Incidence and outcomes of surgical resection for giant pulmonary bullae - a population-based study

Background: Giant pulmonary bullae (GPB) are rare and there is little information on incidence, long-term prognosis, and outcome of treatment.Objectives: To assess the incidence of GPB in the Icelandic population and to evaluate the outcome of surgical treatment.Methods: Twelve consecutive patients (11 males; mean age 60 ± 15.7 years) underwent resection for GPB in Iceland between 1992 and 2009. All were heavy smokers and had bullae occupying > 30% of the involved lung. There were 8 bilateral and 3 unilateral bullectomies and one lobectomy. Pulmonary function tests were performed preoperatively, and at one month and 5.4 years postoperatively. Age-standardized incidence rate (ASR) was calculated, complications and operative mortality were registered, and overall survival was estimated. Mean follow-up time was 8.2 years.Results: The ASR for GPB was 0.40 and 0.03 per 100,000 per year for men and women, respectively. There was no operative mortality, but prolonged air leakage (75%) and pneumonia (17%) were the most common postoperative complications. One month postoperatively, mean FEV1 increased from 1.0 ± 0.48 L (33% predicted) to 1.75 ± 0.75 L (57.5% predicted) (p < 0.01), but FVC remained unchanged. RV decreased from 3.9 ± 0.8 L (177% predicted) to 3.0 ± 1.0 L (128% pre-dicted) (p < 0.05), but TLC and DLCO did not change after operation. At long-term follow-up the FEV1 and FVC had declined to near-baseline values. Five-year and 10-year survival were 100% and 60%, respectively.Conclusions: The ASR of GPB in Iceland was 0.21 per 100,000 per year. In this small series, bullectomy was found to be a safe procedure that significantly improved pulmonary function. The functional improvement then declined over time. Prolonged air leakage was a common postoperative complication that prolonged hospital stay.     

Advances in DNA methylation: 5-hydroxymethylcytosine revisited

Mammalian DNA contains two modified cytosine bases; 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Both of these have been known for decades but have received very different levels of attention in the scientific literature. 5mC has been studied extensively, and its role as an epigenetic modification involved in gene regulation, X-chromosome inactivation, genomic imprinting, long-term silencing of transposons and cancer development is well described. 5hmC, on the other hand, has only recently entered center stage when it was shown that the Ten-Eleven-Translocation (TET) family of oxygenases catalyzes the conversion of 5mC to 5hmC, and that one of these enzymes, TET2, is frequently mutated in myeloid neoplasms. The formation of 5hmC can lead to demethylation of DNA, which may contribute to the dynamics of DNA methylation. 5hmC has been found in many cell types and tissues, with particularly high levels in the brain, and TET1 has been shown to be important for self-renewal and maintenance of embryonic stem cells. Future challenges include better understanding the normal molecular, cellular and physiological roles of 5hmC and TET proteins, understanding the exact roles of TET proteins in cancer development, and developing sequencing methodologies that can accurately distinguish among cytosine, 5mC and 5hmC at single-base-pair resolution.     

Tourniquet use in total knee replacement does not improve fixation, but appears to reduce final range of motion: A randomized RSA study involving 50 patients

Background and purpose

Although a tourniquet may reduce bleeding during total knee replacement (TKA), and thereby possibly improve fixation, it might also cause complications. Migration as measured by radiostereometric analysis (RSA) can predict future loosening. We investigated whether the use of a tourniquet influences prosthesis fixation measured with RSA. This has not been investigated previously to our knowledge.

Methods

50 patients with osteoarthritis of the knee were randomized to cemented TKA with or without tourniquet. RSA was performed postoperatively and at 6 months, 1 year, and 2 years. Pain during hospital stay was registered with a visual analog scale (VAS) and morphine consumption was measured. Overt bleeding and blood transfusions were registered, and total bleeding was estimated by the hemoglobin dilution method. Range of motion was measured up to 2 years.

Results

RSA maximal total point motion (MTPM) differed by 0.01 mm (95% CI –0.13 to 0.15). Patients in the tourniquet group had less overt bleeding (317 mL vs. 615 mL), but the total bleeding estimated by hemoglobin dilution at day 4 was only slightly less (1,184 mL vs. 1,236 mL) with a mean difference of –54 mL (95% CI –256 to 152). Pain VAS measurements were lower in the non-tourniquet group (p = 0.01). There was no significant difference in morphine consumption. Range of motion was 11° more in the non-tourniquet group (p = 0.001 at 2 years).

