Required distal mesorectal resection margin in partial mesorectal excision: a systematic review on distal mesorectal spread.

BACKGROUND: The required distal margin in partial mesorectal excision (PME) is controversial. The aim of this systematic review was to determine incidence and distance of distal mesorectal spread (DMS). METHODS: A systematic search was performed using PubMed, Embase and Google Scholar databases. Articles eligible for inclusion were studies reporting on the presence of distal mesorectal spread in patients with rectal cancer who underwent radical resection. RESULTS: Out of 2493 articles, 22 studies with a total of 1921 patients were included, of whom 340 underwent long-course neoadjuvant chemoradiotherapy (CRT). DMS was reported in 207 of 1921 (10.8%) specimens (1.2% in CRT group and 12.8% in non-CRT group), with specified distance of DMS relative to the tumor in 84 (40.6%) of the cases. Mean and median DMS were 20.2 and 20.0 mm, respectively. Distal margins of 40 mm and 30 mm would result in 10% and 32% residual tumor, respectively, which translates into 1% and 4% overall residual cancer risk given 11% incidence of DMS. The maximum reported DMS was 50 mm in 1 of 84 cases. In subgroup analysis, for T3, the mean DMS was 18.8 mm (range 8-40 mm) and 27.2 mm (range 10-40 mm) for T4 rectal cancer. CONCLUSIONS: DMS occurred in 11% of cases, with a maximum of 50 mm in less than 1% of the DMS cases. For PME, substantial overtreatment is present if a distal margin of 5 cm is routinely utilized. Prospective studies evaluating more limited margins based on high-quality preoperative magnetic resonance imaging and pathological assessment are required.

Neurological and neurodevelopmental outcomes after human parechovirus CNS infection in neonates and young children: a systematic review and meta-analysis.

BACKGROUND: Human parechoviruses are a major cause of CNS infection in neonates and young children. They have been implicated in neurological sequelae and neurodevelopmental delay. However, the magnitude of this effect has not been systematically reviewed or assessed with meta-analyses. We investigated short-term, medium-term, and long-term neurological sequelae and neurodevelopmental delay in neonates and young children after parechovirus-CNS-infection. METHODS: In this systematic review and meta-analyses of studies, we searched PubMed, Embase, and PsycInfo, from the inception of the database until March 18, 2019, for reviews, systematic reviews, cohort studies, case series, and case control studies reporting on neurological or neurodevelopmental outcomes of children 3 months or younger with parechovirus infection of the CNS. Studies that were published after Dec 31, 2007, assessed children younger than 16 years, detailed parechoviruses infection of the CNS (confirmed by PCR), and followed up on neurological and neurodevelopmental outcomes were included. Studies published before Dec 31, 2007, were excluded. The predefined primary outcomes were the proportions of children with neurological sequelae, impairment in auditory or visual functions, or gross motor function delay. The proportion of children in whom neurological or neurodevelopmental outcomes were reported was pooled in meta-analyses. For each outcome variable we calculated the pooled proportion with 95% CI. The proportion of children in whom neurological or neurodevelopmental outcomes were reported was extracted by one author and checked by another. Two authors independently assessed the methodological quality of the studies. FINDINGS: 20 studies were eligible for quantitative synthesis. The meta-analyses showed an increasing proportion of children with neurological sequelae over time: 5% during short-term follow-up (pooled proportion 0·05 [95% CI 0·03-0·08], I2=0·00%; p=0·83) increasing to 27% during long-term follow-up (0·27 [0·17-0·40], I2=52·74%; p=0·026). The proportion of children with suspected neurodevelopmental delay was 9% or more during long-term follow-up. High heterogeneity and methodological issues in the included studies mean that the results should be interpreted with caution. INTERPRETATION: This systematic review suggests the importance of long follow-up, preferably up to preschool or school age (5-6 years), of children with parechovirus infection of the CNS. Although not clinically severe, we found an increasing proportion of neonates and young children with CNS infection had associated neurological sequelae and neurodevelopmental delay over time. We recommend the use of standardised methods to assess neurological and neurodevelopmental functions of these children and to compare results with age-matched reference groups. FUNDING: No funding was received for this study.

