Implementation of ultrasound-guided carpal tunnel release.

INTRODUCTION: Ultra-minimally invasive ultrasound-guided carpal tunnel release is a surgical procedure for treatment of carpal tunnel syndrome that is associated with less surgery-related morbidity and faster recovery than open surgery. The objectives of this study were to describe how the surgical technique may be acquired and to report the results obtained after implementation in a clinical setting. METHODS: The study consisted of two parts: 1) description of the surgical skills needed to perform the procedure, and 2) evaluation of the procedure in the first ten consecutively operated patients after 12-month follow-up using questionnaires and magnetic resonance imaging (MRI). RESULTS: The procedure was performed on 29 cadaveric arms and assessed regarding surgical release success and signs of iatrogenic damage. Subsequently, the procedure was performed on ten patients with carpal tunnel syndrome. The results of the six-item Carpal Tunnel Symptoms Scale (1-5) improved from 3.3 ± 0.9 (mean ± standard deviation) preoperatively to 1.2 ± 0.3, p = 0.002, after 12 months. Quick Disabilities of the Arm, Shoulder and Hand (DASH) (0-100) results improved from 33.4 ± 14.8 to 2.3 ± 4.0, p = 0.002. There were no infections or iatrogenic damage to nerves or blood vessels. CONCLUSIONS: This study presents a way to safely acquire the skills needed to perform the procedure and implement it in an out-patient setting. The results were comparable to previous findings regarding both effectiveness and safety. MRI documented the surgical gap in the transverse carpal ligament, release length, cross-sectional area changes in the carpal tunnel and median nerve, and reactive changes in the carpal tunnel. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Complete Genome Sequence of the Lysogenic Pseudomonas Bacteriophage Fyn8.

A temperate bacteriophage infecting Pseudomonas aeruginosa PAO1 was isolated from river water. Nanopore sequencing revealed that it has a circular double-stranded DNA genome of 45,617 bp, containing typical phage structural proteins and lambda-like lysogeny regulators. Putative O-antigen serotype conversion and anti-cyclic oligonucleotide-based antiphage signaling system (CBASS) defense system proteins were also identified.

An Isometric and Functionally Based 4-Stage Progressive Loading Program in Achilles Tendinopathy: A 12-Month Pilot Study.

Background: Achilles tendinopathy (AT) is a common musculoskeletal disorder, and its management remains challenging. Hypothesis/Purpose. By conducting a pilot study, we aimed to assess the feasibility, safety, and clinical improvement of a new home-based 4-stage rehabilitation program with progressive loading including isometric exercises on a small scale prior to setting up a randomized controlled trial. Methods: Ten recreational athletes with chronic midportion AT were included. The primary outcome was change in VISA-A score after 1, 2, 3, 6, and 12 months. Secondary outcomes included tenderness on palpation of the tendon and ultrasonographic changes after 6 months. Results: Average VISA-A improvements of 26.9 points (P=0.004) and 35.4 points (P=0.006) were observed at 6- and 12-month follow-up, respectively. Tenderness on palpation of the tendon (0-10) was reduced from 5.5 to 2.5 (P < 0.001). Color Doppler ultrasound activity (0-4) was reduced by 50%, from an average of grade 2 to grade 1 (P=0.023). The hypoechoic cross-sectional area of the Achilles tendon was reduced from an average of 29.1% to 8.5% (P=0.001). Tendon thickness showed no statistically significant change (P=0.415). Conclusion: Following the 4-stage rehabilitation program for AT based on isometric training and progressive loading, we observed improvement in both VISA-A score and ultrasonography in a group of athletes who had previously failed to benefit from standard AT rehabilitation. The study was feasible in terms of high adherence to the program and with no observed safety issues. The results of this pilot study support a further assessment of this specific approach for rehabilitation in a future randomized controlled trial.

Linking inherent O-Linked Protein Glycosylation of YghJ to Increased Antigen Potential.

