Arthroscopic surgery for degenerative tears of the meniscus: a systematic review and meta-analysis

Background:

Arthroscopic surgery for degenerative meniscal tears is a commonly performed procedure, yet the role of conservative treatment for these patients is unclear. This systematic review and meta-analysis evaluates the efficacy of arthroscopic meniscal débridement in patients with knee pain in the setting of mild or no concurrent osteoarthritis of the knee in comparison with nonoperative or sham treatments.

Methods:

We searched MEDLINE, Embase and the Cochrane databases for randomized controlled trials (RCTs) published from 1946 to Jan. 20, 2014. Two reviewers independently screened all titles and abstracts for eligibility. We assessed risk of bias for all included studies and pooled outcomes using a random-effects model. Outcomes (i.e., function and pain relief) were dichotomized to short-term (< 6 mo) and long-term (< 2 yr) data.

Results:

Seven RCTs (n = 805 patients) were included in this review. The pooled treatment effect of arthroscopic surgery did not show a significant or minimally important difference (MID) between treatment arms for long-term functional outcomes (standardized mean difference [SMD] 0.07, 95% confidence interval [CI] −0.10 to 0.23). Short-term functional outcomes between groups were significant but did not exceed the threshold for MID (SMD 0.25, 95% CI 0.02 to 0.48). Arthroscopic surgery did not result in a significant improvement in pain scores in the short term (mean difference [MD] 0.20, 95% CI −0.67 to 0.26) or in the long term (MD −0.06, 95% CI −0.28 to 0.15). Statistical heterogeneity was low to moderate for the outcomes.

Interpretation:

There is moderate evidence to suggest that there is no benefit to arthroscopic meniscal débridement for degenerative meniscal tears in comparison with nonoperative or sham treatments in middle-aged patients with mild or no concomitant osteoarthritis. A trial of nonoperative management should be the first-line treatment for such patients.Arthroscopic meniscal débridement is one of the most commonly performed procedures in orthopedic surgery. More than 700 000 such procedures are performed each year in the United States, and more than 4 million are performed each year worldwide, with substantial economic and social burdens.^1–6 Many patients who undergo arthroscopic meniscal débridement have concurrent osteoarthritis, and orthopedic surgeons are often challenged to determine the true cause of patients’ symptoms: the meniscal tear, osteoarthritis or a combination of both.⁷Although 2 well-designed randomized controlled trials (RCTs)^8,9 have shown a lack of efficacy for arthroscopic surgery in patients with severe and advanced knee arthritis, many patients present with degenerative meniscal tears and mild or minimal concurrent osteoarthritis.¹⁰ Patients with degenerative meniscal tears in the setting of mild osteoarthritis may experience functional improvement or pain relief with arthroscopic surgery,^11–14 but the role of conservative treatment is unclear.^15–17 Arthroscopic surgery involves the potential for complications, which must be weighed against the prognosis for relief from presenting symptoms.^6,18The objective of this systematic review and meta-analysis was to evaluate the efficacy of arthroscopic meniscal débridement in comparison with nonoperative or sham treatments in patients with degenerative meniscal tears and knee pain with regard to function and pain relief in the short term (< 6 mo) and long term (< 2 yr).     

Externalized glycolytic enzymes are novel, conserved, and early biomarkers of apoptosis

The intriguing cell biology of apoptotic cell death results in the externalization of numerous autoantigens on the apoptotic cell surface, including protein determinants for specific recognition, linked to immune responses. Apoptotic cells are recognized by phagocytes and trigger an active immunosuppressive response ("innate apoptotic immunity" (IAI)) even in the absence of engulfment. IAI is responsible for the lack of inflammation associated normally with the clearance of apoptotic cells; its failure also has been linked to inflammatory and autoimmune pathology, including systemic lupus erythematosus and rheumatic diseases. Apoptotic recognition determinants underlying IAI have yet to be identified definitively; we argue that these molecules are surface-exposed (during apoptotic cell death), ubiquitously expressed, protease-sensitive, evolutionarily conserved, and resident normally in viable cells (SUPER). Using independent and unbiased quantitative proteomic approaches to characterize apoptotic cell surface proteins and identify candidate SUPER determinants, we made the surprising discovery that components of the glycolytic pathway are enriched on the apoptotic cell surface. Our data demonstrate that glycolytic enzyme externalization is a common and early aspect of cell death in different cell types triggered to die with distinct suicidal stimuli. Exposed glycolytic enzyme molecules meet the criteria for IAI-associated SUPER determinants. In addition, our characterization of the apoptosis-specific externalization of glycolytic enzyme molecules may provide insight into the significance of previously reported cases of plasminogen binding to α-enolase on mammalian cells, as well as mechanisms by which commensal bacteria and pathogens maintain immune privilege.     

