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Orthopaedic Surgery Jan 2023Several modifications of the induced membrane technique (IMT) have been reported, but there is no consensus regarding their results and prognosis. Moreover, most studies... (Meta-Analysis)
Meta-Analysis Review
Several modifications of the induced membrane technique (IMT) have been reported, but there is no consensus regarding their results and prognosis. Moreover, most studies have focused on tibial defects; no meta-analysis of the treatment of femoral defects using the IMT has been reported. This systematic review and meta-analysis aimed to identify the potential risk factors of post-procedural complications following the treatment of segmental femoral defects using the IMT. A comprehensive search was performed on the Cochrane Library, EBSCO, EMBASE, Ovid, PubMed, Scopus, and Web of Science databases, using the keywords "femur," "Masquelet technique," and "induced membrane technique." Original articles composed in English, having accessible individual patient data, and reporting more than two cases of bony defect or nonunion of femur or more than five cases of any body part were included. Post-procedural bone graft infections, final union status, and union time after second-stage operation were analyzed. Fourteen reports, including 90 patients, were used in this study. External fixation in second-stage surgery had an odds ratio of 9.267 for post-procedural bone graft infection (p = 0.047). The odds ratio of post-procedural bone graft infection and age >65 years for final non-union status was 51.05 (p = 0.003) and 9.18 (p = 0.042). Shorter union time was related to impregnated antibiotics in the spacer (p = 0.005), transplanting all-autologous grafts (p = 0.042), and the application of intramedullary nails as the second-stage fixation method (p = 0.050). The IMT appears to be reasonable and reproducible for femoral segmental bone defects. Several preoperative and surgical factors may affect post-procedural complications and union time.
Topics: Humans; Aged; Femur; Tibia; Prognosis; Fracture Fixation, Intramedullary; Anti-Bacterial Agents; Bone Transplantation; Treatment Outcome
PubMed: 36444955
DOI: 10.1111/os.13604 -
Frontiers in Oncology 2022Tumors can survive environmental and metabolic stress by triggering homeostatic responses that re-establish the pre-stress status and permit them to grow and thrive. The...
Tumors can survive environmental and metabolic stress by triggering homeostatic responses that re-establish the pre-stress status and permit them to grow and thrive. The endoplasmic reticulum (ER) is the organelle where proteins undergo post-translational modifications and are folded and exported to the secretory pathway. Its environment and activity are therefore fundamental for proteostasis, i.e., the plethora of mechanisms controlling protein formation, folding, degradation, and secretion, needed to assure protein balance and cellular health. In different tumor-related conditions, such as after the activation of oncogenes or under hypoxia and nutrient deprivation, the ER experiences stress, triggered by a high load of proteins to be folded compared to the limited folding capacity of the organelle. As a consequence, three ER membrane sensors and the related unfolded protein response (UPR) are activated. The UPR comprises a complex interconnection between signal transduction pathways that promote a homeostatic response that acts by increasing the amount of protein chaperones and of proteins involved in ER-associated protein degradation (ERAD) on one hand and attenuating protein translation on the other. ER-phagy, literally "eating" the ER, is part of another homeostatic response consisting of the clearance of non-functional ER portions including misfolded proteins. This response is also activated by a set of dedicated ER-phagy receptors after ER stimuli, which overlap the stimuli generating ER stress. Thus, the UPR and ER-phagy are two closely related homeostatic mechanisms that cooperate in re-establishing ER homeostasis. However, while the role of the UPR in favoring cancer growth and thriving by promoting angiogenesis, metastasis, chemotherapy resistance, and epithelial-to-mesenchymal transition is consolidated, that of ER-phagy is still in its infancy. This essay provides an overview of emerging concepts on ER stress, the UPR, and ER-phagy and their crosstalk in tumorigenesis. We also critically review new findings on their pharmacological targeting in cancer.
PubMed: 36408145
DOI: 10.3389/fonc.2022.997235 -
Frontiers in Immunology 2022The complement system is an essential component of our innate defense and plays a vital role in the pathogenesis of many diseases. Assessment of complement activation is...