Interpretation

Tourniquet use did not improve fixation but it may cause more postoperative pain and less range of motion.The use of a tourniquet during total knee replacement (TKA) is routine at many departments. It is believed to facilitate dissection and reduce peroperative bleeding, but the main argument for its use is that bleeding bone surfaces might impair the fixation of cemented prostheses, due to less cement penetration (Alcelik et al. 2011).On the other hand, a tourniquet is associated with reperfusion trauma and oxidative stress. There is also a risk of injury due to pressure on skin, muscle, nerves, and arteriosclerotic vessels, and a risk of deep vein thrombosis (Newman 1984, Irvine and Chan 1986, Silver et al. 1986, Abdel-Salam and Eyres 1995, Clarke et al. 2001, Olivecrona et al. 2006). Tourniquets reduce the surgical field, which might jeopardize sterility of the postoperative wound dressing. They are cumbersome to apply, especially in overweight patients. We have had the clinical impression that postoperative pain is to some extent due to the tourniquet.Because of these drawbacks of tourniquet use, our department stopped using tourniquets in 2003. After a short learning period, we perceived this to be more practical and to be associated with less postoperative pain. To our knowledge, a positive effect of tourniquet use on implant fixation has never been shown. However, this possibility meant that our new routine should be evaluated in a trial.Radiostereometric analysis is performed to measure early postoperative migration. It is generally believed that there is an association between early migration and the risk of late loosening (Nilsson and Karrholm 1996). This has been supported by one study (Ryd et al. 1995), and by theoretical reasoning. Thus, if a relevant difference in early migration between patients operated with or without a tourniquet could be excluded, it would be reasonable to assume that tourniquet use is not related to the quality of the fixation. No RSA data on the effect of tourniquet use are available in the literature.We performed a randomized controlled trial with blind evaluation to study the effects of tourniquet use. We used migration by RSA as the primary effect variable.     

The type of surgical approach influences the risk of revision in total hip arthroplasty: A study from the Swedish Hip Arthroplasty Register of 90,662 total hip replacements with 3 different cemented prostheses

Background and purpose

The most common surgical approaches in total hip arthroplasty in Sweden are the posterior and the anterolateral transgluteal approach. Currently, however, there is insufficient evidence to prefer one over the other regarding risk of subsequent surgery.

Patients and methods

We searched the Swedish Hip Arthroplasty Register between the years 1992 and 2009 to compare the posterior and anterolateral transgluteal approach regarding risk of revision in the 3 most common all-cemented hip prosthesis designs in Sweden. 90,662 total hip replacements met the inclusion criteria. We used Cox regression analysis for estimation of prosthesis survival and relative risk of revision due to dislocation, infection, or aseptic loosening.

Results

Our results show that for the Lubinus SPII prosthesis and the Spectron EF Primary prosthesis, the anterolateral transgluteal approach gave an increased risk of revision due to aseptic loosening (relative risk (RR) = 1.3, 95% CI: 1.0–1.6 and RR = 1.6, CI: 1.0–2.5) but a reduced risk of revision due to dislocation (RR = 0.7, CI: 0.5–0.8 and RR = 0.3, CI: 0.1–0.4). For the Exeter Polished prosthesis, the surgical approach did not affect the outcome for dislocation or aseptic loosening. The surgical approach had no influence on the risk of revision due to infection in any of these designs.

