bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review of fear of falling and related constructs after hip fracture: prevalence, measurement, associations with physical function, and interventions
Authors: Gadhvi Chandini , Bean Debbie , Rice David
Published: June 2023

Background

Hip fracture is a common and debilitating injury amongst older adults. Fear of falling (FoF) and related constructs (balance confidence and falls efficacy) may impede rehabilitation after hip fracture. An updated systematic review to synthesize existing literature on FoF after hip fracture is needed. This review focussed on four research questions: In the hip fracture population: (1) What is the prevalence of FoF?; (2) What FoF assessment tools are validated? (3) What is the relationship between FoF and physical function?; (4) What interventions are effective for reducing FoF?

Methods

A systematic search was undertaken in EBSCO Health, Scopus and PsychINFO in January 2021 (and updated December 2022) for articles on FoF after hip fracture. Data in relation to each research question was extracted and analysed. The quality of the studies was appraised using the ‘Risk of Bias Tool for Prevalence Studies’, ‘COSMIN Risk of Bias checklist for Patient-reported outcome measures’, modified version of the ‘Appraisal Tool for Cross-sectional studies’, and the ‘Cochrane Risk of Bias 2’ tools for each research question, respectively.

Results

36 studies (37 articles) with 5099 participants were included (mean age 80.2 years and average 78% female). Prevalence rates for FoF after hip fracture ranged between 22.5% and 100%, and prevalence tended to decrease as time progressed post hip fracture. The ‘Falls Efficacy Scale – International’ (FES-I) and ‘Fear of Falling Questionnaire – Revised’ (FFQ-R) were found to be reliable, internally consistent, and valid tools in hip fracture patients. FoF after hip fracture was consistently associated with measures of physical function including balance, gait speed, composite physical performance measures and self-reported function. Ten of 14 intervention studies were considered high risk of bias. Exercise-based interventions with or without a psychological component were not effective in reducing FoF after hip fracture compared to a control condition.

Conclusion

FoF is prevalent after hip fracture and is consistently associated with poorer physical function. Only two instruments (FES-I and FFQ-R) have been validated for measuring FoF in the hip fracture population. However, there remains a need for larger, higher quality randomised controlled trials targeting FoF after hip fracture in order to guide clinical practice.

Trial registration

PROSPERO registration: CRD42020221836.
Barriers and facilitators to implementing advance care planning in naïve contexts - where to look when plowing new terrain?
Authors: Westbye Siri Færden , Rostoft Siri , Romøren Maria , Thoresen Lisbeth , Wahl Astrid Klopstad , Pedersen Reidar
Published: June 2023

Background

Advance care planning (ACP) is a way of applying modern medicine to the principle of patient autonomy and ensuring that patients receive medical care that is consistent with their values, goals and preferences. Robust evidence supports the benefits of ACP, but it remains an underutilized resource in most countries. This paper goes from the naïve point of view, and seeks to identify the barriers and facilitators to implementation in unfamiliarized contexts and in a whole system approach involving the clinical, institutional and policy level to improve the implementation of ACP.

Methods

Qualitative interviews were chosen to enable an explorative, flexible design. Qualitative interviews were conducted with 40 health care professionals and chief physicians in hospitals and in municipalities. The thematic analysis was done following Braun and Clarke’s strategy for thematic analysis.

Results

The main reported barriers were the lack of time and space, a lack of culture and leadership legitimizing ACP, lack of common communication systems, and unclear responsibility about who should initiate, resulting in missed opportunities and overtreatment. Policy development, public and professional education, and standardization of documentation were reported as key to facilitate ACP and build trust across the health care system.

Conclusions

Progressively changing the education of health professionals and the clinical culture are major efforts that need to be tackled to implement ACP in unfamiliarized contexts, particularly in contexts where patient's wishes are not legally binding. This will need to be tackled through rectifying the misconception that ACP is only about death, and providing practical training for health professionals, as well as developing policies and legislation on how to include patients and caregivers in the planning of care.
The impact of national and international travel on spatio-temporal transmission of SARS-CoV-2 in Belgium in 2021
Authors: Nguyen Minh Hanh , Nguyen Thi Huyen Trang , Molenberghs Geert , Abrams Steven , Hens Niel , Faes Christel
Published: June 2023

Background

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has rapidly spread over the world and caused tremendous impacts on global health. Understanding the mechanism responsible for the spread of this pathogen and the impact of specific factors, such as human mobility, will help authorities to tailor interventions for future SARS-CoV-2 waves or newly emerging airborne infections. In this study, we aim to analyze the spatio-temporal transmission of SARS-CoV-2 in Belgium at municipality level between January and December 2021 and explore the effect of different levels of human travel on disease incidence through the use of counterfactual scenarios.

Methods

We applied the endemic-epidemic modelling framework, in which the disease incidence decomposes into endemic, autoregressive and neighbourhood components. The spatial dependencies among areas are adjusted based on actual connectivity through mobile network data. We also took into account other important factors such as international mobility, vaccination coverage, population size and the stringency of restriction measures.

Results

The results demonstrate the aggravating effect of international travel on the incidence, and simulated counterfactual scenarios further stress the alleviating impact of a reduction in national and international travel on epidemic growth. It is also clear that local transmission contributed the most during 2021, and municipalities with a larger population tended to attract a higher number of cases from neighboring areas.

