Skeletal metastases are often accompanied by bone pain. To investigate the clinical meaning of bone pain associated with skeletal metastasis in breast cancer patients after surgery, we explored whether the presence of bone pain was due to skeletal-related events (SREs) or survival , retrospectively.Consecutive breast cancer patients undergoing surgery between 1988 and 1998 were examined for signs of skeletal metastasis until December 2006. Patients who were diagnosed as having skeletal metastasis were the subjects of this study. Bone scans were performed annually for 5, 7 or 10 years; they were also conducted if skeletal metastasis was suspected. Data concerning bone pain and tumor markers at the time of skeletal metastasis diagnosis, and data relating to various factors including tumors, lymph nodes and hormone receptors at the time of surgery, were investigated. The relationships between factors such as bone pain, SRE and CSD were analyzed using the Kaplan-Meier method and Cox's analysis.Skeletal metastasis occurred in 668 patients but the pain status of two patients was unknown, therefore 666 patients were included in the study. At the time of skeletal metastasis diagnosis 270 patients complained of pain; however, 396 patients did not. Analysis of data using Cox's and Kaplan-Meier methods demonstrated that patients without pain had fewer SREs and better survival rates than those with pain. Hazard ratios regarding SRE (base = patients without pain) were 2.331 in univariate analysis and 2.243 in multivariate analysis. Hazard ratios regarding CSD (base = patients without pain) were 1.441 in univariate analysis and 1.535 in multivariate analysis. Similar results were obtained when analyses were carried out using the date of surgery as the starting point.Bone pain at diagnosis of skeletal metastasis was an indicator of increased SRE and CSD. However, these data did not support recommendations of follow-up bone surveys in breast cancer patients. Skeletal metastasis is a common complication of breast cancer; more than 70% of patients who die from breast cancer exhibit osseous metastasis at autopsy . HoweverThere have been significant advancements in hormone therapy and chemotherapy for advanced breast cancer sufferers -8. FurthPain is an important indicator of the presence of skeletal metastasis . HoweverBreast cancer patients undergoing surgery at the Cancer Institute Hospital, Tokyo, Japan, between January 1988 and December 1998 formed the patient pool, and were followed up until December 2006. As the aim of this study was to clarify skeletal metastasis after surgery, patients with skeletal metastasis at the time of surgery were excluded from the pool (5429 eligible patients). Six hundred and sixty-eight patients developed skeletal metastasis during the duration of the study. The follow-up protocol after surgery was as follows: patients visited hospital and received a physical check every three months for the first two years, every six months thereafter until five years had elapsed, and then annually after that. Patients who received adjuvant therapy were followed up more frequently. Bone scanning was used to confirm the presence of skeletal metastasis; it was performed at the time of surgery for staging purposes, annually thereafter for five years, and then seven and 10 years after the date of surgery. Bone scanning was also performed if physicians suspected the presence of skeletal metastasis or wanted to exclude it as a possibility. In the event of positive or equivocal bone scans, other imaging techniques including X-ray, computed tomography and magnetic resonance imaging were used to confirm the diagnosis. The above procedures were conducted as routine clinical practice at the Cancer Institute Hospital, Tokyo, Japan.The presence of bone pain at the time of diagnosis of skeletal metastasis was investigated using the card record, predominantly in the form of an inquiry card that was given to patients. In the inquiry card, patients were asked about the presence or absence of pain, and sites of pain. The grade of pain  was obtained from a limited number of patients. Therefore, the focus was on the presence or absence of pain. The values for tumor markers  when osseous metastasis was diagnosed were classified as below, equal to or above the reference value. Reference values were 5.0 ng/ml for CEA and 30 ng/ml for CA 15-3.The following factors were used in a Cox proportional hazards mode: age at surgery (Age), menstruation state, breast tumor (T) with minor modification  or large (3.1-5.0 cm)), clinical and pathological lymph node state (N and pN), histopathology, and estrogen receptor and progesterone receptor status. Tumors were classified as: in situ, non-invasive cancer; T0, no detectable tumor; T1, ≤ 2.0 cm; T2 small, 2.1-3.0 cm; T2 large, 3.1-5.0 cm; T3, ≥ 5.1 cm; T4, any size with direct extension to chest wall or skin according to the 2002 UICC-TNM classification . HistoloData were analyzed as follows. First, the percentages of patients with or without pain and with or without elevation of CEA or CA15-3 at the diagnosis of skeletal metastasis were calculated, and the time from surgery to the appearance of skeletal metastasis with or without pain was calculated and tested using the Mann-Whitney U test. Secondly, Kaplan-Meier's method with a log-rank test was used to compare SREs  and survival  in patients with and without pain at diagnosis of skeletal metastasis. Therefore, two types of events were used for the analysis: SRE and CSD. Deaths due to other causes were treated as censored. The starting point of the study was the date of diagnosis of skeletal metastasis. Thirdly, a Cox proportional hazards regression model was used to investigate whether the presence of pain was a significant factor using univariate and multivariate analysis. The proportionality of each hazard was confirmed by plotting a log-minus-log curve. Multivariate Cox proportional hazards regression analysis was conducted using a backward stepwise method . All analyses were performed using SAS version 8.2 . Finally, as a lead-time effect could influence the results, a similar analysis (second and third steps) using the initial surgery date as a starting point was also performed.In addition, the number of bone metastatic lesions (solitary or multiple) at the time of diagnosis of skeletal metastasis was an important factor. The importance of this factor was reported  as solitThis retrospective study was approved by the Institutional Review Board. Informed consent was not required as this was a retrospective study.Of 668 patients who developed skeletal metastasis, the pain status was unknown in 2 patients, therefore 666 patients were included in this study. Of the total number of individuals, 396 (59.5%) did not complain of pain and 270 (40.5%) did. CEA values were available for 647 patients; 412 (63.7%) had a normal value and 235 (36.3%) were above the reference value. CA15-3 values were available for 649 patients; 391 (60.2%) had normal values and 258 (39.8%) were above the reference value. In 396 osseous metastasis patients without pain, 60 had elevated CEA without elevation of CA 15-3, 55 had elevated CA 15-3 without elevation of CEA, 80 presented with elevation of both CEA and CA 15-3, and in 201 patients both CEA and CA 15-3 were within normal limits. There were 187 (28.1%) patients who did not present with both bone pain and tumor marker elevation.The patients' characteristics are presented in additional file The numbers of patients with and without pain in each SRE are presented in additional file p < 0.001). Figure p 〈0.001). The results of Cox's proportional hazard analysis regarding SRE are given in additional file The Kaplan-Meier curves for SREs in patients with and without pain are presented in figure p < 0.001). Patients without pain survived longer than those with pain (log-rank test: p = 0.007). Cox's proportional hazard analysis was performed for SRE and survival (CSD) from the date of surgery. The presence or absence of pain was a significant factor in both univariate analysis  and multivariate analysis  with regard to SRE. Regarding survival (CSD), presence or absence of pain was a significant factor in both univariate analysis  and multivariate analysis .Figures The Kaplan-Meier curves for patients with or without pain are presented in figure Bone pain is commonly associated with skeletal metastasis. However, in this study approximately 60% of patients did not complain of bone pain at diagnosis. Patients who developed skeletal metastasis without pain had fewer SREs and longer survival (CSD) than those with pain; these differences were statistically significant. The results were consistent irrespective of the analysis method used . Cox's proportional hazards regression analysis using SRE and CSD as endpoints demonstrated that hazard ratios (univariate) of all significant factors were higher in value for CSD than for bone pain; this was also the case in multivariable analysis. Hazard ratio of bone pain was 2.331 for the SRE event, 1.441 for the CSD event , 2.243 for SRE and 1.535 for CSD (multivariable). The presence of bone pain predicted SRE more accurately than CSD. Bone pain could be an important factor in predicting SRE, and other factors could be of more use in predicting CSD.This research was a cohort study in a single institute that compared SRE and CSD of asymptomatic and symptomatic patients who had developed osseous metastasis. This type of comparison can be biased by lead time (early detection simply increases the period during which osseous metastasis is observed) and length time . Differences in SREs and survival (CSD) could be due to the lead time bias. However, additional analysis taking the starting point as the date of surgery produced similar results. There was no difference in the chronological period of diagnosis of skeletal metastasis between patients with or without pain (data not shown), indicating that therapy after the diagnosis of skeletal metastasis did not differ between these groups of patients. There was no difference in the use of bisphosphonates for patients without pain and those with pain (data not shown). These findings indicate that fewer SREs and longer survival (CSD) were not due to the lead time bias. Length time bias could not be eliminated from this study even though the time from initial surgery to diagnosis of osseous metastasis was no different in patients with or without pain. Patients with painful bone metastases could have different disease biology from asymptomatic individuals , which could account for their poor prognosis. The results presented herein do not predict that routine bone surveys will detect more asymptomatic patients and improve their outcome. However, the results do reveal that asymptomatic patients diagnosed with skeletal metastasis had lesser SRE and CSD than symptomatic patients. Kohno et al. reported that the SRE rate was higher among patients with pathological fractures before diagnosis than in patients with no prior fracture , and thiDrawbacks with this retrospective study include using a database of breast cancer patients in our institute, where data collection began approximately 30 years ago. The records lacked several important pieces of information including tumor grade and HER2/neu status, and it employed the local (Japanese) pathological classification system. A second database was utilized for data analysis of skeletal metastasis in breast cancer patients. This database lacked information regarding the type of skeletal metastasis , and both databases lacked information regarding the pain condition of individuals. Patients' records (cards) were checked for the presence or absence of pain at diagnosis of skeletal metastasis but there was no detailed information about the pain condition of individuals.Therapy for breast cancer has changed over time with the advancement of chemotherapeutic agents and their combination, hormones and molecular targeting agents (HER2/neu). The concept of standard therapy for skeletal metastasis has changed with the advent of bisphosphonates. In Japan, bisphosphonates were first approved for use in the treatment of skeletal metastasis at the end of 2004, and actual use began in 2005. Therefore, there were limited data regarding the use of