Interpretation

This observational study shows that the surgical approach affected the risk of revision due to aseptic loosening and dislocation for 2 of the most commonly used cemented implants in Sweden. Further studies are needed to determine whether these results are generalizable to other implants and to uncemented fixation.The posterior approach and the anterolateral transgluteal (ALT) approach, also called the direct lateral approach, without trochanteric osteotomy are—with various variations—probably the 2 most common approaches used to insert a total hip arthroplasty (THA). The ALT incision offers good exposure of the acetabulum, which could facilitate cup positioning. Patients operated with an ALT approach run a higher risk of postoperative limp because of a risk of interference with the abductor muscles and the superior gluteal nerve (Baker and Bitounis 1989, Downing et al. 2001). The posterior incision may give better access to the femur and may facilitate stem positioning. This may reduce the risk of malalignment and in turn give a poor cement mantle, which could cause loosening (Garellick et al. 1999). However, the posterior approach has been associated with increased frequency of instability and dislocation (Woo and Morrey 1982, Masonis and Bourne 2002). A meta-analysis of clinical trials did not find any convincing evidence that either the posterior approach or the ALT approach was superior in THA for osteoarthritis (Jolles and Bogoch 2006).Between 1999 and 2008, use of the ALT approach with the patients on their side (the Gammer approach (Gammer 1985)), increased in Sweden from 18% to 42%. This has mainly been done at the expense (i.e. decreasing frequency) of the posterior approach (Moore 1957), which changed in frequency of use from 63% to 52% during the same period (Garellick et al. 2008). One reason for this may have been reports of increasing dislocation rates due to hip fracture after THA performed with the posterior approach (Enocson et al. 2009). Another reason may have been that if the orthopedic surgeon operates without an assistant, which has become more common, for the nurse it is easier to hold the leg when the ALT approach is used. The possible effect of this development on the overall outcome regarding risk of revision is, however, unclear.In this observational cohort study based on prospective collected data from the Swedish Hip Arthroplasty Register (SHAR), we therefore investigated the outcome of surgical approach regarding risk of revision. We hypothesized that the influence of surgical approach on the risk of revision would vary depending on the reason for revision selected and that the outcomes would differ depending on the type of stem analyzed.     

Elevated plasma levels of TIMP-1 in patients with rotator cuff tear

Background and purpose

Extracellular matrix remodeling is altered in rotator cuff tears, partly due to altered expression of matrix metalloproteinases (MMPs) and their inhibitors. It is unclear whether this altered expression can be traced as changes in plasma protein levels. We measured the plasma levels of MMPs and their tissue inhibitors (TIMPs) in patients with rotator cuff tears and related changes in the pattern of MMP and TIMP levels to the extent of the rotator cuff tear.

Methods

Blood samples were collected from 17 patients, median age 61 (39–77) years, with sonographically verified rotator cuff tears (partial- or full-thickness). These were compared with 16 age- and sex-matched control individuals with sonographically intact rotator cuffs. Plasma levels of MMPs and TIMPs were measured simultaneously using Luminex technology and ELISA.

Results

The plasma levels of TIMP-1 were elevated in patients with rotator cuff tears, especially in those with full-thickness tears. The levels of TIMP-1, TIMP-3, and MMP-9 were higher in patients with full-thickness tears than in those with partial-thickness tears, but only the TIMP-1 levels were significantly different from those in the controls.

