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Journal of Diabetes Research 2020Recombinant proteins and growth factors are emerging therapies for diabetic foot ulcers. Despite several clinical reports, there has been no comprehensive and systematic...
BACKGROUND
Recombinant proteins and growth factors are emerging therapies for diabetic foot ulcers. Despite several clinical reports, there has been no comprehensive and systematic assessment of the totality of clinical evidence on the efficacy and safety of recombinant proteins and growth factors in diabetic foot ulcers. We tried to address this gap through an updated systematic review of randomized controlled trials (RCTs).
METHODS
PubMed, the Cochrane Library, Scopus, Embase, and Google Scholar databases were searched, and RCTs on the efficacy of recombinant proteins and growth factors in the treatment of cutaneous wounds in diabetic patients were selected. The literature search and assessment were performed by two independent reviewers. Methodological quality of studies was appraised using the Jadad scale.
RESULTS
We identified 26 RCTs involving diabetic patients with ulcer that evaluated the effectiveness of platelet-derived growth factor, epidermal growth factor, fibroblast growth factor, granulocyte colony-stimulating factor, vascular endothelial growth factor, erythropoietin, transforming growth factor, talactoferrin, and rusalatide acetate. The main primary outcome was complete healing though different indices were employed to define this such as wound closure, granulation tissue formation, or complete reepithelialization. Few studies had a follow-up period to report any recurrence and amputation rate. No adverse effect was reported due to the intervention.
CONCLUSION
Overall, there is a greater agreement on the effectiveness of EGF to enhance the healing of diabetic ulcers. Nevertheless, extant evidence is lacking for other agents since few trials have been conducted for most of the growth factors and available studies are heterogeneous in their methodologies.
Topics: Diabetic Foot; Disease Management; Humans; Intercellular Signaling Peptides and Proteins; Randomized Controlled Trials as Topic; Recombinant Proteins; Wound Healing
PubMed: 32733969
DOI: 10.1155/2020/6320514 -
The Cochrane Database of Systematic... Jul 2020Burn injuries are an important health problem. They occur frequently in the head and neck region. The face is the area central to a person's identity that provides our...
BACKGROUND
Burn injuries are an important health problem. They occur frequently in the head and neck region. The face is the area central to a person's identity that provides our most expressive means of communication. Topical interventions are currently the cornerstone of treatment of burns to the face.
OBJECTIVES
To assess the effects of topical interventions on wound healing in people with facial burns of any depth.
SEARCH METHODS
In December 2019 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that evaluated the effects of topical treatment for facial burns were eligible for inclusion in this review.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection, data extraction, risk of bias assessment and GRADE assessment of the certainty of the evidence.
MAIN RESULTS
In this first update, we included 12 RCTs, comprising 507 participants. Most trials included adults admitted to specialised burn centres after recent burn injuries. Topical agents included antimicrobial agents (silver sulphadiazine (SSD), Aquacel-Ag, cerium-sulphadiazine, gentamicin cream, mafenide acetate cream, bacitracin), non-antimicrobial agents (Moist Exposed Burn Ointment (MEBO), saline-soaked dressings, skin substitutes (including bioengineered skin substitute (TransCyte), allograft, and xenograft (porcine Xenoderm), and miscellaneous treatments (growth hormone therapy, recombinant human granulocyte-macrophage colony-stimulating factor hydrogel (rhGMCS)), enzymatic debridement, and cream with Helix Aspersa extract). Almost all the evidence included in this review was assessed as low or very low-certainty, often because of high risk of bias due to unclear randomisation procedures (i.e. sequence generation and allocation concealment); lack of blinding of participants, providers and sometimes outcome assessors; and imprecision resulting from few participants, low event rates or both, often in single studies. Topical antimicrobial agents versus topical non-antimicrobial agents There is moderate-certainty