The quality of research synthesis in surgery: the case of laparoscopic surgery for colorectal cancer

Peer reviewedPublisher PD

Rapid Covalent-Probe Discovery by Electrophile-Fragment Screening

Covalent probes can display unmatched potency, selectivity, and duration of action; however, their discovery is challenging. In principle, fragments that can irreversibly bind their target can overcome the low affinity that limits reversible fragment screening, but such electrophilic fragments were considered nonselective and were rarely screened. We hypothesized that mild electrophiles might overcome the selectivity challenge and constructed a library of 993 mildly electrophilic fragments. We characterized this library by a new high-throughput thiol-reactivity assay and screened them against 10 cysteine-containing proteins. Highly reactive and promiscuous fragments were rare and could be easily eliminated. In contrast, we found hits for most targets. Combining our approach with high-throughput crystallography allowed rapid progression to potent and selective probes for two enzymes, the deubiquitinase OTUB2 and the pyrophosphatase NUDT7. No inhibitors were previously known for either. This study highlights the potential of electrophile-fragment screening as a practical and efficient tool for covalent-ligand discovery

Migraine in women: the role of hormones and their impact on vascular diseases

Migraine is a predominantly female disorder. Menarche, menstruation, pregnancy, and menopause, and also the use of hormonal contraceptives and hormone replacement treatment may influence migraine occurrence. Migraine usually starts after menarche, occurs more frequently in the days just before or during menstruation, and ameliorates during pregnancy and menopause. Those variations are mediated by fluctuation of estrogen levels through their influence on cellular excitability or cerebral vasculature. Moreover, administration of exogenous hormones may cause worsening of migraine as may expose migrainous women to an increased risk of vascular disease. In fact, migraine with aura represents a risk factor for stroke, cardiac disease, and vascular mortality. Studies have shown that administration of combined oral contraceptives to migraineurs may further increase the risk for ischemic stroke. Consequently, in women suffering from migraine with aura caution should be deserved when prescribing combined oral contraceptives

Italian guidelines for primary headaches: 2012 revised version

The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105–190 (2001). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedicated to non-pharmacological treatment. This article reports a summary of the revised version published in extenso in an Italian version

Laparoscopic extraperitoneal rectal cancer surgery: the clinical practice guidelines of the European Association for Endoscopic Surgery (EAES)

BACKGROUND: The laparoscopic approach is increasingly applied in colorectal surgery. Although laparoscopic surgery in colon cancer has been proved to be safe and feasible with equivalent long-term oncological outcome compared to open surgery, safety and long-term oncological outcome of laparoscopic surgery for rectal cancer remain controversial. Laparoscopic rectal cancer surgery might be efficacious, but indications and limitations are not clearly defined. Therefore, the European Association for Endoscopic Surgery (EAES) has developed this clinical practice guideline. METHODS: An international expert panel was invited to appraise the current literature and to develop evidence-based recommendations. The expert panel constituted for a consensus development conference in May 2010. Thereafter, the recommendations were presented at the annual congress of the EAES in Geneva in June 2010 in a plenary session. A second consensus process (Delphi process) of the recommendations with the explanatory text was necessary due to the changes after the consensus conference. RESULTS: Laparoscopic surgery for extraperitoneal (mid- and low-) rectal cancer is feasible and widely accepted. The laparoscopic approach must offer the same quality of surgical specimen as in open surgery. Short-term outcomes such as bowel function, surgical-site infections, pain and hospital stay are slightly improved with the laparoscopic approach. Laparoscopic resection of rectal cancer is not inferior to the open in terms of disease-free survival, overall survival or local recurrence. Laparoscopic pelvic dissection may impair genitourinary and sexual function after rectal resection, like in open surgery. CONCLUSIONS: Laparoscopic surgery for mid- and low-rectal cancer can be recommended under optimal conditions. Still, most level 1 evidence is for colon cancer surgery rather than rectal cancer. Upcoming results from large randomised trials are awaited to strengthen the evidence for improved short-term results and equal long-term results in comparison with the open approach.</p

Saying no to the staff: an analysis of refusals in a care home for people with severe communication difficulties.

