Friday, September 28, 2012

The Effect of Smoking on Ligament and Cartilage Surgery in the Knee

The Effect of Smoking on Ligament and Cartilage Surgery in the Knee

The Effect of Smoking on Ligament and Cartilage Surgery in the Knee

A Systematic Review

  1. David C. Flanigan, MD*,
+ Author Affiliations
  1. *The Ohio State University Sports Medicine Center and Cartilage Restoration Program, Columbus, Ohio
  2. Department of Orthopedic Surgery, Washington University School of Medicine, St Louis, Missouri
  3. Penn Center for Advanced Cartilage Repair and Osteochondritis Dissecans Treatment Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
  4. §Department of Orthopaedic Surgery and Sports Medicine, University of Kentucky, Lexington, Kentucky
  5. Investigation performed at The Ohio State University Sports Medicine Center, Columbus, Ohio
  1. David C. Flanigan, MD, The Ohio State University Sports Medicine Center, 2050 Kenny Rd, Suite 3100, Columbus, OH 43221-3502 (e-mail: david.flanigan@osumc.edu).

Abstract

Background: The adverse effects of smoking on various health conditions such as cancer, diabetes, and cardiovascular disease have been well documented. Many orthopaedic conditions, such as fracture healing, wound repair, and bone mineral density, have been reported to be adversely affected by smoking. However, no known systematic reviews have investigated the effects of smoking on ligament and cartilage knee surgery.
Purpose: We hypothesized that smoking would have a negative influence from both a basic science and clinical outcome perspective on these types of knee surgeries.
Study Design: Systematic review.
Methods: A systematic review of multiple medical databases was performed evaluating clinical and basic science studies to determine the effects of smoking on ligament and cartilage knee surgery.
Results: Fourteen studies were found for inclusion and analysis. Eight of these studies addressed the relationship between smoking and knee ligaments, and 6 investigated the relationship between smoking and articular cartilage. With the exception of 1, all of the basic science and clinical studies exploring the relationship between smoking and knee ligaments found a negative association of smoking, either molecularly, biomechanically, or clinically. One basic science and 3 clinical studies found a negative influence of smoking on articular cartilage of the knee. No studies were found that investigated the relationship of smoking and menisci.
Conclusion: The current literature reveals a negative influence of smoking on the results of knee ligament surgery, both from a basic science and clinical perspective, implying that smoking cessation would benefit patients undergoing these procedures. The association between smoking and knee articular cartilage was less clear, although the literature still suggests an overall negative influence and highlights the need for further investigation.

Keywords:

Monday, September 24, 2012

New hydrogel may help cartilage regeneration research | Orthopedics

New hydrogel may help cartilage regeneration research | Orthopedics

New hydrogel may help cartilage regeneration research

  • September 24, 2012
A new synthesized hydrogel may help replace lost cartilage in joint replacement patients with osteoarthritis, according to Harvard researchers.
“For a gel to work in those settings, it has to be able to stretch and expand under compression and tension without breaking,” Jeong-Yun Sun, a postdoctoral fellow at the Harvard School of Engineering and Applied Sciences, stated in a press release.
Using a combination of polyacrylamide and alginate, the synthesized gel can stretch up to 21 times its size and is stronger than gels formed by either material alone, researchers said. Compared to other hydrogels often used as scaffolds for cartilage regeneration, this new “super gel” maintains its mechanical stability and elasticity over multiple stretches.
Sun and colleagues found that, even after the gel cracked, it was able to stretch to 17 times its own size. The researchers said they hope the gel will be an alternative to more invasive-based approaches, such as autologous chondrocyte implantation or joint replacement, in the treatment of patients with osteoarthritis.