evidence that there is probably little or no difference between antimicrobial agents and non-antimicrobial agents (SSD and MEBO) in time to complete wound healing (hazard ratio (HR) 0.84 (95% confidence interval (CI) 0.78 to 1.85, 1 study, 39 participants). Topical antimicrobial agents may make little or no difference to the proportion of wounds completely healed compared with topical non-antimicrobial agents (comparison SSD and MEBO, risk ratio (RR) 0.94, 95% CI 0.68 to 1.29; 1 study, 39 participants; low-certainty evidence). We are uncertain whether there is a difference in wound infection (comparison topical antimicrobial agent (Aquacel-Ag) and MEBO; RR 0.38, 95% CI 0.12 to 1.21; 1 study, 40 participants; very low-certainty evidence). No trials reported change in wound surface area over time or partial wound healing. There is low-certainty evidence for the secondary outcomes scar quality and patient satisfaction. Two studies assessed pain but it was incompletely reported. Topical antimicrobial agents versus other topical antimicrobial agents It is uncertain whether topical antimicrobial agents make any difference in effects as the evidence is low to very low-certainty. For primary outcomes, there is low-certainty evidence for time to partial (i.e. greater than 90%) wound healing (comparison SSD versus cerium SSD: mean difference (MD) -7.10 days, 95% CI -16.43 to 2.23; 1 study, 142 participants). There is very low-certainty evidence regarding whether topical antimicrobial agents make a difference to wound infection (RR 0.73, 95% CI 0.46 to 1.17; 1 study, 15 participants). There is low to very low-certainty evidence for the proportion of facial burns requiring surgery, pain, scar quality, adverse effects and length of hospital stay. Skin substitutes versus topical antimicrobial agents There is low-certainty evidence that a skin substitute may slightly reduce time to partial (i.e. greater than 90%) wound healing, compared with a non-specified antibacterial agent (MD -6.00 days, 95% CI -8.69 to -3.31; 1 study, 34 participants). We are uncertain whether skin substitutes in general make any other difference in effects as the evidence is very low certainty. Outcomes included wound infection, pain, scar quality, adverse effects of treatment and length of hospital stay. Single studies showed contrasting low-certainty evidence. A bioengineered skin substitute may slightly reduce procedural pain (MD -4.00, 95% CI -5.05 to -2.95; 34 participants) and background pain (MD -2.00, 95% CI -3.05 to -0.95; 34 participants) compared with an unspecified antimicrobial agent. In contrast, a biological dressing (porcine Xenoderm) might slightly increase pain in superficial burns (MD 1.20, 95% CI 0.65 to 1.75; 15 participants (30 wounds)) as well as deep partial thickness burns (MD 3.00, 95% CI 2.34 to 3.66; 10 participants (20 wounds)), compared with antimicrobial agents (Physiotulle Ag (Coloplast)). Miscellaneous treatments versus miscellaneous treatments Single studies show low to very low-certainty effects of interventions. Low-certainty evidence shows that MEBO may slightly reduce time to complete wound healing compared with saline soaked dressing (MD -1.7 days, 95% CI -3.32 to -0.08; 40 participants). In addition, a cream containing Helix Aspersa may slightly increase the proportion of wounds completely healed at 14 days compared with MEBO (RR 4.77, 95% CI 1.87 to 12.15; 43 participants). We are uncertain whether any miscellaneous treatment in the included studies makes a difference in effects for the outcomes wound infection, scar quality, pain and patient satisfaction as the evidence is low to very low-certainty.
AUTHORS' CONCLUSIONS
There is mainly low to very low-certainty evidence on the effects of any topical intervention on wound healing in people with facial burns. The number of RCTs in burn care is growing, but the body of evidence is still hampered due to an insufficient number of studies that follow appropriate evidence-based standards of conducting and reporting RCTs.
Topics: Administration, Topical; Anti-Infective Agents; Bias; Burns; Carboxymethylcellulose Sodium; Facial Injuries; Humans; Randomized Controlled Trials as Topic; Skin, Artificial; Wound Healing
PubMed: 32725896
DOI: 10.1002/14651858.CD008058.pub3 -
JDR Clinical and Translational Research Apr 2021The use of recombinant human platelet-derived growth factor-BB (rhPDGF) has received Food and Drug Administration approval for the treatment of periodontal and...
