Leenders G. J. L. H. , van Leliveld A. M. , Meijer R. P. , van Moorselaar R. J. A. , Mulder S. F. , Nooter R. I. , Noteboom J. L. , Oddens J. R. , de Reijke T. M. , van Rhijn B. W. G. , van Roermund J. G. H. , Smilde T. J. , Vanderbosch G. W. J. , Wijsman B. P. , Kiemeney L. A. , Aben K. K. H.
Published: December 2022

Background

Quality of Life (QoL) of bladder cancer patients has been largely neglected. This is partly due to the lack of well-validated QoL questionnaires. The aim of this study is to examine the structural validity, reliability (i.e., internal consistency and test-retest reliability), construct validity (i.e., divergent validity and known group validity) and responsiveness of the Dutch version of the European Organisation for Research and Treatment of Cancer QoL questionnaire for muscle invasive bladder cancer (EORTC-QLQ-BLM30).

Methods

Patients with newly diagnosed muscle invasive bladder cancer (MIBC) participating in the population-based ‘Blaaskankerzorg In Beeld’ (BlaZIB) study who completed the EORTC-QLQ-BLM30 at baseline were included. BlaZIB is a Dutch nationwide population-based prospective cohort study collecting clinical data and QoL data of bladder cancer patients. QoL is assessed with a self-administered questionnaire at four points in time: 6 weeks (baseline), 6 months, 12 months and 24 months after diagnosis. Confirmatory factor analysis and multitrait scaling analysis were used to investigate and adapt the scale structure. Reliability, construct validity and responsiveness of the revised scales were evaluated.

Results

Of the 1542 patients invited to participate, 650 patients (42.2%) completed the QLQ-BLM30 at baseline. The questionnaire’s scale structure was revised into seven scales and eight single items. Internal consistency and test-reliability were adequate for most scales (Cronbach’s α ≥0.70 and intraclass correlation coefficient ≥ 0.70, respectively), with the exception of the revised urostomy problem scale and abdominal bloating and flatulence scale. The questionnaire exhibited little overlap with the EORTC-QLQ-C30: all correlations were < 0.40, except for the correlation between emotional function (QLQ-C30) and future worries (QLQ-BLM30). The questionnaire was able to distinguish between patient subgroups formed on the basis of physical function, but not – as hypothesized– based on stage. Changes in health due to treatment were captured by the questionnaire, indicating that the questionnaire is responsive to change.

Conclusions

This study shows that the adapted scale structure of the EORTC-QLQ-BLM30 generally exhibits good measurement properties in Dutch patients, but needs to be validated in other languages and settings.

Trial registration

BlaZIB, NL8106, www.trialregister.nl
Device-measured physical activity and sedentary time in a national sample of Luxembourg residents: the ORISCAV-LUX 2 study
Authors: Collings Paul J. , Backes Anne , Aguayo Gloria A. , Malisoux Laurent ,   on behalf of the ORISCAV-LUX study group, Alkerwi Ala’a , Noppe Stephanie , Delagardelle Charles , Beissel Jean , Chioti Anna , Stranges Saverio , Schmit Jean-Claude , Lair Marie-Lise , D’Incau Marylène , Pastore Jessica , Le Coroller Gwenaëlle , Appenzeller Brice , Couffignal Sophie , Gantenbein Manon , Devaux Yvan , Vaillant Michel , Huiart Laetitia , Bejko Dritan , Bohn Torsten , Samouda Hanen , Fagherazzi Guy , Perquin Magali , Ruiz Maria , Ernens Isabelle
Published: December 2022

Background

Existing information about population physical activity (PA) levels and sedentary time in Luxembourg are based on self-reported data.

Methods

This observational study included Luxembourg residents aged 18-79y who each provided ≥4 valid days of triaxial accelerometry in 2016-18 (n=1122). Compliance with the current international PA guideline (≥150 min moderate-to-vigorous PA (MVPA) per week, irrespective of bout length) was quantified and variability in average 24h acceleration (indicative of PA volume), awake-time PA levels, sedentary time and accumulation pattern were analysed by linear regression. Data were weighted to be nationally representative.