BACKGROUND
The complement system is an essential component of our innate defense and plays a vital role in the pathogenesis of many diseases. Assessment of complement activation is critical in monitoring both disease progression and response to therapy. Complement analysis requires accurate and standardized sampling and assay procedures, which has proven to be challenging.
OBJECTIVE
We performed a systematic analysis of the current methods used to assess complement components and reviewed whether the identified studies performed their complement measurements according to the recommended practice regarding pre-analytical sample handling and assay technique. Results are supplemented with own data regarding the assessment of key complement biomarkers to illustrate the importance of accurate sampling and measuring of complement components.
METHODS
A literature search using the Pubmed/MEDLINE database was performed focusing on studies measuring the key complement components C3, C5 and/or their split products and/or the soluble variant of the terminal C5b-9 complement complex (sTCC) in human blood samples that were published between February 2017 and February 2022. The identified studies were reviewed whether they had used the correct sample type and techniques for their analyses.
RESULTS
A total of 92 out of 376 studies were selected for full-text analysis. Forty-five studies (49%) were identified as using the correct sample type and techniques for their complement analyses, while 25 studies (27%) did not use the correct sample type or technique. For 22 studies (24%), it was not specified which sample type was used.
CONCLUSION
A substantial part of the reviewed studies did not use the appropriate sample type for assessing complement activation or did not mention which sample type was used. This deviation from the standardized procedure can lead to misinterpretation of complement biomarker levels and hampers proper comparison of complement measurements between studies. Therefore, this study underlines the necessity of general guidelines for accurate and standardized complement analysis.
Topics: Humans; Complement C5; Complement Activation; Complement C3; Complement Membrane Attack Complex; Biomarkers
PubMed: 36330514
DOI: 10.3389/fimmu.2022.1007102 -
EFORT Open Reviews Oct 2022The aim of this study was to systematically review clinical studies on the employed definitions of longitudinal forearm instabilities referred to as Essex-Lopresti (EL)... (Review)
Review
PURPOSE
The aim of this study was to systematically review clinical studies on the employed definitions of longitudinal forearm instabilities referred to as Essex-Lopresti (EL) injuries, interosseous membrane (IOM) injuries or longitudinal radioulnar dissociation.
METHODS
A systematic literature search was performed in MEDLINE, Embase, CINAHL, Web of Science and Cochrane databases, adhering to PRISMA guidelines. All data on diagnosis and treatment were collected.
RESULTS
In total, 47 clinical studies involving 266 patients were included. Thirty-nine of 47 studies did not mention an IOM lesion as part of the EL injury. The amount of preoperative positive ulnar variance varied from >1 to >12 mm. Nine studies used some form of dynamic pre-operative or intraoperative test of longitudinal radioulnar instability.
CONCLUSIONS
There is no accepted definition of EL injury in the literature. In order to prevent underdetection of acute EL injury, a radial head fracture in a patient with wrist and/or forearm pain should raise awareness of the possibility of an EL injury. In this case, comparative radiographic studies and some form of dynamic assessment of longitudinal radioulnar stability should be performed.
PubMed: 36287106
DOI: 10.1530/EOR-22-0066 -
The Lancet. Respiratory Medicine Mar 2023Venovenous extracorporeal membrane oxygenation (ECMO) can be considered for patients with COVID-19-associated acute respiratory distress syndrome (ARDS) who continue to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Venovenous extracorporeal membrane oxygenation (ECMO) can be considered for patients with COVID-19-associated acute respiratory distress syndrome (ARDS) who continue to deteriorate despite evidence-based therapies and lung-protective ventilation. The Extracorporeal Life Support Organization has emphasised the importance of patient selection; however, to better inform these decisions, a comprehensive and evidence-based understanding of the risk factors associated with poor outcomes is necessary. We aimed to summarise the association between pre-cannulation prognostic factors and risk of mortality in adult patients requiring venovenous ECMO for the treatment of COVID-19.
METHODS
In this systematic review and meta-analysis, we searched MEDLINE and Embase from Dec 1, 2019, to April 14, 2022, for randomised controlled trials and observational studies involving adult patients who required ECMO for COVID-19-associated ARDS and for whom pre-cannulation prognostic factors associated with in-hospital mortality were evaluated. We conducted separate meta-analyses of unadjusted and adjusted odds ratios (uORs), adjusted hazard ratios (aHRs), and mean differences, and excluded studies if these data could not be extracted. We assessed the risk of bias using the Quality in Prognosis Studies tool and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Our protocol was registered with the Open Science Framework registry, osf.io/6gcy2.
