Background
The functional and clinical basis on which to choose whether or not to retain the posterior cruciate ligament during total knee arthroplasty surgery remained unclear after a Cochrane ...systematic review and meta‐analysis in 2005, which contained eight clinical trials. Several new trials have been conducted since then. Hence, an update of the review was performed.
Objectives
Our aim was to assess the benefits and harms of retention compared to sacrifice of the posterior cruciate ligament in total knee arthroplasty in patients with osteoarthritis of the knee.
Search methods
An extensive search was conducted in CENTRAL, MEDLINE (PubMed), EMBASE, Web of Science, CINAHL, Academic Search Premier, Current Contents Connect and Science Direct. All databases were searched, without any limitations, up to 6 December 2012. References of the articles were checked and citation tracking was performed.
Selection criteria
Randomised and quasi‐randomised controlled trials comparing retention with sacrifice of the posterior cruciate ligament in primary total knee arthroplasty in patients with osteoarthritis of the knee.
Data collection and analysis
Data were collected with a pre‐developed form. Risk of bias was assessed independently by two authors (WV, LB). The level of evidence was graded using the GRADE approach. Meta‐analysis was performed by pooling the results of the selected studies, when possible. Subgroup analyses were performed for posterior cruciate ligament retention versus sacrifice using the same total knee arthroplasty design, and for studies using a posterior cruciate ligament retaining or posterior stabilised design, and when sufficient studies were available subgroup analyses were performed for the same brand.
Main results
Seventeen randomised controlled trials (with 1810 patients and 2206 knees) were found, described in 18 articles. Ten of these were new studies compared to the previous Cochrane Review. One study from the original Cochrane review was excluded. Most new studies compared a posterior cruciate ligament retaining design with a posterior stabilised design, in which the posterior cruciate ligament is sacrificed (a posterior stabilised design has an insert with a central post which can engage on a femoral cam during flexion).
The quality of evidence (graded with the GRADE approach) and the risk of bias were highly variable, ranging from moderate to low quality evidence and with unclear or low risk of bias for most domains, respectively.
The performance outcome 'range of motion' was 2.4 ° higher in favour of posterior cruciate ligament sacrifice (118.3 ° versus 115.9 °; 95% confidence interval (CI) of the difference 0.13 to 4.67; P = 0.04), however the results were heterogeneous. On the item 'knee pain' as experienced by patients, meta‐analysis could be performed on the Knee Society knee pain score; this score was 48.3 in both groups, yielding no difference between the groups. Implant survival rate could not be meta‐analysed adequately since randomised controlled trials lack the longer term follow‐up in order to evaluate implant survival. A total of four revisions in the cruciate‐retention and four revisions in the cruciate‐sacrifice group were found. The well‐validated Western Ontario and McMaster Universities osteoarthritis index (WOMAC) total score was not statistically significantly different between the groups (16.6 points for cruciate‐retention versus 15.0 points for cruciate‐sacrifice). One study reported a patient satisfaction grade (7.7 points for cruciate‐retention versus 7.9 points for cruciate‐sacrifice on a scale from 0 to 10, 10 being completely satisfied) which did not differ statistically significantly. Complications were distributed equally between both groups. Only one study reported several re‐operations other than revision surgery; that is patella luxations, surgical manipulation because of impaired flexion.
The mean functional Knee Society Score was 2.3 points higher (81.2 versus 79.0 points; 95% CI of the difference 0.37 to 4.26; P = 0.02) in the posterior cruciate ligament sacrificing group. Results from the outcome Knee Society functional score were homogeneous. All other outcome measures (extension angle, knee pain, adverse effects, clinical questionnaire scores, Knee Society clinical scores, radiological rollback, radiolucencies, femorotibial angle and tibial slope) showed no statistically significant differences between the groups. In the subgroup analyses that allowed pooling of the results of the different studies, no homogeneous statistically significant differences were identified.
Authors' conclusions
The methodological quality and the quality of reporting of the studies were highly variable. With respect to range of motion, pain, clinical, and radiological outcomes, no clinically relevant differences were found between total knee arthroplasty with retention or sacrifice of the posterior cruciate ligament. Two statistically significant differences were found; range of motion was 2.4 ° higher in the posterior cruciate ligament sacrificing group, however results were heterogeneous; and the mean functional Knee Society Score was 2.3 points higher in the posterior cruciate ligament sacrificing group. These differences are clinically not relevant.
