Tissue Stromal Vascular Fraction Improves Early Scar Healing: A Prospective Randomized Multicenter Clinical Trial.

BACKGROUND: Wound healing and scar formation depends on a plethora of factors. Given the impact of abnormal scar formation, interventions aimed to improve scar formation would be most advantageous. The tissue stromal vascular fraction (tSVF) of adipose tissue is composed of a heterogenous mixture of cells embedded in extracellular matrix. It contains growth factors and cytokines involved in wound-healing processes, eg, parenchymal proliferation, inflammation, angiogenesis, and matrix remodeling. OBJECTIVES: The aim of this study was to investigate the hypothesis that tSVF reduces postsurgical scar formation. METHODS: This prospective, double-blind, placebo-controlled, randomized trial was conducted between 2016 and 2020. Forty mammoplasty patients were enrolled and followed for 1 year. At the end of the mammoplasty procedure, all patients received tSVF in the lateral 5 cm of the horizontal scar of 1 breast and a placebo injection in the contralateral breast to serve as an intrapatient control. Primary outcome was scar quality measure by the Patient and Observer Scar Assessment Scale (POSAS). Secondary outcomes were obtained from photographic evaluation and histologic analysis of scar tissue samples. RESULTS: Thirty-four of 40 patients completed follow-up. At 6 months postoperation, injection of tSVF had significantly improved postoperative scar appearance as assessed by the POSAS questionnaire. No difference was observed at 12 months postoperation. No improvement was seen based on the evaluation of photographs and histologic analysis of postoperative scars between both groups. CONCLUSIONS: Injection of tSVF resulted in improved wound healing and reduced scar formation at 6 months postoperation, without any noticeable advantageous effects seen at 12 months.

Complete pseudoepiphyses with associated enhanced growth in hands and feet: a report of 2 siblings--case report.

We present 2 siblings with multiple complete pseudoepiphyses in their hands and feet with associated symptomatic enhanced growth. Physical examination of the 6-year-old boy revealed long slender fingers and hyperplastic great toes. Radiography showed complete pseudoepiphyses in the first metacarpals, proximal and middle phalanges of the hands, and proximal phalanges of the feet. The patient's younger brother had a similar phenotype with slightly milder functional complaints. Genetic analysis did not reveal an underlying syndrome in these siblings.

Clinical significance of diastasis recti: Literature review and awareness amongst health care professionals.

BACKGROUND: A variety of physical complaints have been related to chronic diastasis recti (DR), including back pain, pelvic pain, and urinary incontinence. However, its clinical significance is still subject of debate, leaving many patients to feel unheard when experiencing symptoms. This study aims to assess current knowledge on DR, its potential treatments, and the awareness of this condition amongst involved health care professionals. METHODS: A literature review was performed to analyze current available knowledge on DR and its treatment. Then, a survey was conducted to investigate the awareness on DR amongst general practitioners, midwives, gynecologists, general surgeons, and plastic surgeons. RESULTS: Over 500 health care professionals completed our survey, including 46 general practitioners, 39 midwives, 249 gynecologists, 33 general surgeons, and 74 plastic surgeons. Although the majority of respondents (>78% in all groups) reported to encounter DR in daily practice, opinions differed markedly on most significant symptoms, associated physical complaints, best first referral for treatment, and best treatment modality. CONCLUSION: Current literature is not unanimous on the relation between DR and physical complaints and on its most suitable treatment. This incongruity is corroborated by the variety of responses from involved health care professionals in our survey. More clinical data are needed to provide clarity on this issue.

Tubular epithelial syndecan-1 maintains renal function in murine ischemia/reperfusion and human transplantation.