Interpretation

The observed elevation of TIMP-1 in plasma might reflect local pathological processes in or around the rotator cuff, or a genetic predisposition in these patients. That the levels of TIMP-1 and of certain MMPs were found to differ significantly between partial and full-thickness tears may reflect the extent of the lesion or different etiology and pathomechanisms.The subacromial pain syndrome includes a range of disorders from reversible inflammation to massive rotator cuff tearing (Shindle et al. 2011). The etiology appears to be multifactorial, and several anatomic structures may be involved. Repetitive damage of the supraspinatus tendon by mechanical wear from the coraco-acromial ligament and the anterior acromion was described by Neer 1972, and for a long time it was considered the major cause of cuff tearing (Neer 1983). Others have reported age-related tendon degeneration, associated with alterations in extracellular matrix remodeling as a contributing factor (Lo et al. 2004, Millar et al. 2009, Pasternak and Aspenberg 2009, Shindle et al. 2011). Histopathological changes associated with rotator cuff tendinosis have been documented, but it is unclear whether they are a result of a subacromial impingement or an endogenous process, and whether tendinosis might predispose to tendon tears (Lo et al. 2004).Regardless of whether mechanical or degenerative factors initiates tearing, there are alterations in the cellular and extracellular matrix (Gwilym et al. 2009). It has been suggested that genetic factors may influence apoptosis or regeneration (Gwilym et al. 2009, Shindle et al. 2011). Still, the molecular changes associated with rotator cuff tearing are largely unknown (Lo et al. 2004, Garofalo et al. 2011). Turnover of the extracellular matrix (ECM) is mediated by matrix metalloproteinases (MMPs), a family of at least 24 zinc-dependent endopeptidases. The MMPs are classified according to their main degradative activity, into for example collagenases, gelatinases, and stromelysins (Pasternak and Aspenberg 2009). Their activity is regulated by endogenous inhibitors: tissue inhibitors of metalloproteinases (TIMPs). There are 4 known TIMPs, which reversibly inhibit all MMPs by 1:1 interaction with the zinc-binding site (Lo et al. 2004, Pasternak and Aspenberg 2009). MMP production is induced by factors such as cytokines and tumor necrosis factor-α. MMPs are secreted by connective tissue and inflammatory cells and then activated in the extracellular space (Garofalo et al. 2011). The composition of the ECM is dependent on the balance between MMPs and TIMPs (Lo et al. 2004, Pasternak and Aspenberg 2009, Garofalo et al. 2011). Levels of MMP mRNA and TIMP mRNA were found to be altered in biopsies from torn rotator cuff tendon (Lo et al. 2004). It is not known, however, whether these changes are causative or whether they are secondary to tendon tearing.Studies on MMP and TIMP levels in patients with rotator cuff syndrome and cuff tears have used samples collected at surgery from the subacromial bursa, synovial fluid, or the tendons (Lo et al. 2004, Lakemeier et al. 2010, Shindle et al. 2011). To date, there have been no data on systemic levels. Alterations in MMP and TIMP levels in systemic blood samples have been identified in other musculoskeletal diseases such as Dupuytren’s disease, ankylosing spondylitis, and fracture non-union, suggesting that alterations associated with rotator cuff disease may also be measurable systemically (Ulrich et al. 2003, Henle et al. 2005, Pasternak and Aspenberg 2009). In osteoarthritis, circulating MMP-3 has been suggested to be a marker of disease severity and has been used as a prognostic tool (Lohmander et al. 2005).We measured plasma levels of MMPs and TIMPs in patients with rotator cuff tears and compared partial- and full-thickness tears, in order to find disease-associated changes in the expression patterns of MMP and TIMP.     

Epidemiology of adult ankle fractures in Sweden between 1987 and 2004: a population-based study of 91,410 Swedish inpatients

Background and purpose

Previous national epidemiological data on the characteristics and trends of patients with ankle fractures have been limited. We therefore analyzed data on Swedish inpatients with ankle fractures in this nationwide population study, based on data from 1987 through 2004.

Patients and methods

Data on all inpatients aged 15 years and older with ankle fracture were extracted from the Swedish National Patient Register for the period 1987–2004.

Results

We identified 91,410 hospital admissions with ankle fracture, corresponding to an annual incidence rate of 71 per 10⁵ person-years. During the study period, the number of hospital admissions increased by 0.2% annually, mainly from increase in fracture incidence in the elderly women. Mean age at admission was 45 (SD 19) years for men and 58 (18) for women. The major mechanism of injury was falling at the same level (64%).

Interpretation

This nationwide study of inpatients with ankle fractures showed an increase in fracture incidence, particularly in elderly women.Ankle fractures are among the most common fractures treated in orthopaedic surgery today. They are also a significant source of morbidity in both the young and the elderly (Donaldson et al. 1990, Jones et al. 1994, van Staa et al. 2001). Previous epidemiological studies have shown trends of increasing incidence over time, mainly in elderly women (Bengnér et al. 1986, Daly et al. 1987, Baron et al. 1996, Kannus et al. 1996, Court-Brown et al. 1998, van Staa et al. 2001, Kannus et al. 2002). However, most of these studies have included limited numbers of patients, and mostly originated from single hospitals or limited areas.Basic epidemiological data such as incidence, fracture type, age and sex distribution, mechanisms of injury, and surgical procedures can provide estimates when discussing disease burden and in the planning and provision of healthcare.The purpose of this study was to perform an epidemiological analysis of all adult ankle fractures requiring hospital admission in Sweden from 1997 through 2004, including incidence, causes of fracture, surgical procedures, patient characteristics, and trends over time.     

Impaired net hepatic glycogen synthesis in insulin-dependent diabetic subjects during mixed meal ingestion. A 13C nuclear magnetic resonance spectroscopy study.