Conclusions

Although transmission between municipalities was observed, local transmission was dominant. We highlight the positive association between the mobility data and the infection spread over time. Our study provides insight to assist health authorities in decision-making, particularly when the disease is airborne and therefore likely influenced by human movement.
Clinical predictors of surgical intervention for gastrointestinal magnetic foreign bodies in children
Authors: Zhang Rui Yun , Cai Peng , Zhang Ting Ting , Zhu Jie , Chen Jian Lei , Zhao Hao Wei , Jiang Yu Liang , Wang Qi , Zhu Meng Lei , Zhou Xiao Gang , Xiang Xian Lan , Hu Fei Long , Gu Zhi Cheng , Zhu Zhen Wei
Published: June 2023

Background/aims

To investigate the clinical situation, treatment methods, and clinical predictors of surgical intervention in children with magnetic foreign bodies in the digestive tract.

Materials and methods

From January 2019 to June 2022, we retrospectively analyzed the clinical data of 72 children who ingested magnetic foreign bodies inadvertently in our hospital, including their general information, admissions, clinical manifestations, and treatment methods, as well as pertinent literature and statistical data. Following software processing, univariate and multivariate logistic regression analyses were conducted to determine the independent risk factors of this study.

Results

In this study, 16 patients (22.2%) were discharged smoothly following conservative treatment and 19 patients (26.4%) were cured by gastroscopy. The remaining 37 patients (51.4%) were underwent surgery, in which 26 cases developed gastrointestinal perforation. There were statistical differences between surgery group and non- surgery group in the days of eating by mistake, clinical manifestations (nausea and vomiting, intermittent abdominal pain, abdominal muscle tension) and movement trajectory by every 24-h radiograph (P < 0.01). Logistic regression analysis showed that intermittent abdominal pain and abdominal muscle tension were independent risk factors for surgical treatment.

Conclusion

Magnetic foreign bodies seriously endanger children’s health. This study offers a single-center basis for the choice of surgical opportunity for intestinal obstruction or perforation caused by magnetic foreign bodies. Clinicians need immediate surgical intervention if the child shows symptoms of abdominal pain or abdominal tension.
Association of homelessness and psychiatric hospital readmission—a retrospective cohort study 2016–2020
Authors: Russolillo Angela , Moniruzzaman Akm , Carter Michelle , Raudzus Julia , Somers Julian M.
Published: June 2023

Background

A large proportion of adult psychiatric inpatients experience homelessness and are often discharged to unstable accommodation or the street. It is unclear whether homelessness impacts psychiatric hospital readmission. Our primary objective was to examine the association between homelessness and risk for 30-day and 90-day readmission following discharge from a psychiatric unit at a single urban hospital.

Methods

A retrospective cohort study involving health administrative data among individuals (n = 3907) in Vancouver, Canada with an acute psychiatric admission between January 2016 and December 2020. Participants were followed from the date of index admission until censoring (December 30, 2020). Homelessness was measured at index admission and treated as a time-varying exposure. Adjusted Hazard Ratios (aHRs) of acute readmission (30-day and 90-day) for psychiatric and substance use disorders were estimated using multivariable Cox proportional hazards regression.

Results

The cohort comprised 3907 individuals who were predominantly male (61.89%) with a severe mental illness (70.92%), substance use disorder (20.45%) and mean age of 40.66 (SD, 14.33). A total of 686 (17.56%) individuals were homeless at their index hospitalization averaging 19.13 (21.53) days in hospital. After adjusting for covariates, patients experiencing homelessness had a 2.04 (1.65, 2.51) increased rate of 30-day readmission and 1.65 (1.24, 2.19) increased rate of 90-day readmission during the observation period.

Conclusions

Homelessness was significantly associated with increased 30-day and 90-day readmission rates in a large comprehensive sample of adults with mental illness and substance use disorders. Interventions to reduce homelessness are urgently needed.

Question

Is homelessness associated with risk for 30-day and 90-day psychiatric hospital readmission?

Findings

In this retrospective cohort study of 3907 individuals, homelessness at discharge was associated with increased 30-day and 90-day psychiatric readmission.

Meaning

Housing status is an important risk factor for hospital readmission. High-quality interventions focused on housing supports have the potential to reduce psychiatric readmission.
Optimising engagement in a digital parenting intervention to prevent violence against adolescents in Tanzania: protocol for a cluster randomised factorial trial
Authors: Janowski Roselinde , Green Ohad , Shenderovich Yulia , Stern David , Clements Lily , Wamoyi Joyce , Wambura Mwita , Lachman Jamie M. , Melendez-Torres G. J. , Gardner Frances , Baerecke Lauren , Te Winkel Esmee , Booij Anna , Setton Orli , Tsoanyane Sibongile , Mjwara Sussie , Christine Laetitia , Ornellas Abigail , Chetty Nicole , Klapwijk Jonathan , Awah Isang , Manjengenja Nyasha , Sokoine Kudely , Majikata Sabrina , Cluver Lucie D.
Published: June 2023

Background

Violence against adolescents is a universal reality, with severe individual and societal costs. There is a critical need for scalable and effective violence prevention strategies such as parenting programmes, particularly in low- and middle-income countries where rates of maltreatment are highest. Digital interventions may be a scalable and cost-effective alternative to in-person delivery, yet maximising caregiver engagement is a substantial challenge. This trial employs a cluster randomised factorial experiment and a novel mixed-methods analytic approach to assess the effectiveness, cost-effectiveness, and feasibility of intervention components designed to optimise engagement in an open-source parenting app, ParentApp for Teens. The app is based on the evidence-based Parenting for Lifelong Health for Teens programme, developed collaboratively by academic institutions in the Global South and North, the WHO, and UNICEF.

