Background Many youth in out-of-home care (OOHC) have experienced victimization in their lifetime making them vulnerable to mental health problems and further victimization. However, little is known about mechanisms behind this continuing victimization, e.g. in the form of bullying victimization, and about possible mediating and moderating factors. Objective This study examined the association between lifetime poly-victimization and later bullying victimization, as well as mediation by internalizing problems, and moderation by OOHC. Participants and setting In total n = 226 youth (n = 117 OOHC, n = 109 biological families) participated, with one of their social/biological caregivers when possible, resulting in subsamples of n = 159 participants (11–21 years) for self-report, and n = 210 participants (8–21 years) for caregiver report. Methods An online survey assessed self-report of bullying victimization in the past six months, as well as self-report and caregiver report of lifetime poly-victimization and internalizing problems. Results Based on both self-report and caregiver report, youth in OOHC showed higher levels of poly-victimization and internalizing problems than youth in biological families. In self-report, a conditional direct effect of lifetime poly-victimization on bullying victimization was found for youth in OOHC, c′ = 0.18, SE = 0.07, p = .007, while the association was mediated by internalizing problems for youth in biological families, ab = 0.13, 95 % CI [0.020; 10.805]. In the caregiver report, there was neither a direct nor a mediated effect of lifetime poly-victimization on bullying victimization. Conclusions The results stress the importance of considering the high impact of poly-victimization in predicting bullying victimization, particularly for youth in OOHC. For youth in biological families, a mediating effect of internalizing problems was found.
Abstract Although male Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) patients have higher Intensive Care Unit (ICU) admission rates and a worse disease course, a comprehensive analysis of female and male ICU survival and underlying factors such as comorbidities, risk factors, and/or anti-infection/inflammatory therapy administration is currently lacking. Therefore, we investigated the association between sex and ICU survival, adjusting for these and other variables. In this multicenter observational cohort study, all patients with SARS-CoV-2 pneumonia admitted to seven ICUs in one region across Belgium, The Netherlands, and Germany, and requiring vital organ support during the first pandemic wave were included. With a random intercept for a center, mixed-effects logistic regression was used to investigate the association between sex and ICU survival. Models were adjusted for age, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, comorbidities, and anti-infection/inflammatory therapy. Interaction terms were added to investigate effect modifications by sex with country and sex with obesity. A total of 551 patients (29% were females) were included. Mean age was 65.4 ± 11.2 years. Females were more often obese and smoked less frequently than males (p-value 0.001 and 0.042, respectively). APACHE II scores of females and males were comparable. Overall, ICU mortality was 12% lower in females than males (27% vs 39% respectively, p-value 0.23 and 0.84, respectively). ICU survival in female SARS-CoV-2 patients was higher than in male patients, independent of age, disease severity, smoking, obesity, comorbidities, anti-infection/inflammatory therapy, and country. Sex-specific biological mechanisms may play a role, emphasizing the need to address diversity, such as more sex-specific prediction, prognostic, and therapeutic approach strategies.
Background The efficacy and safety of platelet-rich plasma (PRP) augmentation for arthroscopic meniscal repair is controversial. This meta-analysis compared arthroscopic meniscal repair performed in isolation or augmented with PRP. Methods The present study was conducted according to PRISMA 2020 guidelines. Pubmed, Web of Science, Google Scholar and Embase were accessed in August 2021. All the clinical trials which compared arthroscopic meniscal repair performed in isolation or augmented with PRP were included. Results Eight hundred thirty-seven patients were included: 38% (318 of 837 patients) were women; the mean age of the patients was 35.6 (range, 20.8–64.3) years; the mean follow-up was 26.2 (range, 6–54) months. Similarity was found in analogue scale (VAS) ( P = 0.5) and Lysholm ( P = 0.9), and International Knee Documentation Committee (IKDC) scores ( P = 0.9). Similarity was found in the rate of failure ( P = 0.4) and rate of revision ( P = 0.07). Conclusion The current published scientific evidence does not support PRP augmentation for arthroscopic meniscal repair.