Effect of early surgery after hip fracture on mortality and complications: systematic review and meta-analysis

Background

Guidelines exist for the surgical treatment of hip fracture, but the effect of early surgery on mortality and other outcomes that are important for patients remains unclear. We conducted a systematic review and meta-analysis to determine the effect of early surgery on the risk of death and common postoperative complications among elderly patients with hip fracture.

Methods

We searched electronic databases (including MEDLINE and EMBASE), the archives of meetings of orthopedic associations and the bibliographies of relevant articles and questioned experts to identify prospective studies, published in any language, that evaluated the effects of early surgery in patients undergoing procedures for hip fracture. Two reviewers independently assessed methodologic quality and extracted relevant data. We pooled data by means of the DerSimonian and Laird random-effects model, which is based on the inverse variance method.

Results

We identified 1939 citations, of which 16 observational studies met our inclusion criteria. These studies had a total of 13 478 patients for whom mortality data were complete (1764 total deaths). Based on the five studies that reported adjusted risk of death (4208 patients, 721 deaths), irrespective of the cut-off for delay (24, 48 or 72 hours), earlier surgery (i.e., within the cut-off time) was associated with a significant reduction in mortality (relative risk [RR] 0.81, 95% confidence interval [CI] 0.68–0.96, p = 0.01). Unadjusted data indicated that earlier surgery also reduced in-hospital pneumonia (RR 0.59, 95% CI 0.37–0.93, p = 0.02) and pressure sores (RR 0.48, 95% CI 0.34–0.69, p < 0.001).

Interpretation

Earlier surgery was associated with a lower risk of death and lower rates of postoperative pneumonia and pressure sores among elderly patients with hip fracture. These results suggest that reducing delays may reduce mortality and complications.Among elderly patients, hip fracture is associated with a one-year mortality rate ranging from 14% to 36%¹ and also with profound temporary and sometimes permanent impairment of independence and quality of life.² As the elderly population increases, the annual number of hip fractures globally is expected to exceed 7 million over the next 40 to 50 years.³Current guidelines⁴ indicate that surgery for hip fracture should be performed within 24 hours of injury, as earlier surgery has been associated with better functional outcome, shorter hospital stay, shorter duration of pain and lower rates of nonunion, postoperative complications and mortality.^5–11Proponents of early treatment argue that this approach minimizes the length of time a patient is confined to bed rest, thereby reducing the risk of associated complications, such as pressure sores, deep vein thrombosis and urinary tract infections.⁸ However, those favouring a delay believe it provides the opportunity to optimize patients’ medical status, thereby decreasing the risk of perioperative complications.⁸ A further challenge to resolving the debate is the lack of an accepted definition of early surgery.¹² Uncertainty exists about whether 24, 48 or 72 hours, or a longer period, should be considered to represent an “unacceptable delay” for hip fracture surgery.We undertook a systematic review and meta-analysis to inform this debate. More specifically, we addressed the following question: Among patients 60 years of age or older who underwent surgery for hip fracture, what was the effect of early surgery, relative to delayed surgery, on all-cause mortality and postoperative complications?     

Design and implementation of transaction privacy by virtue of ownership and traceability in blockchain based supply chain

Cluster Computing - Blockchain was at the top of the 2016 Gartner hype cycle and has been integrated into business profiles by numerous start-ups. Since the emergence of blockchain through Bitcoin,...     

