Topical growth factor preparations for facial skin rejuvenation: A systematic review.

BACKGROUND: Cosmeceutical preparations containing growth factors (GFs) are widely used for facial rejuvenation. OBJECTIVE: We performed a systematic review to assess the evidence regarding their safety and effectiveness for facial rejuvenation. METHODS: Electronic databases (Cochrane Library, EMBASE, MEDLINE, and Scopus) were searched from 2000 to October 2022 for prospective trials and case series assessing topical GF preparations for facial rejuvenation in 10 or more participants. RESULTS: Thirty-three studies, including 9 randomized controlled trials (RCTs) and 24 uncontrolled case series, representing 1180 participants receiving 23 different topical preparations containing GFs met the inclusion criteria and were included. Of the 33 studies, nine used a placebo or active control. The GF preparations were applied twice daily in all except two studies, with a mean treatment duration of 3 months. Based on the investigator's assessment, preparations containing GFs induce a modest improvement in skin texture (median < 50%), fine lines/wrinkles (median < 35%), and overall facial appearance (median < 20%) versus baseline. Participant-assessed improvement was generally higher than investigator-assessed response. Three comparative RCTs showed no statistically significant differences between treatments. Studies were limited by heterogeneity with regard to the source and number of GFs used in the preparations, information about additional ingredients, and lack of standardization in the outcome measures. The preparations were associated with a low risk of adverse events. The persistence of the clinical improvements beyond 6 months is not known. CONCLUSIONS: Administration of topical preparations containing GFs appears to be effective for facial skin rejuvenation, as demonstrated by the investigator- and participant-reported outcome measures.

Topical growth factors and home-based microneedling for facial skin rejuvenation.

BACKGROUND: Cosmeceutical products are an important therapeutic option for facial rejuvenation. Of these, topical application of growth factors has been shown to increase dermal collagen synthesis, improve skin texture, and reduce fine lines and wrinkles. Limited data exist for the use of growth factors in combination with microneedling. OBJECTIVE: This prospective, single-center, uncontrolled study evaluated the efficacy of topical growth factor treatment in conjunction with transdermal delivery of growth factors via home-based microneedling for facial skin rejuvenation. PATIENTS/METHODS: Eleven healthy female individuals aged 33-61 years, with mild-moderate facial wrinkling were included in the study. Over 3 months, participants received twice-daily application of a topical recombinant human growth factor preparation (SkinGenuity® Regenerative and Reparative Serums) along with twice-weekly transdermal delivery of growth factors using a home-based microneedling (0.2 mm) device. Objective skin analysis (VISIA® ) and a subjective patient-reported outcome (FACE-Q® ) assessment measuring satisfaction with appearance were performed at baseline and after 3 months. RESULTS: Objective skin analysis showed a significant improvement in skin texture (17.6%, p < 0.001), wrinkles (17.3%, p < 0.001), red areas (12.4%, p =0.004), and brown spots (6.0%, p =0.03) at 3 months follow-up. FACE-Q scales showed a significant improvement from baseline, including satisfaction with skin, facial appearance, nasolabial folds, cheeks, and lower face/jawline (all p ≤ 0.02). Numerical improvement in adverse effects related to skin was also observed (p = 0.07). No serious adverse effects were reported. CONCLUSIONS: Three months of twice-daily topical growth factor treatment in conjunction with transdermal delivery of growth factors via microneedling improved skin analysis parameters and participant-reported outcome measures, indicative of facial skin rejuvenation.

Injectable platelet-rich fibrin for perioral rejuvenation as assessed by 3D lip volume imaging.