Background In individuals suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis often extends over many years. Factors contributing to delayed diagnosis include health care professionals' limited knowledge of rare diseases and frequent (co-)occurrence of mental disorders that may complicate and delay the diagnostic process. The ZSE-DUO study aims to assess the benefits of a combination of a physician focusing on somatic aspects with a mental health expert working side by side as a tandem in the diagnostic process. Study design This multi-center, prospective controlled study has a two-phase cohort design. Methods Two cohorts of 682 patients each are sequentially recruited from 11 university-based German Centers for Rare Diseases (CRD): the standard care cohort (control, somatic expertise only) and the innovative care cohort (experimental, combined somatic and mental health expertise). Individuals aged 12 years and older presenting with symptoms and signs which are not explained by current diagnoses will be included. Data will be collected prior to the first visit to the CRD’s outpatient clinic (T0), at the first visit (T1) and 12 months thereafter (T2). Outcomes Primary outcome is the percentage of patients with one or more confirmed diagnoses covering the symptomatic spectrum presented. Sample size is calculated to detect a 10 percent increase from 30% in standard care to 40% in the innovative dual expert cohort. Secondary outcomes are (a) time to diagnosis/diagnoses explaining the symptomatology; (b) proportion of patients successfully referred from CRD to standard care; (c) costs of diagnosis including incremental cost effectiveness ratios; (d) predictive value of screening instruments administered at T0 to identify patients with mental disorders; (e) patients’ quality of life and evaluation of care; and f) physicians’ satisfaction with the innovative care approach. Conclusions This is the first multi-center study to investigate the effects of a mental health specialist working in tandem with a somatic expert physician in CRDs. If this innovative approach proves successful, it will be made available on a larger scale nationally and promoted internationally. In the best case, ZSE-DUO can significantly shorten the time to diagnosis for a suspected rare disease. Trial registration ClinicalTrials.gov; Identifier: NCT03563677; First posted: June 20, 2018, https://clinicaltrials.gov/ct2/show/NCT03563677 .
Physical activity impacts immune homeostasis and leads to rapid and marked increase in cell-free DNA (cfDNA). However, the origin of cfDNA during exercise remains elusive and it is unknown if physical activity could improve or interfere with methylation based liquid biopsy. We analyzed the methylation levels of four validated CpGs representing cfDNA from granulocytes, lymphocytes, monocytes, and non-hematopoietic cells, in healthy individuals in response to exercise, and in patients with hematological malignancies under resting conditions. The analysis revealed that physical activity almost exclusively triggered DNA release from granulocytes, highlighting the relevance as a pre-analytical variable which could compromise diagnostic accuracy. Graphical Abstract
Background In severe cases, SARS-CoV-2 infection leads to acute respiratory distress syndrome (ARDS), often treated by extracorporeal membrane oxygenation (ECMO). During ECMO therapy, anticoagulation is crucial to prevent device-associated thrombosis and device failure, however, it is associated with bleeding complications. In COVID-19, additional pathologies, such as endotheliitis, may further increase the risk of bleeding complications. To assess the frequency of bleeding events, we analyzed data from the German COVID-19 autopsy registry (DeRegCOVID). Methods The electronic registry uses a web-based electronic case report form. In November 2021, the registry included N = 1129 confirmed COVID-19 autopsy cases, with data on 63 ECMO autopsy cases and 1066 non-ECMO autopsy cases, contributed from 29 German sites. Findings The registry data showed that ECMO was used in younger male patients and bleeding events occurred much more frequently in ECMO cases compared to non-ECMO cases (56% and 9%, respectively). Similarly, intracranial bleeding (ICB) was documented in 21% of ECMO cases and 3% of non-ECMO cases and was classified as the immediate or underlying cause of death in 78% of ECMO cases and 37% of non-ECMO cases. In ECMO cases, the three most common immediate causes of death were multi-organ failure, ARDS and ICB, and in non-ECMO cases ARDS, multi-organ failure and pulmonary bacterial ± fungal superinfection, ordered by descending frequency. Interpretation Our study suggests the potential value of autopsies and a joint interdisciplinary multicenter (national) approach in addressing fatal complications in COVID-19.