FINDINGS
Our search identified 2888 studies, of which 42 observational cohort studies involving 17 449 patients were included. Factors that had moderate or high certainty of association with increased mortality included patient factors, such as older age (adjusted hazard ratio [aHR] 2·27 [95% CI 1·63-3·16]), male sex (unadjusted odds ratio [uOR] 1·34 [1·20-1·49]), and chronic lung disease (aHR 1·55 [1·20-2·00]); pre-cannulation disease factors, such as longer duration of symptoms (mean difference 1·51 days [95% CI 0·36-2·65]), longer duration of invasive mechanical ventilation (uOR 1·94 [1·40-2·67]), higher partial pressure of arterial carbon dioxide (mean difference 4·04 mm Hg [1·64-6·44]), and higher driving pressure (aHR 2·36 [1·40-3·97]); and centre factors, such as less previous experience with ECMO (aOR 2·27 [1·28-4·05].
INTERPRETATION
The prognostic factors identified highlight the importance of patient selection, the effect of injurious lung ventilation, and the potential opportunity for greater centralisation and collaboration in the use of ECMO for the treatment of COVID-19-associated ARDS. These factors should be carefully considered as part of a risk stratification framework when evaluating a patient for potential treatment with venovenous ECMO.
FUNDING
None.
Topics: Adult; Humans; Male; COVID-19; Extracorporeal Membrane Oxygenation; Prognosis; Respiratory Distress Syndrome; Respiration, Artificial; Observational Studies as Topic
PubMed: 36228638
DOI: 10.1016/S2213-2600(22)00296-X -
Antibiotics (Basel, Switzerland) Aug 2022The challenging severity of some infections, especially in critically ill patients, makes the diffusion of antimicrobial drugs within tissues one of the cornerstones of... (Review)
Review
The challenging severity of some infections, especially in critically ill patients, makes the diffusion of antimicrobial drugs within tissues one of the cornerstones of chemotherapy. The knowledge of how antibacterial agents penetrate tissues may come from different sources: preclinical studies in animal models, phase I-III clinical trials and post-registration studies. However, the particular physiopathology of critically ill patients may significantly alter drug pharmacokinetics. Indeed, changes in interstitial volumes (the ) and/or in glomerular filtration ratio may influence the achievement of bactericidal concentrations in peripheral compartments, while inflammation can alter the systemic distribution of some drugs. On the contrary, other antibacterial agents may reach high and effective concentrations thanks to the increased tissue accumulation of macrophages and neutrophils. Therefore, the present review explores the tissue distribution of beta-lactams and other antimicrobials acting on the cell wall and cytoplasmic membrane of bacteria in critically ill patients. A systematic search of articles was performed according to PRISMA guidelines, and tissue/plasma penetration ratios were collected. Results showed a highly variable passage of drugs within tissues, while large interindividual variability may represent a hurdle which must be overcome to achieve therapeutic concentrations in some compartments. To solve that issue, off-label dosing regimens could represent an effective solution in particular conditions.
PubMed: 36139944
DOI: 10.3390/antibiotics11091164 -
Journal of Clinical Medicine Jul 2022Despite an increase in the use of mechanical circulatory support (MCS) devices for acute myocardial infarction cardiogenic shock (AMI-CS), there is currently no...
OBJECTIVES
Despite an increase in the use of mechanical circulatory support (MCS) devices for acute myocardial infarction cardiogenic shock (AMI-CS), there is currently no randomised data directly comparing the use of Impella and veno-arterial extra-corporeal membrane oxygenation (VA-ECMO).
METHODS
Electronic databases of MEDLINE, EMBASE and CENTRAL were systematically searched in November 2021. Studies directly comparing the use of Impella (CP, 2.5 or 5.0) with VA-ECMO for AMI-CS were included. Studies examining other modalities of MCS, or other causes of cardiogenic shock, were excluded. The primary outcome was in-hospital mortality.
