META Score: An International Consensus Scoring System on Mesh-Tissue Adhesions.

BACKGROUND: Currently, the lack of consensus on postoperative mesh-tissue adhesion scoring leads to incomparable scientific results. The aim of this study was to develop an adhesion score recognized by experts in the field of hernia surgery. METHODS: Authors of three or more previously published articles on both mesh-tissue adhesion scores and postoperative adhesions were marked as experts. They were queried on seven items using a modified Delphi method. The items concerned the utility of adhesion scoring models, the appropriateness of macroscopic and microscopic variables, the range and use of composite scores or subscores, adhesion-related complications and follow-up length. This study comprised two questionnaire-based rounds and one consensus meeting. RESULTS: The first round was completed by 23 experts (82%), the second round by 18 experts (64%). Of those 18 experts, ten were able to participate in the final consensus meeting and all approved the final proposal. From a total of 158 items, consensus was reached on 90 items. The amount of mesh surface covered with adhesions, tenacity and thickness of adhesions and organ involvement was concluded to be a minimal set of variables to be communicated separately in each future study on mesh adhesions. CONCLUSION: The MEsh Tissue Adhesion scoring system is the first consensus-based scoring system with a wide backing of renowned experts and can be used to assess mesh-related adhesions. By including this minimal set of variables in future research interstudy comparability and objectivity can be increased and eventually linked to clinically relevant outcomes.

Negative pressure wound therapy versus standard wound care on quality of life: a systematic review.

OBJECTIVE: Negative pressure wound therapy (NPWT) is a widely accepted treatment modality for open or infected wounds. Premature ending of NPWT occasionally occurs due to negative effects on the quality of life (QoL), however, the actual impact on QoL is unknown. The aim of this review is to analyse the effect of NPWT versus standard wound care (SWC) on QoL when used for the treatment of open or infected wounds. METHOD: A systematic literature search in a range of databases (PubMed, CINAHL, Medline, Web of Science, Science Direct Freedom Collection, SwetsWise, PSYCArticles and Infrotrac Custom Journals) using the following search terms; 'standard wound care', 'wound dressing', 'dressing', 'treatment', OR 'negative pressure wound therapy [MESH]', OR 'vacuum assisted closure' AND 'quality of life [MESH]', 'patient-satisfaction', OR 'experiences' was performed. Methodological quality was assessed using the methodological index for non-randomised studies (MINORS) checklist. RESULTS: There were 42 studies identified, five matched the inclusion criteria: two randomised clinical trials (RCTs), one clinical comparative study, one exploratory prospective cohort study and one quasi experimental pilot study. Median MINORS-score was 75% (58%-96%). There were seven different questionnaires used to measure QoL or a subsidiary outcome. QoL in the NPWT group was lower in the first week, though no difference in QoL was observed thereafter. CONCLUSION: This systematic review observed that QoL improved at the end of therapy independent of which therapy was used. NPWT led to a lower QoL during the first week of treatment, possible due to aniexty, after which a similar or better QoL was reported when compared with SWC. It could be suggested that NPWT might be associated with increased anxiety. DECLARATION OF INTEREST: All authors of this publication have received no financial support or have personal interests conflicting with the objectivity of this manuscript.

The effects of low-intensity pulsed ultrasound and pulsed electromagnetic fields bone growth stimulation in acute fractures: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: The aim of this systematic review and meta-analysis was to evaluate the best currently available evidence from randomized controlled trials comparing pulsed electromagnetic fields (PEMF) or low-intensity pulsed ultrasound (LIPUS) bone growth stimulation with placebo for acute fractures. MATERIALS AND METHODS: We performed a systematic literature search of the medical literature from 1980 to 2013 for randomized clinical trials concerning acute fractures in adults treated with PEMF or LIPUS. Two reviewers independently determined the strength of the included studies by assessing the risk of bias according to the criteria in the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Seven hundred and thirty-seven patients from 13 trials were included. Pooled results from 13 trials reporting proportion of nonunion showed no significant difference between PEMF or LIPUS and control. With regard to time to radiological union, we found heterogeneous results that significantly favoured PEMF or LIPUS bone growth stimulation only in non-operatively treated fractures or fractures of the upper limb. Furthermore, we found significant results that suggest that the use of PEMF or LIPUS in acute diaphyseal fractures may accelerate the time to clinical union. CONCLUSIONS: Current evidence from randomized trials is insufficient to conclude a benefit of PEMF or LIPUS bone growth stimulation in reducing the incidence of nonunions when used for treatment in acute fractures. However, our systematic review and meta-analysis suggest that PEMF or LIPUS can be beneficial in the treatment of acute fractures regarding time to radiological and clinical union. PEMF and LIPUS significantly shorten time to radiological union for acute fractures undergoing non-operative treatment and acute fractures of the upper limb. Furthermore, PEMF or LIPUS bone growth stimulation accelerates the time to clinical union for acute diaphyseal fractures.