Results

Participants spent 51% of daily time sedentary (mean (95% confidence interval (CI)): 12.1 (12.0 to 12.2) h/day), 11% in light PA (2.7 (2.6 to 2.8) h/day), 6% in MVPA (1.5 (1.4 to 1.5) h/day), and remaining time asleep (7.7 (7.6 to 7.7) h/day). Adherence to the PA guideline was high (98.1%). Average 24h acceleration and light PA were higher in women than men, but men achieved higher average accelerations across the most active periods of the day. Women performed less sedentary time and shorter sedentary bouts. Older participants (aged ≥55y) registered a lower average 24h acceleration and engaged in less MVPA, more sedentary time and longer sedentary bouts. Average 24h acceleration was higher in participants of lower educational attainment, who also performed less sedentary time, shorter bouts, and fewer bouts of prolonged sedentariness. Average 24h acceleration and levels of PA were higher in participants with standing and manual occupations than a sedentary work type, but manual workers registered lower average accelerations across the most active periods of the day. Standing and manual workers accumulated less sedentary time and fewer bouts of prolonged sedentariness than sedentary workers. Active commuting to work was associated with higher average 24h acceleration and MVPA, both of which were lower in participants of poorer self-rated health and higher weight status. Obesity was associated with less light PA, more sedentary time and longer sedentary bouts.

Conclusions

Adherence to recommended PA is high in Luxembourg, but half of daily time is spent sedentary. Specific population subgroups will benefit from targeted efforts to replace sedentary time with PA.
Outdoor time, screen time and sleep reported across early childhood: concurrent trajectories and maternal predictors
Authors: Downing Katherine L. , del Pozo Cruz Borja , Sanders Taren , Zheng Miaobing , Hnatiuk Jill A. , Salmon Jo , Hesketh Kylie D.
Published: December 2022

Background

Understanding the developmental trajectories of outdoor time, screen time and sleep is necessary to inform early interventions that promote healthy behaviours. This study aimed to describe concurrent trajectories of outdoor time, screen time and sleep across the early childhood period and their maternal predictors.

Methods

Data across five time points at child age 4, 9, 19, 42 and 60 months from the INFANT intervention were analysed. Mothers reported their child’s usual outdoor time, screen time and sleep duration, in addition to a range of maternal beliefs, attitudes, expectations and behaviours. Group-based multi-trajectory modelling was used to model concurrent trajectories of children’s behaviours. Multinomial logistic regression models determined the associations of maternal predictors with trajectory groups, adjusting for child sex and baseline age, intervention allocation, and clustering by recruitment.

Results

Of the 542 children recruited, 528 had data for outdoor time, screen time and sleep at one or more time points and were included in trajectory analyses Four trajectories were identified: ‘unstable sleep, increasing outdoor time, low screen’ (~ 22% of sample), ‘high outdoor time, low screen, high sleep’ (~ 24%), ‘high sleep, increasing outdoor time, low screen’ (~ 45%), ‘high screen, increasing outdoor time, high sleep’ (~ 10%). The ‘high sleep, increasing outdoor time, low screen’ group, comprising the largest percentage of the sample, demonstrated the healthiest behaviours. Predictors of group membership included: views of physically active children, screen time knowledge, screen time use, self-efficacy, physical activity optimism, future expectations for children’s physical activity and screen time, perceptions of floor play safety, and maternal physical activity, screen time, and sleep quality.