bisphosphonates in this study and this prevented analysis of the impact of bisphosphonate treatment. The strategy of using radiotherapy for treating skeletal metastasis changed during the study period. The inclusion of radiotherapy treatment in the SRE classification could result in an overestimation of the incidence of SRE in this study. We have also performed another analysis in which first RT was not regarded as SRE and RT at least three months apart from first RT was counted as SRE. Although the distribution of kinds of SREs has been changed  were diagnosed as having skeletal metastasis without pain. This is in contrast to other reports in which only a small percentage of patients were diagnosed with skeletal metastasis without pain. Front et al. reported that 21/66 (21%) patients did not have bone pain at diagnosis . This diTwo randomized clinical trials (RCT) regarding breast cancer follow-up were published in 1994, although the studies were conducted almost 20 years ago. They concluded that regular physical examinations and annual mammography were as effective as more intensive approaches, based on laboratory and imaging tests in terms of timelessness of recurrence detection and overall survival and quality of life -5. ThereResearch into a new method of detecting skeletal metastasis using bone metabolic markers is underway . AlthougBreast cancer patients who were diagnosed with skeletal metastasis without pain had fewer SREs than those with pain, and pain was a predictor of SRE. Other factors were predictors for CSD. Detection of skeletal metastasis in patients who do not have bone pain leads to a lower incidence of SREs. However, the data did not support a recommendation for bone surveys in the follow-up of breast cancer patients. These results could lead to a new randomized clinical trial to investigate whether early detection of skeletal metastasis has clinical significance.The authors declare that they have no competing interests.MK carried out planning of the study, data collection, analysis and interpretation, and writing the manuscript. MY, FK and TI performed patients' collection, management, and joined in discussions. All authors have read and approved the final manuscript. EO advised about the planning of the study and led the discussions, and he recently deceased.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/10/423/prepubPatient demographics and tumor characteristics. Additional file Click here for fileSkeletal related events and pain. Additional file Click here for fileCox propotional hazard analysis as predicotors of SRE. Additional file Click here for fileCox propotional hazard analysis as predicotors of CSD. Additional file Click here for fileRevised skeletal related events* and pain. Additional file Click here for fileCox propotional hazard analysis as predicotors of revised SRE. Additional file Click here for file


Pelvic adhesions are found in up to 50% of women with CPP during investigative surgeries and adhesiolysis is often performed as part of their management although the causal or casual association of adhesions, and the clinical benefit of adhesiolysis in the context of CPP is still unclear. Our aim was to test the hypothesis of whether laparoscopic adhesiolysis leads to significant pain relief and improvement in quality of life (QoL) in patients with chronic pelvic pain (CPP) and adhesions.This was a double-blinded RCT. This study was conducted in 2 tertiary referral hospitals in United Kingdom over 4 years. Women with chronic pelvic pain (CPP) were randomized into having laparoscopic adhesiolysis or diagnostic laparoscopy. Women were assessed at 0, 3 and 6 months for Visual analogue scale scores (VAS) and Quality of Life (QoL) measures (SF-12 and EHP-30).A total of 92 participants were recruited; 50 qualified to be randomized, with 26 in the adhesiolysis and 24 in the control group. The results are expressed in median (interquartile ranges). In women who underwent adhesiolysis, there was a significant improvement at 6 months in VAS scores (-17.5 (-36.0 - -5.0) compared to controls ; SF-12 scores physical component score (25.0 (18.8 – 43.8)) compared to controls (6.3 (-6.3 – 18.8); p = 0.021), SF-12 emotional component score 32.5 (4.4 – 48.8) compared to controls -5 (-21.3 – 15.0); p < 0.0074) and EHP-30 emotional well being domain 32.5 (4.4 – 48.8) compared to the controls -5 .This study stopped before recruitment reached the statistically powered sample size due to difficulty with enrollment and lack of continued funding. In selected population of women presenting to the gynecological clinic with chronic pelvic pain, adhesiolysis in those who have adhesions may be of benefit in terms of improvement of pain and their quality of life.ISRCTN 43852269 Chronic pelvic pain (CPP) is a debilitating condition with a heterogeneous aetiology and a high disease burden worldwide. CPP hasOnly two randomized controlled trial has evaluated the role of adhesiolysis in pain,13. The This study was therefore designed with the objective to evaluate the hypothesis that laparoscopic adhesiolysis leads to significant pain relief and improvement in quality of life (QoL) in patients with CPP and adhesions in order to provide scientific basis for sound clinical practice which in turn can benefit patients who suffer from this distressing condition.This was a two-center study performed in the Princess Anne Hospital, Southampton University Hospitals NHS Trust and Jessop Wing, Sheffield University Hospital Trusts, UK. It was a double-blinded randomised controlled trial where the participants were randomised to either undergo laparoscopic adhesiolysis or diagnostic laparoscopy. Prior to surgery, standard demographic details were obtained and surgical details were obtained during the surgery including the adhesion site, severity and extent in accordance to a standard adhesion scoring system. The follow up intervals were 3, 6, and an optional 12 months after surgery. At the initial and subsequent follow up visits, the following outcome measures were obtained: Pain scores: VAS  from the McGill pain questionnaire , SF-12  women age over 18 years old; 2) presence of chronic pelvic pain defined as pelvic pain which is constant/cyclical in nature for greater or equal to 6 months duration; 3) written consent; criteria for exclusion: 1) malignancy; 2) psychiatric disorders for which the patient is taking medication; 3) pathology which requires urgent treatment, such as ovarian cyst or pelvic abscess; 4) women taking central nervous system stimulants and 5) pregnancy. The intraoperative criteria were: 1) non-endometriosis related adhesions detected at laparoscopy (determined by gross inspection) and 2) the nature and extent of adhesions considered suitable for laparoscopic adhesiolysis (not via laparotomy). Patients are screened for inclusion of the study using the pre-operative eligibility criteria. Once the preoperative criteria were satisfied, and the laparoscopy begun, the intraoperative criteria were then determined.2 was used for creating a pneumo-peritoneum of 20 mmHg before a 10 mm trocar was inserted into the intra-umbilical incision. Two or three more lateral ports were inserted depending on the site and extent of surgery. During surgery, the principles of microsurgery were followed, including meticulous haemostatic control and usage of constant irrigation to prevent tissue desiccation. One litre of 4% Icodextrin  was instilled intraperitoneally after surgery, in the study as well as the control group.Patients were randomised to have either laparoscopic adhesiolysis or diagnostic laparoscopy. Randomisation was performed using a computer generated random numbers and the concealed, opaque unlabeled envelope was opened after it had been determined that the patient met the intraoperative criteria. The patients were blinded to the allocation of treatment and the assessor during follow up was blinded to the treatment. The assessor who administered the questionnaires and recruited the patients was the research nurse who did not have prior knowledge of what type of surgery the patients underwent. Consent was obtained prior to any baseline assessments. The operation notes were stored in a sealed enveloped within the patient notes and not accessed except during an emergency. In the latter case, the data would be used to the point of unblinding. The randomization code was broken at the end of the follow up period and patients who wished to know were informed of their treatment groups. Laparoscopic surgeons who were skilled in advanced laparoscopy performed the surgery. Entry into the abdomen was either via the traditional Veress needle or a modified Hasson’s technique of open entry. COThe patients’ histories, clinical examination and operative findings were documented on standard proforma. The extent, severity and site of adhesions was scored using a well-validated adhesion scoring system and the The primary outcome measure was pain score denoted by VAS  from the McGill pain questionnaire and the secondary outcomes were a) Quality of life scores - SF-12 Health related quality of life scores ; the modified EHP-30 core questionnaire for pelvic pain and b) clinical outcomes - including complications and adverse events.A sample size of 50 patients per group was needed to detect a difference of 10 points on a 100 point  VAS scaThe study was reviewed and approved by the South Sheffield Ethics Committee (05/Q2305/159) and Southampton R&D approval from University Hospital Southampton NHS Foundation Trust (ISRCTN 43852269).Between December 2008 and December 2012, 94 women who satisfied the eligibility criteria for the study were recruited  compared to controls (-1.5 (-15.0 – 4.5); p = 0.048).In women who underwent adhesiolysis, there was a signficant improvement in the SF-12 physical component score (25.0 (18.8 – 43.8)) compared to controls (6.3 (-6.3 – 18.8); p = 0.021) as well as an improvement in the emotional component score (adhesiolysis: 32.5 (4.4 – 48.8); controls -5 (-21.3 – 15.0); p < 0.0074) at 6 months.Except for the EHP-pain and control domains, all other EHP domains showed a trend of general improvement. There was a signficant improvement in the emotional well being domain in women who underwent adhesiolysis, EHP-30 score 32.5 (4.4 – 48.8) compared to the controls -5 (-21.3 – 15.0); p < 0.0074 at 6 months. There was also a significant improvement in the EHP-30 social support domain in the adhesiolysis group -12.5 (-71.9 – 0.0) compared to the controls -6.25 (-18.8 – 12.5), p < 0.045 at 3 months although this improvement is not sustained at the 6 months follow up.There were no complications or adverse events associated with the surgery. Earlier unblinding of any of the patients’ data was not required.Despite over twenty years of debate over the role of surgical adhesiolysis in women with CPP,19, therModern management strategies of the woman with adhesions and pain range from conservative management of the ‘neurotic’ patient to more In theory, women with adhesions removed are more likely to suffer from adhesion reformation, which may result in the lack of improvement or worst pain, and QoL outcomes at follow up. All the participants who underwent adhesiolysis had 4% Icodextrin as an adhesion reduction agent although recent studies have shown this product to be inefficacious; the benOur study can be criticised in that the study group had a higher adhesion score compared to the controls. Despite this being a randomised controlled trial, due to the small sample size, there was disparity in the baseline characteristics of adhesion score, which may have inadvertently, confounded the results. We observe a large variation in individual scores, denoted by the large interquartile range, which suggests a significant degree of clinical heterogeneity in the study population. However, our study is too small to show effects of surgery on specific types of adhesions or individual surgeon’s effect. The study had a follow up period that spanned a 6-month duration, and this is deemed sufficient to overcome the placebo impact of surgery and large randomised trials have shown little change of pain and QoL scores between the 6 – 12 month follow up mark,25.CPP is a complex disorder with a high degree of disease burden worldwide. The oftIn conclusion, adhesiolysis for women with CPP may improve their pain and QoL in terms of better emotional and physical well being at their 6 month follow up. The potential benefit of adhesiolysis will need to be further evaluated but our study at the least, supports offering adhesiolysis as potentially beneficial treatment modality in some as yet not well characterized instances.The authors declared that they have no competing interest.YC conceived the idea, is the chief investigator and the main supervisor for the project, was involved with data analysis and wrote the paper. IR analysed and co-wrote the paper. SB and KS conducted the study and co-wrote the paper. WL and TL conducted the study and co-wrote the paper. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6874/14/36/prepub