RESULTS
No randomised trials comparing VA-ECMO to Impella in patients with AMI-CS were identified. Six cohort studies (five retrospective and one prospective) were included for systematic review. All studies, including 7093 patients, were included in meta-analysis. Five studies reported in-hospital mortality, which, when pooled, was 42.4% in the Impella group versus 50.1% in the VA-ECMO group. Impella support for AMI-CS was associated with an 11% relative risk reduction in in-hospital mortality compared to VA-ECMO (risk ratio 0.89; 95% CI 0.83-0.96, I 0%). Of the six studies, three studies also adjusted outcome measures via propensity-score matching with reported reductions in in-hospital mortality with Impella compared to VA-ECMO (risk ratio 0.72; 95% CI 0.59-0.86, I 35%). Pooled analysis of five studies with 6- or 12-month mortality data reported a 14% risk reduction with Impella over the medium-to-long-term (risk ratio 0.86; 95% CI 0.76-0.97, I 0%).
CONCLUSIONS
There is no high-level evidence comparing VA-ECMO and Impella in AMI-CS. In available observation studies, MCS with Impella was associated with a reduced risk of in-hospital and medium-term mortality as compared to VA-ECMO.
PubMed: 35887718
DOI: 10.3390/jcm11143955 -
The Cochrane Database of Systematic... Jul 2022Idiopathic sudden sensorineural hearing loss (ISSNHL) is common, and defined as a sudden decrease in sensorineural hearing sensitivity of unknown aetiology. Systemic... (Review)
Review
BACKGROUND
Idiopathic sudden sensorineural hearing loss (ISSNHL) is common, and defined as a sudden decrease in sensorineural hearing sensitivity of unknown aetiology. Systemic corticosteroids are widely used, however their value remains unclear. Intratympanic injections of corticosteroids have become increasingly common in the treatment of ISSNHL.
OBJECTIVES
To assess the effects of intratympanic corticosteroids in people with ISSNHL.
SEARCH METHODS
The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; CENTRAL (2021, Issue 9); PubMed; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials (search date 23 September 2021).
SELECTION CRITERIA
We included randomised controlled trials (RCTs) involving people with ISSNHL and follow-up of over a week. Intratympanic corticosteroids were given as primary or secondary treatment (after failure of systemic therapy).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods, including GRADE to assess the certainty of the evidence. Our primary outcome was change in hearing threshold with pure tone audiometry. Secondary outcomes included the proportion of people whose hearing improved, final hearing threshold, speech audiometry, frequency-specific hearing changes and adverse effects.
MAIN RESULTS
We included 30 studies, comprising 2133 analysed participants. Some studies had more than two treatment arms and were therefore relevant to several comparisons. Studies investigated intratympanic corticosteroids as either primary (initial) therapy or secondary (rescue) therapy after failure of initial treatment. 1. Intratympanic corticosteroids versus systemic corticosteroids as primary therapy We identified 16 studies (1108 participants). Intratympanic therapy may result in little to no improvement in the change in hearing threshold (mean difference (MD) -5.93 dB better, 95% confidence interval (CI) -7.61 to -4.26; 10 studies; 701 participants; low-certainty). We found little to no difference in the proportion of participants whose hearing was improved (risk ratio (RR) 1.04, 95% CI 0.97 to 1.12; 14 studies; 972 participants; moderate-certainty). Intratympanic therapy may result in little to no difference in the final hearing threshold (MD -3.31 dB, 95% CI -6.16 to -0.47; 7 studies; 516 participants; low-certainty). Intratympanic therapy may increase the number of people who experience vertigo or dizziness (RR 2.53, 95% CI 1.41 to 4.54; 1 study; 250 participants; low-certainty) and probably increases the number of people with ear pain (RR 15.68, 95% CI 6.22 to 39.49; 2 studies; 289 participants; moderate-certainty). It also resulted in persistent tympanic membrane perforation (range 0% to 3.9%; 3 studies; 359 participants; very low-certainty), vertigo/dizziness at the time of injection (1% to 21%, 3 studies; 197 participants; very low-certainty) and ear pain at the time of injection (10.5% to 27.1%; 2 studies; 289 participants; low-certainty). 