Conclusions

Four distinct trajectories of outdoor time, screen time and sleep were identified, with the most common (and healthiest) characterized by high levels of sleep. Maternal beliefs, attitudes, expectations and behaviours are important in the development of movement behaviour trajectories across early childhood. Future interventions and public policy may benefit from targeting these factors to support healthy movement behaviours from a young age.
SAMHD1 silencing cooperates with radiotherapy to enhance anti-tumor immunity through IFI16-STING pathway in lung adenocarcinoma
Authors: Li Yangyi , Gao Yuke , Jiang Xueping , Cheng Yajie , Zhang Jianguo , Xu Liexi , Liu Xinyu , Huang Zhengrong , Xie Conghua , Gong Yan
Published: December 2022

Background

Sterile alpha motif domain and histidine-aspartate domain-containing protein 1 (SAMHD1) is a DNA end resection factor, which is involved in DNA damage repair and innate immunity. However, the role of SAMHD1 in anti-tumor immunity is still unknown. This study investigated the effects of SAMHD1 on stimulator of interferon genes (STING)-type I interferon (IFN) pathway and radiation-induced immune responses.

Methods

The roles of SAMHD1 in the activation of cytosolic DNA sensing STING pathway in lung adenocarcinoma (LUAD) cells were investigated with flow cytometry, immunofluorescence, immunoblotting and qPCR. The combined effects of SAMHD1 silencing and radiation on tumor cell growth and STING pathway activation were also evaluated with colony formation and CCK8 assay. The Lewis lung cancer mouse model was used to evaluate the combined efficiency of SAMHD1 silencing and radiotherapy in vivo. Macrophage M1 polarization and cytotoxic T cell infiltration were evaluated with flow cytometry.

Results

The single-stranded DNA (ssDNA) accumulated in the cytosol of SAMHD1-deficient lung adenocarcinoma (LUAD) cells, accompanied by upregulated DNA sensor IFN-γ-inducible protein 16 (IFI16) and activated STING pathway. The translocation of IFI16 from nucleus to cytosol was detected in SAMHD1-deficient cells. IFI16 and STING were acquired in the activation of STING-IFN-I pathway in SAMHD1-deficient cells. SAMHD1 silencing in LUAD cells promoted macrophage M1 polarization in vitro. SAMHD1 silencing synergized with radiation to activate ssDNA-STING-IFN-I pathway, inhibit proliferation, promote apoptosis and regulate cell cycle. SAMHD1 silencing cooperated with radiotherapy to inhibit tumor growth and increase CD86+MHC-IIhigh M1 proportion and CD8+ T cell infiltration in vivo.

Conclusions

SAMHD1 deficiency induced IFN-I production through cytosolic IFI16-STING pathway in LUAD cells. Moreover, SAMHD1 downregulation and radiation cooperated to inhibit tumor growth and enhance anti-tumor immune responses through macrophage M1 polarization and CD8+ T cell infiltration. Combination of SAMHD1 inhibition and radiotherapy may be a potentially therapeutic strategy for LUAD patients.
Breastfeeding and human milk bank in a neonatal intensive care unit: impact of the COVID-19 pandemic in an Italian cohort of very low birth weight infants
Authors: Bresesti Ilia , Morlacchi Laura , Cazzaniga Caterina , Sangiorgio Camilla , Bertù Lorenza , Bolis Maria Elena , Bossi Angela , Agosti Massimo
Published: December 2022

Background

Parental stress in neonatal intensive care units (NICU) is well known, as is the stress induced by the COVID-19 pandemic. This combination might increase stress to the extent of affecting the availability of maternal expressed milk and the success of establishing breastfeeding. This is particularly relevant in very preterm infants.

Methods

We conducted a single-centre retrospective analysis in two cohorts of very low birth weight infants born in a hospital in Italy. Babies born before the pandemic (September 2017 – December 2019) (n = 101) and during the pandemic (March 2020 – December 2021) (n = 67) were included in the analysis. We compared the rate of babies fed with maternal milk (both expressed and / or donated) at the achievement of full enteral feeding and the rate of those exclusively breastfed at discharge in the two groups. Then, we analysed the impact of donated human milk availability on infant formula use. We also compared mother’s need for psychological support during NICU stay and the duration of psychological follow-up after discharge.