Enterotoxigenic Escherichia coli (ETEC) is a WHO priority pathogen and vaccine target which causes infections in low-income and middle-income countries, travelers visiting endemic regions. The global urgent demand for an effective preventive intervention has become more pressing as ETEC strains have become increasingly multiple antibiotic resistant. However, the vaccine development pipeline has been slow to address this urgent need. To date, vaccine development has focused mainly on canonical antigens such as colonization factors and expressed toxins but due to genomic plasticity of this enteric pathogen, it has proven difficult to develop effective vaccines. In this study, we investigated the highly conserved non-canonical vaccine candidate YghJ/SsLE. Using the mass spectrometry-based method BEMAP, we demonstrate that YghJ is hyperglycosylated in ETEC and identify 54 O-linked Set/Thr residues within the 1519 amino acid primary sequence. The glycosylation sites are evenly distributed throughout the sequence and do not appear to affect the folding of the overall protein structure. Although the glycosylation sites only constitute a minor subpopulation of the available epitopes, we observed a notable difference in the immunogenicity of the glycosylated YghJ and the non-glycosylated protein variant. We can demonstrate by ELISA that serum from patients enrolled in an ETEC H10407 controlled infection study are significantly more reactive with glycosylated YghJ compared to the non-glycosylated variant. This study provides an important link between O-linked glycosylation and the relative immunogenicity of bacterial proteins and further highlights the importance of this observation in considering ETEC proteins for inclusion in future broad coverage subunit vaccine candidates.

Recurrent Urinary Tract Infections: Unraveling the Complicated Environment of Uncomplicated rUTIs.

Urinary tract infections (UTIs) are frequent in humans, affecting the upper and lower urinary tract. Present diagnosis relies on the positive culture of uropathogenic bacteria from urine and clinical markers of inflammation of the urinary tract. The bladder is constantly challenged by adverse environmental stimuli which influence urinary tract physiology, contributing to a dysbiotic environment. Simultaneously, pathogens are primed by environmental stressors such as antibiotics, favoring recurrent UTIs (rUTIs), resulting in chronic illness. Due to different confounders for UTI onset, a greater understanding of the fundamental environmental mechanisms and microbial ecology of the human urinary tract is required. Such advancements could promote the tandem translation of bench and computational studies for precision treatments and clinical management of UTIs. Therefore, there is an urgent need to understand the ecological interactions of the human urogenital microbial communities which precede rUTIs. This review aims to outline the mechanistic aspects of rUTI ecology underlying dysbiosis between both the human microbiome and host physiology which predisposes humans to rUTIs. By assessing the applications of next generation and systems level methods, we also recommend novel approaches to elucidate the systemic consequences of rUTIs which requires an integrated approach for successful treatment. To this end, we will provide an outlook towards the so-called 'uncomplicated environment of UTIs', a holistic and systems view that applies ecological principles to define patient-specific UTIs. This perspective illustrates the need to withdraw from traditional reductionist perspectives in infection biology and instead, a move towards a systems-view revolving around patient-specific pathophysiology during UTIs.

Elucidating the Influence of Chromosomal Architecture on Transcriptional Regulation in Prokaryotes - Observing Strong Local Effects of Nucleoid Structure on Gene Regulation.

Both intrinsic and extrinsic mechanisms regulating bacterial expression have been elucidated and described, however, such studies have mainly focused on local effects on the two-dimensional structure of the prokaryote genome while long-range as well as spatial interactions influencing gene expression are still only poorly understood. In this paper, we investigate the association between co-expression and distance between genes, using RNA-seq data at multiple growth phases in order to illuminate whether such conserved patterns are an indication of a gene regulatory mechanism relevant for prokaryotic cell proliferation, adaption, and evolution. We observe recurrent sinusoidal patterns in correlation of pairwise expression as function of genomic distance and rule out that these are caused by transcription-induced supercoiling gradients, gene clustering in operons, or association with regulatory transcription factors (TFs). By comparing spatial proximity for pairs of genomic bins with their correlation of pairwise expression, we further observe a high co-expression proportional with the spatial proximity. Based on these observations, we propose that the observed patterns are related to nucleoid structure as a product of transcriptional spilling, where genes actively influence transcription of spatially proximal genes through increases within shared local pools of RNA polymerases (RNAP), and actively spilling transcription onto neighboring genes.

Clinical Value of Ultrasonographic Assessment in Lateral Epicondylitis Versus Asymptomatic Healthy Controls.