A solution to reducing inflammation

A solution to reducing inflammation

Contact: Morwenna Grills
Morwenna.Grills@manchester.ac.uk
44-016-127-52111
University of Manchester

A solution to reducing inflammation

Research carried out at The University of Manchester has found further evidence that a simple solution, which is already used in IV drips, is an effective treatment for reducing inflammation.
The researchers also identified that hypertonic solution, which is a solution with an elevated concentration of salt, can ease inflammation purely through bathing in it – proving the Victorians were right to visit spa towns to "take the waters" for ailments like rheumatoid arthritis.
The research team, led by Dr Pablo Pelegrin, was investigating how cell swelling can control inflammation; the immune system's first response to injury or infection.
They discovered that white blood cells swell in a similar way to how tissue swells around a wound. The team then went on to look at what causes the swelling.
The researchers injected solutions with low ions into mice. They found that these solutions acted as a danger signal, causing cells to swell. The swelling then activates a group of proteins called NLRP3 which then release inflammatory mediators. These activate neighbouring cells to increase inflammation.
However, when a hypertonic solution was administered to the mouse it drew the water out of the cells shrinking them back to their original size. This in turn deactivated the signal for inflammation.
Dr Pelegrin's research provides further evidence for the use of hypertonic fluid therapy for the reduction of inflammation in the brain, a treatment that can reduce the amount of damage caused by illnesses such as stroke and epilepsy. His team has been able to show for the first time why the solution works at a molecular level.
Dr Pelegrin says: "Hypertonic solutions have been used in the treatment of stroke for many years. Clinicians have found that their use not only reduces brain swelling, but also alleviates brain inflammation. However, because there wasn't a molecular target for hypertonic solutions there has been a lot of debate about the clinical effect. Here we have indentified a target for hypertonic solutions by blocking the NLRP3 inflammasome which triggers inflammatory mediators at a molecular level".
The team also looked at the benefits of hypertonic solutions when used outside of the body. They soaked bandages in the solution before using them on the legs of mice. They also tested bathing the inflamed area in a hypertonic solution and in both cases the inflammation was reduced.
It appears the hypertonic solution produces an osmotic gradient through the skin, which explains why hot springs, which have a hypertonic make up, can ease the pain of conditions such as rheumatoid arthritis.
Vincent Compan worked with Dr Pelegrin on this research in the Faculty of Life Sciences. He says: "This research opens up exciting opportunities for the use of hypertonic solution as a treatment for inflammatory illnesses such as arthritis. What we've identified has the potential to be used to help so many patients."
Another aspect of the team's research identified that the signalling process to activate inflammation is one of the oldest evolutionary processes. The researchers found that the same mechanism of cell swelling causes NLRP3 inflammasome activation in fish as well as mammals. This means it is one of oldest responses in the body leading to inflammation.
The research has recently been published in the journal Immunity.

Anti-inflammatory cytoki... [Knee Surg Sports Traumatol Arthrosc. 2012] - PubMed - NCBI

Anti-inflammatory cytoki... [Knee Surg Sports Traumatol Arthrosc. 2012] - PubMed - NCBI

Knee Surg Sports Traumatol Arthrosc. 2012 Sep 15. [Epub ahead of print]

Anti-inflammatory cytokine profile in early human tendon repair.

Source

Integrative Orthopedic Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden, paul.ackermann@karolinska.se.

Abstract

PURPOSE:

The aim of this study was to assess inflammation and the presence and relative levels of cytokines, which may be involved in regulating early human Achilles tendon healing.

METHODS:

Nine patients with acute Achilles tendon rupture were included, operated on and post-operatively immobilized. Two weeks post-operatively, microdialysis of the peritendinous interstitial compartment was performed in the healing and intact contralateral Achilles tendons. Quantification of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70 and IL-17A was accomplished using a cytometric bead array. Prostaglandin (PG) E(2) levels were measured by enzyme immunoassay.

RESULTS:

None of the patients displayed detectable PGE(2) levels. Pro-inflammatory cytokines were below detection levels (IFNγ, IL-12, and IL-17) or did not differ between injured and control tendons (IL-1β and TNF). Notably, IL-6, IL-8 and IL-10 concentrations in the healing Achilles tendon were significantly elevated: 13-fold (p = 0.009), 28-fold (p = 0.02), and 3.7-fold (p = 0.03), respectively.

CONCLUSION:

At 2 weeks post-human Achilles tendon rupture, healing is characterized by a resolving inflammatory phase and up-regulation of IL-6, IL-8 and IL-10. The absence of inflammation suggests that at this time point, these cytokines may be associated with anti-inflammatory and regenerative effects on the tendon healing process.