The male rectus diastasis: a different concept?

PURPOSE: More interest in the treatment of rectus diastasis has been evoked lately. Following the postpartum females from a great distance, the middle-aged males living with obesity are the second most common group of rectus diastasis patients. Although gender differences are considered frequently in regard to cosmetic appearance and symptoms, it is less obvious in classifications and subsequent treatment strategies. Is a unisex approach of rectus diastasis still applicable? The lack of a firm answer warrants this review of the current literature. METHODS: An explorative free-text multi-database bibliographic search (Pubmed/CENTRAL/EMBASE/PEDro/Scholar) was performed with the focus on the rectus diastasis in males. Anticipating the limited references, the design was a non-systematic review. All studies, regardless of study type, language or time period, describing etiology, symptoms, classification and/or treatment options were eligible for inclusion. From the articles retrieved out of this search, additional references were identified by a manual search among the cited references. RESULTS: The multi-database search resulted in a total of 7633 records. Based on the title and abstract 95 records were full text assessed for eligibility. Eleven studies were identified as relevant, six by cross-reference and another four by hand-search were added to provide an insight in gender-specific aspects in rectus diastase. Hereditary causes are differences in collagen-like composition of types and concomitant abdominal aneurysm as well as gender differences in the linea alba architecture. Acquired etiology is distributed into both absolute pressure by visceral obesity and relative pressure caused by weight lifting or improper exercises. Furthermore, the impact of muscle thickness and age are considered as influencers of biomechanics. Gender differences can also play a role in symptoms of body image and core stability. It is known that there are anatomical differences between male and female persons; more transverse fibers are found in infra-umbilical region in women. In classifications the awareness of male rectus diastasis is limited, treatment outcome studies are scarce on males. CONCLUSION: An overview of male-specific aspects of rectus diastasis is provided, underlining that key aspects surrounding rectus diastasis in males differ from females. Although males are the minority of rectus diastasis patients, we recommend that the male rectus diastasis as a concept should be specifically acknowledged in classifications systems and study outcome reporting to evaluate this subgroup more accurately in the future.

Meta-analysis of postoperative pain using non-sutured or sutured single-layer open mesh repair for inguinal hernia.

Background: Chronic postoperative pain occurs in up to 21·7 per cent of patients undergoing open inguinal hernia repair. Several mesh fixation techniques using glue or self-gripping meshes have been developed to reduce postoperative pain. The aim of this meta-analysis was to evaluate RCTs comparing adhesional/self-gripping and sutured single-layer open mesh fixations in the repair of inguinal herniation, with postoperative pain as endpoint. Methods: PubMed, Embase and Cochrane CENTRAL databases were searched systematically for RCTs according to the PRISMA guidelines; the study was registered at PROSPERO (CRD42017056373). Different fixation methods were analysed. The primary outcome, chronic pain, was defined as a postoperative visual analogue scale (VAS) score of at least 3 at 12 months. Secondary outcomes were mean VAS score at 1 week and at 1 month after surgery. Results: Twenty-three studies including 5190 patients were included in the meta-analysis. Adhesional (self-adhering or glued) or self-gripping fixation methods were associated with a significantly lower VAS score at 1 week (mean difference -0·49, 95 per cent c.i. -0·81 to -0·17; P = 0·003) and at 1 month (mean difference -0·31, -0·58 to -0·04; P = 0·02) after surgery than suture fixation, but the incidence of chronic pain after 12 months was similar in the two groups (odds ratio 0·70, 95 per cent c.i. 0·30 to 1·66). Differences in recurrences and complications between groups did not reach statistical significance. Conclusion: There was no difference in the incidence of chronic pain 12 months after different mesh repair fixation techniques despite significant reductions in short-term postoperative pain favouring a non-sutured technique. There were no differences in recurrence rates or in rates of other complications at 1 year.