A systematic review on surgical treatment of primary epigastric hernias.

OBJECTIVE: In this systematic review, we evaluated all literature reporting on the surgical treatment of primary epigastric hernias, primarily focusing on studies comparing laparoscopic and open repair, and mesh reinforcement and suture repair. METHODS: A literature search was conducted in Embase.com, PubMed and the Cochrane Library up to 24 April 2019. This review explicitly excluded literature on incisional hernias, ventral hernias not otherwise specified, and isolated (para)umbilical hernias. Primary outcome measures of interest were early and late postoperative complications. RESULTS: We obtained a total of 8516 articles and after a strict selection only seven retrospective studies and one randomised controlled trial (RCT) on treatment of primary epigastric hernia were included. In one study (RCT) laparoscopic repair led to less postoperative pain (VAS) compared to open repair (3.6 versus 2.4, p < 0.001). No significant differences in early postoperative complications and recurrences were observed. Mesh reinforcement was associated with lower recurrence rates than suture repair in two studies (2.2% versus 5.6%, p = 0.001 and 3.1% versus 14.7%, p = 0.0475). This result was not sustained in all studies. No differences were observed in early postoperative complications after mesh or suture repair. CONCLUSIONS: This review demonstrated that studies investigating surgical treatment of primary epigastric hernias are scarce. The best available evidence suggests that mesh reinforcement in primary epigastric hernia repair possibily leads to less recurrences and that laparoscopic repair leads to less postoperative pain. Due to the high risk of selection bias of included studies and heterogenic study populations, no clear recommendations can be conducted. High-quality studies with well-defined patient groups and clear endpoints, primarily focusing on primary epigastric hernias, are mandatory.

Determinants of weight loss maintenance: a systematic review.

BACKGROUND: Discerning the determinants of weight loss maintenance is important in the planning of future interventions and policies regarding overweight and obesity. We have therefore systematically synthesized recent literature on determinants of weight loss maintenance for individuals with overweight and obesity. METHODS: With the use of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, prospective studies were identified from searches in PubMed and PsycINFO from 2006 to 2016. We included articles investigating adults with overweight and obesity undergoing weight loss without surgery or medication. Included articles were scored on their methodological quality, and a best-evidence synthesis was applied to summarize the results. RESULTS: Our search resulted in 8,222 articles of which 67 articles were selected. In total, 124 determinants were identified of which 5 were demographic, 59 were behavioural, 51 were psychological/cognitive and 9 were social and physical environmental determinants. We found consistent evidence that demographic determinants were not predictive of weight loss maintenance. Behavioural and cognitive determinants that promote a reduction in energy intake, an increase in energy expenditure and monitoring of this balance are predictive determinants. CONCLUSION: This review identifies key determinants in weight loss maintenance. However, more research regarding cognitive and environmental determinants of weight loss maintenance is needed to advance our knowledge on determinants of weight loss maintenance.

Optimal use of anti-EGFR monoclonal antibodies for patients with advanced colorectal cancer: a meta-analysis.