Methods/design

Sixteen neighbourhoods, i.e., clusters, will be randomised to one of eight experimental conditions which consist of any combination of three components (Support: self-guided/moderated WhatsApp groups; App Design: sequential workshops/non-sequential modules; Digital Literacy Training: on/off). The study will be conducted in low-income communities in Tanzania, targeting socioeconomically vulnerable caregivers of adolescents aged 10 to 17 years (16 clusters, 8 conditions, 640 caregivers, 80 per condition). The primary objective of this trial is to estimate the main effects of the three components on engagement. Secondary objectives are to explore the interactions between components, the effects of the components on caregiver behavioural outcomes, moderators and mediators of programme engagement and impact, and the cost-effectiveness of components. The study will also assess enablers and barriers to engagement qualitatively via interviews with a subset of low, medium, and high engaging participants. We will combine quantitative and qualitative data to develop an optimised ParentApp for Teens delivery package.

Discussion

This is the first known cluster randomised factorial trial for the optimisation of engagement in a digital parenting intervention in a low- and middle-income country. Findings will be used to inform the evaluation of the optimised app in a subsequent randomised controlled trial.

Trial registration

Pan African Clinical Trial Registry, PACTR202210657553944. Registered 11 October 2022, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=24051.
Association between dietary intake of flavonoids and hyperuricemia: a cross-sectional study
Authors: Li Houlin , Shi Lin , Chen Xuelan , Wang Mo
Published: June 2023

Background

Previous research has demonstrated flavonoid intake was closely related to hyperuricemia. The purpose of this study was to examine whether flavonoid intake was associated with serum uric acid and hyperuricemia in U.S. adults.

Methods

The study sample consisted of 8,760 participants enrolled in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2010. Flavonoid consumption was measured using a two-day recall questionnaire on dietary intake. Hyperuricemia was defined based on the serum uric acid levels, determined as ≥ 7 mg/dL for males and ≥ 6 mg/dL for females. The study utilized multivariate linear regression to determine the correlation between flavonoid consumption and serum uric acid levels. Additionally, analyses involving multivariate logistic regression and restricted cubic splines (RCS) were conducted to evaluate the potential link between flavonoid consumption and hyperuricemia. All analyses were adjusted for possible confounding variables.

Results

The study revealed a negative correlation between serum uric acid levels and elevated levels of anthocyanidins and flavanones, with significant p-trends of < 0.001 and 0.02 respectively. The multivariate analysis showed that anthocyanidins and flavanones intake had a significant negative association with the risk of hyperuricemia, with p-trend value being < 0.001 and 0.01, respectively. Flavan-3-ols, flavonols, and all flavonoids exhibited a non-linear association with the incidence of hyperuricemia, with significant p-nonlinear values of < 0.001, 0.04, and 0.01 respectively.

Conclusion

Our study demonstrated that individuals who follow a diet rich in anthocyanins and flavanones had significantly lower serum uric acid levels and a lower incidence of hyperuricemia.
Selection of bone graft type for the surgical treatment of thoracolumbar spinal tuberculosis based on the spinal instability neoplastic score: a retrospective single-center cohort study
Authors: Huang Tianji , Han Zhenghan , Luo Wei , He Bin , Zhu Yong , Zhao Zenghui
Published: June 2023

Objectives

This study aimed to establish a standard for selecting bone graft type for thoracolumbar spinal tuberculosis surgery based on the spinal instability neoplastic score (SINS).

Methods

Patients with thoracolumbar tuberculosis who underwent one-stage debridement posteriorly and instrumentation were divided into a structural bone graft group (SBG) (51 cases) and a non-structural bone graft group (NSBG) (54 cases) according to their SINS. SBG was performed when the SINS was ≥ 13 and NSBG was performed when it was 7 ≤ SINS ≤ 12. Baseline data, clinical outcomes, and imaging outcomes were collected and statistically analyzed between the two groups.

Results

Significant improvements in clinical and imaging outcomes were achieved in both groups. Compared to the SBG group, the operation time of the NSBG group was shorter, the intraoperative blood loss of the NSBG group was less, the bone fusion time of the NSBG group was faster.

Conclusion

Non-structural and structural bone grafting can achieve comparable therapeutic effects in patients with spinal tuberculosis, and a suitable selection of bone grafts based on quantitative SINS will make full use of the advantages of different bone grafts.
Predictive value of total psoas muscle index for postoperative physical functional decline in older patients undergoing emergency abdominal surgery
Authors: Yamaguchi Keishi , Matsumoto Shokei , Abe Takeru , Nakajima Kento , Senoo Satomi , Shimizu Masayuki , Takeuchi Ichiro
Published: June 2023

Background

Older individuals increasingly require emergency abdominal surgeries. They are susceptible to surgical stress and loss of independence in performing daily activities. We hypothesized that the psoas muscle volume would be significantly associated with postoperative functional decline (FD) in older patients undergoing emergency abdominal surgery and aimed to evaluate the use of the psoas muscle volume on computed tomography (CT) scans.