People with severe communication difficulties may attempt to exercise control over their lives by verbally or non-verbally refusing an activity proposed by supporters. We detail examples in which such refusals are treated by care home staff as a temporary reluctance, warranting further attempts to persuade the individual to co-operate. We identify the following conversational (and bodily) practices by which staff achieve their institutional ends: appreciating a resident's behaviour as something other than refusal; formulating the invitation again in a no-blame format; minimising the task required; escalating the invitation to a request and an order; moving the person bodily; and positively glossing the proceedings. Dealing with refusals illustrates the dilemma faced by institutional personnel in health and care settings in accepting choices which might disrupt the efficient management of the service

Systematic review of quality of life following laparoscopic and open colorectal surgery

Objective To compare the health-related quality of life (HRQoL) of patients following laparoscopic and open colorectal surgery. Method A systematic review was performed according to Quorum guidelines. Prospective studies comparing the HRQoL of patients after laparoscopic and open colorectal surgery were identified. The primary outcome measure was postoperative quality of life; performance status and cosmesis were secondary outcome measures. Results Twenty-three studies were identified that satisfied the inclusion criteria; 18 assessed HRQoL, four performance status, and three cosmesis. It was not possible to perform a meta-analysis due to study heterogeneity. The studies reported outcomes for 2946 patients. The most frequent HRQoL instruments employed were Short Form 36, European Organization for Research and Treatment of Cancer, and gastrointestinal quality of life index. Six studies, using a total of 12 separate measures, evaluated QoL during the first three postoperative months: 10 of these measures showed no significant difference, and two showed an improved HRQoL with laparoscopy. Twelve further studies evaluated HRQoL up to 5 years postoperatively: nine showed no difference between the two groups, and three demonstrated a benefit for laparoscopy. Three of four studies assessing performance status on discharge, and all three studies assessing cosmesis, reported benefits with the laparoscopic approach. Conclusions The current evidence suggests there is no significant difference in HRQoL following laparoscopic and open colorectal surgery, although there is a lack of good quality data. There is a trend towards improved quality of life outcomes and performance status with laparoscopy in the early postoperative period. There is a need for further research, particularly assessing quality of life in the early postoperative period

Systematic review of quality of life following laparoscopic and open colorectal surgery

Objective To compare the health-related quality of life (HRQoL) of patients following laparoscopic and open colorectal surgery. Method A systematic review was performed according to Quorum guidelines. Prospective studies comparing the HRQoL of patients after laparoscopic and open colorectal surgery were identified. The primary outcome measure was postoperative quality of life; performance status and cosmesis were secondary outcome measures. Results Twenty-three studies were identified that satisfied the inclusion criteria; 18 assessed HRQoL, four performance status, and three cosmesis. It was not possible to perform a meta-analysis due to study heterogeneity. The studies reported outcomes for 2946 patients. The most frequent HRQoL instruments employed were Short Form 36, European Organization for Research and Treatment of Cancer, and gastrointestinal quality of life index. Six studies, using a total of 12 separate measures, evaluated QoL during the first three postoperative months: 10 of these measures showed no significant difference, and two showed an improved HRQoL with laparoscopy. Twelve further studies evaluated HRQoL up to 5 years postoperatively: nine showed no difference between the two groups, and three demonstrated a benefit for laparoscopy. Three of four studies assessing performance status on discharge, and all three studies assessing cosmesis, reported benefits with the laparoscopic approach. Conclusions The current evidence suggests there is no significant difference in HRQoL following laparoscopic and open colorectal surgery, although there is a lack of good quality data. There is a trend towards improved quality of life outcomes and performance status with laparoscopy in the early postoperative period. There is a need for further research, particularly assessing quality of life in the early postoperative period

The ground-based mimicking of space continuous-flow electrop horesis electrohydromechanics

通过相似性分析得到了空间连续流电流体力学过程地基模拟的相似性准则，数值模拟表明，所得相似性准则是有效（近似）的，基于此，建立了空间连续流电泳电流体力学过程地基模拟实验系统，并进行了生物样品分离实验，当然，相似准则的最终检验有待于空间实验