Syndecan-1, a heparan sulfate proteoglycan, has an important role in wound healing by binding several growth factors and cytokines. As these processes are also crucial in damage and repair after renal transplantation, we examined syndecan-1 expression in human control kidney tissue, renal allograft protocol biopsies, renal allograft biopsies taken at indication, and non-transplant interstitial fibrosis. Syndecan-1 expression was increased in tubular epithelial cells in renal allograft biopsies compared with control. Increased epithelial syndecan-1 in allografts correlated with low proteinuria and serum creatinine, less interstitial inflammation, less tubular atrophy, and prolonged allograft survival. Knockdown of syndecan-1 in human tubular epithelial cells in vitro reduced cell proliferation. Selective binding of growth factors suggests that syndecan-1 may promote epithelial restoration. Bilateral renal ischemia/reperfusion in syndecan-1-deficient mice resulted in increased initial renal failure and tubular injury compared with wild-type mice. Macrophage and myofibroblast numbers, tubular damage, and plasma urea levels were increased, and tubular proliferation reduced in the kidneys of syndecan-1 deficient compared with wild-type mice 14 days following injury. Hence syndecan-1 promotes tubular survival and repair in murine ischemia/reperfusion injury and correlates with functional improvement in human renal allograft transplantation.

ADAM17 up-regulation in renal transplant dysfunction and non-transplant-related renal fibrosis.

BACKGROUND: Interstitial fibrosis and tubular atrophy (IF/TA) is an important cause of renal function loss and ischaemia-reperfusion (I/R) injury is considered to play an important role in its pathophysiology. The aim of the present study was to investigate the role of a disintegrin and metalloproteinase 17 (ADAM17) in human renal allograft disease and in experimental I/R injury of the kidney. METHODS: We studied the expression of ADAM17 messenger RNA (mRNA) in IF/TA and control kidneys by reverse transcription-polymerase chain reaction and in situ hybridization. Moreover, we assessed ADAM17-mediated heparin-binding epidermal growth factor (HB-EGF) shedding in immortalized human cells. Finally, we studied the effect of pharmacological ADAM17 inhibition in a model of renal I/R injury in rats. RESULTS: ADAM17 mRNA was up-regulated in IF/TA when compared to control kidneys. In normal kidneys, ADAM17 mRNA was weakly expressed in proximal tubules, peritubular capillaries, glomerular endothelium and parietal epithelium. In IF/TA, tubular, capillary and glomerular ADAM17 expression was strongly enhanced with de novo expression in the mesangium. In interstitial fibrotic lesions, we observed co-localization of ADAM17 with HB-EGF protein. In vitro, inhibition of ADAM17 with TNF484 resulted in a dose-dependent reduction of HB-EGF shedding in phorbol 12-myrisate 13-acetate-stimulated cells and non-stimulated cells. In vivo, ADAM17 inhibition significantly reduced the number of glomerular and interstitial macrophages at Day 4 of reperfusion. CONCLUSIONS: In conclusion, HB-EGF co-expresses with ADAM17 in renal interstitial fibrosis, suggesting a potential interaction in IF/TA. Targeting ADAM17 to reduce epidermal growth factor receptor phosphorylation could be a promising way of intervention in human renal disease.

Heparin binding epidermal growth factor in renal ischaemia/reperfusion injury.

The epidermal growth factor (EGF) receptor and its ligands are crucially involved in the renal response to ischaemia. We studied the heparin binding-epidermal growth factor (HB-EGF), a major ligand for the EGF receptor, in experimental and human ischaemia/reperfusion injury (IRI). HB-EGF mRNA and protein expression was studied in rat kidneys and cultured human tubular (HK-2) cells that were subjected to IRI and in human donor kidneys during transplantation. The effect of EGF receptor inhibition was investigated in vivo and in vitro. Furthermore, urinary HB-EGF protein excretion was studied after renal transplantation. Finally, HB-EGF KO and WT mice were subjected to IRI to study the role of HB-EGF in renal injury. HB-EGF mRNA was significantly up-regulated in the early phase of IRI in rats, cells, and human donor biopsies. Treatment with PKI-166 reduces macrophage accumulation and interstitial alpha-SMA in the early phase of IRI in rats. In vitro, PKI-166 causes a marked reduction in HB-EGF-induced cellular proliferation. Urinary HB-EGF is increased after transplantation compared with control urines from healthy subjects. HB-EGF KO mice subjected to IRI revealed significantly less morphological damage after IRI, compared with WT mice. We conclude that IRI results in early induction of HB-EGF mRNA and protein in vivo and in vitro. Absence of HB-EGF and inhibition of the EGF receptor in the early phase of IRI has protective effects, suggesting a modulating role for HB-EGF.