AIM
The use of recombinant human platelet-derived growth factor-BB (rhPDGF) has received Food and Drug Administration approval for the treatment of periodontal and orthopedic bone defects and dermal wound healing. Many studies have investigated its regenerative potential in a variety of other oral clinical indications. The aim of this systematic review was to assess the efficacy, safety, and clinical benefit of recombinant human platelet-derived growth factor (rhPDGF) use for alveolar bone and/or soft tissue regeneration.
MATERIAL AND METHODS
Comprehensive electronic and manual literature searches according to the PRISMA guidelines were performed to identify interventional and observational studies evaluating the regenerative applications of rhPDGF-BB. The primary outcomes were the safety, efficacy, and overall clinical benefit of rhPDGF use in oral regenerative procedures.
RESULTS
Sixty-three human clinical studies (mean ± SD follow-up period of 10.7 ± 3.3 mo) were included in the qualitative analysis. No serious adverse effects were reported in any of the 63 studies, aside from the postoperative complications routinely associated with surgical therapy. Use of rhPDGF was shown to be beneficial when combined with allografts, xenografts, and alloplasts (the latter tricalcium phosphate [β-TCP]) for the treatment of periodontal defects and gingival recession. The use of rhPDGF also led to favorable clinical outcomes when combined with allografts or xenografts for guided bone regeneration (GBR) and alveolar ridge preservation. While favorable clinical results support the use of the combination of rhPDGF plus allograft or xenograft for GBR, ARP, and sinus floor augmentation, current data support the use of rhPDGF and alloplasts (e.g., β-TCP) only in periodontal defects and gingival recession.
CONCLUSIONS
Based on the clinical evidence, rhPDGF is safe and provides clinical benefits when used in combination with bone allografts, xenograft, or β-TCP for the treatment of intrabony and furcation periodontal defects and gingival recession or when used with allografts or xenograft for GBR and ARP (PROSPERO CRD42020142446).
KNOWLEDGE TRANSFER STATEMENT
Clinicians should be aware that rhPDGF is a safe and effective approach for the treatment of intrabony and furcation periodontal defects and gingival recession or when used with allografts or xenograft for bone regeneration and alveolar ridge preservation. With consideration of cost and patient preference, this result could lead to more appropriate therapeutic decisions.
Topics: Alveolar Bone Loss; Becaplermin; Humans; Proto-Oncogene Proteins c-sis; Recombinant Proteins; Sinus Floor Augmentation; United States
PubMed: 32392438
DOI: 10.1177/2380084420921353 -
Prostate Cancer and Prostatic Diseases Dec 2020A great number of DNA-damage repair (DDR) pathways have been recognized to be frequently dysregulated in advanced stages of prostate cancer. DNA-repair defects in...
BACKGROUND
A great number of DNA-damage repair (DDR) pathways have been recognized to be frequently dysregulated in advanced stages of prostate cancer. DNA-repair defects in prostate cancer represents a clinically relevant disease subset. Tumors whose ability to repair double-strand DNA breaks by homologous recombination is compromised, are highly sensitive to blockade of the repair of DNA single-strand breaks via the inhibition of the enzyme poly(ADP) ribose polymerase (PARP).
METHODS
A systematic review of the literature has been conducted in January 2020 using PubMed Medline database in line with the recommendations from the PRISMA guidelines. The following string terms were used for searching clinical trial articles: castration resistant OR castrate resistance OR castration refractory AND prostate cancer AND PARP OR poly(ADP-ribose) polymerase inhibitor OR DNA-repair OR homologous recombination repair. On-going clinical trials with olaparib, niraparib, talazoparib, veliparib, and rucaparib in mCRPC were searched on the clinicalTrials.gov website.