Complications and recurrence rates of patients with Ehlers-Danlos syndrome undergoing ventral hernioplasty: a case series.

PURPOSE: Ventral hernia repair is one of the most frequently performed surgical procedures, though recurrences are common. Recurrence can be caused by impaired collagen formation or maturation; hence, patients with Ehlers-Danlos syndrome (EDS) are potentially at increased risk for hernia recurrence. EDS causes altered collagen metabolism, though little is known about the influence of EDS on ventral hernioplasty outcomes. This study aims to analyze these patients to report complication rates, recurrence rates, and, if possible, to give recommendations for surgical intervention. METHODS: A retrospective analysis between January 2000 and January 2017 was performed in a university hospital Belgium (UZ Ghent). Data on baseline characteristics, primary surgery, and hernias were extracted from patients' medical charts. Noted endpoints were postoperative complications and recurrences. RESULTS: Fourteen patients (50% males) were included. Ten (71%) had an incisional hernia and four (29%) had a primary ventral hernia. Median age was 45 years (IQR 37.75-52.75), median BMI was 24.82 (IQR 22.43-26.87). Four patients (29%) smoked, one patient (7.1%) had diabetes mellitus, and five patients (36%) had an aneurysm of the abdominal aorta. All patients underwent elective open hernioplasty with mesh reinforcement. Three patients (21%) had a postoperative complication (two infections, one seroma). Recurrence rate was 7.1% (one patient). CONCLUSIONS: This series describes 14 patients with a median follow-up of 50 months and a recurrence rate of 7.1%. The low recurrence rate could be explained by the use of large meshes that reinforce the entire midline to compensate for the reduced collagen strength in EDS patients.

A modified Chevrel technique for ventral hernia repair: long-term results of a single centre cohort.

PURPOSE: To evaluate the short- and long-term results after a modified Chevrel technique for midline incisional hernia repair, regarding surgical technique, hospital stay, wound complications, recurrence rate, and postoperative quality of life. These results will be compared to the literature derived reference values regarding the original and modified Chevrel techniques. METHODS: In this large retrospective, single surgeon, single centre cohort all modified Chevrel hernia repairs between 2000 and 2012 were identified. Results were obtained by reviewing patients' medical charts. Postoperative quality of life was measured using the Carolina Comfort Scale. A multi-database literature search was conducted to compare the results of our series to the literature based reference values. RESULTS: One hundred and fifty-five patients (84 male, 71 female) were included. Eighty patients (52%) had a large incisional hernia (width ≥ 10 cm) according the definition of the European Hernia Society. Fourteen patients (9%) underwent a concomitant procedure. Median length-of-stay was 5 days. Within 30 days postoperative 36 patients (23.2%) had 39 postoperative complications of which 30 were mild (CDC I-II), and nine severe (CDC III-IV). Thirty-one surgical site occurrences were observed in thirty patients (19.4%) of which the majority were seroma (16 patients 10.3%). There was no hernia-related mortality during follow-up. Recurrence rate was 1.8% after a median follow-up of 52 months (12-128 months). Postoperative quality of life was rated excellent. CONCLUSIONS: The modified Chevrel technique for midline ventral hernias results in a moderate complication rate, low recurrence rate and high rated postoperative quality of life.

Patient-reported outcomes (PROs) after total extraperitoneal hernia repair (TEP).