Methods

A retrospective, single-center study of patients aged ≥ 65 years who had undergone emergency abdominal surgery between January 2019 and June 2021 was performed. We assessed patients’ activities of daily living using the Barthel Index. FD was defined as a ≥ 5-point decrease between preoperative and 28-day postoperative values. The psoas muscle volume was measured by CT, which was used for diagnosis, and normalized by height to calculate total psoas muscle index (TPI). We evaluated associations between FD and TPI using receiver operating characteristics (ROC) analysis and multiple logistic regression analysis.

Results

Of 238 eligible patients, 71 (29.8%) had clinical postoperative FD. Compared to the non-FD group, the FD group was significantly older and had a higher proportion of females, higher Charlson Comorbidity Index, lower body mass index, higher American Society of Anesthesiology score, lower serum albumin level, and lower TPI. ROC analyses revealed that TPI had the highest area under the curve (0.802; 95% confidence interval [CI], 0.75–0.86). A multivariable logistic regression model revealed that low TPI was an independent predictor of postoperative FD (odds ratio, 0.14; 95% CI, 0.06–0.32).

Conclusions

TPI can predict postoperative FD due to emergency abdominal surgery. Identification of patients who are at high risk of FD before surgery may be useful for enhancing the regionalized system of care for emergency general surgery.
An active and targeted survey reveals asymptomatic malaria infections among high-risk populations in Mondulkiri, Cambodia
Authors: Doum Dyna , Mclver David J. , Hustedt John , Hii Jeffrey , Sovannaroth Siv , Lek Dysoley , Richardson Jason H. , Tatarsky Allison , Lobo Neil F.
Published: June 2023

Background

Malaria is a mosquito-borne disease that is one of the most serious public health issues globally and a leading cause of mortality in many developing countries worldwide. Knowing the prevalence of both symptomatic and asymptomatic malaria on a subnational scale allows for the estimation of the burden of parasitaemia present in the transmission system, enabling targeting and tailoring of resources towards greater impact and better use of available capacity. This study aimed to determine the PCR-based point prevalence of malaria infection, by parasite species, among three high-risk populations in Mondulkiri province, Cambodia: forest rangers, forest dwellers, and forest goers.

Methods

A cross-sectional survey was performed during the transmission season in November and December 2021. Blood samples collected on filter paper from participants (n = 1301) from all target groups were screened for Plasmodium spp using PCR.

Results

Malaria prevalence among all study participants was 6.7% for any Plasmodium species. Malaria prevalence in the forest ranger group was 8.1%, was 6.8% in forest goers, and 6.4% in forest dwellers; all infections were asymptomatic. Plasmodium vivax was detected in all participant groups, while the few Plasmodium falciparum infections were found in goers and dwellers. 81% of all infections were due to P. vivax, 9% were due to P. falciparum, 3% due to Plasmodium cynomolgi, and the rest (7%) remained undefined. Gender was associated with malaria infection prevalence, with male participants having higher odds of malaria infection than female participants (OR = 1.69, 95% CI 1.08–2.64). Passively collected malaria incidence data from the Cambodian government were also investigated. Health facility-reported malaria cases, based on rapid diagnostic tests, for the period Jan-Dec 2021 were 521 Plasmodium vivax (0.89% prevalence), 34 P. falciparum (0.06%) and four P. falciparum + mixed (0.01%)—a total of 559 cases (0.95%) for all of Mondulkiri.

Conclusion

This reservoir of asymptomatic parasitaemia may be perpetuating low levels of transmission, and thus, new strategies are required to realize the goal of eliminating malaria in Cambodia by 2025.
The new insights into autophagy in thyroid cancer progression
Authors: Shi Yu-Bo , Chen Shu-Yuan , Liu Ren-Bin
Published: June 2023

In recent decades, the incidence of thyroid cancer keeps growing at a shocking rate, which has aroused increasing concerns worldwide. Autophagy is a fundamental and ubiquitous biological event conserved in mammals including humans. Basically, autophagy is a catabolic process that cellular components including small molecules and damaged organelles are degraded for recycle to meet the energy needs, especially under the extreme conditions. The dysregulated autophagy has indicated to be involved in thyroid cancer progression. The enhancement of autophagy can lead to autophagic cell death during the degradation while the produced energies can be utilized by the rest of the cancerous tissue, thus this influence could be bidirectional, which plays either a tumor-suppressive or oncogenic role. Accordingly, autophagy can be suppressed by therapeutic agents and is thus regarded as a drug target for thyroid cancer treatments. In the present review, a brief description of autophagy and roles of autophagy in tumor context are given. We have addressed summary of the mechanisms and functions of autophagy in thyroid cancer. Some potential autophagy-targeted treatments are also summarized. The aim of the review is linking autophagy to thyroid cancer, so as to develop novel approaches to better control cancer progression.
Intensive cycles of neoadjuvant camrelizumab combined with chemotherapy in locally advanced esophageal squamous cell carcinoma: a single-arm, phase II trial
Authors: Yang Guozhen , Su Xiaodong , Huang Yuanheng , Luo Guangyu , Wang Zhiqiang , Cai Peiqiang , Zheng Yating , Bei Ting , Huang Mengli , Bai Yuezong , He Haoqiang , Xiang Jin , Cai Muyan , Zhong Jiudi , Guo Qiyu , Zhang Xu
Published: June 2023