BACKGROUND: Ultrasonography (US) is often used in the assessment of lateral epicondylitis (LE). The strength of evidence supporting its role is, however, not well-documented. PURPOSE: To describe and compare the US tendinopathic changes observed in patients with LE and the general population, including any correlation between patient characteristics and US outcomes. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Tendon thickness, color Doppler activity, and bone spur were assessed by US in 264 participants with healthy elbows and 60 patients with chronic LE. In addition to patient characteristics, Patient-Rated Tennis Elbow Evaluation (PRTEE) score, pain, and disability were recorded. RESULTS: Depending on the measurement technique used, mean LE tendon thickness increased by 0.53 mm (10.2%) or 0.70 mm (14.5%) as compared with the contralateral arm and 0.40 mm (7.9%) or 0.41 mm (8.5%) as compared with the general population. Mean color Doppler activity (scale, 0-4) was 3.47 in the LE arm versus 0.13 in the contralateral asymptomatic arm and 0.26 in the general population. Bone spur was observed in 78% of the LE arms as opposed to 45% in the contralateral arms and 50% in the general population. In the LE group and the general population, the prevalence of bone spur increases with age. No correlations were observed with pain, disability, PRTEE, and disease duration. CONCLUSION: Increased common extensor tendon thickness is part of the tendinopathic changes observed in LE. However, given the marked variation in natural tendon thickness and small increases in tendon thickness in patients with LE, this technique cannot be used as a stand-alone diagnostic tool but rather as a supplement to the overall assessment. The contralateral elbow (if asymptomatic) is a better tendon thickness comparator than a general population mean value. Color Doppler activity is an indicator of ongoing tendinopathy and supports the LE diagnosis, but it is not pathognomonic for the condition. Absence of Doppler activity in a patient with suspected LE should raise suspicion of other diagnoses. Identification of a bone spur is of very limited clinical value given the high prevalence in the general population. The important outcomes of pain, disability, PRTEE, and disease duration did not correlate with any of the investigated US techniques.

Impact of Chromosomal Architecture on the Function and Evolution of Bacterial Genomes.

The bacterial nucleoid is highly condensed and forms compartment-like structures within the cell. Much attention has been devoted to investigating the dynamic topology and organization of the nucleoid. In contrast, the specific nucleoid organization, and the relationship between nucleoid structure and function is often neglected with regard to importance for adaption to changing environments and horizontal gene acquisition. In this review, we focus on the structure-function relationship in the bacterial nucleoid. We provide an overview of the fundamental properties that shape the chromosome as a structured yet dynamic macromolecule. These fundamental properties are then considered in the context of the living cell, with focus on how the informational flow affects the nucleoid structure, which in turn impacts on the genetic output. Subsequently, the dynamic living nucleoid will be discussed in the context of evolution. We will address how the acquisition of foreign DNA impacts nucleoid structure, and conversely, how nucleoid structure constrains the successful and sustainable chromosomal integration of novel DNA. Finally, we will discuss current challenges and directions of research in understanding the role of chromosomal architecture in bacterial survival and adaptation.

HldE Is Important for Virulence Phenotypes in Enterotoxigenic Escherichia coli.

Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of diarrheal illness in third world countries and it especially affects children and travelers visiting these regions. ETEC causes disease by adhering tightly to the epithelial cells in a concerted effort by adhesins, flagella, and other virulence-factors. When attached ETEC secretes toxins targeting the small intestine host-cells, which ultimately leads to osmotic diarrhea. HldE is a bifunctional protein that catalyzes the nucleotide-activated heptose precursors used in the biosynthesis of lipopolysaccharide (LPS) and in post-translational protein glycosylation. Both mechanisms have been linked to ETEC virulence: Lipopolysaccharide (LPS) is a major component of the bacterial outer membrane and is needed for transport of heat-labile toxins to the host cells, and ETEC glycoproteins have been shown to play an important role for bacterial adhesion to host epithelia. Here, we report that HldE plays an important role for ETEC virulence. Deletion of hldE resulted in markedly reduced binding to the human intestinal cells due to reduced expression of colonization factor CFA/I on the bacterial surface. Deletion of hldE also affected ETEC motility in a flagella-dependent fashion. Expression of both colonization factors and flagella was inhibited at the level of transcription. In addition, the hldE mutant displayed altered growth, increased biofilm formation and clumping in minimal growth medium. Investigation of an orthogonal LPS-deficient mutant combined with mass spectrometric analysis of protein glycosylation indicated that HldE exerts its role on ETEC virulence both through protein glycosylation and correct LPS configuration. These results place HldE as an attractive target for the development of future antimicrobial therapeutics.

Long-Term Prognosis of Plantar Fasciitis: A 5- to 15-Year Follow-up Study of 174 Patients With Ultrasound Examination.