Mesenchymal stem cells from several sources  can differentiate into variable parts , representing a promising new therapy in regenerative medicine. In animal models, mesenchymal stem cells have been used successfully to regenerate cartilage and bones. However, there have been no follow-up studies on humans treated with adipose-tissue-derived stem cells (ADSCs) for the chondromalacia patellae. To obtain ADSCs, lipoaspirates were obtained from lower abdominal subcutaneous adipose tissue. The stromal vascular fraction was separated from the lipoaspirates by centrifugation after treatment with collagenase. The stem-cell-containing stromal vascular fraction was mixed with calcium chloride-activated platelet rich plasma and hyaluronic acid, and this ADSCs mixture was then injected under ultrasonic guidance into the retro-patellar joints of all three patients. Patients were subjected to pre- and post-treatment magnetic resonance imaging (MRI) scans. Pre- and post-treatment subjective pain scores and physical therapy assessments measured clinical changes. One month after the injection of autologous ADSCs, each patient's pain improved 50–70%. Three months after the treatment, the patients' pain improved 80–90%. The pain improvement persisted over 1 year, confirmed by telephone follow ups. Also, all three patients did not report any serious side effects. The repeated magnetic resonance imaging scans at three months showed improvement of the damaged tissues (softened cartilages) on the patellae-femoral joints. In patients with chondromalacia patellae who have continuous anterior knee pain, percutaneous injection of autologous ADSCs may play an important role in the restoration of the damaged tissues (softened cartilages). Thus, ADSCs treatment presents a glimpse of a new promising, effective, safe, and non-surgical method of treatment for chondromalacia patellae. Inclusion criteria: (i) MRI evidence of chondromalacia patellae; (ii) either male or female; (iii) under 60 years of age; (iv) an unwillingness to proceed with surgical intervention; (v) the failure of conservative management; and (vi) ongoing disabling pain. Exclusion criteria: (i) active inflammatory or connective tissue disease thought to impact pain condition ; (ii) active endocrine disorder that might impact pain condition ; (iii) active neurological disorder that might impact pain condition ; and (iv) active pulmonary disease requiring medication usage. Outcome endpoints (obtained at three months after treatment): (i) pre- and post-treatment VAS  walking index; (ii) pre- and post-treatment Functional Rating Index; (iii) pre- and post-treatment MRI; and (iv) telephone questionnaires every six months: at 6, 12, and 18 months.Functional rating index (FRI) and visual analog scale (VAS) were determined as previously described Patients were restricted from taking steroids, aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), and Asian herbal medications for one week prior to the procedure.In the operating room, approximately 40 mL of packed adipose tissue were obtained by liposuction of the subcutaneous layer of the lower abdominal area using sterile techniques g) g, then 1000 g), 4.4 mL of PRP along with the Buffy coat were obtained. 0.5% (w/v) hyaluronic acid  was added as a scaffold to this mixture, and 3% (w/v) CaCl2  was added to activate PRP. These ADSCs along with PRP, hyaluronic acid, and CaCl2 stand for the ADSCs mixture.ADSCs were extracted through the use of digestive enzymes  and centrifugation  was injected as the same fashion as the first day. On the fourteenth day after the initial injection, a low-dose (254.8 nmol/L) dexamethasone  was added to PRP with CaCl2. On day 28, the last dose of PRP with CaCl2 was injected.After the left knee was cleaned with 5% povidone-iodine  and draped in a sterile fashion, the injection site was anesthetized with 2% lidocaine . The ADSCs mixture (15 mL) was injected into the retro-patellar joint on the day of liposuction with a 20-gauge, 1 1/2-inch needle under ultrasonic guidance. On the third and seventh day after the initial injection, another dose of PRP with CaClAccording to Korean law (Rules and Regulations of the Korean Food and Drug Administration), this study does not need approval by ethical and scientific committees Further, this study was approved and classified as exempt by the Solutions Institutional Review Board . After obtaining written informed consents from all the participants, Jaewoo Pak, M.D. made the clinical decisions on treatments.The patient #1 is a 43-year-old Korean female with more than one year history of right AKP. The patient started having AKP without any history of trauma. She was seen by a physician and was diagnosed with chondromalacia of the knee after MRI imaging studies. After taking NSAIDs for few weeks along with physical therapy (PT), the AKP improved. However, approximately 6 months prior to our clinic visit, the patient started having AKP again. The pain was worse when standing up, walking, exercising, but improved with rest. The pain was not much relieved with NSAIDS and PT, this time. At the time of initial evaluation, the patient reported mild pain (VAS score: 2) on rest, increased pain when walking . The FRI was 17 . The phyThe patient #2 is a 54-year-old Korean male with 3 to 4 year history of right AKP. The patient started having AKP without any history of trauma except vigorous uses of knees, such as mountain hiking. He was seen by a physician and was diagnosed with CMP of the knee after MRI imaging studies. The patient took NSAIDs along with PT, without much improvement. At the time of initial evaluation in our clinic, the patient reported mild AKP (VAS score: 2) on rest, increased pain when walking (VWI: 7). The FRI was 15 . The phyThe patient #3 is a 63-year-old Korean female with more than 5 year history of right AKP. With the diagnosis of osteoarthritis, she had received one dose of steroid injection and multiple doses of PRP and hyaluronic acid injections over the last few years. However, she did not experience any improvement of AKP. The patient was seen by an orthopedic surgeon and was offered a total knee replacement (TKR). She was reluctant to go through TKR due to possible side effects. Since then, the patient had been receiving only PT without much improvement. At the time of initial evaluation in our clinic, the patient reported moderate AKP (VAS score: 5) on rest. AKP increased when walking (VWI: 8). The patient also complained of mild knee swelling. The FRI was 24 . On physAll patients were followed up with telephone questionnaires every six months: at 6, 12, and 18 months. Each time, patients were asked the following questions: (i) did you experience the pain improvement due to the procedure? If no, please comment; (ii) did you experience any complications  you believe may be due to the procedure? If yes, please explain; and (iii) have you been diagnosed with any form of cancer since the procedure? If yes, please explain.Two young patients , only with diagnosis of AKP, had failed conservative treatments comprising NSAIDs and PT. Their MRI scans of right knees showed retro-patellar signal changes consistent with CMP. Another patient, an elderly female with AKP and osteoarthritis, who failed conservative treatments consisting with multiple doses of PRP, hyaluronic acid, and/or steroid injections, was reluctant to go through a TKR due to possible side effects. The MRI scan showed retro-patellar signal changes consistent with CMP along with medial meniscal maceration and cartilage thinning consistent with osteoarthritis. Being wary of no non-invasive therapy for the cure of CMP, three patients wanted to try autologous, non-cultured ADSCs mixture-based treatments for the restoration of CMP. From June 2009, autologous, non-cultured ADSCs can now be used as a source of MSCs in Korea 2 with (or without) hyaluronic acid or a very low dose of dexamethasone (254.8 nmol/l) were injected in the same manner as that done in the first day. One month after the ADSCs mixture injection, each patient's pain improved 50–70%  other joint diseases.All three patients did not report any serious side effects. All patients experienced 2–3 days of joint discomfort after the first injection of ADSCs mixture. The discomfort was attributed to the volume expansion after the injection and completely disappeared after 2–3 days. Since ADSCs and PRP are autologous in nature, no rejection was expected and none occurred.For diagnosis, MRIs of right knees were performed on three patients before ADSCs-mixture treatment. Consequently, post-treatment MRIs were repeated to compare pre- and post-treatment images. The MRI T2 sequence was used for its ability to differentiate bony anatomy from the cartilage. Due to slight differences in patient positioning and slight movement of patients during the MRI procedures, there was some difficulty in capturing the exact treatment locations. However, the pre-and post-treatment MRI results can be compared with sequential views to compensate for any possible errors In this study, significant MRI signal changes were apparent in the T2 views of right knees along the retro-patellar joint injection sites. These significant signal changes can be interpreted as possible signs of persistent and restored probable cartilages. Due to dramatic reduction in AKP, all three patients were reluctant to undergo knee cartilage biopsies to determine the true nature of the cartilage-like tissues. Although the true nature of the restored tissues is unclear, the damaged tissues (probable cartilages) have been believed to be restored, based on previous studies showing same tissue recovery using MSCs in patients with osteonecrosis, osteoarthritis, and meniscal injury With regard to the mechanism of the restoration, there are few plausible possibilities: (i) direct differentiation of the stem cells  Although the patients' symptoms and signs have improved, it is worthwhile to note that the improvement appeared gradually over three months. It can be postulated that three-months-time period is necessary for ADSCs to restore the softened cartilages.It has been estimated that approximately 400,000 ADSCs are contained in 1 mL of adipose tissue These three clinical reports were not the randomized and controlled trial, and the key clinical feature in this study is performing the potentially effective and non-invasive treatment in the patients with continuous AKP and without history of trauma. Therefore, there is not a placebo (ADSCs-free) group. However, patient 3 had received PRP and hyaluronic acid injections without ADSCs over the last few years but she did not experience any improvement of AKP. She has experienced the dramatic reduction of AKP in CMP by percutaneously injection of ADSCs mixture. This clinical study was in compliance with the Declaration of Helsinki and regulation guidelines of KFDA (Korean Food and Drug Administration).In conclusion, CMP of the knee is managed conservatively with NSAIDs and PT. When such conservative treatment fails, there is no definite cure for CMP thus presenting a major therapeutic challenge. However, this pilot study presents an alternative and safe way through which physicians may be able to manage CMP by percutaneous injections of autologous ADSCs mixture without culture expansion. Further studies with a larger number of patients with CMP are needed to confirm the short- and long-term efficacy and safety of ADSCs mixture-based treatment of CMP that are resistant to conventional therapies.