BACKGROUND: Various injectable autologous platelet aggregate preparations have been developed and used for facial rejuvenation. Limited evidence exists for the use of these for augmentation of the lip. OBJECTIVES: This prospective, uncontrolled, single-center study evaluated the qualitative and quantitative effects of an injectable platelet-rich fibrin preparation (known as i-PRF+) for lip augmentation. PATIENTS/METHODS: PRF® PROCESS system technology was used to prepare i-PRF+ supernatant. Ten healthy females were included in the study and received a single intradermal injection of i-PRF+ in the upper and lower lips (5 ml in each quadrant, total ~2 ml). Participants were followed for 3 months post-procedure. The efficacy of the procedure was assessed qualitatively by a subjective patient-reported outcome (FACE-Q) assessment and quantitatively by objective 3D skin surface volume analysis (ProFace® ) at baseline and after 3 months. RESULTS: FACE-Q scales that measure satisfaction with skin and lip showed a statistically significant improvement from baseline (p = 0.04 and p = 0.02, respectively). Satisfaction with lip lines showed a numerical improvement with mean total scores for adverse effect scales related to the skin and lips reduced at 2 weeks post-procedure (p = 0.03 and p = 0.13, respectively). Overall lip volume at 3-month follow-up was unchanged (p = 0.11). The treatment was well tolerated with only minor adverse effects. CONCLUSIONS: A single session of i-PRF+ injections resulted in significant lip rejuvenation at 3-month follow-up, shown by improved patient-reported outcome measure. No significant change in lip volume was observed.

Vascularity of Intra-testicular Lesions: Inter-observer Variation in the Assessment of Non-neoplastic Versus Neoplastic Abnormalities After Vascular Enhancement With Contrast-Enhanced Ultrasound.

The aim of this study is to assess the additional benefit of contrast-enhanced ultrasound (CEUS) over conventional ultrasonography (US) in identifying intra-testicular abnormalities among observers of different experiences. In this study, 91 focal testicular lesions (46 neoplastic, 45 non-neoplastic) imaged with gray-scale US/Doppler US and CEUS were classified using a 5-point scale. Three experienced and four inexperienced observers rated each lesion using gray-scale/color Doppler US alone and then with the addition of CEUS. Improved diagnostic specificity and accuracy with the addition of CEUS was observed for both experienced (specificity: 71.1% vs. 59.3%, p = 0.005; accuracy: 83.5% vs. 76.9%, p = 0.003) and inexperienced observers (specificity: 75.6% vs. 51.7%, p = 0.005; accuracy: 80.2% vs. 72.0%, p < 0.001). Significant inter-observer variability between the experienced and inexperienced observers when assessing conventional US alone was eliminated with the addition of CEUS. CEUS improves diagnostic accuracy of focal intra-testicular lesions for both experienced and inexperienced observers and reduces inter-observer variability in inexperienced operators.

Injectable platelet-rich fibrin for facial rejuvenation: A prospective, single-center study.

BACKGROUND: Autologous platelet-derived preparations have been used in many surgical fields to improve healing outcomes, with benefits reported in several aesthetic indications. AIMS: This single-center, prospective, uncontrolled study evaluated the efficacy of injectable platelet-rich fibrin (i-PRF) for facial skin rejuvenation using an objective skin analysis system and validated patient-reported outcome measures. PATIENTS/METHODS: PRF® PROCESS system technology was used to prepare i-PRP. Eleven healthy female individuals were included in the study and over 3-months received monthly intradermal injections of i-PRF in 3 facial regions: malar areas (1 mL each side), nasolabial fold (0.5 mL each side), and upper lip skin above the vermilion border (1 mL). The efficacy of the procedures was assessed by objective skin analysis (VISIA® ) and a subjective patient-reported outcome (FACE-Q) assessment at baseline and after 3 months. RESULTS: A significant improvement in skin surface spots (P = .01) and pores (P = .03) was seen at 3-months follow-up. Other variables, such as skin texture, wrinkles, ultraviolet spots, and porphyrins, showed a numerical improvement. FACE-Q scales that measure satisfaction with appearance all showed a significant improvement from baseline, including satisfaction with skin (P = .002), satisfaction with facial appearance (P = .025), satisfaction with cheeks (P = .001), satisfaction with lower face and jawline (P = .002), and satisfaction with lips (P = .04). No major adverse effects were reported. CONCLUSIONS: A series of three i-PRF injections resulted in significant rejuvenation of the face skin at 3-month follow-up, as shown by improved skin analysis parameters and patient self-assessment scores.

Strain elastography for noninvasive assessment of liver fibrosis: A prospective study with histological comparison.