This meta-analysis was performed to determine the optimal use of anti-EGFR mAb in the treatment of metastasized colorectal cancer (mCRC). Seventeen randomized clinical trials were included, all evaluating the added value of anti-EGFR mAb to standard treatment line in patients with KRAS wild-type mCRC. Hazard and odds ratios were pooled using a random effect model, weighted according to cohort size. Pooled data of six first- and two second-line studies demonstrated a significantly improved ORR (OR 1.62, CI 1.27-2.04; OR 4.78, CI 3.39-6.75, respectively) and PFS (HR 0.79, CI 0.67-0.94; HR 0.80, CI 0.71-0.91, respectively) with the addition of anti-EGFR mAb to chemotherapy, while OS remained similar. Two third-line anti-EGFR mAb monotherapy studies revealed an improved PFS and OS (HR 0.44, CI 0.35-0.52; HR 0.55, CI 0.41-0.74). Addition of anti-EGFR versus anti-VEGF mAb to first-line chemotherapy was evaluated in three studies; ORR and PFS were comparable, while OS was improved (HR 0.8, CI 0.65-0.97). The influence of the chemotherapy backbone on anti-EGFR mAb efficacy, evaluated with meta-regression, indicated a higher ORR with irinotecan-based versus oxaliplatin-based regimens, but comparable PFS and OS. Reported toxicity (≥3 grade) increased ~20% in all treatment lines with the addition of anti-EGFR mAb. Anti-EGFR treatment significantly improves response and survival outcome of patients with (K)RAS wild-type mCRC, regardless of treatment line or chemotherapeutic backbone. Saving anti-EGFR mAb as third-line monotherapy is a valid and effective option to prevent high treatment burden caused by combination therapy. Combination treatment with anti-EGFR mAb to achieve radical resection of metastases needs further investigation.

Do grape polyphenols improve metabolic syndrome components? A systematic review.

BACKGROUND/OBJECTIVES: Epidemiological, in vitro and animal studies suggest that grape polyphenols, such as those present in wine, have favorable effects on the metabolic syndrome. However, controversy remains whether treatment with grape polyphenols is effective in humans. Here, we aimed to systemically review the effects of grape polyphenols on metabolic syndrome components in humans. SUBJECTS/METHODS: We systematically searched Medline, EMBASE and the Cochrane database for all clinical trials assessing the effects of grape polyphenols on insulin sensitivity, glycemia, blood pressure or lipid levels. We screened all titles and reviewed abstracts of potentially relevant studies. Full papers were assessed for eligibility and quality-rated according to the Jadad scale by two independent assessors. RESULTS: Thirty-nine studies met the eligibility criteria. In individuals without component criteria of the metabolic syndrome, only low- and medium-quality studies were found with primarily neutral results. In individuals with the metabolic syndrome or related conditions, one of two high-quality studies suggested improvement in insulin sensitivity. Glycemia was improved in 2 of 11 lower-quality studies and 2 of 4 high-quality studies. Seven of 22 studies demonstrated a significant decrease in blood pressure, but only one was of high quality. Two of four high-quality studies pointed towards effects on total cholesterol while other lipidemic parameters were not affected. CONCLUSIONS: No compelling data exist that grape polyphenols can positively influence glycemia, blood pressure or lipid levels in individuals with or without the metabolic syndrome. Limited evidence suggests that grape polyphenols may improve insulin sensitivity.

Does severe toxicity affect global quality of life in patients with metastatic colorectal cancer during palliative systemic treatment? A systematic review.

Background: New palliative systemic treatment regimens in patients with metastatic colorectal cancer (mCRC) have significantly improved overall survival and prognosis. These treatment regimens are often accompanied by increased toxicity, which may impair patients' quality of life (QOL). We systematically reviewed whether severe toxicity affects global QOL in patients with mCRC receiving palliative systemic treatment in recent published randomized controlled trials (RCTs). Materials and methods: Phase III RCTs evaluating palliative systemic treatments in patients with mCRC and published between 2004 and 2016 were considered. Studies were evaluated on the basis of global QOL scores, toxicity during treatment (assessed by scoring relevant adverse events) and primary outcomes (POs). Results: A total of 30 studies were identified in which 19863 patients were included. In 25 out of these 30 trials (83%), no difference in global QOL between treatment arms was observed. In contrast, 22 out of 30 trials (73%) showed increased toxicity during treatment in the experimental arm as compared with the control arm. In 19 out of 22 trials with higher toxicity (86%) global QOL outcomes remained unaffected or improved. In ten out of eleven studies with a better PO, no improvement in global QOL was seen. Conclusion: Global QOL of patients with mCRC included in phase III RCTs evaluating palliative systemic treatment did not differ across treatment arms despite consistently higher toxicity during treatment of the experimental compared with the standard treatment arms. Based on these findings we conclude that the use of global QOL for comparing treatment arms in RCTs for patients with mCRC does not provide information of clinical relevance. Further consideration of how to better assess the net effect of new agents on patients' QOL is urgently needed.