Background

Two cycles of neoadjuvant PD-1 blockade plus chemotherapy induced favorable pathological response and tolerant toxicity in patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, approximately 25% of patients relapsed within 1 year after surgery, indicating that a short course of treatment may not be sufficient. Therefore, exploring the effects of intensive treatment is needed for optimal clinical outcomes.

Methods

Locally advanced ESCC patients were administered three cycles of camrelizumab plus nab-paclitaxel and capecitabine, followed by thoracoscopic esophagectomy. The primary endpoint was pathologic response. Secondary endpoints included safety, feasibility, radiologic response, survival outcomes, and immunologic/genomic correlates of efficacy.

Results

Forty-seven patients were enrolled in the study. Forty-two patients received surgery, and R0 resection was achieved in all cases. The complete and major pathological response rates were 33.3% and 64.3%, respectively, and the objective response rate was 80.0%. Three cycles of treatment significantly improved T down-staging compared to two cycles (P = 0.03). The most common treatment-related adverse events were grades 1–2, and no surgical delay was reported. With a median follow-up of 24.3 months, the 1-year disease-free survival and overall survival rates were both 97.6%, and the 2-year disease-free survival and overall survival rates were 92.3% and 97.6%, respectively. Three patients experienced disease recurrence or metastasis ranging from 12.5 to 25.8 months after surgery, and one patient died 6 months after surgery due to cardiovascular disease. Neither programmed death-ligand 1 expression nor tumor mutational burden was associated with pathological response. An increased infiltration of CD56dim natural killer cells in the pretreatment tumor was correlated with better pathological response in the primary tumor.

Conclusions

It seems probable that intensive cycles of neoadjuvant camrelizumab plus nab-paclitaxel and capecitabine increased tumor regression and improved survival outcomes. Randomized controlled trials with larger sample sizes and longer follow-up periods are needed to validate these findings.

Trial registration Chinese Clinical Trial Registry, ChiCTR2000029807, Registered February 14, 2020, https://www.chictr.org.cn/showproj.aspx?proj=49459.
Detection of reed using cnn method and analysis of the dry reed (phragmites australis) for a sustainable lake area
Authors: Obreja Cristian Dragos , Buruiana Daniela Laura , Mereuta Elena , Muresan Alina , Ceoromila Alina Mihaela , Ghisman Viorica , Axente Roxana Elena
Published: June 2023

Background

Common reed (Phragmites australis L.) is a highly productive wetland plant and a possible valuable resource of renewable biomass worldwide. For a sustainable management the exploitation of reed is beneficial because the increasing demand for sustainable biomass which presents reed bed areas and wetlands. Knowing the properties of plant biomass obtained from reeds is essential both for the effect on combustion equipment and for the impact on the environment. Brates Lake, situated in Galati, Romania is a natural watershed with reed plantations.

Results

We used the convolutional neural network method combined with the cropped image techniques represent a powerful tool for high-precision image-based biomass detection in lake areas. The study aimed to investigate the morphological and chemical parameters through SEM–EDX analysis and pH, conductivity, nitrate anion, nitrite anion, total nitrogen, sulphate anion, sulphide anion, phosphate anion concentrations were determined from reed extract. The samples have a moderately acidic reaction pH 4.91–4.98. The number of soluble salts in the reed extract is in the range of 3.24–4.70 g/L, the values are within normal limits, providing the plant with the necessary nutrients.

Conclusions

This is the first time that neural networks are used for the detection and prediction of areas at risk for biodiversity (reduction of water gloss until it disappears, imbalances caused by keeping reeds dry in water) caused by the aggressive and uncontrolled growth of reeds.
Assessing and managing frailty in emergency laparotomy: a WSES position paper
Authors: Tian Brian W. C. A. , Stahel Philip F. , Picetti Edoardo , Campanelli Giampiero , Di Saverio Salomone , Moore Ernest , Bensard Denis , Sakakushev Boris , Galante Joseph , Fraga Gustavo P. , Koike Kaoru , Di Carlo Isidoro , Tebala Giovanni D. , Leppaniemi Ari , Tan Edward , Damaskos Dimitris , De’Angelis Nicola , Hecker Andreas , Pisano Michele , YunfengCui  , Maier Ron V. , De Simone Belinda , Amico Francesco , Ceresoli Marco , Pikoulis Manos , Weber Dieter G. , Biffl Walt , Beka Solomon Gurmu , Abu-Zidan Fikri M. , Valentino Massimo , Coccolini Federico , Kluger Yoram , Sartelli Massimo , Agnoletti Vanni , Chirica Mircea , Bravi Francesca , Sall Ibrahima , Catena Fausto
Published: June 2023