The aim of this study was to prospectively evaluate the diagnostic performance of strain elastography for the assessment of liver fibrosis in patients with chronic liver disease using Ishak (0-6) histology stage as a reference standard. Ninety-eight consecutive patients with suspected chronic liver disease scheduled for liver biopsy (n = 78) or histologically confirmed cirrhosis (n = 20) were enrolled. Liver fibrosis Index (LF Index) calculated by strain elastography, liver stiffness by transient elastography and serum fibrosis markers (aspartate aminotransferase-to-platelet ratio index and King's Score) were measured. Spearman's correlation coefficient between the LF Index, liver stiffness, serum fibrosis markers and fibrosis stage were calculated and compared using areas under the receiver-operating characteristics (AUROCs) curves. Among 73 patients who underwent strain elastography, there was weak correlation between fibrosis stage and the LF Index (Spearman's: ρ = 0.385 for Ishak score; P = 0.001). Among 52 patients who underwent strain elastography and transient elastography, the AUROC values using LF Index, transient elastography, aspartate aminotransferase-to-platelet ratio index and King's Score for diagnosing significant fibrosis (Ishak score ≥ 3) were 0.79, 0.87, 0.86 and 0.85, respectively (P < 0.0001) and for diagnosing severe fibrosis/cirrhosis (Ishak score ≥ 5) were 0.83, 0.94, 0.92 and 0.92, respectively (P < 0.0001). When comparing the diagnostic performance using LF Index, transient elastography, aspartate aminotransferase-to-platelet ratio index and King's Score, transient elastography shows a significantly higher AUROC value than LF Index in detecting severe fibrosis (P = 0.0149). The diagnostic performance of LF Index calculated by strain elastography was not statistically significantly different to the other noninvasive tests for the assessment of significant liver fibrosis but inferior to transient elastography for the assessment of severe fibrosis/cirrhosis.

Therapeutic effect of Northern Labrador tea extracts for acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy that is one of the more common pediatric malignancies in addition to occurring with high incidence in the aging population. Unfortunately, these patient groups are quite sensitive to toxicity from chemotherapy. Northern Labrador tea, or Rhododendron tomentosum Harmaja (a.k.a. Ledum palustre subsp. decumbens) or "tundra tea," is a noteworthy medicinal plant used by indigenous peoples in Alaska, Canada, and Greenland to treat a diversity of ailments. However, laboratory investigations of Northern Labrador tea, and other Labrador tea family members, as botanical sources for anticancer compounds have been limited. Utilizing an AML cell line in both in vitro and in vivo studies, as well as in vitro studies using primary human AML patient samples, this study demonstrated for the first time that Northern Labrador tea extracts can exert anti-AML activity and that this may be attributed to ursolic acid as a constituent component. Therefore, this medicinal herb holds the potential to serve as a source for further drug discovery efforts to isolate novel anti-AML compounds.

Reducing the Number of Measurements in Liver Point Shear-Wave Elastography: Factors that Influence the Number and Reliability of Measurements in Assessment of Liver Fibrosis in Clinical Practice.

Purpose To identify the minimum number of measurements required for the noninvasive assessment of liver fibrosis by using point shear-wave elastography (pSWE) and determine whether the use of a reliability indicator such as interquartile range [IQR]-to-median ratio will affect diagnostic performance. Materials and Methods Ten liver shear-wave velocity (SWV) measurements by pSWE were obtained in 232 participants. Interclass correlation coefficients (ICC) between the median of the first two through the first nine measurements and all 10 measurements were calculated; the minimum number of measurements with ICC greater than 0.95 versus all 10 measurements was determined. The diagnostic performance of the minimum number of measurements and 10 measurements in identifying significant (Ishak stage, ≥3) and severe fibrosis or cirrhosis (Ishak stage, ≥5) was compared by using areas under the receiver operating characteristic curve. These were compared between measurements that demonstrated higher or lower reliability (IQR-to-median ratio of ≤ 30% and IQR-to-median ratio of > 30%, respectively). Results Compared with 10 measurements, a minimum of six SWV measurements was required. The overall area under the curve for diagnosing significant (areas under the receiver operating characteristic curve, 0.828 vs 0.839; P = .487) and severe fibrosis or cirrhosis (0.953 vs 0.969, respectively; P = .145) did not differ according to number of measurements (six vs 10); a median of six measurements resulted in only limited disagreement (nine of 232 [3.9%]) versus histologic evaluation. When using 10 measurements, higher reliability measurements showed a lower percentage of discordance between pSWE and significant fibrosis and severe fibrosis or cirrhosis (22 [14.7%] and three [2.0%] of 150 cases, respectively) compared with lower reliability measurements (26 [31.7%] and eight [9.8%] of 82 cases, respectively). Significant fibrosis was an independent predictor for lower reliability (hazard ratio, 2.22; P < .020). Conclusion A limited number of SWV measurements (median six vs median 10) were required for the assessment of liver fibrosis by using pSWE. The number of measurements had less influence on the diagnostic accuracy compared with lower reliability measurements. © RSNA, 2018 Online supplemental material is available for this article.