Some Cardiomyopathy-Causing Troponin I Mutations Stabilize a Functional Intermediate Actin State

We examined four cardiomyopathy-causing mutations of troponin I that appear to disturb function by altering the distribution of thin filament states. The R193H (mouse) troponin I mutant had greater than normal actin-activated myosin-S1 ATPase activity in both the presence and absence of calcium. The rate of ATPase activity was the same as that of the wild-type at near-saturating concentrations of the activator, N-ethylmaleimide-S1. This mutant appeared to function by stabilizing the active state of thin filaments. Mutations D191H, R146G, and R146W had lower ATPase activities in the presence of calcium, but higher activities in the absence of calcium. These effects were most pronounced with mutations at position 146. For all three mutants the rates were similar to those of the wild-type at near-saturating concentrations of N-ethylmaleimide-S1. These results, combined with previous results, show that any alteration in the normal distribution of actomyosin states is capable of producing cardiomyopathy. The results of the D191H, R146G, and R146W mutations are most readily explained if the intermediate state of regulated actin has a unique function. The intermediate state appears to have an ability to accelerate the rate of ATP hydrolysis by myosin that exceeds that of the inactive state.     

Glucosamine prevents <Emphasis Type="Italic">in vitro</Emphasis> collagen degradation in chondrocytes by inhibiting advanced lipoxidation reactions and protein oxidation

Osteoarthritis (OA) affects a large segment of the aging population and is a major cause of pain and disability. At present, there is no specific treatment available to prevent or retard the cartilage destruction that occurs in OA. Recently, glucosamine sulfate has received attention as a putative agent that may retard cartilage degradation in OA. The precise mechanism of action of glucosamine is not known. We investigated the effect of glucosamine in an in vitro model of cartilage collagen degradation in which collagen degradation induced by activated chondrocytes is mediated by lipid peroxidation reaction. Lipid peroxidation in chondrocytes was measured by conjugated diene formation. Protein oxidation and aldehydic adduct formation were studied by immunoblot assays. Antioxidant effect of glucosamine was also tested on malondialdehyde (thiobarbituric acid-reactive substances [TBARS]) formation on purified lipoprotein oxidation for comparison. Glucosamine sulfate and glucosamine hydrochloride in millimolar (0.1 to 50) concentrations specifically and significantly inhibited collagen degradation induced by calcium ionophore-activated chondrocytes. Glucosamine hydrochloride did not inhibit lipid peroxidation reaction in either activated chondrocytes or in copper-induced oxidation of purified lipoproteins as measured by conjugated diene formation. Glucosamine hydrochloride, in a dose-dependent manner, inhibited malondialdehyde (TBARS) formation by oxidized lipoproteins. Moreover, we show that glucosamine hydrochloride prevents lipoprotein protein oxidation and inhibits malondialdehyde adduct formation in chondrocyte cell matrix, suggesting that it inhibits advanced lipoxidation reactions. Together, the data suggest that the mechanism of decreasing collagen degradation in this in vitro model system by glucosamine may be mediated by the inhibition of advanced lipoxidation reaction, preventing the oxidation and loss of collagen matrix from labeled chondrocyte matrix. Further studies are needed to relate these in vitro findings to the retardation of cartilage degradation reported in OA trials investigating glucosamine.     

Metabolic stress-induced programmed cell death in Xanthomonas

Xanthomonas campestris pv. glycines (Xcg), an etiological agent of the bacterial pustule disease of soybean, displayed nutritionally regulated caspase-dependent programmed cell death (PCD). Experiments showed that Xcg was under metabolic stress during PCD, as evident from the intracellular accumulation of NADH and ATP. Further, the accumulation of reactive oxygen species (ROS), as confirmed by 2',7'-dichlorofluorescein diacetate labeling, electron spin resonance spectroscopy, and scopoletin assay, was also observed along with the activation of caspase-3. ROS scavengers such as dimethylsulfoxide, glutathione, n-propyl gallate, and catalase significantly inhibited caspase biosynthesis as well as its activity, eventually leading to the inhibition of PCD. The presence of a sublethal concentration of an electron transport chain uncoupler, 2,4-dinitrophenol, was found to reduce the ROS generation and the increase in the cell survival. These results indicated that Xcg cells grown in a protein-rich medium experienced metabolic stress due to electron leakage from the electron transport chain, leading to the generation of ROS and the expression as well as the activation of caspase-3, and resulting in PCD. A bacterial DNA gyrase inhibitor, nalidixic acid, was also found to inhibit PCD. Gyrase, which regulates DNA superhelicity, and consequently DNA replication and cell multiplication, appears to be involved in the process.