Results

In our NICU the availability of expressed maternal milk significantly decreased during the COVID-19 pandemic (86.1% before the pandemic vs 44.8% during the pandemic, p < 0.001) at the time of full enteral feeding achievement. Thanks to the availability of donated human milk, the rate of formula-fed babies remained almost unchanged (13.9% vs 14.9%). At discharge, the rate of breastfeeding was similar (73.3% vs 72.7%). The maternal need for psychological support was significantly higher during the pandemic (33% vs 64%, p < 0.001), as well as the duration of follow-up > 6 months (1% vs 15%, p < 0.001). No differences in the main clinical outcomes were found.

Conclusion

Pandemic-induced stress had a significant impact on the availability of expressed maternal milk in NICU. However, the presence of human donated milk was fundamental in preventing increased use of infant formula during NICU stays. This underlines how strategies to implement the widespread establishment of donor milk banks on a national level are warranted. Further research is desirable to optimise the use of donated human milk banks during emergency situations.
Does matching degree matter for proximal femoral intramedullary nail on reoperation rate in intertrochanteric fractures?
Authors: Wang Fei , Zou Ji-Long , Shang Jian
Published: December 2022

Introduction

Previous articles reported on the tip–apex distance, lag screw placement, fracture pattern, reduction quality, osteoporosis and other factors associated with second surgery. The current study focused on investigating the association of the matching degree between proximal femoral intramedullary nail and femoral medullary cavity on reoperation rate.

Patients and methods

A retrospective cohort study was conducted. It included patients with intertrochanteric fracture who were treated with proximal femoral anti-rotatory intramedullary nail (PFNA) between January 2016 and April 2021. The gap between the intramedullary nail and the femoral medullary cavity was equal to the difference in diameter between the two. According to the gap size, all patients were divided into three groups, as follows: high-matching group: gap ≤ 2 mm; middle-matching group: 2 < gap < 4 mm; and low-matching group: gap ≥ 4 mm. The mean gap was measured through standard images. The primary observational index was whether the reoperation was needed, and secondary observational indexes included operative time, length of hospital stay. Patient characteristics were recorded, as follows: age, sex, follow-up time, fracture pattern, reduction grade and length of intramedullary nail.

Results

A total of 203 eligible patients were recorded, including 78 males (38.4%) and 125 females (61.6%). They had a mean age of 77.8 ± 9.9 years old and an average follow-up time of 58.1 ± 24.0 weeks. Twenty-seven patients (13.3%) needed a second operation. Coxa varus combined with screw cutting was the most common reason for reoperation (11 cases). Unstable fracture pattern with poor reduction grade tended to contribute to reoperation, whose odds ratio (OR) was 6.61 (95% confidence interval [CI], 1.98–22.09; P = 0.002). The three groups had 11 cases (13.7%), 12 cases (13.8%) and 4 cases (11.1%) of reoperation, respectively, and logistic regression showed no significant association was noted between matching degree of intramedullary nail and reoperation rate.

Conclusions

The matching degree between proximal femoral intramedullary nail and femoral medullary cavity did not seem to be an important factor for reoperation, which offered more options of intramedullary nail size intraoperatively and reduced implants stock from inventory.
FTL004, an anti-CD38 mAb with negligible RBC binding and enhanced pro-apoptotic activity, is a novel candidate for treatments of multiple myeloma and non-Hodgkin lymphoma
Authors: Zhang Guangbing , Guo Cuiyu , Wang Yan , Zhang Xianda , Liu Shuang , Qu Wen , Chen Chunxia , Yan Lingli , Yang Zhouning , Zhang Zhixiong , Jiang Xiaohua , Chen Xiaofeng , Liu Hong , Lai Qinhuai , Wei Xian , Lu Ying , Zhao Shengyan , Deng Han , Wang Yuxi , Yu Lin , Yu Hongbin , Wu Yu , Su Zhaoming , Chen Pengyu , Ren Ziqing , Yu Meng , Qu Feng , Luo Yong , Gou Lantu , Li Qing , Huang Ying , Ma Fanxin , Yang Jinliang
Published: December 2022