Reproducibility of 2-Dimensional Shear Wave Elastography Assessment of the Liver: A Direct Comparison With Point Shear Wave Elastography in Healthy Volunteers.

OBJECTIVES: Two-dimensional shear wave elastography (2D-SWE) imaging for the noninvasive assessment of tissue stiffness was assessed for reproducibility in healthy volunteers in quantifying liver elasticity, compared with an established point shear wave elastography (p-SWE) technique also known as virtual touch quantification (VTQ) (SIEMENS). METHODS: Eleven healthy volunteers were examined by four experienced operators on two occasions, separated by two weeks (sessions A and B). Ten 2D-SWE using LOGIQ E9 and p-SWE measurements using VTQ (in meters per second) were consecutively taken from deep portions of liver segments 5 or 6 away from vascular structures, using standard techniques. Inter- and intra-observer agreement was assessed by intraclass coefficient (ICC). RESULTS: A total of 880 2D-SWE and p-SWE velocities were recorded. Mean values from the four operators ranged between 1.188 and 1.196 m/s for 2D-SWE and 1.170 to 1.207 m/s for p-SWE. Interobserver reproducibility was good for both sessions with ICCs of 0.88 and 0.93 (2D-SWE) and 0.87 and 0.93 (p-SWE). The overall intra-operator reproducibility between sessions A and B was good for both p-SWE and 2D-SWE with ICC of 0.87 and 0.83, respectively. For inter- and intra-observer variability, the ICC was more than or equal to 0.71, indicating that the results were reliable. There was a strong and significant correlation between the 2D-SWE and p-SWE measurements (r = 0.87, P = .0006), but their velocities did not agree equally across different velocities. CONCLUSIONS: Two-dimensional SWE using LOGIQ E9 is a reliable and reproducible method for measuring elasticity in healthy volunteers and has a similar degree of reliability as p-SWE using VTQ, but absolute measurements from the two techniques should not be used interchangeably.

Laboratory Monitoring of Non-Vitamin K Antagonist Oral Anticoagulant Use in Patients With Atrial Fibrillation: A Review.

Importance: The non-vitamin K antagonist oral anticoagulants (NOACs) apixaban, dabigatran, edoxaban, and rivaroxaban are administered in fixed doses without anticoagulant monitoring. Randomized trials show that unmonitored NOAC therapy is at least as effective as and safer than dose-adjusted warfarin for stroke prevention in patients with nonvalvular atrial fibrillation. Subgroup analyses indicate that plasma drug levels or anticoagulant activity of the NOACs predict stroke and bleeding. This review examines the historical basis for anticoagulant monitoring, discusses methods to measure and interpret drug levels, and critically assesses the role of routine laboratory monitoring in the management of NOAC therapy. Observations: The predictable anticoagulant response of NOACs has provided the pharmacological basis for their administration in fixed doses without routine coagulation monitoring. Although it is possible to accurately measure NOAC drug levels, within-patient variability complicates interpretation of these results. Furthermore, patient characteristics, such as age and renal function, confound the association between NOAC drug levels and clinical outcomes. Information is lacking on the optimal drug level in particular patient groups (eg, elderly, the renally impaired, and those with high bleeding risk), the appropriate dose adjustment to achieve expected levels, and whether routine laboratory monitoring and dose adjustment will improve clinical outcomes. A benefit of a management strategy that incorporates routine therapeutic drug monitoring and dose adjustment over current standard-of-care metrics without such monitoring remains unproven. Conclusions and Relevance: Robust evidence from patients with atrial fibrillation randomized to NOACs or warfarin demonstrates that unmonitored NOAC therapy is at least as effective and safe as monitored warfarin, with lower rates of intracranial hemorrhage and reduced mortality. Further research is required to determine whether routine laboratory monitoring might provide a net benefit for patients. Until such data are available, clinicians should continue to prescribe NOACs in fixed doses without routine monitoring.