The objective of this study is to use the pain numeric rating scale (NRS) to evaluate associations between change in pain severity and changes in sleep, function, and mood assessed via patient-reported outcomes (PROs) in patients with posttraumatic pain.This is a secondary analysis of a clinical trial evaluating pregabalin in patients with posttraumatic peripheral neuropathic pain (N = 254). Regression models were used to determine associations between changes in pain (0-10 NRS) as the predictor and scores on the following PRO measures as the outcome: Pain Interference Index; Hospital Anxiety and Depression Scale anxiety and depression subscales; Medical Outcomes Study-Sleep Scale 9-item Sleep Problems Index and Sleep Disturbance subscale; and Daily Sleep Interference Scale (0-10 NRS).P <.001). Results from subgroup analyses  tended to be consistent with results from the overall sample.Change in pain severity showed clear, direct relationships with changes in function, anxiety, depression, and sleep PROs, all of which were statistically significant .Overall, a direct relationship exists between pain and various aspects of patient's well-being and functioning, which can provide a quantitative assessment of how improvements in pain may be expected to relate to other patient outcomes. ( Because the complexity and subjective nature of pain complicates evaluation of its severity and impact, various patient self-report instruments have been developed to assess pain and other patient-reported outcomes (PROs) in the research and clinical settings . The 11-When evaluating these outcomes, we believe that because the presence of pain generally interferes with daily functions, improvement in pain will be associated with improved functioning and other health benefits such as sleep and mood--specific outcomes that can be quantified and expressed. Therefore, characterizing and quantifying the relationship between pain severity and corresponding levels of interference with daily function, sleep, and mood can inform treatment decisions and guide assessment of outcomes. Previous studies in painful diabetic peripheral neuropathy have evaluated the relationship between pain and other PROs to categorize patients with mild, moderate, and severe pain ,9. One oThis study is a secondary analysis using data derived from a placebo-controlled clinical trial evaluating the efficacy of pregabalin in patients with posttraumatic peripheral neuropathic pain (N = 254). The methodology and primary analysis of the trial have been reported elsewhere .All patients gave written, informed consent. Institutional review boards reviewed and approved the protocol and the study was conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines and local laws and regulations. Patients were eligible for participation if they received a diagnosis of posttraumatic peripheral neuropathic pain  that was confirmed by a qualified pain specialist and persisted for a minimum of three months following the traumatic event. Patients were enrolled if they had a score of ≥40 mm on the visual analog scale of the short-form McGill Pain Questionnaire and completed ≥ 4 daily pain diaries during the last week of the screening period prior to randomization, with the mean score being ≥4 on the 11-point (0-10) NRS.Patients with neuropathic pain that was not due to trauma , was central rather than peripheral  or was due to Complex Regional Pain Syndrome (Type 1 or Type II) were excluded. Also, patients suffering from clinically significant or unstable conditions that, in the opinion of the investigators, would compromise participation in the study were excluded.The current report focuses on the association between changes in pain severity and changes in PROs of pain interference on daily functions, sleep, and mood; these analyses are independent of the treatment allocation  and comparative results reported in the primary analysis.We evaluated the association between change in pain, assessed daily using a 0-to-10 NRS  and then averaged to give a weekly result, and several other PROs assessed at baseline and end of double-blind treatment at week 8. These PROs included the following: the Pain Interference Index (PII) from the modified Brief Pain Inventory - short form (mBPI-sf) , a compoThe above-specified relationships between change in pain and PROs were examined using linear regression models. The changes in PRO scores were evaluated as a function of the change in pain NRS score (from baseline to end point).The model was populated with all available patients who provided data in the clinical trial regardless of treatment allocation or treatment effects. To evaluate the model for consistency and robustness, six sensitivity analyses were performed using subgroups from the clinical trial. These cohorts included patients achieving ≥30% pain response (30% responders), patients achieving ≥50% pain response (50% responders), pregabalin-treated patients, placebo-treated patients, patients aged ≤ 51 years and patients > 51 years. Fifty-one years was chosen as the cut-off value since it is the median age of all patients. The 30% and 50% responders are those patients who achieved at least a 30% and 50% reduction in pain NRS scores, respectively, from baseline to endpoint.P value <.05 was taken to confer statistical significance.All analyses were performed using SAS version 9.2 . A The population consisted of 254 patients with a mean age of 51.7 years; 50.8% of the patients were female. In the original placebo-controlled clinical study , pregabaP <.001) between changes in pain and changes in patient-reported sleep disruption . Mean changes in the PII ranged from -4.5 (± 2.2) for patients with ≥ 50% NRS reduction and -0.2 (± 2.0) for patients with < 10% NRS reduction (P < .0001). Similar differences were observed for the EQ-5D. Thus, changes in pain severity were associated with changes in daily functioning and health status, findings similar to those reported in the presented study.The data in the present study are consistent with results from a recent study by Hoffman et al. . Using dA two-point reduction on pain is taken to correspond to a clinically meaningful improvement on the other PROs. Psychometric studies on specific PRO scales provide evidence supporting the clinical importance of these changes. For example, a large study assessing the psychometric properties of the Daily Sleep Interference Scale demonstrated significant correlations between this scale and other outcome measures, including pain, and the results suggest that a 1-2 point change from baseline to end of treatment may be interpreted as clinically important , a changIn a similar study that evaluated the reliability and validity of the MOS Sleep Scale in patients with painful diabetic neuropathy , the MOSA study evaluating the psychometric properties of the BPI for painful diabetic peripheral neuropathy showed that scores on the PII  correlate highly and significantly with other outcome measures related to pain, sleep, health status, quality of life and mood . FurtherAn important limitation of this study is that while it may be reasonable to expect that reductions in pain severity will result in improvements in other outcomes, the associations demonstrated by the reported data do not imply causation. Furthermore, these data are derived from patients with nonmalignant chronic pain and do not imply a general physiologic or pathophysiologic parallel regulation. For example, it has been shown that change in depression scores is not necessarily paralleled by change in pain thresholds in patients treated for major depression . The useThe generalizability of this study is another limitation that should be considered when interpreting the results within the context of clinical trials or clinical practice. Consequently, these results should be used as a guide for further exploring the relationships underlying pain and pain interference with function.Models with pain as a categorical predictor, which do not impose any functional relationship between outcome and predictor, were also investigated. Results of these models (not reported here) supported the results with pain as a continuous predictor. We believe that the best choice to depict the appropriateness of a model is through probability plots and residual plots. If the probability plot forms a linear pattern and the residual plot forms no pattern, then we can conclude that the fitted relationship (in this case linear) is appropriate. We extensively studied these two types of plots and found the model to be suitable. The use of pain as a continuous predictor not only increases the sensitivity of observed relationships but also lends a simplified and meaningful interpretation of the relationship through the slope as a measure of change.In summary, the results reported here provide evidence of a direct and tangible relationship between pain and PROs in patients with chronic, nonmalignant neuropathic pain. Importantly, the data additionally demonstrate that pain responders show other benefits that are quantifiable in relation to the change in pain severity and are clinically significant. This novel analysis can be applied for determining individual responses that can be expected in patients being treated for pain, with the observed relationships providing a framework for quantitatively assessing how improvements in pain may be expected to result in improvement in other patient-centered outcomes. Such information may be useful in the research setting for trial design and in the clinical setting for informing treatment decisions and enhancing assessment of outcomes. Additional confirmatory studies are encouraged.RV, MS, FWB, and BM were investigators in this study but were not compensated for the development of this manuscript.In the past 5 years, RV has received a fee from Pfizer for speaking at an international conference, and his institution received financial compensation for conducting this study.MS is a consultant and senior lecturer, and works for the Greater Glasgow & Clyde NHS Trust and for the University of Glasgow. In the past 5 years, he has been a member of an advisory board for NAPP and Astellas. He has received honoraria and expenses for lectures or chairing educational meetings from NAPP, Pfizer, Grünenthal and GW Pharmaceuticals. His institution has also received remuneration for performing clinical drug trials from NAPP, Pfizer, Grünenthal, GW Pharmaceuticals, CeNeS and GlaxoSmithKline.FWB has received honoraria for teaching sessions and advisory board services from Pfizer, MSD, Norpharma, and Eli-Lilly.BM is a speaker, consultant, and/or clinical science investigator for several pharmaceutical companies involved in analgesics research, but receives no royalty (cash or otherwise) from the sale of any product.This study was funded by Pfizer. GZ, AGB, JCC, and MN are full-time employees of Pfizer. GZ and AGB are Pfizer stockholders. Pfizer provided funding for journal charges.The authors prepared this manuscript in collaboration. Each author made substantial contributions to the study conception and design, acquisition of data, statistical analysis, drafting of the manuscript, and final approval of the manuscript.