2. Intratympanic plus systemic corticosteroids (combined therapy) versus systemic corticosteroids alone as primary therapy We identified 10 studies (788 participants). Combined therapy may have a small effect on the change in hearing threshold (MD -8.55 dB better, 95% CI -12.48 to -4.61; 6 studies; 435 participants; low-certainty). The evidence is very uncertain as to whether combined therapy changes the proportion of participants whose hearing is improved (RR 1.27, 95% CI 1.15 to 1.41; 10 studies; 788 participants; very low-certainty). Combined therapy may result in slightly lower (more favourable) final hearing thresholds but the evidence is very uncertain, and it is not clear whether the change would be important to patients (MD -9.11 dB, 95% CI -16.56 to -1.67; 3 studies; 194 participants; very low-certainty). Some adverse effects only occurred in those who received combined therapy. These included persistent tympanic membrane perforation (range 0% to 5.5%; 5 studies; 474 participants; very low-certainty), vertigo or dizziness at the time of injection (range 0% to 8.1%; 4 studies; 341 participants; very low-certainty) and ear pain at the time of injection (13.5%; 1 study; 73 participants; very low-certainty). 3. Intratympanic corticosteroids versus no treatment or placebo as secondary therapy We identified seven studies (279 participants). Intratympanic therapy may have a small effect on the change in hearing threshold (MD -9.07 dB better, 95% CI -11.47 to -6.66; 7 studies; 280 participants; low-certainty). Intratympanic therapy may result in a much higher proportion of participants whose hearing is improved (RR 5.55, 95% CI 2.89 to 10.68; 6 studies; 232 participants; low-certainty). Intratympanic therapy may result in lower (more favourable) final hearing thresholds (MD -11.09 dB, 95% CI -17.46 to -4.72; 5 studies; 203 participants; low-certainty). Some adverse effects only occurred in those who received intratympanic injection. These included persistent tympanic membrane perforation (range 0% to 4.2%; 5 studies; 185 participants; very low-certainty), vertigo or dizziness at the time of injection (range 6.7% to 33%; 3 studies; 128 participants; very low-certainty) and ear pain at the time of injection (0%; 1 study; 44 participants; very low-certainty). 4. Intratympanic plus systemic corticosteroids (combined therapy) versus systemic corticosteroids alone as secondary therapy We identified one study with 76 participants. Change in hearing threshold was not reported. Combined therapy may result in a higher proportion with hearing improvement, but the evidence is very uncertain (RR 2.24, 95% CI 1.10 to 4.55; very low-certainty). Adverse effects were poorly reported with only data for persistent tympanic membrane perforation (rate 8.1%, very low-certainty).
AUTHORS' CONCLUSIONS
Most of the evidence in this review is low- or very low-certainty, therefore it is likely that further studies may change our conclusions. For primary therapy, intratympanic corticosteroids may have little or no effect compared with systemic corticosteroids. There may be a slight benefit from combined treatment when compared with systemic treatment alone, but the evidence is uncertain. For secondary therapy, there is low-certainty evidence that intratympanic corticosteroids, when compared to no treatment or placebo, may result in a much higher proportion of participants whose hearing is improved, but may only have a small effect on the change in hearing threshold. It is very uncertain whether there is additional benefit from combined treatment over systemic steroids alone. Although adverse effects were poorly reported, the different risk profiles of intratympanic treatment (including tympanic membrane perforation, pain and dizziness/vertigo) and systemic treatment (for example, blood glucose problems) should be considered when selecting appropriate treatment.
Topics: Adrenal Cortex Hormones; Dizziness; Hearing Loss, Sensorineural; Humans; Pain; Tympanic Membrane Perforation; Vertigo
PubMed: 35867413
DOI: 10.1002/14651858.CD008080.pub2 -
Frontiers in Plant Science 2022Vegetables are a distinct collection of plant-based foods that vary in nutritional diversity and form an important part of the healthy diet of the human being. Besides...