Wednesday, September 12, 2012

Family history, gender affect survival of ACL graft at 15-year follow-up

Family history, gender affect survival of ACL graft at 15-year follow-up

Bourke H. Am J Sports Med. 2012. doi:10.1177/0363546512454414.

  • September 12, 2012
Patients who underwent primary ACL surgery 15 years ago report an 86% or higher survival rate for their graft at latest follow-up, according to this study.
Surgeons performed a single-incision endoscopic technique using either an autologous bone-patellar tendon-bone graft (BPTB) or hamstring tendon (HT) graft in 755 patients. At minimum 15 years follow-up, 689 patients completed a subjective questionnaire. The mean International Knee Documentation Committee subjective score was 85 at 15 years and 73% of patients reported return-to-sport preinjury levels, with 51% still performing strenuous or very strenuous activities, according to the abstract.
“Anterior cruciate ligament reconstruction using this technique is a reliable and reproducible procedure when using either the BPTB or HT autograft and allowed 73% of patients a return to their preinjury sports with an ACL graft rupture rate of less than 1% per year,” Henry E. Bourke, FRCS (Tr&Orth) stated in the study.
After the 2-, 5-, 10- and 15-year follow-up, expected survival of the ACL graft was 95%, 93%, 91% and 89%, respectively, according to the abstract. Expected survival of the contralateral ACL graft was 97%, 93%, 90% and 87% during the same respective follow-up periods. Although graft choice did not affect the risk of rupture, contralateral ACL grafts were twice as likely to rupture in the BPTB group as in the HT group.
Researchers also noted that risk factors for rupture included male gender, which lowered the chances of survival, and a family history of ACL rupture, which doubled the chances of rupture in both the ACL and contralateral ACL groups.

Clinician calls for further study on platelet-rich plasma formulations and impact

Clinician calls for further study on platelet-rich plasma formulations and impact

  • Orthopedics Today, September 2012
MONTREAL — While there is evidence of successful treatment using platelet-rich plasma for various pathologies, the lack of unfailing positive clinical outcomes points to variability among patients and materials, according to a lecturer at the International Cartilage Repair Society World Congress 2012.
In his lecture, Scott A. Rodeo, MD, described his and others’ clinical experiences with platelet-rich plasma (PRP). His message — more research is needed about these materials and understanding the variability inherent in PRP formulations, patients and their pathologies is key.
“One of the fundamental issues, as a clinician if you are thinking of using PRP, is the tremendous variability,” Rodeo, of the Hospital for Special Surgery in New York, said. “All PRPs are not the same. There is variability between the various commercial systems that are available. There is also variability, of course, within the individual patient and the underlying biology.”
Scott Rodeo 
Scott A. Rodeo
He noted that cytokines influence several biological aspects of connective tissue.
“Clearly, connective tissue healing requires a complex timing and sequence of cytokine expression, so the rationale and attraction of PRP is the ability to deliver numerous cytokines in potentially physiologically relevant proportions,” Rodeo said. “It is complex, and it is a bit of a leap of faith. In fact, despite vast basic science and laboratory data [that] demonstrate a positive effect of PRP on these tissues, this has not translated into a consistently positive clinical effect.”

Variability

A reason for this, Rodeo suggested, could be that PRP formulations differ among manufacturers and patients. Even within each individual, formulations can vary throughout the day.
With these variations, it becomes impossible to determine whether a formulation that works in one study will have the same effect in another patient for a similar application or what may be the content of a given formulation.
“What are we putting in the patient? With a drug, it is easy. We know it is a precise composition,” Rodeo said. “That contrasts with the PRP materials we are using in patients.”