BACKGROUND: Plantar fasciitis (PF) affects 7% to 10% of the population. The long-term prognosis is unknown. PURPOSE: Our study had 4 aims: (1) to assess the long-term prognosis of PF, (2) to evaluate whether baseline characteristics (sex, body mass index, age, smoking status, physical work, exercise-induced symptoms, bilateral heel pain, fascia thickness, and presence of a heel spur) could predict long-term outcomes, (3) to assess the long-term ultrasound (US) development in the fascia, and (4) to assess whether US-guided corticosteroid injections induce atrophy of the heel fat pad. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: From 2001 to 2011 (baseline), 269 patients were diagnosed with PF based on symptoms and US. At follow-up (2016), all patients were invited to an interview regarding their medical history and for clinical and US re-examinations. Kaplan-Meier survival estimates were used to estimate the long-term prognosis, and a multiple Cox regression analysis was used for the prediction model. RESULTS: In all, 174 patients (91 women, 83 men) participated in the study. All were interviewed, and 137 underwent a US examination. The mean follow-up was 9.7 years from the onset of symptoms and 8.9 years from baseline. At follow-up, 54% of patients were asymptomatic (mean duration of symptoms, 725 days), and 46% still had symptoms. The risk of having PF was 80.5% after 1 year, 50.0% after 5 years, 45.6% after 10 years, and 44.0% after 15 years from the onset of symptoms. The risk was significantly greater for women (P < .01) and patients with bilateral pain (P < .01). Fascia thickness decreased significantly in both the asymptomatic and symptomatic groups (P < .01) from 6.9 mm and 6.7 mm, respectively, to 4.3 mm in both groups. Fascia thickness (P = .49) and presence of a heel spur (P = .88) at baseline had no impact on prognosis. At follow-up, fascia thickness and echogenicity had normalized in only 24% of the asymptomatic group. The mean fat pad thickness was 9.0 mm in patients who had received a US-guided corticosteroid injection and 9.4 mm in those who had not been given an injection (P = .66). CONCLUSION: The risk of having PF in this study was 45.6% at a mean 10 years after the onset of symptoms. The asymptomatic patients had PF for a mean 725 days. The prognosis was significantly worse for women and patients with bilateral pain. Fascia thickness decreased over time regardless of symptoms and had no impact on prognosis, and neither did the presence of a heel spur. Only 24% of asymptomatic patients had a normal fascia on US at long-term follow-up. A US-guided corticosteroid injection did not cause atrophy of the heel fat pad. Our observational study did not allow us to determine the efficacy of different treatment strategies.

Ultrasonographic Characteristics of the Common Extensor Tendon of the Elbow in Asymptomatic Individuals: Thickness, Color Doppler Activity, and Bony Spurs.

BACKGROUND: Ultrasonography (US) of the common extensor tendon (CET) of the elbow is often part of the assessment of patients with lateral epicondylitis. This US assessment is currently based on general tendinopathy references and not well-defined US entities. PURPOSE: To describe CET thickness, color Doppler activity, and bony spurs on US in asymptomatic volunteers and to investigate the influence of sex, age, height, body mass index (BMI), weight, and elbow dominance on the measurements. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Tendon thickness, color Doppler activity, and bony spurs of the CET were measured sonographically in 264 adults (50% women) aged 20 to 96 years. Two different tendon-thickness measuring techniques were applied, labeled the "plateau measure" and the "1-cm measure." Color Doppler activity was based on a 0 to 4 rating scale (negative, grades 0 and 1; positive, grades 2-4). A bony spur was defined as a bony outgrowth (≥0.3 mm) arising at the insertional site of the CET. RESULTS: With both tendon-thickness measuring techniques, the CET in the dominant elbow was thicker than that in the nondominant elbow, and male tendons were thicker than female tendons (all P ≤ .03). In regression analysis, tendon thickness correlated with weight, color Doppler activity, and arm dominance for both measuring techniques in multiple regression analysis. In addition, the plateau measure correlated with height and the presence of bony spurs. No correlations were observed regarding BMI, sex, or age. Positive color Doppler activity was found in 9% of examined elbows, with no difference between the sexes regarding dominant versus nondominant elbows (all P ≥.20). Bony spurs were found to increase with age, from 23% for people in their 20s to 74% in people older than 70 years. Bony spurs were more common in the dominant elbow (P ≤ .01). Women had a higher prevalence of bony spurs than men, but only in the dominant elbow (P = .03). CONCLUSION: This study presents the US characteristics and normal values of the CET. In 264 asymptomatic participants, the CET was found to be thicker in men and in the dominant elbow. No difference in tendon thickness could be demonstrated with regard to different age groups. Color Doppler activity was found to be positive in nearly 1 of 10 asymptomatic subjects. Bony spurs were a common finding; they increased in prevalence with every decade in age and were considered part of the aging process. Normal variations in CET morphologic characteristics should therefore be considered when implementing US in trials and clinical practice.