BACKGROUND: Patient-reported outcomes (PROs) such as quality of life (QoL), patient satisfaction, and work impairment, are arguably the most important outcomes of any medical treatment. In 2011, Staerkle and Villiger developed the Core Outcome Measurements Index (COMI) to standardise PROs and PRO measurement for inguinal hernia patients, in an attempt to increase inter-study comparability. The aim of this study is to prospectively evaluate the short- and long-term postoperative QoL, function, patient well-being, pain, and social/work disability, after total extraperitoneal (TEP) inguinal hernia repair and to provide the first clinical experience with the COMI-hernia questionnaire. METHODS: Between January 2013 and December 2014, all patients ≥18 years that were scheduled for elective uni- or bilateral TEP in a regional hospital were approached to participate in this study. Measurements were taken preoperatively, and 6 weeks and 1 year postoperatively. RESULTS: One hundred and twenty patients (113 men, 7 women), mean age 59 years (SD ±12), completed the follow-up of 1 year. Ninety-seven percent of the population reported that the operation improved their complaints. QoL, function, well-being, and pain all improved after 6 weeks and 1 year after surgery. Patients experienced more social and work-related limitations 6 weeks after surgery compared to baseline measurements, though this improved to normal 1 year postoperatively. The incidence of chronic pain was 14% (VAS ≥ 2), which had a negative impact on the patients' sense of well-being. CONCLUSION: Patients recovered well after TEP repair with a good quality of life and fast restore of function. Patient well-being was lower than expected due to a 14% incidence of chronic pain. The COMI-hernia scale provided reasonable insight into the patients' experience, though it was difficult to interpret for both patient and physician.

Levels of hypoxia-inducible factor-1 alpha during breast carcinogenesis.

BACKGROUND: Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates gene expression in critical pathways involved in tumor growth and metastases. In this report, we investigated whether the level of HIF-1 alpha is increased during carcinogenesis in breast tissue and is associated with other tumor biomarkers. METHODS: Paraffin-embedded clinical specimens from five pathologic stages of breast tumorigenesis and from normal breast tissue were used. HIF-1 alpha protein and the biomarkers vascular endothelial growth factor (VEGF), HER-2/neu, p53, Ki-67, and estrogen receptor (ER) were identified immunohistochemically, and microvessel density (a measure of angiogenesis) was determined. Associations among levels of HIF-1 alpha and these biomarkers were tested statistically. All statistical tests are two-sided. RESULTS: The frequency of HIF-1 alpha-positive cells in a specimen increased with the specimen's pathologic stage (P<.001, chi(2) test for trend) as follows: normal breast tissue (0 specimens with > or = 1% HIF-1 alpha-positive cells in 10 specimens tested), ductal hyperplastic lesions (0 in 10), well-differentiated ductal carcinomas in situ (DCIS) (11 in 20), well-differentiated invasive breast cancers (12 in 20), poorly differentiated DCIS (17 in 20), and poorly differentiated invasive carcinomas (20 in 20). Increased levels of HIF-1 alpha were statistically significantly associated with high proliferation and increased expression of VEGF and ER proteins. In DCIS lesions, increased levels of HIF-1 alpha were statistically significantly associated with increased microvessel density. HIF-1alpha showed a borderline association with HER-2/neu but no association with p53. CONCLUSIONS: The level of HIF-1 alpha increases as the pathologic stage increases and is higher in poorly differentiated lesions than in the corresponding type of well-differentiated lesions. Increased levels of HIF-1 alpha are associated with increased proliferation and increased expression of ER and VEGF. Thus, increased levels of HIF-1 alpha are potentially associated with more aggressive tumors.

How to perform the endoscopically assisted components separation technique (ECST) for large ventral hernia repair.

BACKGROUND: The components separation technique (CST) is frequently used for reconstructing large ventral hernias. Unfortunately, it is associated with a high wound complication rate up to 50 %, caused by large wound surface and inherent trauma to abdominal skin vascularization. An endoscopically assisted modification of the original technique (ECST) spares skin vascularization and reduces wound surface, supposedly reducing wound complications. This study accurately describes ECST step by step with detailed illustrations and report the results of a 27 patient cohort. METHODS: Since September 2012 patients with midline hernias without previous subcutaneous dissection and a maximum diameter of approximately 10-15 cm underwent ECST in an expert centre for abdominal wall reconstructions. Prospective data was gathered during inpatient care and 3-6 monthly follow-up. RESULTS: Twenty-seven patients (17 male/10 female) with median age of 60 years (range 35-77), average BMI 27 (SD ±2) kg/m(2) and median ASA classification 2 (range 1-3) underwent ECST. Two patients were excluded due to bilateral conversion to conventional CST and finding of peritoneal metastases. Median defect size was 116 ± 48 cm(2). Median length of stay was 5 days (range 3-15). Wound complication rate was 11 %. Recurrence rate was 29 % after a median follow-up of 13 months. CONCLUSIONS: Endoscopically assisted modification of the original technique can be used for reconstructing large and complex ventral hernias up to 15 cm in diameter. The results of this small sized cohort study showed that ECST is feasible in patients with a uro-, or enterostomy and suggest that ECST reduces wound complication rate when compared to CST.