Cholangiocarcinoma (CCA) is the second most common primary liver cancer and associated with a dismal prognosis due to the lack of an efficient systemic therapy. In contrast to other cancers, new immunotherapies have demonstrated unsatisfactory results in clinical trials, underlining the importance of a deeper understanding of the special tumor microenvironment of CCA and the role of immune cells interacting with the tumor. Tumor-infiltrating lymphocytes (TILs) are an important component of the adaptive immune system and the foundation of current immunotherapy. Therefore, the aim of this systemic review is to summarize the current literature focusing on the proportions and distribution, molecular pathogenesis, prognostic significance of TILs and their role in immunotherapy for CCA patients. In CCA, CD8+ and CD4+ T lymphocytes represent the majority of TILs and are mostly sequestered around the cancer cells. CD20+ B lymphocytes and Natural Killer (NK) cells are less frequent. In contrast, Foxp3+ cells (regulatory T cells, Tregs) are observed to infiltrate into the tumor. In the immune microenvironment of CCA, cancer cells and stromal cells such as TAMs, TANs, MSDCs and CAFs inhibit the immune protection function of TILs by secreting factors like IL-10 and TGF-β. With respect to molecular pathogenesis, the Wnt/-catenin, TGF-signaling routes, aPKC-i/P-Sp1/Snail Signaling, B7-H1/PD-1Pathway and Fas/FasL signaling pathways are connected to the malignant potential and contributed to tumor immune evasion by increasing TIL apoptosis. Distinct subtypes of TILs show different prognostic implications for the long-term outcome in CCA. Although there are occasionally conflicting results, CD8+ and CD4+ T cells, and CD20+ B cells are positively correlated with the oncological prognosis of CCA, while a high number of Tregs is very likely associated with worse overall survival. TILs also play a major role in immunotherapy for CCA. In summary, the presence of TILs may represent an important marker for the prognosis and a potential target for novel therapy, but more clinical and translational data is needed to fully unravel the importance of TILs in the treatment of CCA.
The 7th Cardiovascular Outcome Trial (CVOT) Summit on Cardiovascular, Renal, and Glycemic Outcomes, was held virtually on November 18–19, 2021. Pursuing the tradition of the previous summits, this reference congress served as a platform for in-depth discussion and exchange on recently completed CVOTs. This year’s focus was placed on the outcomes of EMPEROR-Preserved, FIGARO-DKD, AMPLITUDE-O, SURPASS 1–5, and STEP 1–5. Trial implications for diabetes and obesity management and the impact on new treatment algorithms were highlighted for endocrinologists, diabetologists, cardiologists, nephrologists, and general practitioners. Discussions evolved from outcome trials using SGLT2 inhibitors as therapy for heart failure, to CVOTs with nonsteroidal mineralocorticoid receptor antagonists and GLP-1 receptor agonists. Furthermore, trials for glycemic and overweight/obesity management, challenges in diabetes management in COVID-19, and novel guidelines and treatment strategies were discussed. Trial registration The 8th Cardiovascular Outcome Trial Summit will be held virtually on November 10–11, 2022 ( http://www.cvot.org )
Background There has been a growing interest in imageless navigation for primary total hip arthroplasty (THA). Its superiority over standard THA is debated. This meta-analysis compared surgical duration, implant positioning, Harris Hip Score and rate of dislocation of imageless navigation versus conventional THA. Methods The present study was conducted according to the PRISMA 2020 guidelines. All the clinical trials comparing imageless navigation versus conventional for primary THA were accessed. In January 2022, the following databases were accessed: PubMed, Web of Science, Google Scholar and Embase. No time constraints were used for the search. The outcomes of interest were to compare cup inclination and anteversion, leg length discrepancy, surgical duration, Harris Hip Score and rate of dislocation of imageless navigation versus conventional THA. Results Twenty-one studies (2706 procedures) were retrieved. Fifty-two percent of patients were women. There was between-group comparability at baseline in terms of age, body mass index (BMI), visual analogue scale, Harris Hip Score and leg length discrepancy ( P > 0.1). Compared with conventional THA, the navigated group demonstrated slightly lower leg length discrepancy ( P = 0.02) but longer duration of the surgical procedure ( P < 0.0001). Cup anteversion ( P = 0.6) and inclination ( P = 0.5), Harris Hip Score ( P = 0.1) and rate of dislocation ( P = 0.98) were similar between the two interventions. Conclusion Imageless navigation may represent a viable option for THA.