Novel oral anticoagulants for thromboprophylaxis after orthopaedic surgery.

The direct thrombin inhibitor, dabigatran, and the selective factor Xa inhibitors, rivaroxaban and apixaban, are new oral anticoagulants that are approved in many countries for prevention of venous thromboembolism in patients undergoing elective hip or knee arthroplasty. All have a rapid onset of action, a low potential for food and drug interactions and a predictable anticoagulant effect that obviates the need for routine coagulation monitoring. These agents offer a convenient alternative to conventional anticoagulant drug regimens, including parenteral low-molecular-weight heparins and fondaparinux, and oral adjusted-dose vitamin K antagonists, for the prevention of venous thromboembolism in this surgical setting. This review summarizes the pharmacology, clinical trial results, bleeding risk and practical use of these new oral anticoagulants in clinical orthopaedic practice. Potential issues to be considered when using these oral anticoagulants include renal impairment, potential drug interactions, neuraxial anaesthesia and management of bleeding.

Implications of variability in definition and reporting of major bleeding in randomized trials of oral P2Y12 inhibitors for acute coronary syndromes.

AIMS: Various definitions of major bleeding have been used to evaluate safety in randomized controlled trials of antiplatelet therapy. We compared the definitions and rates of major bleeding in phase III randomized controlled trials of oral P2Y(12) inhibitors in the management of patients with acute coronary syndromes (ACS). METHODS AND RESULTS: Electronic searches identified six phase III randomized controlled oral P2Y(12) inhibitor trials published between 2001 and 2010 involving 119 020 patients with ACS. The trials compared clopidogrel standard-dose (300-mg loading dose, 75-mg daily thereafter) vs. placebo (CURE, CLARITY-TIMI 28, COMMIT), clopidogrel standard-dose vs. prasugrel (TRITON-TIMI 38) or ticagrelor (PLATO) and clopidogrel standard-dose vs. clopidogrel double-dose (600-mg loading dose, 150-mg daily for 6-days, 75-mg daily thereafter) (CURRENT-OASIS 7). Using the trial definition, major bleeding rates in patients treated with standard-dose clopidogrel ranged from 0.6% in COMMIT to 11.2% in PLATO. The contrast in bleeding rates of standard-dose clopidogrel among the trials was attenuated when using the thrombolysis in myocardial infarction (TIMI) definition for major bleeding (range 1.1-7.7%) and bleeding rates in all the trials were less than 2% when comparing 30 day rates of non-coronary artery bypass graft surgery-related TIMI major bleeding (range 0.3-1.9%). CONCLUSION: Differences in major bleeding rates between trials of P2Y(12) inhibitors in patients with ACS are minimized after standardization of bleeding definitions, timing of reporting of bleeding outcomes, and procedure rates. Interpretation of the risk of bleeding associated with different P2Y(12) inhibitors would be facilitated by a consistent approach to the definition and reporting of bleeding.

Novel oral factor Xa and thrombin inhibitors in the management of thromboembolism.