Postoperative pain is one of the most important complications encountered after surgery. A number of options are available for treating pain following surgery. One of those options is the use of intravenous patient-controlled analgesia (PCA). Ketamine is an anesthetic drug relieving pain with its NMDA receptor antagonistic effect.This study is aiming at better pain management after abdominal surgery; the effects of adding ketamine to intravenous fentanyl plus acetaminophen PCA were evaluated.In a double-blind randomized clinical trial 100 patients, ASA I or II, 20 - 60 years old were divided into two groups. These patients were abdominal surgery candidates. In order to control postoperative pain in the control group an IV patient-control analgesia (PCA) containing fentanyl 10 μg/mL plus acetaminophen 10 mg/mL was instructed to be used for the patients, but the patients in ketamine group received ketamine 0.5 mg/mL plus control group PCA content. During the first 48 hours after surgery, ketamine patients were evaluated every 8 hours  to determine their pain scores using VAS scale, sedation score, additional analgesics, nausea and vomiting.There were no significant demographic differences between two groups. Pain scores  during the first 48 hours were not significantly different between two groups . Nausea scores were significantly lower in the ketamine group (P = 0.026).The addition of ketamine to intravenous fentanyl plus acetaminophen PCA had not extra effects in relieving post abdominal surgery pain. Postoperative pain is considered as one of the most important problems encountered by the patients after abdominal surgery. A Physician may employ various treatments to control the pain . That isPoor postoperative analgesia occurred in different reasons such as extensive range of interpatient/intrapatient requirements in analgesia, serum drug levels (particularly in intramuscular injections) and delays in administration . Usual PSome analgesic techniques use certain medicines to improve the effectiveness of opioids. For instance, they benefit from adding chlorpromazine, promethazine, midazolam and clonidine to morphine PCA .By triggering N-methyl-D-aspartate (NMDA) receptor, nociceptive stimulation can generate spinal cord hyperexcitability. Spinal cord hyperexcitability plays a considerable role in severe pain pathophysiology. Administering excessive doses of opioids can trigger the NMDA pain facilitating procedures leading to hyperalgesia. It also might relieve the pain after surgery. Consequently, the NMDA antagonist ketamine can play a part in the management of pain after surgery .Ketamine is an anesthetic drug  with N-MThe aim of the present study is to investigate the effects of adding ketamine to intravenous fentanyl plus acetaminophen in patient controlled analgesia (PCA) on controlling pain after abdominal surgeries.After ethical approval, 100 patients were divided randomly into two groups to evaluate the postoperative pain control in a double-blinded clinical trial.ASA physical status 1 and 2, 20 - 60 years old and candidates for abdominal surgery under general anesthesia.Exclusion criteria: current drug abuse, allergy to medications, alcohol and psychotropic drugs abuse, pregnancy and lactation or not using a reliable method of contraception by women, patients who refused and failed to cooperate in the study, impaired liver function or liver enzyme disorders, a history of seizures, psychological disorders, chronic pain or daily use of analgesics, contraindications of the drug under study, and concurrent use of drugs or enzyme inducers.General anesthesia methods were the same in all subjects. After IV administration of fentanyl (3 μg/kg) and midazolam (1 mg) for premedication, thiopental (5 mg/kg), cisatracurium (0.2 mg/kg) and remifentanil (1 μg/kg) were used to induce anesthesia. In order to maintain anesthesia, propofol (100 mg/kg/min) and remifentanil (1 - 2 mcg/kg/min) and repeated doses of 2 mg cisatracurium (every 30 minutes) were administered.After the surgery and return of breathe to the normal level, reversal of atracurium with neostigmine (0.04 mg/kg) and atropine (0.02 mg/kg) was done and the patients were extubated after regaining consciousness and were taken to the recovery room where they were all hemodynamically monitored until fully achieving recovery room discharge criteria.For the control group, each mL of the PCA contained fentanyl (10 μg) and acetaminophen (10 mg) but the patients in the ketamine group received ketamine 0.5 mg/mL plus control group PCA content. Infusion rate was set to 4 mL/h.To have a “double-blind” study, intravenous PCAs  administered the contents of which were only known to the project observer. In order to relieve post abdominal surgery pain, the patients were instructed the use of PCA in the recovery room. IV PCA administered before the onset of pain, and maximum 2 hours after the surgery. We informed patients about visual analogue scale (VAS from zero (no pain) to 10 (unbearable pain)). The patients were evaluated every 8 hours during the first 48 hours . Other parameters assessed included sedation score  and showed neurological and psychological complications, the medication was discontinued.The data obtained were analyzed using the statistical software SPSS 15. Quantitative data are shown as mean and qualitative data was shown as frequency. In case of normal distribution in both groups, Chi-square test and independent t-test were used to analyze qualitative variables and quantitative data respectively. Furthermore, due to repeated variables measurements and minimize the alpha error, the repeated measure test was applied. In this study P value was 0.05.0 was the time of the patient arrival into the recovery room. Two patients in the ketamine group received 500 mg IV Acetaminophen at the 8th hour which was not statistically significant. Changes in pain scores  were not significantly different between the two groups   . T0 was ctively) . 0 + 24, 32, 40 and 48 hours. The difference was significant after 24 and 48 fours  but it was not significant at T0+32 and 40 . In each of the two groups 5 patients had taken one dose of ondansetron on the first day.Although on the first day the grade 2 of nausea was not observed in any of the patients in both groups, some in the control group suffered from grade 2 of nausea at T0, T0 + 1, 8, 16, 24, 32, 40 and 48 hours indicated no significant difference between the two groups. However, at T0 + 16 hours, 5 patients in the ketamine group had become agitated (Ramsay score 1). At this time the other patients in ketamine group and all subjects in the control group were located in Ramsay score 2. Therefore sedation score at this time turned out to be significant in Chi-square test (P = 0.022) but not significant in Fisher’s exact test (P = 0.056). Our evaluation at 8-hour intervals (up to 48 hours) showed no significant difference in the incidence of itching among the patients of both groups and no neurological and psychological complications were observed. Assessment of the sedation score at T0,T0 + 8, 16, 24, 32, 40 and 48 hours.In this study the effects of adding ketamine to intravenous fentanyl plus acetaminophen PCA were investigated, which revealed no significant differences in pain scores between the control and ketamine group (while resting), moving and coughing, at TWhen NMDA antagonist administration is accompanied with an opioid in animals, a synergistic or additive analgesic effect is observed. This could lead to administration of reduced doses of both drugs and lesser consequent side effects. Studies carried out on animals indicated that NMDA antagonists block the course of resistance to continuous morphine exposure; in fact opioid-induced resistance is decreased and reversed .Taking opioids usually resulted in side effects such as nausea, heavy sedation and rarely respiratory depression. Resistance to the analgesic effect can rise even during the early stages of treatment with opioids .In one study, the addition of ketamine to tramadol after major abdominal surgeries resulted in more relief in pain and less tramadol consumption .A combination of analgesia and synergisms is probably the reason for this effect and it is reinforced by taking advantage of lower PCA bolus doses in the ketamine and magnesium groups that have the same VRS scores. It is also likely to reach a synergistic effect of tramadol with magnesium or ketamine .In a survey, administration of ketamine has relieved the postoperative pain after laparotomy . IntramuUnlugenc and colleagues found that the addition of ketamine to morphine in intravenous PCA relieved the pain and reduced morphine consumption . In a stSeveral studies are available in the field of managing abdominal postoperative pain which investigated the effects of adding ketamine to opioids .Evaluating the negative results of the study, some influences must also be taken into account; these factors include administration method, the number of patients, stability of ketamine-morphine solution, concentration ratio of ketamine-morphine solution, the design of the study, ketamine dose, pain type and pharmacokinetics .Eight placebo-controlled studies investigated the effects of intravenous and intramuscular ketamine on postoperative pain and 7 of them showed analgesic effects .Different ketamine doses (4 - 30 mg) have been experimented epidurally but a small number of these studies have been carried out in randomized, double-blind trial and placebo-control forms .Sveticic examined twelve different combinations of morphine and ketamine. The least severe pain and the least adverse effects were achieved with a ketamine/morphine ratio of 1:1 and at a bolus dose of 0.7 - 1.8 mg of each drug repeated every 8 minutes .It is possible that various bolus dose amounts