Background Cholangiocarcinoma (CCA) is still a deadly tumour. Histological and molecular aspects of thioacetamide (TAA)-induced intrahepatic CCA (iCCA) in rats mimic those of human iCCA. Carcinogenic changes and therapeutic vulnerabilities in CCA may be captured by molecular investigations in bile, where we performed bile proteomic and metabolomic analyses that help discovery yet unknown pathways relevant to human iCCA. Methods Cholangiocarcinogenesis was induced in rats (TAA) and mice ( Jnk Δhepa + CCl 4 + DEN model). We performed proteomic and metabolomic analyses in bile from control and CCA-bearing rats. Differential expression was validated in rat and human CCAs. Mechanisms were addressed in human CCA cells, including Huh28-KRAS G12D cells. Cell signaling, growth, gene regulation and [U- ¹³ C]-D-glucose-serine fluxomics analyses were performed. In vivo studies were performed in the clinically-relevant iCCA mouse model. Results Pathways related to inflammation, oxidative stress and glucose metabolism were identified by proteomic analysis. Oxidative stress and high amounts of the oncogenesis-supporting amino acids serine and glycine were discovered by metabolomic studies. Most relevant hits were confirmed in rat and human CCAs (TCGA). Activation of interleukin-6 (IL6) and epidermal growth factor receptor (EGFR) pathways, and key genes in cancer-related glucose metabolic reprogramming, were validated in TAA-CCAs. In TAA-CCAs, G9a, an epigenetic pro-tumorigenic writer, was also increased. We show that EGFR signaling and mutant KRAS G12D can both activate IL6 production in CCA cells. Furthermore, phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in serine-glycine pathway, was upregulated in human iCCA correlating with G9a expression. In a G9a activity-dependent manner, KRAS G12D promoted PHGDH expression, glucose flow towards serine synthesis, and increased CCA cell viability. KRAS G12D CAA cells were more sensitive to PHGDH and G9a inhibition than controls. In mouse iCCA, G9a pharmacological targeting reduced PHGDH expression. Conclusions In CCA, we identified new pro-tumorigenic mechanisms: Activation of EGFR signaling or KRAS mutation drives IL6 expression in tumour cells; Glucose metabolism reprogramming in iCCA includes activation of the serine-glycine pathway; Mutant KRAS drives PHGDH expression in a G9a-dependent manner; PHGDH and G9a emerge as therapeutic targets in iCCA.
Background Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs. Methods Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021). Results This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation. Conclusions This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease. ClinicalTrials.gov Identifier : NCT00628745.
Background Some patients have demonstrated evidence of heterotopic ossification (HO) following total hip arthroplasty (THA). Selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) are used as prophylaxis for HO following THA. This meta-analysis compared selective versus non-selective NSAIDs as prophylaxis for HO following THA. Material and methods The present study was conducted according to the PRISMA 2020 guidelines. All the clinical investigations comparing selective versus non-selective NSAIDs as prophylaxis for HO following THA were accessed in February 2022. An assessment of the methodological quality and statistical analyses were performed through the risk of bias summary tool of the Review Manager 5.3 software (Cochrane Collaboration, Copenhagen). The modified Brooker staging system was used to rate the efficacies of the interventions. Results Data from 8 studies and 1526 patients were collected. 60.8% were female. No difference was found in the sample size, mean age, and percentage of females between the two groups at baseline. No statistically significant difference was found between selective and non-selective NSAIDs in term of efficacy. 72% (1078 of 1502) of the patients were classified as Brooker 0, 21% (322 of 1502) as Brooker I, 5% (80 of 1502) as Brooker II, 1% (16 of 1502) as Brooker III, and 0.1% (2 of 1502) as Brooker IV. Conclusion Selective and non-selective NSAIDs were equally effective when used as prophylaxis for HO following THA. Level of evidence Level III, systematic review and meta-analysis.