Anti-CD38 monoclonal antibodies (mAbs), daratumumab, and isatuximab have represented a breakthrough in the treatment of multiple myeloma (MM). Recently, CD38-based mAbs were expected to achieve increasing potential beyond MM, which encouraged us to develop new anti-CD38 mAbs to meet clinical needs. In this study, we developed a novel humanized anti-CD38 antibody, FTL004, which exhibited enhanced pro-apoptotic ability and negligible binding to red blood cells (RBCs). FTL004 presented a better ability to induce direct apoptosis independent of Fc-mediated cross-linking against lymphoma and MM cell lines as well as primary myeloma cells derived from MM patients. For instance, FTL004 induced RPMI 8226 cells with 55% early apoptosis cells compared with 20% in the isatuximab-treated group. Of interest, FTL004 showed ignorable binding to CD38 on human RBCs in contrast to tumor cells, even at concentrations up to 30 μg/mL. Furthermore, with an engineered Fc domain, FTL004 displayed stronger antibody-dependent cellular cytotoxicity (ADCC) against CD38+ malignant cells. In vivo MM and non-Hodgkin lymphoma tumor xenograft models showed that FTL004 possessed an effective anti-tumor effect. Cryo-electron microscopy structure resolved two epitope centers of FTL004 on CD38: one of which was unique while the other partly overlapped with that of isatuximab. Taken together, FTL004 distinguishes it from other CD38 targeting mAbs and represents a potential candidate for the treatment of MM and non-Hodgkin lymphoma.
Prader-Willi syndrome patient with atypical phenotypes caused by mosaic deletion in the paternal 15q11-q13 region: a case report
Authors: Wu Jinying , Lei Meifang , Wang Xuetao , Liu Nan , Xu Xiaowei , Gu Chunyu , Yu Yuping , Liu Wei
Published: December 2022

Background

Prader-Willi syndrome (PWS) is a multisystemic complex genetic disorder caused by the loss of paternally expressed genes in the human chromosome region 15q11.2-q13. It is characterized by severe hypotonia and feeding difficulties in early infancy, followed in later infancy or early childhood by excessive eating and gradual development of morbid obesity. Motor milestones and language development are delayed and most patients have intellectual disability.

Case presentation

Here we describe a rare PWS case caused by mosaic imprinting defect in the region 15q11.2-q13 of paternal origin. The proband was a male child with a clinical presentation of global developmental delay and hypotonia with specific facial features. Karyotype of the child was noted as mosaic: 45XY,der(15)?t(15;21),-21[26]/46,XY[24]. Whole-exome sequencing (WES) identified a deletion of 22.7 Mb in size at chr15q11.2q21.1 region and a deletion of 2.1 Mb in size at chr21q22.3 region. The Methylation-specific multiplex ligation-dependent probe amplification(MS-MLPA) of the 15q11.2-q13 region showed that the loading ratio of methylated alleles was 70% and that of unmethylated alleles was 30%(50% normal), which confirmed that the loss of mosaic imprinted defects in the paternal allele led to the diagnosis of PWS.

Conclusions

We propose that complete clinical criteria for PWS should not be considered sensitive in diagnosing partial atypical PWS due to mosaic imprinting defects. In contrast, clinical suspicion based on less restrictive criteria followed by multiple techniques is a more powerful approach.
Study protocol for ACTIVE study: safety and feasibility evaluation of external ventricular drainage with ACTIVE fluid exchange in intraventricular hemorrhage—a phase 2, multi-center, randomized controlled trial
Authors: Haldrup Mette , Mohamad Niwar , Rasmussen Mads , Thorup Line , Dyrskog Stig , Simonsen Claus Ziegler , Miscov Rares , Bjarkam Carsten Reidies , Grønhøj Mads , Poulsen Frantz Rom , Korshøj Anders Rosendal
Published: December 2022

Background

Primary intraventricular hemorrhage (IVH) or IVH secondary to intracerebral (ICH) and subarachnoid hemorrhage (SAH) are known to have a very poor prognosis, with an expected mortality between 50 and 80% (Hinson et al. Current Neurology and Neuroscience Reports 10:73–82, 2010). Clearance of IVH might improve patient outcome.