Many countries are facing an aging population. As people live longer, surgeons face the prospect of operating on increasingly older patients. Traditional teaching is that with older age, these patients face an increased risk of mortality and morbidity, even to a level deemed too prohibitive for surgery. However, this is not always true. An active 90-year-old patient can be much fitter than an overweight, sedentary 65-year-old patient with comorbidities. Recent literature shows that frailty—an age-related cumulative decline in multiple physiological systems, is therefore a better predictor of mortality and morbidity than chronological age alone. Despite recognition of frailty as an important tool in identifying vulnerable surgical patients, many surgeons still shun objective tools. The aim of this position paper was to perform a review of the existing literature and to provide recommendations on emergency laparotomy and in frail patients. This position paper was reviewed by an international expert panel composed of 37 experts who were asked to critically revise the manuscript and position statements. The position paper was conducted according to the WSES methodology. We shall present the derived statements upon which a consensus was reached, specifying the quality of the supporting evidence and suggesting future research directions.
High return to sport rate and good patient-reported outcomes in recreational athletes following simple elbow dislocations
Authors: Nolte Philip-Christian , Vorm Walde Melina , Elrick Bryant P. , Grützner Paul-Alfred , Porschke Felix , Schnetzke Marc
Published: June 2023

Background

The purpose of this study was to investigate outcomes and return to sport metrics in recreational athletes who suffered simple elbow dislocations and were treated operatively or nonoperatively.

Methods

The study included patients between the ages of 16 and 65 who were recreational athletes and had experienced a simple elbow dislocation, with at least 2 years having passed since the injury. Patient-reported outcomes including Mayo Elbow Performance Score (MEPS), Subjective Elbow Value (SEV), Oxford Elbow Score (OES) and Visual Analog Scale (VAS) were collected. Return to sport metrics were assessed.

Results

A total of 44 patients (21 females, mean age 43.8 years [95% CI, 39.1–48.5]) who were recreational athletes before their injury completed follow-up at mean 7.6 years (95% CI, 6.7–8.5). There were 29 patients (65.9%) who were treated operatively. Mean MEPS was 93.3 (95% CI, 90.2–96.4), mean SEV was 94.9 (95% CI, 91.9–97.9) and mean OES was 43.3 (95% CI, 41.3–45.4). A total of 36 (81.8%) patients returned to their pre-injury sport. Mean time to return to sport was 21.7 (95% CI, 16.8–26.5) weeks. There was a significant difference in OES (P = .019) and SEV (P = .030) that favored the nonoperative group; however, no significant differences for MEPS, VAS, satisfaction, arc of motion and return to sport were present between groups. A total of five (11.4%) complications were observed and one (2.3%) required revision.

Conclusions

Good outcomes and a high return to sport rate can be expected in recreational athletes following operative and nonoperative treatment of simple elbow dislocations. However, as many as one-in-five patients may not return to pre-injury sport.
Long-term clinical benefits of delayed-release cysteamine bitartrate capsules in patients with nephropathic cystinosis (response to “A comparison of immediate release and delayed release cysteamine in 17 patients with nephropathic cystinosis”)
Authors: Langman Craig B.
Published: June 2023

The aim of this letter to the editor is to summarize the results from three clinical trial programs evaluating delayed-release cysteamine bitartrate (DR-CYS), which demonstrated the long-term clinical benefits in patients with nephropathic cystinosis when dosed every 12 h. The authors of “A comparison of immediate release and delayed release cysteamine in 17 patients with nephropathic cystinosis” presented recommendations altering the dosage and dosing scheme from what has been previously approved by the FDA for DR-CYS. In this letter to the editor, we critique the authors’ aforementioned article as it is a retrospective analysis of a small number of patients and does not follow the dosing recommendation by the FDA for equivalent dosing of DR-CYS to immediate-release cysteamine bitartrate (IR-CYS). In addition, the article does not include study data to properly support the authors’ suggestion of increased dosing effects and benefits. We present a summary of the results from the DR-CYS clinical trial program and evidence of the rigor from which the clinical data for DR-CYS were generated and recommendation for usage as prescribed.
Targeted degradation of ⍺-synuclein aggregates in Parkinson’s disease using the AUTOTAC technology
Authors: Lee Jihoon , Sung Ki Woon , Bae Eun-Jin , Yoon Dabin , Kim Dasarang , Lee Jin Saem , Park Da-ha , Park Daniel Youngjae , Mun Su Ran , Kwon Soon Chul , Kim Hye Yeon , Min Joo-Ok , Lee Seung-Jae , Suh Young Ho , Kwon Yong Tae
Published: June 2023

Background

There are currently no disease-modifying therapeutics for Parkinson’s disease (PD). Although extensive efforts were undertaken to develop therapeutic approaches to delay the symptoms of PD, untreated α-synuclein (α-syn) aggregates cause cellular toxicity and stimulate further disease progression. PROTAC (Proteolysis-Targeting Chimera) has drawn attention as a therapeutic modality to target α-syn. However, no PROTACs have yet shown to selectively degrade α-syn aggregates mainly owing to the limited capacity of the proteasome to degrade aggregates, necessitating the development of novel approaches to fundamentally eliminate α-syn aggregates.