Quality specifications in postgraduate medical e-learning: an integrative literature review leading to a postgraduate medical e-learning model.

BACKGROUND: E-learning is driving major shifts in medical education. Prioritizing learning theories and quality models improves the success of e-learning programs. Although many e-learning quality standards are available, few are focused on postgraduate medical education. METHODS: We conducted an integrative review of the current postgraduate medical e-learning literature to identify quality specifications. The literature was thematically organized into a working model. RESULTS: Unique quality specifications (n = 72) were consolidated and re-organized into a six-domain model that we called the Postgraduate Medical E-learning Model (Postgraduate ME Model). This model was partially based on the ISO-19796 standard, and drew on cognitive load multimedia principles. The domains of the model are preparation, software design and system specifications, communication, content, assessment, and maintenance. CONCLUSION: This review clarified the current state of postgraduate medical e-learning standards and specifications. It also synthesized these specifications into a single working model. To validate our findings, the next-steps include testing the Postgraduate ME Model in controlled e-learning settings.

Strategies for disseminating recommendations or guidelines to patients: a systematic review.

BACKGROUND: The aim of this systematic literature review was to assess what dissemination strategies are feasible to inform and educate patients about recommendations (also known as guidelines). METHODS: The search was performed in February 2016 in PubMed, Ebsco/PsycINFO, Ebsco/CINAHL and Embase. Studies evaluating dissemination strategies, involving patients and/or reaching patients, were included. A hand search and a search in the grey literature, also done in February 2016, were added. Searches were not restricted by language or publication type. Publications that referred to (1) guideline(s) or recommendation(s), (2) dissemination, (3) dissemination with patients/patient organisations and (4) dissemination to patients/patient organisations were included in this article. Criteria 1 AND 2 were mandatory together with criteria 3 OR 4. RESULTS: The initial search revealed 3753 unique publications. Forty-seven articles met the inclusion criteria and were selected for detailed review. The hand search and grey literature resulted in four relevant articles. After reading the full text of the 47 articles, 21 were relevant for answering our research question. Most publications had low levels of evidence, 3 or 4 of the Oxford levels of evidence. One article had a level of evidence of 2(b). This article gives an overview of tools and strategies to disseminate recommendations to patients. Key factors of success were a dissemination plan, written at the start of the recommendation development process, involvement of patients in this development process and the use of a combination of traditional and innovative dissemination tools. The lack of strong evidence calls for more research of the effectiveness of different dissemination strategies as well as the barriers for implementing a strategic approach of dissemination. CONCLUSION: Our findings provide the first systematic overview of tools and strategies to disseminate recommendations to patients and patient organisations. Participation of patients in the whole process is one of the most important findings. These findings are relevant to develop, implement and evaluate more (effective) dissemination strategies which can improve health care.

Autologous fat grafting in onco-plastic breast reconstruction: A systematic review on oncological and radiological safety, complications, volume retention and patient/surgeon satisfaction.