Vegetables are a distinct collection of plant-based foods that vary in nutritional diversity and form an important part of the healthy diet of the human being. Besides providing basic nutrition, they have great potential for boosting human health. The balanced consumption of vegetables is highly recommended for supplementing the human body with better nutrition density, dietary fiber, minerals, vitamins, and bioactive compounds. However, the production and quality of fresh vegetables are influenced directly or indirectly by exposure to high temperatures or heat stress (HS). A decline in quality traits and harvestable yield are the most common effects of HS among vegetable crops. Heat-induced morphological damage, such as poor vegetative growth, leaf tip burning, and rib discoloration in leafy vegetables and sunburn, decreased fruit size, fruit/pod abortion, and unfilled fruit/pods in beans, are common, often rendering vegetable cultivation unprofitable. Further studies to trace down the possible physiological and biochemical effects associated with crop failure reveal that the key factors include membrane damage, photosynthetic inhibition, oxidative stress, and damage to reproductive tissues, which may be the key factors governing heat-induced crop failure. The reproductive stage of plants has extensively been studied for HS-induced abnormalities. Plant reproduction is more sensitive to HS than the vegetative stages, and affects various reproductive processes like pollen germination, pollen load, pollen tube growth, stigma receptivity, ovule fertility and, seed filling, resulting in poorer yields. Hence, sound and robust adaptation and mitigation strategies are needed to overcome the adverse impacts of HS at the morphological, physiological, and biochemical levels to ensure the productivity and quality of vegetable crops. Physiological traits such as the stay-green trait, canopy temperature depression, cell membrane thermostability, chlorophyll fluorescence, relative water content, increased reproductive fertility, fruit numbers, and fruit size are important for developing better yielding heat-tolerant varieties/cultivars. Moreover, various molecular approaches such as omics, molecular breeding, and transgenics, have been proved to be useful in enhancing/incorporating tolerance and can be potential tools for developing heat-tolerant varieties/cultivars. Further, these approaches will provide insights into the physiological and molecular mechanisms that govern thermotolerance and pave the way for engineering "designer" vegetable crops for better health and nutritional security. Besides these approaches, agronomic methods are also important for adaptation, escape and mitigation of HS protect and improve yields.
PubMed: 35837452
DOI: 10.3389/fpls.2022.878498 -
Cureus May 2022Resorbable collagen has been utilized to treat wounds, close graft, and tooth extraction sites, and enhance recovery. Collagen-based membranes are also used as barriers... (Review)
Review
Resorbable collagen has been utilized to treat wounds, close graft, and tooth extraction sites, and enhance recovery. Collagen-based membranes are also used as barriers in periodontal and implant therapy to limit epithelial migration and allow cells with the regenerative capacity to fill the problem area. This systematic review was carried out to analyze the studies focusing on collagen structure, synthesis, and its applications. A detailed and extensive search was performed with the help of the keywords "collagen structure", "collagen synthesis" and "collagen applications". There was extensive literature search in reliable and authentic databases like PubMed, Scopus, Web of Sciences, Ovidsp, and Cochrane library to obtain papers focusing on collagen structure, synthesis, and applications. During the systematic review, data were obtained concerning the following parameters. Type of study, nature of aim of the study, size of the sample in the study, gender and age of the subjects included in the study, prevalence of skin diseases where collagen was used for treatment, dose of collagen used, form in which collagen was used, the origin of collagen used, analysis of different variables, structure, and synthesis of collagen. Twenty-two studies were included in this systematic review. The studies discussed the structure, synthesis, and applications of collagen in treatment. In studies focusing on the application of collagen supplements, most of the study subjects were females (68.3%). The study subjects included both healthy and unhealthy subjects. The study subjects were divided into two categories. One category was the intervention group, while another group was the placebo group. Collagen was administered in hydrolysate form (90%) in some studies, bovine form (2.3%), and porcine form (3.4%) in other studies. Collagen supplementation was found to provide better results in both healthy and unhealthy effects in improving the health of skin, cornea, bone, periodontium, face, etc. It can be concluded that collagen is an integral part of the body. The application of collagen supplements can be pretty effective in maintaining the proper health of several important structures of the body like skin, face, cornea, nails, periodontium, etc. Thus, a detailed study of the molecular structure of collagen and genes associated with each type of collagen is essential for further research and treatment of collagen-associated disorders.
PubMed: 35702467
DOI: 10.7759/cureus.24856