Expression of proliferation and apoptosis-related proteins in usual ductal hyperplasia of the breast.

Expression of proliferation- and apoptosis-related proteins was studied by immunohistochemistry in 130 usual ductal hyperplasias of the breast, of which 39 cases (30%) had adjacent invasive cancer. Overexpression of cyclin D1 and Ki-67 was found in 6% and 29% of the cases, respectively. Only two mild ductal hyperplasias were Her-2/neu positive. Overexpression of p21 and reduced expression of p27, both cdk-inhibitors, was seen in 16% and 27% of the lesions, respectively. Reduced expression of bcl-2 was found in 16% of the cases, and p53 accumulation was present in 8%. Expression of six of the seven studied proteins showed no significant difference between mild, moderate, or florid ductal hyperplasias, indicating that there are no important cell biological differences with regard to the studied proteins between the lesions within this morphologically continuous spectrum. In addition, there were no differences between lesions with and without an invasive component. Cyclin D1 positivity was exclusively seen in lesions with 75% or more p27-positive nuclei. No significant correlations were found between other proteins. Twenty-three of 91 lesions (25%) had multiple events, of which five showed altered expressions of three or four proteins. In conclusion, altered protein expression of several proliferation- and apoptosis-related genes that are known to be involved in invasive breast cancer also may be found in usual ductal hyperplastic lesions, including several lesions with multiple events. This implies that usual ductal hyperplastic lesions may be among the earliest lesions within the breast oncogenetic spectrum.

Histopathology of fibroadenoma of the breast.

The aim of this study was to make a thorough inventory of the histologic features of epithelium and stroma within and adjacent to breast fibroadenomas in 396 cases. Breast fibroadenomas seemed to display a wide spectrum of proliferative and nonproliferative histologic changes. Hyperplasia (excluding mild hyperplasia) within the fibroadenoma was found in 32.3% of cases. Carcinoma in situ (CIS; 5 ductal, 3 lobular) was found in 8 fibroadenomas (2.0%) removed from 6 patients, the youngest of whom was 40 years of age. In 3 cases CIS was not confined to the fibroadenoma, but also involved the adjacent parenchyma. No invasive carcinoma was present within this series. Complex histologic features were seen in 40.4% of cases, mostly in relatively older patients (mean age, 35.4 years). Hyperplasia in adjacent tissue was found in 8.8% of cases, usually in older patients (mean age, 45.5 years). Known risk-elevating lesions in and around breast fibroadenomas occur frequently and mostly in patients older than 35 years. These findings may have consequences for the clinical management of a subgroup of patients with fibroadenoma.

Correlation of morphologic and cytogenetic parameters of genetic instability with chromosomal alterations in in situ carcinomas of the breast.

Classification of preinvasive breast disease could be better founded using biologic markers, thereby increasing reproducibility. We studied 57 breast ductal and lobular in situ carcinomas by means of comparative genomic hybridization and correlated these findings with quantitative features such as the mean nuclear area, mitotic index (MI), apoptotic index (AI), and the presence or absence of necrosis. Loss of 8p and gains of 8q and 6q were associated, respectively, with a significantly higher MI and AI, whereas loss of 16q was associated with a lower MI and AI. A significantly higher number of alterations per case were seen in tumors with gains of 6q, 8q, and 17q and tumors with loss of 13q. Loss of 16q and gain of 17q correlated with the absence or presence of necrosis, respectively. Our data clearly demonstrate that distinct cytogenetic changes correlate with phenotypic changes, proliferation, and apoptosis. These data may be used to refine existing classification schemes.

Prevalence of L. loa and M. perstans filariasis in southern Cameroon.