Arthritis treatment

Although a number of studies have demonstrated a clinical improvement in symptoms after PRP injections for the treatment of arthritis, Rodeo noted that most of the data available refer only to the knee.
“There is little data for other joints,” he said. “Most studies do report better results in younger patients with lesser degrees of degeneration. The clinical effect typically wears off in 6 months to 12 months. There is little data demonstrating a positive structural effect — that is, actual cartilage regeneration — so it may be symptom-modifying but it is probably not structure-modifying.”
Rodeo noted that more research is needed about PRP.
“We certainly need more information,” he said. “Keep in mind, arthritis is a heterogeneous condition. The effect of a specific PRP formulation may differ significantly based on the underlying biologic or inflammatory milieu.”
He added, “Clinical results, clearly, are mixed. PRP seems to have the potential to be symptom-modifying, but clearly [it] does not appear to be structure-modifying.”
With regard to the variability of PRP, Rodeo noted clinicians must strive to understand what they are delivering to the patient. This means analyses of PRP samples, so these formulations can be correlated with clinical results.
“We know cytokines can increase production of matrix proteins, but a critical deficiency with all this work is that tissue microstructure is not reformed,” Rodeo said. “We do not regenerate normal cartilage, tendon or meniscus. [It] appears growth factors, such as PRP, still do not provide the proper cellular and molecular signals to truly drive regenerative healing. I would submit that both cells and the signals are needed to reconstitute both tissue composition and structure.” – by Robert Press
Reference:
  • Rodeo SA. Clinical experience with platelet-rich plasma. Paper 15.1.3. Presented at the International Cartilage Repair Society World Congress 2012. May 12-15. Montreal.

Saturday, September 8, 2012

Highly stretchable and tough hydrogels : Nature : Nature Publishing Group

Highly stretchable and tough hydrogels : Nature : Nature Publishing Group

Highly stretchable and tough hydrogels

Nature
489,
133–136
(06 September 2012)
doi:10.1038/nature11409
Received
Accepted
Published online
Hydrogels are used as scaffolds for tissue engineering1, vehicles for drug delivery2, actuators for optics and fluidics3, and model extracellular matrices for biological studies4. The scope of hydrogel applications, however, is often severely limited by their mechanical behaviour5. Most hydrogels do not exhibit high stretchability; for example, an alginate hydrogel ruptures when stretched to about 1.2 times its original length. Some synthetic elastic hydrogels6, 7 have achieved stretches in the range 10–20, but these values are markedly reduced in samples containing notches. Most hydrogels are brittle, with fracture energies of about 10Jm−2 (ref. 8), as compared with ~1,000Jm−2 for cartilage9 and ~10,000Jm−2 for natural rubbers10. Intense efforts are devoted to synthesizing hydrogels with improved mechanical properties11, 12, 13, 14, 15, 16, 17, 18; certain synthetic gels have reached fracture energies of 100–1,000Jm−2 (refs 11, 14, 17). Here we report the synthesis of hydrogels from polymers forming ionically and covalently crosslinked networks. Although such gels contain ~90% water, they can be stretched beyond 20 times their initial length, and have fracture energies of ~9,000Jm−2. Even for samples containing notches, a stretch of 17 is demonstrated. We attribute the gels’ toughness to the synergy of two mechanisms: crack bridging by the network of covalent crosslinks, and hysteresis by unzipping the network of ionic crosslinks. Furthermore, the network of covalent crosslinks preserves the memory of the initial state, so that much of the large deformation is removed on unloading. The unzipped ionic crosslinks cause internal damage, which heals by re-zipping. These gels may serve as model systems to explore mechanisms of deformation and energy dissipation, and expand the scope of hydrogel applications.

Friday, September 7, 2012

The Madman :: How I Became a Madman

The Madman :: How I Became a Madman

You ask me how I became a madman. It happened thus: One day, long before many gods were born, I woke from a deep sleep and found all my masks were stolen -- the seven masks I have fashioned and worn in seven lives, -- I ran maskless through the crowded streets shouting, "Thieves, thieves, the curséd thieves."
Men and women laughed at me and some ran to their houses in fear of me.
And when I reached the market place, a youth standing on a house-top cried, "He is a madman." I looked up to behold him; the sun kissed my own naked face for the first time. For the first time the sun kissed my own naked face and my soul was inflamed with love for the sun, and I wanted my masks no more. And as if in a trance I cried, "Blessed, blessed are the thieves who stole my masks."
Thus I became a madman.
And I have found both freedom and safety in my madness; the freedom of loneliness and the safety from being understood, for those who understand us enslave something in us.
But let me not be too proud of my safety. Even a Thief in a jail is safe from another thief.