A novel mass spectrometric strategy "BEMAP" reveals Extensive O-linked protein glycosylation in Enterotoxigenic Escherichia coli.

The attachment of sugars to proteins via side-chain oxygen atoms (O-linked glycosylation) is seen in all three domains of life. However, a lack of widely-applicable analytical tools has restricted the study of this process, particularly in bacteria. In E. coli, only four O-linked glycoproteins have previously been characterized. Here we present a glycoproteomics technique, termed BEMAP, which is based on the beta-elimination of O-linked glycans followed by Michael-addition of a phosphonic acid derivative, and subsequent titanium dioxide enrichment. This strategy allows site-specific mass-spectrometric identification of proteins with O-linked glycan modifications in a complex biological sample. Using BEMAP we identified cell surface-associated and membrane vesicle glycoproteins from Enterotoxigenic E. coli (ETEC) and non-pathogenic E. coli K-12. We identified 618 glycosylated Serine and Threonine residues mapping to 140 proteins in ETEC, including several known virulence factors, and 34 in E. coli K-12. The two strains had 32 glycoproteins in common. Remarkably, the majority of the ETEC glycoproteins were conserved in both strains but nevertheless were only glycosylated in the pathogen. Therefore, bacterial O-linked glycosylation is much more extensive than previously thought, and is especially important to the pathogen.

Ultrasound-Guided Injection Therapy of Achilles Tendinopathy With Platelet-Rich Plasma or Saline: A Randomized, Blinded, Placebo-Controlled Trial.

BACKGROUND: Achilles tendinopathy (AT) is a common and difficult to treat musculoskeletal disorder. PURPOSE: To examine whether 1 injection of platelet-rich plasma (PRP) would improve outcomes more effectively than placebo (saline) after 3 months in patients with AT. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 24 patients with chronic AT (median disease duration, 33 months) were randomized (1:1) to receive either a blinded injection of PRP (n = 12) or saline (n = 12). The primary endpoint was improvement in Victorian Institute of Sports Assessment-Achilles (VISA-A) score at 3 months. Secondary outcomes were pain at rest, pain while walking, pain when tendon was squeezed, ultrasonographic changes in tendon thickness, and color Doppler activity. Patients were informed that they could drop out after 3 months if they were dissatisfied with the treatment. RESULTS: After 3 months, all 24 patients were reassessed (no dropouts). No difference between the PRP and the saline group could be observed with regard to the primary outcome (VISA-A score: mean difference [MD], -1.3; 95% CI, -17.8 to 15.2; P = .868). Secondary outcomes were pain at rest (MD, 1.6; 95% CI, -0.5 to 3.7; P = .137), pain while walking (MD, 0.8; 95% CI, -1.8 to 3.3; P = .544), pain when tendon was squeezed (MD, 0.3; 95% CI, -0.2 to 0.9; P = .208), color Doppler activity (MD, 0.3; 95% CI, -0.2 to 0.8; P = .260), and tendon thickness (MD, 0.8 mm; 95% CI, 0.1 to 1.6 mm; P = .030). After the 3-month follow-up, a large dropout was observed: 75% of patients in the PRP group and 33% in the saline group. CONCLUSION: PRP injection did not result in an improved VISA-A score over a 3-month period in patients with chronic AT compared with placebo. The only secondary outcome demonstrating a statistically significant difference between the groups was change in tendon thickness; this difference indicates that a PRP injection could increase tendon thickness compared with saline injection. The conclusions are limited to the 3 months after treatment owing to the large dropout rate.

Draft Genome Sequence of Parabacteroides goldsteinii with Putative Novel Metallo-ß-Lactamases Isolated from a Blood Culture from a Human Patient.

Parabacteroides goldsteinii was isolated from a blood culture. Genomic DNA was sequenced using a MiSeq sequencer and assembled using the SPAdes genome assembler. The draft genome sequence was 6,851,868 bp, spanning 282 contigs of 5,253 coding sequences, 66 tRNAs, and 5 rRNAs. Several putative novel metallo-ß-lactamases were discovered.