Adamalysins in biology and disease.

ADAMs (a disintegrin and metalloprotease) are membrane-bound enzymes, capable of shedding a multitude of proteins from the surface of the cell. They are therefore considered crucial modulators of physiological and pathophysiological processes. The structure and function of ADAMs is related to those of a family of snake venom metalloproteases which also possess a potential adhesion domain as well as a potential protease domain. Mammalian ADAMs are involved in various biological and disease-related processes, such as cell-cell fusion, adhesion and intracellular signalling. Functional involvement has been described in sperm-egg binding and fusion, trophoblast invasion and matrix degradation during pregnancy, angiogenesis and neovascularization. Clinically, ADAMs are implicated in pathological processes, including cancer, inflammation, neurodegeneration and fibrosis, through shedding of the apoptosis-inducing FAS ligand, cytokines and growth factors. A second group of proteins within the ADAM family has recently been discovered. These contain several thrombospondin-like repeats in their C-terminal regions, in the absence of the transmembrane domain known to be present in ADAMs. These proteins were called the ADAMTS (ADAM with thrombospondin domains) family. The relevance of ADAMTS enzymes has become evident in patients with a deficiency in ADAMTS-13, a von Willebrand factor cleaving protease. These patients develop thrombotic thrombocytopenic purpura, a devastating thrombotic disorder caused by widespread microvascular thrombi composed of platelets and von Willebrand factor (VWF). Here we focus on the genetic, developmental, functional and disease-related aspects of ADAMs and ADAMTS. Finally we discuss the perspectives of the therapeutical potential of ADAMs in disease.

Nerve decompression surgery as treatment for peripheral diabetic neuropathy: literature overview and awareness among medical professionals.

Peripheral diabetic neuropathy (PDN) is one of the major complications arising in patients with diabetes. Since PDN is traditionally considered an irreversible disorder, treatment has been aimed to prevent the development of complications. In a novel concept, however, it is postulated that decompression surgery of the affected nerve may reverse the natural course of PDN. In this review, we will discuss experimental and human studies that addressed the value of nerve decompression surgery in PDN. Furthermore, we report on the awareness of this novel treatment strategy among medical professionals that are primarily involved in diabetes care.

Arnica Ointment 10% Does Not Improve Upper Blepharoplasty Outcome: A Randomized, Placebo-Controlled Trial.

BACKGROUND: It has been suggested that arnica can reduce postoperative edema and ecchymosis associated with cosmetic surgical procedures and improve outcome. Despite a high incidence of arnica use among upper blepharoplasty patients, evidence to support its treatment effect is lacking. The authors performed a randomized, double-blind, placebo-controlled trial to investigate the efficacy of arnica ointment after upper blepharoplasty. METHODS: One hundred thirty-six bilateral upper blepharoplasty patients were randomized between arnica ointment 10% and placebo ointment. In both study arms, one periorbital area was designated as the treatment side (either arnica or placebo ointment), and the contralateral side served as an untreated (no ointment) internal control. As the primary endpoint, the overall periorbital appearance as based on light photography and judged by a medical and nonmedical panel, was assessed after 3 days, 7 days, and 6 weeks. Secondary endpoints were swelling, ecchymosis, erythema, pain, and patient satisfaction with recovery and outcome. RESULTS: There was no significant difference between arnica and placebo in overall judgment of periorbital appearance 3 days, 7 days, and 6 weeks after surgery. Furthermore, swelling, ecchymosis, erythema, pain, and patient satisfaction with recovery and outcome did not differ between arnica and placebo. Postoperative outcome in untreated eyelids was not different from eyelids treated with either arnica or placebo on any of the studied outcome measures. CONCLUSION: The authors' study demonstrates that topical arnica ointment after upper blepharoplasty does not improve postoperative outcome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

The effect of eyelid cooling on pain, edema, erythema, and hematoma after upper blepharoplasty: a randomized, controlled, observer-blinded evaluation study.