OBJECTIVE: This study presents an up-to-date overview of the literature on autologous fat grafting (AFG) in onco-plastic breast reconstruction, with respect to complications, oncological and radiological safety, volume retention and patient/surgeon satisfaction. BACKGROUND: Although AFG is increasingly being applied in onco-plastic breast reconstruction, a comprehensive overview of the available evidence for this procedure is still lacking. METHODS: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was conducted. Case series, cohort studies and randomized controlled trials (RCTs) reporting on relevant outcomes of breast reconstruction with supplemental AFG were included. RESULTS: In total, 43 studies were included reporting on 6260 patients with a follow-up period ranging from 12 to 136 months. The average locoregional and distant oncological recurrence rates after breast reconstruction with AFG were 2.5% (95% confidence interval (CI) 1.7-3.7) and 2.0% (95% CI 1.1-3.5), respectively. Fewer cysts and calcifications were seen on radiological images for this procedure than for other types of breast surgery. However, more biopsies were performed based on radiological findings (3.7% vs. 1.6%), and more cases of fat necrosis (9.0% vs 4.7%) were seen after treatment with AFG. The total complication rate of 8.4% (95% CI 7.6-9.1) is lower than those reported following other reconstructive breast procedures. The mean volume retention was 76.8% (range 44.7-82.6%) with a satisfaction rate of 93.4% for patients and 90.1% for surgeons. CONCLUSIONS: AFG in breast reconstruction is a promising technique. Safety is not compromised as cancer recurrence and complications are not observed. Whether AFG interferes with radiological follow-up remains to be elucidated. Randomized trials with sound methodology are needed to confirm these conclusions.

Reproductive hormone concentrations in pregnancy and neonates: a systematic review.

Although much research focuses on hormones during gestation, little is known about the actual hormone concentrations within the fetal surroundings. The aim of this study was to combine all available oestrogen, androgen, sex hormone-binding globulin (SHBG), anti-Müllerian hormone (AMH), inhibin, gonadotrophin and dehydroepiandrosterone sulphate (DHEAS) concentrations during gestation and post partum into graphical representations reporting weighted mean hormone values. A systematic search was performed in Pubmed and Embase from inception to March 2012. Studies were evaluated by two reviewers; manuscripts were included if the actual hormone concentrations were reported together with the gestational age at time of sampling. A total of 97 articles were found eligible for this review. Maternal serum oestrogens, inhibin A, SHBG, androstenedione and testosterone rise during gestation, which is followed by a rapid decline in the post-partum period. For AMH and DHEAS, an inverse relationship is found, while gonadotrophin concentrations are negligible during gestation. For girls cord blood oestriol and post-partum FSH concentrations are higher, while for boys cord blood FSH and neonatal testosterone, inhibin B, LH and AMH concentrations are higher. In conclusion, longitudinally measured endocrine data during gestation and in the peri- and post-natal period are lacking, especially for twin pregnancies.

Why does ovarian surgery in PCOS help? Insight into the endocrine implications of ovarian surgery for ovulation induction in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a complex disorder with heterogeneity of clinical and endocrine features. Ovarian surgery for ovulation induction has been used in the management of clomiphene citrate-resistant anovulatory women with PCOS. Various types of ovarian surgery have been employed (wedge resection, electrocautery, laser vaporization, multiple ovarian biopsies and others) and all procedures result in an altered endocrine profile after surgery. The mechanism behind the reversal of endocrinological dysfunction in PCOS after ovarian surgery remains incompletely understood. This review scans the literature systematically to identify the endocrine changes after ovarian surgery in PCOS, in order to glean some knowledge of the mechanism involved. After ovarian surgery in PCOS, a rapid reduction in serum levels of all ovarian hormones is seen, in combination with increased serum levels of pituitary hormones. Folliculogenesis is then initiated and ovarian hormone production increases, synchronically with a reduction of pituitary hormones. Continuation of follicle growth in subsequent cycles after ovarian surgery occurs in an environment with less androgens and lower LH and FSH levels compared with pretreatment levels. The endocrine changes found after ovarian surgery in PCOS women seem to be governed by the ovaries themselves. Rapid reduced secretion of all ovarian hormones restores feedback to the hypothalamus and pituitary, resulting in appropriate gonadotrophin secretion. Initiation of follicular development seems to be induced by increasing FSH levels following a reduction of the follicle excess and (intra-ovarian) androgen levels. Additionally, anti-Müllerian hormone and gonadotrophin surge attenuating factor probably have a role in the endocrine changes.