Methods

The study is designed as an investigator-initiated, comparative, prospective, multi-center, 1:1 randomized phase 2 trial evaluating the efficacy and safety of active irrigation in external ventricular drainage (intervention arm—IRRAflow) compared to passive external ventricular drainage (control arm—EVD).

The trial will enroll 58 patients with primary or secondary IVH. Major eligibility criteria include age ≥18 years of age, IVH documented on head CT or MRI scan (Graeb score ≥3), need of cerebrospinal fluid drainage, deterioration of consciousness or medical sedation at the time of enrollment, and indication for active treatment evaluated by the treating physicians. Exclusion criteria included patients with fixed and dilated pupils and pregnant or nursing women.

The primary endpoint of the study is catheter occlusion evaluated by time to first observed occlusion from VC placement. Secondary endpoints include clearance of ventricular blood as measured by head CT scan, rates of catheter-related infection and shunt dependency, length of intensive care unit stay, functional status—Extended Glascow Outcome Scale (eGOS) and modified Rankin scale (mRS) at discharge to rehabilitation and 90 days—and mortality rates at 30 days and 90 days.

Discussion

With no standardized treatment for IVH and a poor prognosis, new treatments are needed. IVH patients often need CSF drainage to treat hydrocephalus and to decrease ICP. Standard treatment with passive external ventricular drainage is related to an increased risk of infections which is found in up to 22% of treated cases. The passive VC is known to have a risk of occlusion and is seen in 19–47% of the cases.

We hypothesize that the use of active fluid change using the IRRAflow system will be safe and feasible and will reduce the occlusion and infection rates in patients with IVH.

Trial registration

ClicalTrials.gov NCT05204849. Registered 15 December 2021. Updated 24 January 2022
Subjective cognitive decline is a better marker for future cognitive decline in females than in males
Authors: Oliver Michael D. , Morrison Cassandra , Kamal Farooq , Graham Jillian , Dadar Mahsa
Published: December 2022

Background

The identification of biomarkers for early detection of Alzheimer’s disease (AD) is critical to the development of therapies and interventions targeted at symptom management and tracking the pathophysiology of disease. The endorsement of subjective cognitive decline (SCD) has emerged as a potential indicator of early change in cognitive status that may be predictive of future impairment at a time when measurable declines in neuropsychological performance cannot be detected. While there are numerous findings revealing sex differences in the prevalence of AD, there is a paucity of research examining sex differences in SCD. Therefore, the goal of this project was to determine if the relationship between the endorsement of SCD and future cognitive changes differ as a function of biological sex.

Methods

A sample of 3019 male and female healthy older adults (2188 without SCD, 831 with SCD), with a mean follow-up time of 5.7 years, were included from the Rush Alzheimer’s Disease Center Research Sharing Hub. Linear regressions were performed to determine group differences in baseline cognitive scores, while linear mixed-effects models were completed to determine group differences in the rate of cognitive change over time.

Results

Individuals endorsing SCD had significantly lower baseline cognitive scores and increased rates of decline in all cognitive domains compared to those without SCD. Males exhibited significantly lower scores in baseline performance in global cognition, episodic memory, and perceptual speed regardless of SCD classification. Females with SCD were found to decline at significantly faster rates than both males with SCD and males and females without SCD in all cognitive domains over a maximum 15-year follow-up period.

Conclusions

SCD is related to lower baseline cognitive performance and faster cognitive decline compared to those who do not endorse SCD. Females with SCD have the fastest rate of decline suggesting that SCD may be more predictive of future decline in females than in males. Targeted assessments of SCD may allow for the identification of individuals for inclusion in intervention trials, and other research studies, aiming to attenuate casual disease processes, which may ultimately aid in the mitigation of sex disparities in AD.