The prevalence and microfilarial density of Loa loa and Mansonella perstans filariasis have been determined in three successive surveys in one village in the dense rainforest of Southern Cameroon. The prevalence of L. loa microfilaraemia was 30.9% with a geometric mean density of 81.4 microfilariae/30 microliter blood. There was no difference between men and women. The prevalence increased with age from 14.5% at 0-9 years to 52.9% at 40-49 years, whereafter it stablized. The microfilarial density increased until the age of 30-39 years. The highest densities have been found around noon, although the difference was not significant. The prevalence of M. perstans microfilaraemia was 26.6% with a median density of 2.0 microfilariae/30 microliter blood. Both prevalence and density were increasing with age and were higher for men than for women. The time of day that the blood sample was taken had no influence on the microfilarial density of M. perstans.

Depletion of CD4+ or CD8+ T-cells prevents Plasmodium berghei induced cerebral malaria in end-stage disease.

The role of T-cells in development of experimental cerebral malaria was analysed in C57B1/6J and C57B1/10 mice infected with Plasmodium berghei K173 or Plasmodium berghei ANKA by treatment with anti-CD4 or anti-CD8 mAbs. Mice were protected against cerebral malaria (CM) when anti-CD4 or anti-CD8 mAbs were injected before or during infection. Even in mice in end-stage disease, i.e. with a body temperature below 35.5 degrees C, treatment with anti-CD4 or anti-CD8 antibodies or the combination protected against CM, whereas chloroquine treatment was completely ineffective in inhibiting further development of the cerebral syndrome.

Oxidative stress in malaria; implications for prevention and therapy.

Malaria affects world-wide more than 200 million people, of which 1-2 million die every year. New drugs and treatment strategies are needed to face the rapidly increasing problems of drug resistance. During a malaria infection, both host and parasite are under oxidative stress. Increased production levels of reactive oxygen species (ROS, e.g superoxide anion and the hydroxyl radical) are produced by activated neutrophils in the host and during degradation of haemoglobin in the parasite. The effects of ROS in malaria can be both beneficial and pathological, depending on the amount and place of production. Enhanced ROS production after the administration of pro-oxidants, which is directed against the intra-erythrocytic parasite, inhibits the infection both in vitro and in vivo. However, ROS are also involved in pathological changes in host tissue like damage of the vascular endothelial lining during a malaria infection (cerebral malaria). Pro-oxidants support the host defense against the parasite when working in or near the infected cell but potentially cause vascular damage when working on or near the vascular lining. Examples of pro-oxidants are found among xenobiotics and food components. Important new drugs belonging to the class of pro-oxidants are artemisinin and its derivatives. Anti-oxidants potentially counteract these agents. Treatment with anti-oxidants or chelators of metals to prevent their catalytic function in the generation of ROS may prevent vascular pathology. In addition, the iron chelator desferrioxamine, exhibits an antiparasitic activity, because iron is also essential for the proliferation of the parasite. Cytokines play an important role in ROS-related pathology of malaria, though their mechanism of action is not completely elucidated. This field might bring up new treatment concepts and drugs. Drugs which prevent host pathology, such as the cerebral complications might be life saving.

Risk biomarker assessment for breast cancer progression: replication precision of nuclear morphometry.

Nuclear morphometry is a method for quantitative measurement of histopathologic changes in the appearance of stained cell nuclei. Numerous studies have indicated that these assessments may provide clinically relevant information related to the degree of progression and malignant potential of breast neoplasia. Nuclear features are derived from computerized analysis of digitized microscope images, and a quantitative Feulgen stain for DNA was used. Features analyzed included: (1) DNA content; (2) nuclear size and shape; and (3) texture features, describing spatial features of chromatin distribution. In this study replicated measurements are described on a series of 54 breast carcinoma specimens of differing pathologic grades. Duplicate measurements were performed using two serial sections, which were processed and analyzed separately. The value of a single feature measurement, the nuclear area profile, was shown to be the strongest indicator of progression. A quantitative nuclear grade was derived and shown to be strongly correlated with not only the pathologic nuclear grade, but also with tubule formation, mitotic grade, and with the overall histopathologic grade. Analysis of replication precision showed that the standard methods of the histopathology laboratory, if practiced in a uniform manner, are sufficient to ensure reproducibility of these assessments. We argue that nuclear morphometry provides a standardized and reproducible framework for quantitative pathologic assessments.