Methods

We employed AUTOTAC (Autophagy-Targeting Chimera), a macroautophagy-based targeted protein degradation (TPD) platform developed in our earlier studies. A series of AUTOTAC chemicals was synthesized as chimeras that bind both α-syn aggregates and p62/SQSTM1/Sequestosome-1, an autophagic receptor. The efficacy of Autotacs was evaluated to target α-syn aggregates to phagophores and subsequently lysosomes for hydrolysis via p62-dependent macroautophagy. The target engagement was monitored by oligomerization and localization of p62 and autophagic markers. The therapeutic efficacy to rescue PD symptoms was characterized in cultured cells and mice. The PK/PD (pharmacokinetics/pharmacodynamics) profiles were investigated to develop an oral drug for PD.

Results

ATC161 induced selective degradation of α-syn aggregates at DC50 of ~ 100 nM. No apparent degradation was observed with monomeric α-syn. ATC161 mediated the targeting of α-syn aggregates to p62 by binding the ZZ domain and accelerating p62 self-polymerization. These p62-cargo complexes were delivered to autophagic membranes for lysosomal degradation. In PD cellular models, ATC161 exhibited therapeutic efficacy to reduce cell-to-cell transmission of α-syn and to rescue cells from the damages in DNA and mitochondria. In PD mice established by injecting α-syn preformed fibrils (PFFs) into brain striata via stereotaxic surgery, oral administration of ATC161 at 10 mg/kg induced the degradation of α-syn aggregates and reduced their propagation. ATC161 also mitigated the associated glial inflammatory response and improved muscle strength and locomotive activity.

Conclusion

AUTOTAC provides a platform to develop drugs for PD. ATC161, an oral drug with excellent PK/PD profiles, induces selective degradation of α-syn aggregates in vitro and in vivo. We suggest that ATC161 is a disease-modifying drug that degrades the pathogenic cause of PD.
Dynamics of hospitalizations and staffing of Ukraine’s mental health services during the Russian invasion
Authors: Pinchuk Irina , Goto Ryunosuke , Kolodezhny Oleksiy , Pimenova Nataliia , Skokauskas Norbert
Published: June 2023

Background

Since February 2022, the people of Ukraine have experienced devastating losses due to the Russian invasion, increasing the demand for mental healthcare across the nation. Using longitudinal data on mental health facilities across the nation up to summer 2022, we aimed to provide an updated picture of Ukrainian mental health services during the 2022 Russian invasion.

Methods

We conducted a nationwide longitudinal study on Ukrainian inpatient mental health facilities during the Russian invasion since February 2022. We obtained responses from the heads of 30 inpatient mental health facilities, which represent 49.2% of all psychiatric hospitals in Ukraine. Information on hospitalizations and the number, displacement, and injuries of staff in April and July-September 2022 was obtained from each facility.

Results

Facilities across Ukraine reported similar staff shortages in both April and August-September 2022, despite an increase in the number of hospitalizations in July 2022 and a similar percentage of hospitalizations related to war trauma (11.6% in July vs. 10.2% in April, Wilcoxon signed-rank test P = 0.10). Hospitalizations related to war trauma became more dispersed across the nation in July 2022, likely reflecting the return of internally and externally displaced persons to their original locations.

Conclusions

The mental health needs and services changed drastically in the first half-year of the Russian invasion of Ukraine, with those in need more dispersed across the country over time. International aid may need to be scaled up to stably provide mental healthcare, given the displacement of the mental healthcare workforce.
Randomized controlled trial for selective preventive transdiagnostic intervention for adolescents at risk for emotional disorders
Authors: Vivas-Fernandez Manuel , Garcia-Lopez Luis-Joaquin , Piqueras Jose A. , Muela-Martinez Jose-Antonio , Canals-Sans Josefa , Espinosa-Fernandez Lourdes , Jimenez-Vazquez David , Diaz-Castela Maria del Mar , Morales-Hidalgo Paula , Rivera Maria , Ehrenreich-May Jill
Published: June 2023

Significant evidence does exist on the effectiveness of transdiagnostic interventions to improve emotional problems in clinical populations, and their application as universal and indicated prevention programs. However, no randomized controlled trials (RCT) studying selective transdiagnostic prevention intervention have been published. This is the first known RCT to evaluate the efficacy/effectiveness of an evidence-based selective prevention transdiagnostic program for emotional problems in adolescents. The impact of three different interventions was evaluated: (1) PROCARE (Preventive transdiagnostic intervention for Adolescents at Risk for Emotional disorders), which is a group-based, abbreviated version of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A), along with adding a booster session to reduce risk of onset of anxiety and depression, (2) PROCARE + , which includes the PROCARE protocol along with personalized add-on modules tailored to match adolescents’ risk factors, and (3) an active control condition (ACC) based on emotional psychoeducation. In total, 208 adolescents (48.5% girls) evidencing high risk and low protective factors were randomized and allocated to PROCARE, PROCARE + or ACC. Data from 153 adolescents who completed all assessments in the different phases of the study were analyzed. Self- and parent-reported measures were taken at baseline, as well as after the intervention, a 6 month follow-up was carried out, together with a 1 month follow-up after the booster session. Differences between conditions were significant on most of the outcome measures, with superior effect sizes for PROCARE + in the short and long term. Interventions were acceptable in terms of acceptability, with good satisfaction rates. Tailored targeted selective transdiagnostic interventions focused on mitigating risk factors and promoting protective factors in vulnerable adolescents are promising.
Development and validation of a clinical tool to semi‐automatic measure three‐dimensional TAR alignment on two‐dimensional radiographs
Authors: van Hoogstraten Sanne W. G. , Hermus Joris , Verbiest Vera , van Rietbergen Bert , Arts Jacobus J. C.
Published: June 2023