RESULTS
From this research 176 articles were identified. After title screening and abstract reading, five papers and four abstract were considered for the systematic review. Thirty-two clinical trials were also identified: from these 16 trials which did not include mCRPC patients or only prostate cancer patients, trials not yet recruiting and trials including radio-metabolic treatments were excluded. Sixteen trials were included and discussed in the paper.
CONCLUSIONS
Olaparib has been the first agent showing a benefit in terms of rPFS and ORR alone or in combination with abiraterone plus prednisone in patients with DDR deficiency prostate cancer. Also rucaparib showed a benefit in terms of PSA response rate and ORR in patients with BRCA2 and BRCA1 mutation in a phase-II study. Other phase-III clinical trials are evaluating niraparib and talazoparib, alone or in combination with AR signaling inhibitors.
Topics: BRCA1 Protein; BRCA2 Protein; Clinical Trials as Topic; Humans; Male; Mutation; Neoplasm Metastasis; Poly(ADP-ribose) Polymerase Inhibitors; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Survival Rate; Treatment Outcome
PubMed: 32367009
DOI: 10.1038/s41391-020-0233-3 -
The Cochrane Database of Systematic... May 2020Several agents are used to clear secretions from the airways of people with cystic fibrosis. Mannitol increases mucociliary clearance, but its exact mechanism of action... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several agents are used to clear secretions from the airways of people with cystic fibrosis. Mannitol increases mucociliary clearance, but its exact mechanism of action is unknown. The dry powder formulation of mannitol may be more convenient and easier to use compared with established agents which require delivery via a nebuliser. Phase III trials of inhaled dry powder mannitol for the treatment of cystic fibrosis have been completed and it is now available in Australia and some countries in Europe. This is an update of a previous review.
OBJECTIVES
To assess whether inhaled dry powder mannitol is well tolerated, whether it improves the quality of life and respiratory function in people with cystic fibrosis and which adverse events are associated with the treatment.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic databases, handsearching relevant journals and abstracts from conferences. Date of last search: 12 December 2019.
SELECTION CRITERIA
All randomised controlled studies comparing mannitol with placebo, active inhaled comparators (for example, hypertonic saline or dornase alfa) or with no treatment.
DATA COLLECTION AND ANALYSIS
Authors independently assessed studies for inclusion, carried out data extraction and assessed the risk of bias in included studies. The quality of the evidence was assessed using GRADE.
MAIN RESULTS
Six studies (reported in 36 unique publications) were included with a total of 784 participants. Duration of treatment in the included studies ranged from 12 days to six months, with open-label treatment for an additional six months in two of the studies. Five studies compared mannitol with control (a very low dose of mannitol or non-respirable mannitol) and the final study compared mannitol to dornase alfa alone and to mannitol plus dornase alfa. Two large studies had a similar parallel design and provided data for 600 participants, which could be pooled where data for a particular outcome and time point were available. The remaining studies had much smaller sample sizes (ranging from 22 to 95) and data could not be pooled due to differences in design, interventions and population. Pooled evidence from the two large parallel studies was judged to be of low to moderate quality and from the smaller studies was judged to be of low to very low quality. In all studies, there was an initial test to see if participants tolerated mannitol, with only those who could tolerate the drug being randomised; therefore, the study results are not applicable to the cystic fibrosis population as a whole. While the published papers did not provide all the data required for our analysis, additional unpublished data were provided by the drug's manufacturer and the author of one of the studies. Pooling the large parallel studies comparing mannitol to control, up to and including six months, lung function (forced expiratory volume at one second) measured in both mL and % predicted was significantly improved in the mannitol group compared to the control group (moderate-quality evidence). Beneficial results were observed in these studies in adults and in both concomitant dornase alfa users and non-users in these studies. In the smaller studies, statistically significant improvements in lung function were also observed in the mannitol groups compared to the non-respirable mannitol groups; however, we