stem from the familiar interindividual differences in the required drug amount in order to benefit from adequate analgesia. Lack of consistency in lockout times does not seem to impose an effect on the pain scores generally .Studies carried out by Reeves do not reinforce the theory that lower doses of ketamine can have a beneficial role in boosting morphine PCA in patients while they are in post abdominal surgery recovery. Nevertheless, lower doses of ketamine are proved to possess a number of influences that can be recognized clinically, especially reduced cognitive performance. Long period sleep was another result but statistically it is not significant. Therefore the ketamine dose examined in the present study was sufficient. Higher doses of ketamine might lead to notable results but most probably will bring about more problems .In those studies the ketamine has increased the analgesia, the initial low-dose (0.125 - 2 mg/kg) had usually been used but it has not been effective in those studies where the initial dose had not been administered .The present study tried to minimize the side effects of the drugs by reducing the total dose of fentanyl and acetaminophen as a continuous infusion in PCA. To compensate for the reduced total dose of fentanyl and acetaminophen, ketamine was administered as a concomitant drug to increase the analgesic effects .Generally, the pain score at the beginning was larger in the ketamine group compared with the control group. In this study we did not measure the ketamine plasma levels. When fentanyl is combined with ketamine the electrical current pain threshold dose response curve is substantially sharper than only fentanyl dose response curve. 30 ng/mL concentration of ketamine serum in itself made no modifications in electrical pain threshold but when added to fentanyl, it led to a larger rise in pain threshold compared to that of fentanyl in itself. Ketamine did not enhance the anti-nociceptive features of fentanyl in the assessment of nociception stimulation (with heat and pressure). Subjective and objective measurements of sedation indicated no differences between fentanyl sedative effect and that of fentanyl combined with ketamine. The administered doses of drug in the study at hand did not affect cardiovascular and respiratory factors. Anti-nociceptive features of fentanyl were enhanced with a serum concentration of ketamine that had made no changes on sedation levels. The improvement of anti-nociceptive features was followed by no rise in sedation. This is a sign that in order to increase the analgesic effect in a clinic, lesser continuous doses of ketamine (30 - 120 ng/mL) can be combined with μ opioid agonists .0, T0 + 8, 16, 24, 32, 40 and 48 hours, no significant differences in pain scores were observed  between the control and ketamine group. At T


Objective: To identify the frequency of signs and symptoms of temporomandibular disorder (TMD) and its seve-rity in individuals with headache. Study Design: 60 adults divided into three groups of 20 individuals: chronic daily headache (CDH), episodic headache (EH) and a control group without headache (WH). Headache diagnosis was performed according to the criteria of International Headache Society and the signs and symptoms of TMD were achieved by using a clinical exam and an anamnestic questionnaire. The severity of TMD was defined by the temporomandibular index (TMI). Results: The TMD signs and symptoms were always more frequent in individuals with headache, especially report of pain in TMJ area , pain to palpation on masseter  which are significantly more frequent in episodic and chronic daily headache. The mean values of temporomandibular and articular index (CDH patients) and muscular index (CDH and EH patients) were statistically higher than in patients of the control group, notably the articular  and muscular  indices. Conclusions: These findings allow us to speculate that masticatory and TMJ pain are more common in headache subjects. Besides, it seems that the TMD is more severe in headache patients. Key words:Temporomandibular dysfunction, headache disorders. Among the most common pain in general population, stand out temporomandibular disorder (TMD) which is the most common cause of pain in the orofacial region of non-dental origin ,2 and heThe specific location of painful areas is essential for treatment planning. In addition, it is of importance whether pain is localized to joint or muscle area only or if patients frequently have pain in other areas as well . HoweverSo, the present study intended to verify the frequency of (TM) signs and symptoms and its severity between subjects with chronic or episodic headache and those without headache at least three months ago. To the best our knowledge the present study is the first to investigate the severity of TMD, using specific tools (TMI), in headache patients.The sample was comprised of 60 individual , 40 with headache and 20 without headache (control group) from Headache Outpatient Service in Federal University of Sergipe. Headache were diagnosed and classified by a neurologist in episodic (n=20) or chronic headache (n=20) based on the International Classification of Headache Disorders, 2nd edition (ICHD-II) . ControlIn order to describe individual TM symptoms, the entire sample filled out a self-reported questionnaire modified by Conti et al. , which cClinical signs of TMD was made by using some questions of a systematically translated Brazilian version of the Research Diagnostic Criteria for TMD (RDC/TMD axis I) , performIn addition, determination of the Temporomandibular Index (TMI) was performed . The TMI-Statistical AnalysisGraphPad Prism version 3.0 was used for statistical analysis. Qualitative variables were presented as relative and/or absolute frequencies, while quantitative data were presented as mean values and standard deviations. The difference between qualitative variables among groups was performed using Fisher’s exact test. To compare TMI values as well as their sub-indices between headache (CDH or EH) and control group was used the Kruskal-Wallis followed by Dunn’s test. A significance level of 0.05 was set.The results of the present study are organized according to the following criteria: characterization of sample , signs aA total of 60 subjects were examined for the presence of TMD signs and symptoms. The characteristics of age and gender for all groups are showed in Relative to controls, subjects with CDH were significantly more likely to have clinical signs of TMD –tenderness in masticatory muscles , pain in posterior mandibular region and TMJ pain. For EH group the clinical signs pain in masseter and temporal muscle was significantly more common related to control group .Although the relationship between headache and TMD had already been demonstrated in several studies ,7-12,15 To the best our knowledge, the present study investigated at the first time the severity of TM signs and symptoms according to temporomandibular index .The sample of the present study was constituted basically by women (n=55), which corroborate to other studies that reported a higher prevalence of TMD ,21 and hRelated to TM symptoms, TMJ pain were significantly more frequent in headache patients (EH and CDH respectively). Additionally, the clinical signs of TMD, such as tenderness in masticatory muscles and TMJ pain were also statically more common in headache patients, especially those ones with CDH in relation to subjects without headache, corroborating with others studies that also found a higher prevalence of masticatory muscle tenderness and TMJ pain in headache patients ,15,24,25It was verified scores significantly higher for TMI and their subgroups MI and AI among CDH patients and for MI in EH subjects. These findings suggest that TMD severity, especially those related to TMJ and masticatory muscle pain, are higher in headache patients, mainly with chronic condition. This allows us to suggest that, even though TMD is common among the general population, its severity is higher in patients with headache. There is no consensus in the literature regarding the cause and effect relationship between TMD and headache, given that some studies report that chronic and episodic headache patients are more prone to TMJ and masticatory muscles pain , thus suIt is well established that neurons in the trigeminal system  integrate nociceptive input from TMJ and masticatory muscles as well as cranial tissues. Graff-Radford  contendsThus, it is possible that headache facilitated  masticatory muscle and/or TMJ pain or these pain conditions could be a trigger of headache which is also suggested by Stuginsky-Barbosa et al.  and GonçDespite the fact that knowing the temporal relationship between headache and TMD is difficult, in the present study the patients were informally asked about this relationship. The most of them related that the headache appeared before pain from TMD, so it is tempting to speculate headache as triggering factor to TMD development. Accordingly, pain from masticatory muscles and TMJ may act as a perpetuating and/or aggravating factor in headache patients. Bevilaqua-Grossi et al.  cited thThese findings allow us to suggest that masticatory and TMJ pain are more common in headache subjects. Besides, it seems that the TMDs are more severe in headache patients. Therefore, in cases in which the neurological treatment fails to eliminate the headache, it is suggested a thorough evaluation of the stomatognathic system, given that headache patients can benefit from evaluation and treatment of TMD.Finally, the data indicates the need for a multidisciplinary diagnosis and treatment of headache patients, given that the associated treatment of headache and TMD could bring more benefits regarding the symptoms relief of such individuals.