The last decade has seen the evaluation of several new oral anticoagulants that directly target thrombin or activated factor X (FXa). All demonstrate a rapid onset of action, a low potential for food and drug interactions, and a predictable anticoagulant effect that obviates the need for routine coagulation monitoring. Those agents at the most advanced stages of clinical development are a direct thrombin inhibitor, dabigatran, and direct FXa inhibitors, rivaroxaban and apixaban. Dabigatran and rivaroxaban are approved in more than 70 countries for prevention of venous thromboembolism in patients undergoing elective hip or knee arthroplasty, and apixaban is being considered for approval by regulatory agencies for this indication. Dabigatran was shown in a large phase III trial to be more effective and safer than warfarin for the prevention of stroke or systemic embolism in patients with atrial fibrillation and has recently been approved for this indication. Edoxaban, an oral FXa inhibitor, is also being evaluated in phase III clinical trials. This review summarizes the pharmacology, clinical trial results, and future role of the new oral anticoagulants in clinical practice.

Enoxaparin versus dabigatran or rivaroxaban for thromboprophylaxis after hip or knee arthroplasty: Results of separate pooled analyses of phase III multicenter randomized trials.

BACKGROUND: Dabigatran and rivaroxaban are novel oral anticoagulants approved for prevention of venous thromboembolism after hip or knee arthroplasty. However, information assessing clinically important efficacy and bleeding outcomes of these 2 new agents versus low-molecular-weight heparin (enoxaparin) is lacking. METHODS AND RESULTS: We separately pooled efficacy and safety data from 6 phase III randomized trials (18 405 participants) comparing equivalent durations of treatment with enoxaparin (40 mg once daily [od] or 30 mg twice daily) versus dabigatran (220 mg od) or versus rivaroxaban (10 mg od) after hip or knee arthroplasty. Odds ratios (OR) for individual outcomes were calculated for each trial and were pooled using the Mantel-Haenszel method. Compared with dabigatran, enoxaparin had a similar risk of symptomatic venous thromboembolism plus all-cause mortality (0.9% versus 1.1%; OR, 0.76; 95% confidence interval [CI], 0.44 to 1.31; I²=76%) and bleeding (5.0% versus 5.6%; OR, 0.90; 95% CI, 0.71 to 1.15; I²=0%). Compared with rivaroxaban, enoxaparin had a 2-fold higher risk of symptomatic venous thromboembolism plus all-cause mortality (1.2% versus 0.6%; OR, 2.04; 95% CI, 1.32 to 3.17; P<0.001; number needed to treat, 167; I²=0%) but demonstrated a significant lower risk of bleeding (2.5% versus 3.1%; OR, 0.79; 95% CI, 0.62 to 0.99; P=0.049; number needed to harm, 167; I²=0%). CONCLUSIONS: In patients undergoing hip or knee arthroplasty, enoxaparin and dabigatran showed similar rates of efficacy and bleeding. Enoxaparin was less effective than rivaroxaban but had a lower risk of bleeding. These results may have important implications for the choice of prophylactic agent in major joint arthroplasty.

Major bleeding, mortality, and efficacy of fondaparinux in venous thromboembolism prevention trials.

BACKGROUND: Bleeding is a strong predictor of death in patients hospitalized for arterial thrombosis who are treated with antithrombotic therapy, but the prognostic importance of bleeding in patients receiving antithrombotic prophylaxis for venous thromboembolism is uncertain. METHODS AND RESULTS: Using Cox proportional hazards modeling, we examined the association between major bleeding and death at 30 days using pooled individual patient data from 8 large randomized controlled trials (n=13 085) comparing fondaparinux with control (low-molecular-weight heparin or placebo) for the prophylaxis of venous thromboembolism in hospitalized surgical or medical patients. Patients who developed major bleeding were older, were more likely to be male, had a lower body weight and lower creatinine clearance, and were more likely to be receiving fondaparinux. At 30 days, the risk of death was 7-fold higher among patients with a major bleeding event (8.6% versus 1.7%; adjusted hazard ratio, 6.96; 95% confidence interval, 4.60 to 10.51). There was a consistent pattern of reduced mortality in patients treated with fondaparinux irrespective of whether patients experienced major bleeding (6.8% versus 11.4%; hazard ratio, 0.58; 95% confidence interval, 0.27 to 1.23) or no major bleeding (1.5% versus 1.9%; hazard ratio, 0.77; 95% confidence interval, 0.59 to 1.02; P for heterogeneity=0.47). CONCLUSIONS: Major bleeding in hospitalized surgical and medical patients participating in venous thromboembolism prevention trials is a strong predictor of mortality.