judged this evidence to be of low to very low quality. For the comparisons of mannitol and control, we found no consistent differences in health-related quality of life in any of the domains except for burden of treatment, which was less for mannitol up to four months in the two pooled studies of a similar design; this difference was not maintained at six months. It should be noted that the tool used to measure health-related quality of life was not designed to assess mucolytics and pooling of the age-appropriate tools (as done in some of the included studies) may not be valid so results were judged to be low to very low quality and should be interpreted with caution. Cough, haemoptysis, bronchospasm, pharyngolaryngeal pain and post-tussive vomiting were the most commonly reported side effects in both treatment groups. Where rates of adverse events could be compared, statistically no significant differences were found between mannitol and control groups; although some of these events may have clinical relevance for people with CF. For the comparisons of mannitol to dornase alfa alone and to mannitol plus dornase alfa, very low-quality evidence from a 12-week cross-over study of 28 participants showed no statistically significant differences in the recorded domains of health-related quality of life or measures of lung function. Cough was the most common side effect in the mannitol alone arm but there was no occurrence of cough in the dornase alfa alone arm and the most commonly reported reason of withdrawal from the mannitol plus dornase alfa arm was pulmonary exacerbations. In terms of secondary outcomes of the review (pulmonary exacerbations, hospitalisations, symptoms, sputum microbiology), evidence provided by the included studies was more limited. For all comparisons, no consistent statistically significant and clinically meaningful differences were observed between mannitol and control treatments (including dornase alfa).
AUTHORS' CONCLUSIONS
There is moderate-quality evidence to show that treatment with mannitol over a six-month period is associated with an improvement in some measures of lung function in people with cystic fibrosis compared to control. There is low to very low-quality evidence suggesting no difference in quality of life for participants taking mannitol compared to control. This review provides very low-quality evidence suggesting no difference in lung function or quality of life comparing mannitol to dornase alfa alone and to mannitol plus dornase alfa. The clinical implications from this review suggest that mannitol could be considered as a treatment in cystic fibrosis; but further research is required in order to establish who may benefit most and whether this benefit is sustained in the longer term. Furthermore, studies comparing its efficacy against other (established) mucolytic therapies need to be undertaken before it can be considered for mainstream practice.
Topics: Administration, Inhalation; Adult; Child; Cystic Fibrosis; Deoxyribonuclease I; Forced Expiratory Volume; Humans; Mannitol; Mucociliary Clearance; Powders; Randomized Controlled Trials as Topic; Recombinant Proteins; Respiratory Function Tests; Vital Capacity
PubMed: 32358807
DOI: 10.1002/14651858.CD008649.pub4 -
International Wound Journal Aug 2020To evaluate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) in treating diabetic foot ulcers (DFUs), we conducted both database searches... (Meta-Analysis)
Meta-Analysis
To evaluate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) in treating diabetic foot ulcers (DFUs), we conducted both database searches (PubMed, MEDLINE, EMBASE, CENTRAL, and Web of Science) and reference searches for randomised controlled trials from the inception of databases to 30 January 2020. Two reviewers independently scrutinised the trials, extracted data, and assessed the quality of trials. The primary outcome was the proportion of complete healing. The secondary outcomes were mean time to complete healing and adverse events. A subgroup analysis was performed by different administration routes. Statistical analyses were performed in RevMan 5.3. The time to complete healing Kaplan-Meier curves was pooled in the R software. Of the 156 citations, 9 trials (720 participants) met eligibility criteria and were included. The rhEGF achieved a higher complete healing rate than placebo (OR: 2.79, [95% CI: 1.99, 3.99]). The rhEGF also significantly shorten complete healing time (MD: -14.10 days, [95% CI: -18.03, -10.16]). Subgroup analysis showed that topical application was superior to intralesional injection, but that may be because of different ulcer severity they included. No significant difference was shown in adverse events. Results were coherent with sensitivity analyses. Therefore, rhEGF is an effective and safe treatment for DFUs.