Bone destruction in the acetabulum caused by metastatic tumors will cause hip pain and joint dysfunction. It results in decreased quality of life for patients. The aim of our study was to explore the clinical effect of metastatic periacetabular tumors treated with percutaneous cementoplasty and interstitial implantation of 125I seeds between February 2003 and June 2011. There were 13 males and 11 females aged 19–80 years with a mean age of 57.3. The primary tumor site was the lung in eight cases, the breast in six, the prostate cancer in eight, and the liver in two. The amount of implanted 125I seeds was 12–20 seeds/person, with a mean of 16.5 seeds/person, and the matching peripheral dosage (MPD) was 80~100Gy. Routine postoperative chemotherapy and other combined treatments were applied to patients after the surgical operation. Changes in the Karnofsky Score(KPS), Harris Hip Score(Harris), and Visual Analog Scale(VAS) were observed during the follow-up period.A retrospective analysis was performed on 24 patients with metastatic periacetabular tumors who underwent combined therapy of percutaneous acetabuloplasty and interstitial implantation of P<0.05).The 24 patients’ operations were all successful. No major complications occurred. Complete pain relief was achieved in 58% (14 of 24) of patients, and pain reduction was achieved in the 42% remaining (10) patients. The mean duration of pain relief was 8.3 months. Pain recurred in one patient 3 months after surgery. Six patients had died and 18 patients were alive at the time of the 1-year follow-up. Comparing the KPS, Harris and VAS scores pre- and postoperativelyat 1, 6, and 12 months, the combined therapy method was significantly effective in metastatic periacetabular tumor patients (125I seeds is an effective treatment method for metastatic periacetabular tumor patients, providing tumor resistance, pain relief, increased bone stability, and improved quality of life for patients.Percutaneous cementoplasty with interstitial implantation of  The periacetabular area is one of the primary sites of metastatic tumors, which often present as osteolytic bone destruction. Bone destruction in the acetabulum caused by metastatic tumors causes hip pain and joint dysfunction, resulting in decreased quality of life for the patients .Radiotherapy and surgery are the commonly used methods to treat acetabular metastases. Radiotherapy achieves pain relief rate in 75% or more of the patients with metastatic tumors, but marked clinical improvement is observed in all patients 1 or 2 weeks after radiotherapy. However, radiotherapy cannot cure structural weakening of the pelvis caused by tumors and also leads to regional osteoporosis caused by radiotherapy, which increases the incidence of pathological fractures . HarringPercutaneous acetabuloplasty is the injection of acrylic bone cement into malignant or benign bone cavities in order to relieve pain and/or stabilize the bone. Bone packing with cement aims to treat or prevent vertebral and extraspinal pathological fractures and relieve pain in patients with osteoporosis and bone metastases, which, if applied in the treatment of acetabular metastases after surgery, could effectively improve the patients' quality of life -15.125I particle implantation, as an effective interstitial brachytherapy (IBT) technique, has been widely reported recently. Interstitial brachytherapy refers to the implantation of radioactive sources, usually in the form of needles, seeds, or wires, which are directly injected into the tumor lesion. Radioactive seed implantation has the advantages of real-time monitoring, precise orientation, being a simple operation, causing no radiation injury, etc., which can efficiently improve local control or increase the survival rate of patients with bone metastases [tastases -18. The 125I seed implantation in the treatment of 24 patients with acetabular metastases enrolled from February 2003 to June 2011.The aim of our study was to evaluate the efficacy of percutaneous puncture of the bone cement combined with  125I particle implantation from February 2003 to June 2011. We obtained approval for the study from the Ethics Committee of Tumor Hospital of Yunnan Province. The subjects and their families were well informed of the details and signed relevant contracts prior to the study. Patient ages ranged from 18 to 80 years; follow-upduration ranged from 8 to 60 months. There were single periacetabular metastases in 8 patients and and multiple bone metastases accompanied by periacetabular metastases in 16 patients. In 6 cases the primary tumors metastasized after resection in 6 months to 7 years; in 13 patients the primary tumor metastasized after radiotherapy and biological treatment within about 6 months to 2 years. Pain from the first metastasis occurred in five patients, and the primary malignancy site was found after inspection. The demographic data and primary malignancy site are shown in Table Twenty-four patients with periacetabular metastatic tumors were treated using percutaneous puncture of the bone cement combined withParticipants were patients with the following conditions: (1) the pathology had been confirmed by cytology in malignant tumor patients; (2) expected survival time of over 3 months; (3) persistent periacetabular pain, and no significant improvement achieved after medication and/or physical therapy. They also had confirmed periacetabular osteolytic destruction after X-ray, CT, and MRI imaging assessment.125I seed implantation according to Maccauro [Indications and contraindications for percutaneous acetabuloplasty and Maccauro  are deta125I source was selected as the radioactive source . The radiation source is cylindrical, and the diameter and height are 0.8 mm and 4.5 mm, respectively, with tissue-penetrating ability of 1.7cm and a half value layer of 0.025 mmPb. It is surfaced with titanium alloy inclusions, with a source activity of 0.3−1 mci. Liquid immersion disinfection was selected using benzalkonium bromide (soaked in Bromogeramine solution for 30 min).A domestic bone cement valvuloplasty device was used in our evaluation; the device included a puncture needle and a precession type injector pressure device . A closed radioactive isotope 125I particles was 2.92cGy/h/particles, and the 90% isodose curve included 90% tumor target volume. The tumor periphery matching dose (MPD) was 80 to100Gy.The treatment planning system was provided by Nuclear Industry Corp., Beijing Kelinzhong Medical Technology Institute. CT/MRI image scan results were obtained with three-dimensional digital image reconstruction in each patient before treatment using the system software according to lesion size, location, and the relationship with surrounding normal tissues. Three-dimensional icons and isodose curves were drawn to indicate the precise formulation and absorbed dose. At the same time, the radiation source initial dose, applicator needle coordinate, and depth indicator were given, and the treatment plan form was printed out. The initial dose of Routine tests of preoperative cardiopulmonary function, blood glucose, blood coagulation, liver and kidney function, and iodine allergy were conducted before the operation. The extent of lesions was determine by X-ray, CT, or MRI examination Figure  to choosStep 1: A lateral patient position was required to confirm the lesion locationusing DSA. The needle was disinfected with 1% lidocaine. The puncture needle was always perpendicular to the cortical bone destruction area in order to facilitate the puncture.125I particles were implanted according to the preoperative TPS treatment planning with an injection distance of 0.3 cm. A beveled needle and changed needle puncture direction were used for optimal implantation of the 125I particles.Step 2: The puncture needle was inserted into the bone fracture zone in an open perspective, then was pulled out. Step 3: The needle core was taken out, and the puncture needle was left in the target area; 5 ml of contrast was injected through the needle, and the contrast medium flow was record by DSA. Polymethyl methacrylate (PMMA) was used as bone cementand was mixed with non-ionic contrast medium during the operation; the injection was conducted under fluoroscopic monitoring to prevent bone cement leakage to the bone Figure .125I particles implanted was 12 to 20; the average number was 16.5.Step 4: The puncture needle was placed in the cortical bone after injection. The needle core was inserted and rotated to avoid gluing of the bone cement. The needle was pulled out before bone cement hardening. The amount of bone cement injected was 4 to 11 ml; the average amount was 5.5 ml. X-rays Figure  and CT sMain outcomes were measured as:• Postoperative observation of symptoms, change of signs, infection, or bone cement leakage.• Preoperative and postoperative pain ratings of patients with follow-up and application of narcotic analgesic drugs.• The Karnofsky Performance Status (KPS) physical status score, the Harris Hip Scale (Harris) score for hip function, and the Visual Analog Scale (VAS) for pain were recorded 1,6 and 12 months before and after the operation in all patients.P<0.05 was considered statistically significant.Basic statistical analyses were performed using the SPSS 20.0 statistical software . Categorical data were given as total numbers (and/or relative frequencies). Continuous data were given as mean ± standard deviation. Student’s t-test was performed to compare means between two groups. A value of 125I particle distribution in tumor foci in the central region presenting as a mass or diffuse distribution  and interstitial brachytherapy (IBT). EBRT requires higher radiation doses to achieve the effect becauseperipheral organs affectthe tumor tissue localization. EBRT only works well before tumor metastasis and its efficacy decreases with tumor cell mitosis [ mitosis ,17. IBT  mitosis .125I seed implantation is a highly effective treatment for patients with localized cancer. With the advantages of a relatively short half-life, use of low-energy photons with a low risk of complications, and the accuracy and consistency of the seeds, 125I seed implantation has been widely used for treatment of all kinds of solid tumors [d tumors ,27.125I seed implantation, the pain disappeared completely in 58% (14 cases) of patients and was alleviated in 42% (10 cases) of patients after the operation, with the average duration of pain relief being 8.3 months, except for pain recurrence in one patient 3 months after the operation. Statistical analysis results for the KPS, Harris and VAS scores before and after 1,6, and 12 months showed significant differences. No acetabular fractures or increase of local lesions was found on postoperative follow-up, and the phenomenon of abusing narcotic analgesic drugs was alleviated. However, it is difficult to evaluate narcotic drug use effects systematically, because patients might abuse drugs because of pain caused by tumor metastasis.Combined therapy using percutaneous radiofrequency ablation (RFA) and cementoplasty has been shown to be a safe and effective technique for palliative treatment of painful neoplastic bone metastasis ,29. In o125I seed implantation plays an important role in the treatment of metastatic bone tumors. Our early study results of 40 patients with spinal metastases showed good clinical results [Percutaneous puncture of the bone cement combined with  results . The resThe combined therapy has antineoplastic characteristics, relieving pain and enhancing skeletal stability. It is a good option to control the development of local tumors and improve patients’ quality of life. Further observation is being conducted to evaluate the prolongation of survival time.The authors declare that they have no competing interests.JZ and ZY was responsible for whole project design and manuscript writing; JW, JW, PL participated in the surgical operation; HS, KL, and YY were in charge of data analysis and correction of manuscript. All the authors had read and approved the final manuscript.The authors Jinlei Zhang, Zuozhang Yang, Jiaping Wang, Jinde Wang and Pengjie Liu contributed equally to this work, and each is considered as first author.