Summary Background Case series suggest that laparoscopic peritoneal lavage might be a promising alternative to sigmoidectomy in patients with perforated diverticulitis. We aimed to assess the ...superiority of laparoscopic lavage compared with sigmoidectomy in patients with purulent perforated diverticulitis, with respect to overall long-term morbidity and mortality. Methods We did a multicentre, parallel-group, randomised, open-label trial in 34 teaching hospitals and eight academic hospitals in Belgium, Italy, and the Netherlands (the Ladies trial). The Ladies trial is split into two groups: the LOLA group comparing laparoscopic lavage with sigmoidectomy and the DIVA group comparing Hartmann's procedure with sigmoidectomy plus primary anastomosis. The DIVA section of this trial is still underway but here we report the results of the LOLA section. Patients with purulent perforated diverticulitis were enrolled for LOLA, excluding patients with faecal peritonitis, aged older than 85 years, with high-dose steroid use (≥20 mg daily), and haemodynamic instability. Patients were randomly assigned (2:1:1; stratified by age <60 years vs ≥60 years) using secure online computer randomisation to laparoscopic lavage, Hartmann's procedure, or primary anastomosis in a parallel design after diagnostic laparoscopy. Patients were analysed according to a modified intention-to-treat principle and were followed up after the index operation at least once in the outpatient setting and after sigmoidoscopy and stoma reversal, according to local protocols. The primary endpoint was a composite endpoint of major morbidity and mortality within 12 months. This trial is registered with ClinicalTrials.gov , number NCT01317485. Findings Between July 1, 2010, and Feb 22, 2013, 90 patients were randomly assigned in the LOLA section of the Ladies trial when the study was terminated by the data and safety monitoring board because of an increased event rate in the lavage group. Two patients were excluded for protocol violations. The primary endpoint occurred in 30 (67%) of 45 patients in the lavage group and 25 (60%) of 42 patients in the sigmoidectomy group (odds ratio 1·28, 95% CI 0·54–3·03, p=0·58). By 12 months, four patients had died after lavage and six patients had died after sigmoidectomy (p=0·43). Interpretation Laparoscopic lavage is not superior to sigmoidectomy for the treatment of purulent perforated diverticulitis. Funding Netherlands Organisation for Health Research and Development.
Background
This study aimed to compare laparoscopic lavage and sigmoidectomy as treatment for perforated diverticulitis with purulent peritonitis during a 36 month follow-up of the LOLA trial.
...Methods
Within the LOLA arm of the international, multicentre LADIES trial, patients with perforated diverticulitis with purulent peritonitis were randomised between laparoscopic lavage and sigmoidectomy. Outcomes were collected up to 36 months. The primary outcome of the present study was cumulative morbidity and mortality. Secondary outcomes included reoperations (including stoma reversals), stoma rates, and sigmoidectomy rates in the lavage group.
Results
Long-term follow-up was recorded in 77 of the 88 originally included patients, 39 were randomised to sigmoidectomy (51%) and 38 to laparoscopic lavage (49%). After 36 months, overall cumulative morbidity (sigmoidectomy 28/39 (72%) versus lavage 32/38 (84%),
p
= 0·272) and mortality (sigmoidectomy 7/39 (18%) versus lavage 6/38 (16%),
p
= 1·000) did not differ. The number of patients who underwent a reoperation was significantly lower for lavage compared to sigmoidectomy (sigmoidectomy 27/39 (69%) versus lavage 17/38 (45%),
p
= 0·039). After 36 months, patients alive with stoma in situ was lower in the lavage group (proportion calculated from the Kaplan–Meier life table, sigmoidectomy 17% vs lavage 11%, log-rank
p
= 0·0268). Eventually, 17 of 38 (45%) patients allocated to lavage underwent sigmoidectomy.
Conclusion
Long-term outcomes showed that laparoscopic lavage was associated with less patients who underwent reoperations and lower stoma rates in patients alive after 36 months compared to sigmoidectomy. No differences were found in terms of cumulative morbidity or mortality. Patient selection should be improved to reduce risk for short-term complications after which lavage could still be a valuable treatment option.