Topics: Adult; Aged; Aged, 80 and over; Diabetes Mellitus; Diabetic Foot; Epidermal Growth Factor; Female; Humans; Injections, Intralesional; Male; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome; Wound Healing
PubMed: 32343054
DOI: 10.1111/iwj.13377 -
BMJ Military Health Oct 2020It is uncertain whether treatment by recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) can promote healing of deep second-degree burns. This... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
It is uncertain whether treatment by recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) can promote healing of deep second-degree burns. This meta-analysis aimed to systematically review and assess randomised controlled trials (RCTs) that investigated the efficacy and safety of rhGM-CSF for treating deep second-degree burns.
METHODS
This meta-analysis conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. The PubMed, Cochrane Library, Medline and Embase databases and relevant references were systematically searched for RCTs (published up to November 2019). Main outcome measures included the wound healing rate, wound healing time and average optical densities of the vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). We performed a meta-analysis using fixed or random effects models.
RESULTS
Seven RCTs comprising 982 patients with 1184 burns (652 patients received rhGM-CSF vs 532 controls) were included. Compared with standard wound care alone, the use of rhGM-CSF significantly reduced wound healing time by 4.77 days (weighted mean difference=-4.77; 95% CI -6.45 to -3.09; p<0.001) and significantly increased the wound healing rate on days 7, 10, 14 and 20 by 6.46%, 19.78%, 17.07% and 11.38%, respectively. There was no significant difference between the groups in the wound healing rate on day 28 and average optical densities of VEGF and FGF. No systematic adverse event occurred. Redder, more swollen and painful wounds were reported after using rhGM-CSF compared with the control.
CONCLUSIONS
rhGM-CSF could be effective and safe for treating deep second-degree burns.
Topics: Burns; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Recombinant Proteins; Time Factors; Wound Healing
PubMed: 32217688
DOI: 10.1136/bmjmilitary-2019-001395 -
Burns : Journal of the International... May 2021The purpose of this meta-analysis was to assess the efficacy and safety of nano-silver dressing combined with recombinant human epidermal growth factor for deep... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The purpose of this meta-analysis was to assess the efficacy and safety of nano-silver dressing combined with recombinant human epidermal growth factor for deep second-degree burns.
METHODS
PubMed, Web of Science, EMBASE, Cochrane Library and other databases were searched to identify relevant randomised controlled trials.
RESULTS
Twelve studies that assessed nano-silver dressing combined with recombinant human epidermal growth factor were identified. Nano-silver dressing combined with recombinant human epidermal growth factor for deep second-degree burns could significantly reduce the duration of wound healing (mean difference -5.68, 95% CI -7.38 - -3.99, P<0.00001), the wound healing rate (risk ratio [RR] 0.34, 95% CI 0.23-0.48, P<0.00001), the rate of scar hyperplasia (RR 0.67, 95% CI 0.54-0.84, P=0.0004), the wound bacterial positive rate (RR 0.50, 95% CI 0.28-0.89, P=0.02), and the adverse reactions rate (RR 0.31, 95% CI 0.16-0.58, P=0.0003).
CONCLUSION
This comprehensive meta-analysis of the available evidence suggest that the use of nano-silver dressing combined with recombinant human epidermal growth factor results in shorter duration of wound healing, reduced wound bacterial positive rates and adverse reactions rate, and improved wound healing rates.
Topics: Biological Dressings; Burns; Epidermal Growth Factor; Humans; Silver; Wound Healing
PubMed: 31982184
DOI: 10.1016/j.burns.2019.12.015 -
Surgical Technology International Nov 2019Given the expansion of commercial and recreational space exploration, orthopaedic surgeons will need to understand the implications of microgravity on cartilaginous...
INTRODUCTION
Given the expansion of commercial and recreational space exploration, orthopaedic surgeons will need to understand the implications of microgravity on cartilaginous damage and to anticipate the resulting pathology from accelerated chondrolysis. The purpose of this systematic review is to evaluate the effects of space and microgravity on hip and knee articular cartilage, including its impact on joint mobility and functional status.