The text-guided diffusion model GLIDE (Guided Language to Image Diffusion for Generation and Editing) is the state of the art in text-to-image generative artificial intelligence (AI). GLIDE has rich representations, but medical applications of this model have not been systematically explored. If GLIDE had useful medical knowledge, it could be used for medical image analysis tasks, a domain in which AI systems are still highly engineered towards a single use-case. Here we show that the publicly available GLIDE model has reasonably strong representations of key topics in cancer research and oncology, in particular the general style of histopathology images and multiple facets of diseases, pathological processes and laboratory assays. However, GLIDE seems to lack useful representations of the style and content of radiology data. Our findings demonstrate that domain-agnostic generative AI models can learn relevant medical concepts without explicit training. Thus, GLIDE and similar models might be useful for medical image processing tasks in the future - particularly with additional domain-specific fine-tuning.
Some COVID-19 patients experience dyspnea without objective impairment of pulmonary or cardiac function. This study determined diaphragm function and its central voluntary activation as a potential correlate with exertional dyspnea after COVID-19 acute respiratory distress syndrome (ARDS) in ten patients and matched controls. One year post discharge, both pulmonary function tests and echocardiography were normal. However, six patients with persisting dyspnea on exertion showed impaired volitional diaphragm function and control based on ultrasound, magnetic stimulation and balloon catheter-based recordings. Diaphragm dysfunction with impaired voluntary activation can be present 1 year after severe COVID-19 ARDS and may relate to exertional dyspnea. This prospective case–control study was registered under the trial registration number NCT04854863 April, 22 2021
Numerous research methods have been developed to detect anomalies in the areas of security and risk analysis. In healthcare, there are numerous use cases where anomaly detection is relevant. For example, early detection of sepsis is one such use case. Early treatment of sepsis is cost effective and reduces the number of hospital days of patients in the ICU. There is no single procedure that is sufficient for sepsis diagnosis, and combinations of approaches are needed. Detecting anomalies in patient time series data could help speed the development of some decisions. However, our algorithm must be viewed as complementary to other approaches based on laboratory values and physician judgments. The focus of this work is to develop a hybrid method for detecting anomalies that occur, for example, in multidimensional medical signals, sensor signals, or other time series in business and nature. The novelty of our approach lies in the extension and combination of existing approaches: Statistics, Self Organizing Maps and Linear Discriminant Analysis in a unique and unprecedented way with the goal of identifying different types of anomalies in real-time measurement data and defining the point where the anomaly occurs. The proposed algorithm not only has the full potential to detect anomalies, but also to find real points where an anomaly starts.
Background This systematic review investigates the role of synthetic graft for primary medial patellofemoral ligament (MPFL) reconstruction in patients with recurrent patellofemoral instability, focusing on clinical scores and the rate of complications. Methods This systematic review was conducted according to the PRISMA statement. The main online databases were accessed in January 2022 without time constraints. All clinical studies investigating the use of synthetic grafts for MPFL reconstruction were accessed. Revision settings were not considered. Only articles reporting data on patients with recurrent patellofemoral instability were eligible. Studies regarding congenital or acute patellofemoral dislocation were excluded. Only studies performing a follow-up longer than 24 months were considered. Results Data on 199 patients [mean age 22.3 (range 19.0–28.0) years] were collected. The mean follow-up was 60.5 (39.0–142.8) months. All the scores of interest improved at last follow-up: Kujala (+ 24.8; P = 0.0002), Lysholm (+ 42.0; P = 0.02), Tegner (+ 1.2; P = 0.03), IKDC (+ 20.9; P = 0.02). Post-operatively, a positive apprehension test was detected in 6.1% (7/115) of patients, and a sensation of instability was reported by 1.5% (3/199) of patients. The rate of re-dislocations was 2.5% (5 of 199 patients), and revision procedures were performed in less than 1% (1 of 199) of patients. Conclusion Synthetic graft may be reliable and feasible for primary MPFL reconstruction in patients with recurrent patellofemoral instability.