Graphical abstract
New diagnostics and vaccines for tuberculosis (TB) are urgently needed, but require an understanding of the requirements for protection from/susceptibility to TB. Previous studies have used unbiased ...approaches to determine gene signatures in single-site populations. The present study utilized a targeted approach, reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA), to validate these genes in a multisite study. We analysed ex vivo whole blood RNA from a total of 523 participants across four sub-Saharan countries (Ethiopia, Malawi, South Africa, and The Gambia) with differences in TB and human immunodeficiency virus (HIV) status. We found a number of genes that were expressed at significantly lower levels in participants with active disease than in those with latent TB infection (LTBI), with restoration following successful TB treatment. The most consistent classifier of active disease was FCGR1A (high-affinity IgG Fc receptor 1 (CD64)), which was the only marker expressed at significantly higher levels in participants with active TB than in those with LTBI before treatment regardless of HIV status or genetic background. This is the first study to identify a biomarker for TB that is not affected by HIV status or geo-genetic differences. These data provide valuable clues for understanding TB pathogenesis, and also provide a proof-of-concept for the use of RT-MLPA in rapid and inexpensive validation of unbiased gene expression findings.
Abstract
Microfluidic systems enable automated and highly parallelized cell culture with low volumes and defined liquid dosing. To achieve this, systems typically integrate all functions into a ...single, monolithic device as a “one size fits all” solution. However, this approach limits the end users’ (re)design flexibility and complicates the addition of new functions to the system. To address this challenge, we propose and demonstrate a modular and standardized plug-and-play fluidic circuit board (FCB) for operating microfluidic building blocks (MFBBs), whereby both the FCB and the MFBBs contain integrated valves. A single FCB can parallelize up to three MFBBs of the same design or operate MFBBs with entirely different architectures. The operation of the MFBBs through the FCB is fully automated and does not incur the cost of an extra external footprint. We use this modular platform to control three microfluidic large-scale integration (mLSI) MFBBs, each of which features 64 microchambers suitable for cell culturing with high spatiotemporal control. We show as a proof of principle that we can culture human umbilical vein endothelial cells (HUVECs) for multiple days in the chambers of this MFBB. Moreover, we also use the same FCB to control an MFBB for liquid dosing with a high dynamic range. Our results demonstrate that MFBBs with different designs can be controlled and combined on a single FCB. Our novel modular approach to operating an automated microfluidic system for parallelized cell culture will enable greater experimental flexibility and facilitate the cooperation of different chips from different labs.
Dynamic flavor release curves from chewing gum were measured using an Artificial Mouth coupled to the AFFIRM®. A flavor distribution model for chewing gum is proposed, where flavor is present as ...droplets in both the hydrophilic (water-soluble) and the hydrophobic (water insoluble) parts of the chewing gum and as molecularly dissolved in the hydrophobic part of the gum. During mastication, the flavor droplets in the water-soluble phase are released and responsible for an initial burst release. The flavor droplets captured in the gum-base are pushed towards the interface by mastication and are responsible for the subsequent release. The flavor molecules dissolved in the gum-base, released by diffusion, are only responsible for the release at very long time scales. It was found that the oil-water partition constant is an important parameter to explain the flavor release, where hydrophobic components show slower and longer release, while more hydrophilic components show more burst release.
Display omitted
•Initial flavor release is primarily induced due to the washing out of the water phase.•Flavor release at later times is caused by release of oil + flavor droplets during mastication.•Release of flavors through diffusion is negligible.•The hydrophobicity of the flavor compound predicts its release from the chewing gum.•Less than 4% of the flavor is released during a 15 min mastication period.
The appendix, an organ of immunological and microbiological importance, could be involved in the pathogenesis of cancers, but results are inconclusive. Our objective was to assess the association ...between appendectomy and the subsequent risk of cancer.
Data were obtained from the Rotterdam Study; a long-term prospective population-based study of individuals aged 55 years and older, of which the first cohort started in 1990 and included 7983 participants. Information on appendectomy was obtained through either medical interview at baseline or linkage with the national automated pathology center (PALGA). Cancer cases were pathology based. End of follow-up was January 1st, 2015. The association between appendectomy and risk of cancer was assessed using Cox proportional hazard models, adjusted for known confounders.
Of 7135 included participants, 1373 (19.2%) had undergone an appendectomy and 1632 individuals developed cancer. After adjustment for age, sex, socioeconomic status, BMI, smoking, prevalent diabetes mellitus and alcohol intake, a history of appendectomy was associated with a significantly lower risk of cancer hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.75-0.98. Subgroup analyses showed similar results for gastrointestinal cancer (HR 0.75, 95% CI 0.56-0.99), in particular colon cancer (HR 0.65, 95% 0.43-0.97), and cancer of the female reproductive organs (HR 0.35, 95% CI 0.15-0.80).
Participants who underwent an appendectomy had a reduced risk of cancer in general after adjustment for potential confounders. Therefore, these results contradict earlier studies suggestive of an increased risk. Further research is necessary to replicate these results and reveal its underlying mechanism.