Median sternotomy provides excellent access to all mediastinal structures in patients undergoing conventional cardiovascular surgery. Although this incision technique is associated with relatively lower complication rates, certain complications such as the sternal dehiscence may pose serious health consequences. In this regard, considerable effort has been paid to develop techniques aiming to improve sternal healing and to enhance postoperative recovery after conventional cardiac surgery. Among these, kryptonite bone cement, a biocompatible polymer with improved mechanical properties when combined with a standard wire cerclage, represents a promising novel approach that may help prevent sternal dehiscence. In this study, the effects of this particular type of bone cement on sternal healing, postoperative pain, and quality of life have been evaluated.Kryptonite bone cement enhanced sternal closure was employed in a total of 100 patients undergoing conventional cardiac surgery between November 2009 and June 2012. Of these patients, 50 expressed their willingness to participate in this study. Each participant underwent a computerized tomography imaging for the radiological assessment of sternal healing. Pain and life quality of these patients have been evaluated by Wong-Baker faces pain scale and SF-36 health survey questionnaire, respectively.2, respectively. Elderly patients (≥70), females and those with chronic obstructive pulmonary disease (COPD) comprised 64%, 26% and 40% of the study population, respectively. No patients had findings suggestive of dehiscence on CT images. No patients reported severe pain . Elderly (≥ 70 yr) subjects had better quality of life scores as compared to the remaining group of patients (< 70 yr) according to SF-36 Health Survey results. Vitality and emotional role scores were lower  in female patients. Patients with COPD had lower quality of life scores than those without COPD, particularly with respect to general health scores .Mean duration of follow-up was 20.14 ± 7.36 months (range: 10–32). Mean age and body mass index were 71.32 ± 7.23 years (range: 55–85) and 28.34 ± 2.62 (21–34) kg/mKryptonite bone cement, when combined with a standard wire cerclage, enhances mechanical strength, prevents sternal dehiscence, reduces postoperative pain and improves quality of life after conventional cardiac surgery. Long-term studies are warranted to better define the role of kryptonite bone cement in the prevention of sternal dehiscence. Every yThe single most important factor in preventing sternal dehiscence and mediastinitis is achieving a stable sternal approximation, and the traditional sternal closure techniques may not always provide optimal fixation.The objective of our study was to evaluate the benefits of a particular sternal closure technique on sternal healing, postoperative pain and quality of life in patients undergoing cardiac surgery. Essentially, this technique is based on enhancement of the standard wire cerclage through the use of a special bone cement, which is a biocompatible polymer composed of naturally occurring fatty acids and calcium carbonate, derived from castor oil .Sternal closure enhanced by kryptonite bone cement was implemented in a total of 100 patients undergoing conventional cardiac surgery between November 2009 and June 2012. This study was approved by ethical boards of Bilim University Hospital and each pateints provided written informed consent. Computed tomography, Wong-Baker faces pain scale, and SF-36 health survey questionnaire have been utilized to assess the benefits of this technique on sternal union, postoperative pain and quality of life. Following discharge, a telephone call invitation was made for study participation to every patient, of whom 50 accepted to participate and give written consent for the study. Twelve patients could not be contacted due to changes in contact information. The remaining declined participation mostly due to radiation concerns associated with the use of computed tomography or due to their remote settlement from the hospital.Five patients between 80 and 89 years of age underwent a vertebral operation during the early postoperative period, on average 1 week after the conventional cardiac surgery. Sternal dehiscence did not occur in these patients and three of them consented to participate in the study.A high-risk patient had sternal dehiscence secondary to mediastinitis and died due to heart failure during early postoperative period. Superficial wound infections were observed in two patients with diabetes mellitus, but these patients were among those who had initially refused to participate in the study.Re-exploration surgery was performed in two patients due to bleeding. These two cases were excluded from the study because the integrity of kryptonite bone cement was disrupted and a second application could not be performed due to personal financial constraints.Written consent for the use of bone cement was obtained from all 100 patients before surgery. However, since study participation required further procedures, additional written consent for the study was obtained from 50 patients who showed their willingness for participation. Hospital database was used to collect information on preoperative, intraoperative and postoperative characteristics of the patients. Follow up visits were performed in office conditions. Sternal union was ascertained with physical examination and computed tomography. Pain and quality of life scores were assessed using Wong-Baker faces pain scale and SF-36 health survey questionnaire, respectively.2, osteoporosis, limited mobility to plan a vertebral surgery in early postoperative period, active smoking until time of hospitilization, chronic obstructive pulmonary disease. Patients with postoperative re-exploration for bleeding were excluded.First-time or redo patients between 50 and 90 years of age presenting with an indication for on-pump cardiac surgery to be carried out through median sternotomy who provided informed consent to participate were included in the study. In addition, each patient should have at least one of the following criteria: age ≥75 years, body mass index (BMI) ≥30 kg/mKryptonite bone cement  is a biocompatible polymer composed of naturally occurring fatty acids and calcium carbonate, derived from castor oil. The porous network within the product allows osteointegration with host bone over time, without fibrosis or inflammation.Following standard cardiopulmonary bypass, sternal closure was performed in all patients using 7-wire interrupted cerclage with (No:6) 18-gauge stainless steel. Then, trabecular bone was cleansed with a sterile brush and irrigated with saline solution to expose the bone trabecular interface. The Kryptonite bone adhesive was mixed for 5 minutes, and then 5 ml of it was applied as a thin layer to each hemisternum. It is an injectable liquid for up to 8 minutes after mixing three components, then, transitions into a highly adhesive taffy state 8–15 minutes after mixing. Through polymerization, it attains bone-like rigidity and strength  is a widely used tool in clinical studies to assess the quality of life and general health perception. It can be used to assess the physical and mental health as well as how the patient perceives his or her health or illness . This quSF-36 consists of 36 questions in 8 domains. These 8 domains include physical functioning , physical role (being able to do his/her job and daily activities), bodily pain (no pain or limitations due to pain), general health perception , vitality (enjoying life), social functioning , emotional role , and mental health . Three domains  show high correlation with the physical component (PCS). Mental health and emotional role items mostly correlate with the mental component (MCS). Vitality, general health, and social functioning correlate with both. Scores are converted to a 0–100 scale, which allows numerical assessment of the domains. Higher scores indicate less limitation and disability.Pain and discomfort were measured by Wong-Baker faces pain scale is a self-rated tool, which utilizes a number of face depictions that range from happy to tearful (0–10). Reliability of the scale has been demonstrated in a well-designed study . It is aP values less than 0.05 are considered statistically significant.All analyses were performed using SPSS  for windows, version 17.0. Mann Whitney U test was used to compare the demographic and clinical characteristics of participants. Chi-Square test was used for the comparisons of frequencies between the groups. All data are expressed as mean ± standard error of the mean. 2 . More than 50% of the patients were overweight or obese. Thirty-six percent of the patients had diabetes and three patients had arthritic conditions including rheumatoid arthritis and gout.Demographic characteristics of the 50 participants are summarized in Table Mean duration of follow-up was 20.14 ± 7.36 months (range: 10–32). Two patients were redo cases and underwent valvular and aortic procedures. In 64% of the subjects, a coronary artery bypass surgery was performed, with bilateral use of internal mammary arteries in five cases. The mean volume of postoperative bleeding in the intensive care unit was 185 ± 69 ml . Seventy-two percent of the patients were on aspirin and 26% were on heparin preoperatively. None of the participants required postoperative re-exploration for bleeding. Intra- and post-operative characteristics of the patients can be seen in Table MCT scans showed the signs of retained kryptonite cement, bone healing, and increased radiodensity between the sternal edges, suggestive of new bone formation. Physical examination showed minimal sternal instability in two patients that correlated with the gaps between the sternal halves seen on CT. However, no patients had dehiscence Figure .2 = 9.18. p = 0.010). The three patients with arthritic conditions in our study population reported mild to moderate pain.Percentage of patients who reported no hurt (0), hurt little (2) and hurt little more (4) according to Wong-Baker faces pain scale was 80%, 16% and 4%, respectively. There was no patient who reported severe pain (4–10). Assessment of the association between risk factors and pain scores showed a significant correlation between the severity of pain and arthritis only . Lowest scores were found for the emotional role (64.91 ± 45), probably associated with the predominance of frail elderly subjects among study participants  and emotional role  scores as compared to male subjects. The observed difference between sexes in these two domains representing the mental component of SF36 may be related to differential psychological reactions of the two sexes to surgery  was lower as compared to those without COPD, particularly in terms of general health , which is physical domain of SF36. Even though all patients had Kryptonite bone cement, COPD had negative effect on life quality  do not correlate with any clinical sternum instability .COPD represents another risk factor for sternal dehiscence. Physical forces generated by coughing can cause dehiscence or separation of the sternal halves. A successful sternal closure must be able to survive cyclic loading from repetitive physiological forces. Increased risk is also associated with the fact that sternotomy results in significant postoperative atelectasis and reduces pulmonary functions. In our study, 40% of the patients had COPD and all achieved sternal union as demonstrated by CT.The reported incidence of dehiscence after coronary artery bypass grafting varies between 1.2 and 2.5%. Use of the internal mammary artery (IMA) for coronary revascularization may cause further increase in this risk. After removal of the main source of sternal blood supply and disruption of the cross-anastomoses between the periosteal plexus by median sternotomy, the collateral flow from intercostal and segmental branches cannot immediately substitute for the missing MA . When boPostoperative pain correlates with stability and alignment of the sternal closure. Early postoperative pain can result in poor mobility and shallow breathing that may lead to complications, including deep vein thrombosis, pulmonary embolus and pneumonia. It is also worth remembering that the use of strong narcotics in the elderly patients can have serious side effects such as hallucinations, confusion and disabling falls . In thisPatient recovery and return to normal activities after cardiac operations is often delayed by a 6 to 8 week period required for osteosynthesis (solid bony union). In most centers, the recommended duration for sternal precaution is 6 to 8 weeks. Due to physical changes occurring through ageing and presence of disabilities, this period may be even longer in the elderly jeopardizing daily functions. In a previous study, patients with adhesive-enhanced closure have been shown to have accelerated recovery of health-related quality of life and a reduction in overall physical disability in the postoperative period compared with control patients . SimilarOur sample size was small and there were no control patients. In addition, thorax CT scans were not performed at uniform time intervals.Kryptonite bone cement as an enhancement to conventional wire cerclage for sternal closure is a safe, simple and quick procedure requiring no special technical skills and is associated with accelerated sternal healing, reduced postoperative pain, and improved quality of life. Longer-term studies with larger sample size may be warranted to better define potential risks and benefits of this innovative technique.MCT: Multislice computed tomography; BMI: Body mass index; SF-36: Short form- 36; PCS: Physical component of summary; MCS: Mental component of summary; COPD: Chronic obstructive pulmonary disease; SPECT: Single- photon emission computed tomography; IMA: Internal mammary artery.The authors declare that they have no competing interests.ZB participated in sequence alignment and drafted the manuscript. YD and MB collected patient data. OLU contributed to the study by radiological analysis. BC, ES and BA participated in the design and coordination. All authors read and approved the final manuscript.