Hepatic glycogen concentration was measured in six subjects with insulin-dependent diabetes mellitus (IDDM) and nine weight-matched control subjects using 13C nuclear magnetic resonance spectroscopy during a day in which three isocaloric mixed meals were ingested. The relative fluxes of the direct and indirect (3 carbon units-->-->glycogen) pathways of hepatic glycogen synthesis were also assessed using [1-13C]glucose in combination with acetaminophen to noninvasively sample the hepatic UDP-glucose pool. Mean fasting hepatic glycogen content was similar in the two groups. After each meal, hepatic glycogen content increased, peaking 4-5 h after the meal in both groups. By 11:00 p.m. the IDDM subjects had synthesized only 30% of the glycogen that was synthesized by the control group [IDDM subjects, net increment = 44 +/- 20 (mean +/- SE) mM; control subjects, net increment = 144 +/- 14 mM; P < 0.05]. After breakfast the flux through the gluconeogenic pathway relative to the direct pathway of hepatic glycogen synthesis was 1.7-fold greater in the IDDM subjects (59 +/- 4%) than in the control subjects (35 +/- 4%, P < 0.0003). In conclusion, under mixed meal conditions, subjects with poorly controlled IDDM have a major defect in net hepatic glycogen synthesis and augmented hepatic gluconeogenesis. The former abnormality may result in an impaired glycemic response to counterregulatory hormones, whereas both abnormalities may contribute to postprandial hyperglycemia.     

Comparison of four different preparation protocols to achieve bladder distension in patients with gross haematuria undergoing a CT urography

IntroductionCT examination has been shown to be effective in detecting bladder cancer. Proper evaluation of the bladder requires it to be well distended. The purpose of the present study was to establish a preparation protocol to achieve satisfactory bladder distension without causing unacceptable patient discomfort.Material and methodWe used four different preparation protocols (1: 0.5 L of fluid intake during a 1-h period, 2: Same as 1 with the addition of IV diuretics when the patient was examined, 3: 1 L of fluid intake during a 2-h period, 4: Same as 3 with the additional instruction to empty the bladder after 1 h. In protocols 1–3, the patients were asked not to empty their bladder during the preparation time). Bladder volume was calculated and bladder distension was judged as satisfactory or not by the radiologist. The patients answered questions about their ability to follow the preparation protocol and were requested to rate their need to empty the bladder pre-, during and post-examination.ResultsProtocol 1 had the lowest bladder volume. Protocols 2, 3 and 4 were similar in bladder volume. However, Protocol 2 caused unacceptable patient discomfort, and the compliance was lowest in Protocol 4.ConclusionProtocol 3, drinking 1 L of fluid during a 2-h period, gave satisfactory bladder distension, did not cause unacceptable discomfort in patients and did not have the lowest compliance.     

Establishment of reference distributions and decision values for thyroid antibodies against thyroid peroxidase (TPOAb), thyroglobulin (TgAb) and the thyrotropin receptor (TRAb).

BACKGROUND: The National Academy of Clinical Biochemistry (NACB) stresses that the reference intervals for thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb) and thyroid stimulating hormone (TSH)-receptor antibodies (TRAb) should be based on young men who lack certain risk factors and have serum TSH between 0.5 and 2.0 mIU/L. However, some young men without any of the risk factors have autoantibodies, and cannot be identified by the present tools. A model for reference intervals and cut-off values should not be influenced by the prevalence of risk factors. METHODS: We developed a model of "composite logarithmic Gaussian distributions" and tested it in 1441 well-characterised subjects without clinically overt thyroid disease. RESULTS: TPOAb and TgAb could be measured in all individuals. The 97.5% upper limits 1) on a traditional non-parametric scale, 2) according to the NACB criteria, and 3) for our model were 284, 24 and 9.8 kIU/L for TPOAb, and 84, 22 and 19 kIU/L for TgAb, respectively. The decision value (defined as the concentration corresponding to 0.1% false positives) was 15 kIU/L for TPOAb and 31 kIU/L for TgAb. Concentrations above our reference intervals affected the corresponding distribution of TSH values. For TRAb the upper reference limits were 1) 0.75 and 2) 0.75 IU/L, while our model was not applicable to TRAb because only 2-3% of the results were above the functional assay sensitivity. CONCLUSIONS: In contrast to the NACB guidelines, our model for TPOAb and TgAb is more robust, as it is independent of the characteristics of the reference population.