Introduction Aging is accompanied by changes in muscle mass, strength and loss of sensory, visual and auditive functions. However, these changes do not occur linearly, most spatiotemporal gait parameters change with aging. Age simulation suits have been invented to give young people an impression of the implications of being older and may be a useful tool in the scientific setting for gerontology research to validate any study concept before it becomes a pilot study. The rationale behind this study was to investigate the effects of an age simulation suit on gait parameters in young healthy adults and to compare the altered gait with healthy older, community-dwelling citizens. Methods Subjects were 14 healthy young adults (6 female) and 8 healthy older (4 female) individuals with a mean (± SD) age of 24.8 ± 3.4 years and 72 ± 1.9 years, respectively. After initial baseline measurements had been taken and a familiarization phase, the younger subjects walked for 15 min without and 15 min with an age simulation suit on an instrumented treadmill. The older subjects walked once for 15 min on the same treadmill without wearing an age simulation suit. The walking speed was self-selected for all subjects. Results The age simulation suit reduced the walking speed from 4.1 ± 0.7 km/h to 3.3 ± 0.5 km/h ( p < 0.001) in young adults with no differences compared to older adults (2.9 ± 0.6 km/h, p = 0.9). Step width increased from 8.7 ± 2.2 cm to 12.1 ± 2.2 cm ( p < 0.001) and did not differ from older participants (11.1 ± 4.3 cm, p = 0.37). The stride length was reduced (132.6 ± 5.9 cm vs 118.1 +—6.6 cm, p < 0.001), but still did not match the old control group (94.5 ± 5.6 cm, p < 0.05). Wearing the suit increased thestride time of young subjects (from 1,152 to 1,316 ms, p < 0.001) and was different compared to the older control group (1,172 ms, p = 0.53). The coefficient of variation (COV) of spatiotemporal parameters did not differ between young (both not wearing the suit and wearing the suit) and older subjects. The standard deviation of lateral symmetry, an in-house marker from the instrumented treadmill that serves as a marker of gait variability, differed between young subjects without the suit and older subjects (5.89 ± 1.9 mm vs 14.6 ± 5.7 mm, p < 0.001) but not between young subjects wearing the suit and older subjects (16.4 ± 7.4 mm vs 14.6 ± 5.7 mm, p = 0.53). Conclusion Wearing an age simulation suit while walking on a treadmill with a self-selected walking speed alters some, but not all, measured spatiotemporal parameters to approximate a gait pattern similar to that of an older individual.
Evidence from both animal and human studies now supports the development of ventilator-induced diaphragm dysfunction (VIDD) starting as early as 24 h after initiation of mechanical ventilation in the intensive care unit (ICU). However, although the concept of VIDD is now widely accepted, there remain several unanswered questions regarding its pathophysiology, rate of development, and (potentially) recovery after mechanical ventilation.This state-of-the-art opinion article briefly explains VIDD and provides an update on its clinical and prognostic relevance. It then focusses on state-of-the-art diagnostic approaches to determine diaphragm function, strength, and control (neural and peripheral), highlights knowledge gaps relevant to VIDD, and discusses the use of diaphragm pacing for VIDD prevention. It is suggested that future research projects in mechanically ventilated patients would ideally use both cortical and cervical phrenic nerve stimulation studies over time (including also diaphragm electromyography) as the gold standard techniques. This approach has not yet been utilized in a longitudinally designed study in the ICU. Application of these gold standard techniques would allow better understanding of the true pathophysiology and rate of development of VIDD. Notably, these techniques would be superior to diaphragm ultrasound, which yields surrogate markers of diaphragm function only without any direct measure of diaphragm strength or control. It is also suggested that such translational research would further advance understanding of diaphragm pacing as a very promising treatment option for VIDD.
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