BACKGROUND: The purpose of this study was to investigate the efficacy of eyelid cooling to reduce postoperative pain, edema, erythema, and hematoma after upper blepharoplasty. METHODS: After bilateral upper blepharoplasty in 38 consecutive patients, one eyelid per patient was randomized for cooling with an ice pack, and the other eyelid was left uncooled. Pain was scored by the patients using a visual analogue scale (0 to 10) 1 hour and 1 day after surgery. Degree of edema, erythema, and hematoma were scored by the patients on a four-point rating scale (no, minimal, moderate, or severe) 1 hour, 1 day, 1 week, and 2 months after surgery. Light photography was obtained 1 week after surgery for scoring the degree of bruising on a four-point rating scale by a blinded observer. RESULTS: Pain did not differ between cooled and uncooled eyelids on the day of surgery. However, pain in cooled eyelids was significantly lower 1 day after surgery (p = 0.046), yet absolute pain scores were low (median, 0 and 0.5, on a scale of 10). Edema, erythema, or hematoma did not differ between cooled and uncooled eyelids on any of the time points studied. CONCLUSIONS: Cooling of eyelids after upper blepharoplasty does not reduce edema, erythema, or hematoma of the eyelids, but reduces pain 1 day after surgery. However, because the degree of pain seems clinically irrelevant and because the majority of patients indicate that they have no preference for cooling over noncooling, eyelid cooling after upper blepharoplasty as a rule of thumb can be abandoned. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

[Masson tumour: a benign vascular lesion]. / Massontumor: een benigne vaatafwijking.

A 39-year-old woman presented with a swelling on the left inner thigh. Physical examination was suggestive of a lipoma. However, peri-operatively the lump appeared to be a vascular tumour arising from the great saphenous vein. Histological examination revealed a benign Masson tumour, a rare vascular tumour that is characterized by endothelial hyperplasia and the presence of papillary structures. It is of clinical importance to distinguish the benign Masson tumour from a malignant angiosarcoma.

Locally acquired hepatitis E in the Netherlands: associated with the consumption of raw pig meat?

We here present 2 patients who developed hepatitis E, without having been abroad or in contact with anyone who did, indicating locally acquired hepatitis E. We point out that the consumption of raw pig meat could be of relevance in HEV-associated hepatitides in the Netherlands.

Expression and response to angiotensin-converting enzyme inhibition of matrix metalloproteinases 2 and 9 in renal glomerular damage in young transgenic rats with renin-dependent hypertension.

Extracellular matrix expansion in the glomerular mesangium contributes to the development of glomerulosclerosis and chronic renal disease in arterial hypertension. Transforming growth factor-beta1 (TGF-beta1), matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs (TIMPs) are involved in this process. Conflicting data are reported on the effects of angiotensin II (Ang II) and the response to angiotensin-converting enzyme inhibition on MMPs and TIMPs in early stages of hypertensive glomerular damage. We therefore investigated the effects of Ang II-dependent hypertension on MMP-2, MMP-9, TIMP-1, and TIMP-2 in isolated glomeruli of 8-week-old homozygous male rats overexpressing the mouse Ren2 gene [TGR(mRen2)27]. At this age, systolic blood pressure was already significantly elevated in Ren2 compared with Sprague-Dawley (SD) rats (197 +/- 38 versus 125 +/- 16 mm Hg, p < 0.01). Ren2 exhibited renal damage as determined by increased urinary albumin excretion, focal glomerulosclerosis, mesangial matrix expansion, and alpha-smooth muscle actin deposition. Quantification of mRNA levels in isolated glomeruli by real-time polymerase chain reaction showed a significant increase of TGF-beta1, a 2.3- and a 2.6-fold increase of MMP-2 and TIMP-1 in Ren2 compared with SD (p < 0.01, respectively) and no strain differences for TIMP-2. In contrast, MMP-9 mRNA expression was markedly suppressed to 10% of control levels in Ren2 (p < 0.01). Early treatment with ramipril completely prevented renal damage in Ren2 and restored mRNA expression of TGF-beta1, MMP-2, and TIMP-1 to SD control levels. Interestingly, down-regulation of MMP-9 mRNA, protein, and activity was not affected by ramipril, indicating that the protective effect of this compound is not attributable to restoration of MMP-9 in the glomerulus.