Background

Malalignment is often postulated as an important reason for the high failure rate of total ankle replacements (TARs). The correlation between TAR malalignment and clinical outcome, however, is not fully understood. Improving and expanding radiographic TAR alignment measurements in the clinic might lead to a better insight into the correlation between malalignment and the clinical outcome. This study aims to develop and validate a tool to semi‐automatic measure TAR alignment, and to improve alignment measurements on radiographs in the clinic.

Methods

A tool to semi‐automatically measure TAR alignment on anteroposterior and lateral radiographs was developed in MATLAB. Using the principle of edge contouring and the perpendicular relationship between the anteroposterior and lateral radiographs, the exact configuration of the TAR components can be found. Two observers validated the tool by measuring TAR alignment of ten patients using the tool. The Intraclass Coefficient (ICC) was calculated to assess the reliability of the developed method. The results obtained by the tool were compared to clinical results during radiographic follow‐up in the past, and the accuracy of both methods was calculated using three‐dimensional CT data.

Results

The tool showed an accuracy of 76% compared to 71% for the method used during follow‐up. ICC values were 0.94 (p < 0.01) and higher for both inter‐and intra‐observer reliability.

Conclusions

The tool presents a reproducible method to measure TAR alignment parameters. Three‐dimensional alignment parameters are obtained from two‐dimensional radiographs, and as the tool can be applied to most TAR designs, it offers a valuable addition in the clinic and for research purposes.
VarID2 quantifies gene expression noise dynamics and unveils functional heterogeneity of ageing hematopoietic stem cells
Authors: Rosales-Alvarez Reyna Edith , Rettkowski Jasmin , Herman Josip Stefan , Dumbović Gabrijela , Cabezas-Wallscheid Nina , Grün Dominic
Published: June 2023

Variability of gene expression due to stochasticity of transcription or variation of extrinsic signals, termed biological noise, is a potential driving force of cellular differentiation. Utilizing single-cell RNA-sequencing, we develop VarID2 for the quantification of biological noise at single-cell resolution. VarID2 reveals enhanced nuclear versus cytoplasmic noise, and distinct regulatory modes stratified by correlation between noise, expression, and chromatin accessibility. Noise levels are minimal in murine hematopoietic stem cells (HSCs) and increase during differentiation and ageing. Differential noise identifies myeloid-biased Dlk1+ long-term HSCs in aged mice with enhanced quiescence and self-renewal capacity. VarID2 reveals noise dynamics invisible to conventional single-cell transcriptome analysis.
Synthesis and tyrosinase inhibitory activities of novel isopropylquinazolinones
Authors: Hashemi Arshia , Noori Milad , Dastyafteh Navid , Sadat-Ebrahimi Seyed Esmaeil , Fazelzadeh Haghighi Negin , Mehrpour Katayoun , Sattarinezhad Elahe , Jalali Zafrei Fatemeh , Irajie Cambyz , Daneshmehr Mohammad Ali , Heydari Majid , Larijani Bagher , Iraji Aida , Mahdavi Mohammad
Published: June 2023

To find new anti-browning and whitening agents in this study, new series of isopropylquinazolinone derivatives were designed and synthesized. All derivatives were evaluated as possible tyrosinase inhibitors and compound 9q bearing 4-fluorobenzyl moieties at the R position exhibited the best potencies with an IC50 value of 34.67 ± 3.68 µM. The kinetic evaluations of 9q as the most potent derivatives recorded mix-type inhibition. Compounds 9o and 9q also exhibited potent antioxidant capacity with IC50 values of 38.81 and 40.73 µM, respectively confirming their antioxidant potential. Molecular docking studies of 9q as the most potent derivative were exacuated and it was shown that quinazolinone and acetamide moieties of compound 9q participated in interaction with critical His residues of the binding site. The obtained results demonstrated that the 9q can be considered a suitable pharmacophore to develop potent tyrosinase inhibitors.
Association study between drug prescriptions and Alzheimer’s disease claims in a commercial insurance database
Authors: Hu Eric , Li Tong Shu , Wineinger Nathan E. , Su Andrew I.
Published: June 2023

In the ongoing effort to discover treatments for Alzheimer’s disease (AD), there has been considerable focus on investigating the use of repurposed drug candidates. Mining of electronic health record data has the potential to identify novel correlated effects between commonly used drugs and AD. In this study, claims from members with commercial health insurance coverage were analyzed to determine the correlation between the use of various drugs on AD incidence and claim frequency. We found that, within the insured population, several medications for psychotic and mental illnesses were associated with higher disease incidence and frequency, while, to a lesser extent, antibiotics and anti-inflammatory drugs were associated with lower AD incidence rates. The observations thus provide a general overview of the prescription and claim relationships between various drug types and Alzheimer’s disease, with insights into which drugs have possible implications on resulting AD diagnosis.