MATERIALS AND METHODS
A review of the current literature was performed utilizing the terms "joints," "joint mobility," "articular cartilage," "knee," "hip," "space," "microgravity," and "osteoarthritis" in PubMed and Google Scholar from 1990 to 2018, yielding a total of 1,400 citations following the removal of 500 duplicates. Following screening by eligibility criteria, five reports were included.
RESULTS
Dysregulation of osteogenesis and weakened structural integrity of hip and knee cartilage were demonstrated secondary to microgravity. Adequate cartilage repair requires Earth-like conditions as signified by a statistically significant increase in serum cartilage oligomeric matrix protein concentrations in astronauts. Reduced loading led to the degradation of knee ligaments and menisci which may pose a risk for subluxation or dislocation. Murine studies demonstrated decreased articular cartilage thickness in the medial femoral condyle and patella as assessed by ultrasound. Additionally, glycosaminoglycan levels in unloaded rats were lower than weight-bearing rats, with a concomitant increase in matrix metalloproteinase-13 protein, degrading collagen. Return to weight-bearing demonstrated partial recovery of cartilaginous degeneration.
CONCLUSIONS
Space and associated microgravity conditions adversely impact articular cartilage as demonstrated in murine and human studies. The pathogenetic process occurs due to the mechanically responsive nature of cartilage, with an increase in cartilage metabolism in microgravity. There remains a marked paucity of literature regarding the gravitational force necessary for adequate cartilage survival and the impact of space-related radiation on cartilage repair. Additionally, further studies should assess pharmacologic interventions, such as recombinant human fibroblast growth factor to stimulate cartilaginous growth.
Topics: Animals; Cartilage, Articular; Humans; Knee Joint; Mice; Orthopedic Procedures; Orthopedics; Rats; Space Flight; Weightlessness
PubMed: 31687778
DOI: No ID Found -
Journal of Human Genetics Jan 2020Partner and localiser of BRCA2 forms part of a macromolecular complex with BRCA1 and BRCA2, which is critical for the repair of double-strand DNA breaks by homologous...
Partner and localiser of BRCA2 forms part of a macromolecular complex with BRCA1 and BRCA2, which is critical for the repair of double-strand DNA breaks by homologous DNA recombination. Germline loss-of-function variants in the PALB2 gene may confer an increased lifetime risk of breast, pancreatic, ovarian and other cancers. However, the complete spectrum of predicted pathogenic PALB2 variants associated with each tissue type of cancer remains unknown. A systematic review is performed with the aim of cataloguing predicted pathogenic PALB2 variants in breast, ovary and pancreas cancers. All catalogued predicted pathogenic variants are analysed to assess for overlap and mutational "hotspots" within gene exons. Our results showed that 911 (92.5%) cases were described in breast cancer patients, 49 (5.0%) cases were described in ovarian cancer patients, and 24 (2.4%) cases were described in pancreatic cancer patients. The top five most frequently reported predicted pathogenic PALB2 variants were c.509_510delGA, c.3113G > A, c.1592delT, c.172_175delTTGT, and c.1240C > T, accounting for 57.3% of all cases. Breast and pancreatic cancers share five variants while breast and ovarian cancers share 12 variants. Breast, ovarian and pancreatic cancers share eight common variants. Exons with the highest mutation rates were exons 2 (6.7%), 1 (6.3%) and 3 (5.8%). This systematic review provides a quantitative catalogue of predicted pathogenic PALB2 variants described in cancers. This comprehensive analysis of the PALB2 mutational spectrum represents a useful resource for clinicians overseeing PALB2-related cancer surveillance and provides a valuable resource for future PALB2-specific research.
Topics: BRCA1 Protein; BRCA2 Protein; Breast Neoplasms; Carcinoma, Ovarian Epithelial; Exons; Fanconi Anemia Complementation Group N Protein; Female; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Ovarian Neoplasms; Pancreatic Neoplasms
PubMed: 31619740
DOI: 10.1038/s10038-019-0680-7