•History of appendectomy is not associated with an increased risk of developing cancer.•Risk of developing gastro-intestinal cancer was decreased after appendectomy.•Similar decreased risks were found in colorectal and female reproductive organs cancer.•This is the first prospective study on this topic to adjust for potential confounders other than age and sex.
SETTING: Patients with smear-positive, newly diagnosed pulmonary tuberculosis (TB) presenting to the out- patient TB clinic in Kampala, Uganda.OBJECTIVE: To compare colony-forming unit (cfu) counting ...and time to positive (TTP) in Mycobacteria Growth Indicator Tube (MGIT) culture
as measures of early bactericidal activity (EBA).DESIGN: Patients were enrolled in an EBA feasibility study of standard TB chemotherapy. Sixteen-hour overnight sputum collections were obtained before and on days 2, 4, 7, 10, 12 and 14 of treatment for quantitative culture on selective
Middlebrook 7H11 agar media and TTP in the MGIT liquid culture system.RESULTS: Log cfu and TTP were correlated over all time points (rs = −0.71, P < 0.001). Within-subject (day to day) variation as a percentage of total variation was very similar between
the two measures: 25.7% for cfu and 25% for TTP. Mean EBA 0-14, 0-2 and 2-14 measured by TTP were similar to those previously reported.CONCLUSION: TTP measured by an automated, standardized, commercially available culture system correlates with cfu determinations. EBA
measured by TTP provides similar information to cfu counting, and is reproducible across sites and in different patient populations. These findings support replacing cfu counting with TTP as the primary measurement in EBA studies.
Summary Testing new drugs is critical to improving the treatment of tuberculosis. Quantitative cultures of Mycobacterium tuberculosis on solid media have been used in Phase 1 and 2 trials, but are ...time and resource intensive. Time to detection (TTD) of growth of M. tuberculosis in automated liquid culture systems is an alternative. TTD has been shown to correlate with CFU in quantitative cultures, and is faster and simpler to perform. We compared TTD in the BACTEC 460 liquid culture system with CFU in a clinical trial that included 110 subjects. Comparing all sputum cultures collected between baseline and 2 months we found a strong negative correlation between log10 CFU and TTD (rho = −0.91). In addition, when TTD at baseline was compared with 1 and 2 month sputum culture positivity, subjects whose cultures were negative after 1 and 2 months had a significantly longer median baseline TTD compared with subjects whose cultures were positive at 1 and 2 months (5 vs. 3 days and 3 vs. 2 days, respectively). TTD compares closely with CFU and represents a faster, simpler alternative to quantitative cultures.
Recently, excellent results are reported on laparoscopic lavage in patients with purulent perforated diverticulitis as an alternative for sigmoidectomy and ostomy.The objective of this study is to ...determine whether LaparOscopic LAvage and drainage is a safe and effective treatment for patients with purulent peritonitis (LOLA-arm) and to determine the optimal resectional strategy in patients with a purulent or faecal peritonitis (DIVA-arm: perforated DIVerticulitis: sigmoidresection with or without Anastomosis).
In this multicentre randomised trial all patients with perforated diverticulitis are included. Upon laparoscopy, patients with purulent peritonitis are treated with laparoscopic lavage and drainage, Hartmann's procedure or sigmoidectomy with primary anastomosis in a ratio of 2:1:1 (LOLA-arm). Patients with faecal peritonitis will be randomised 1:1 between Hartmann's procedure and resection with primary anastomosis (DIVA-arm). The primary combined endpoint of the LOLA-arm is major morbidity and mortality. A sample size of 132:66:66 patients will be able to detect a difference in the primary endpoint from 25% in resectional groups compared to 10% in the laparoscopic lavage group (two sided alpha = 5%, power = 90%). Endpoint of the DIVA-arm is stoma free survival one year after initial surgery. In this arm 212 patients are needed to significantly demonstrate a difference of 30% (log rank test two sided alpha = 5% and power = 90%) in favour of the patients with resection with primary anastomosis. Secondary endpoints for both arms are the number of days alive and outside the hospital, health related quality of life, health care utilisation and associated costs.
The Ladies trial is a nationwide multicentre randomised trial on perforated diverticulitis that will provide evidence on the merits of laparoscopic lavage and drainage for purulent generalised peritonitis and on the optimal resectional strategy for both purulent and faecal generalised peritonitis.
Nederlands Trial Register NTR2037.