SILAC-based comparative analysis of pathogenic Escherichia coli secretomes.

Comparative studies of pathogenic bacteria and their non-pathogenic counterparts has led to the discovery of important virulence factors thereby generating insight into mechanisms of pathogenesis. Protein-based antigens for vaccine development are primarily selected among unique virulence-related factors produced by the pathogen of interest. However, recent work indicates that proteins that are not unique to the pathogen but instead selectively expressed compared to its non-pathogenic counterpart could also be vaccine candidates or targets for drug development. Modern methods in quantitative proteome analysis have the potential to discover both classes of proteins and hence form an important tool for discovering therapeutic targets. Adherent-invasive Escherichia coli (AIEC) and Enterotoxigenic E. coli (ETEC) are pathogenic variants of E. coli which cause intestinal disease in humans. AIEC is associated with Crohn's disease (CD), a chronic inflammatory condition of the gastrointestinal tract whereas ETEC is the major cause of human diarrhea which affects hundreds of millions annually. In spite of the disease burden associated with these pathogens, effective vaccines conferring long-term protection are still needed. In order to identify proteins with therapeutic potential, we have used mass spectrometry-based Stable Isotope Labeling with Amino acids in Cell culture (SILAC) quantitative proteomics method which allows us to compare the proteomes of pathogenic strains to commensal E. coli. In this study, we grew the pathogenic strains ETEC H10407, AIEC LF82 and the non-pathogenic reference strain E. coli K-12 MG1655 in parallel and used SILAC to compare protein levels in OMVs and culture supernatant. We have identified well-known virulence factors from both AIEC and ETEC, thus validating our experimental approach. In addition we find proteins that are not unique to the pathogenic strains but expressed at levels different from the commensal strain, including the colonization factor YghJ and the surface adhesin antigen 43, which is involved in pathogenesis of other Gram-negative bacteria. The described method provides a framework for further understanding E. coli pathogenesis but can also be applied to interrogate relative protein expression levels of other pathogens that have non-pathogenic counterparts thereby facilitating the discovery of new vaccine targets.

Natural LacI from E. coli yields faster response and higher level of expression than the LVA-tagged LacI.

The lac promoter is one of the most commonly used promoters for expression control of recombinant genes in E. coli. In the absence of galactosides, the lac promoter is repressed by its repressor protein LacI. Since the lac promoter is regulated by a repressor, overexpression of LacI is necessary for regulation when the promoter is introduced on a high-copy plasmid. For that purpose, a modified variant of LacI, a LVA-tagged LacI, was submitted to the Registry of Standard Biological Parts and has been used for more than 500 constructs since then. We have found, however, that natural LacI is superior to the LVA-tagged LacI as controller of expression.

Treatment of lateral epicondylitis with platelet-rich plasma, glucocorticoid, or saline: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Lateral epicondylitis (LE) is a common musculoskeletal disorder for which an effective treatment strategy remains unknown. PURPOSE: To examine whether a single injection of platelet-rich plasma (PRP) is more effective than placebo (saline) or glucocorticoid in reducing pain in adults with LE after 3 months. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 60 patients with chronic LE were randomized (1:1:1) to receive either a blinded injection of PRP, saline, or glucocorticoid. The primary end point was a change in pain using the Patient-Rated Tennis Elbow Evaluation (PRTEE) questionnaire at 3 months. Secondary outcomes were ultrasonographic changes in tendon thickness and color Doppler activity. RESULTS: Pain reduction at 3 months (primary end point) was observed in all 3 groups, with no statistically significant difference between the groups; mean differences were the following: glucocorticoid versus saline: -3.8 (95% CI, -9.9 to 2.4); PRP versus saline: -2.7 (95% CI, -8.8 to 3.5); and glucocorticoid versus PRP: -1.1 (95% CI, -7.2 to 5.0). At 1 month, however, glucocorticoid reduced pain more effectively than did both saline and PRP; mean differences were the following: glucocorticoid versus saline: -8.1 (95% CI, -14.3 to -1.9); and glucocorticoid versus PRP: -9.3 (95% CI, -15.4 to -3.2). Among the secondary outcomes, at 3 months, glucocorticoid was more effective than PRP and saline in reducing color Doppler activity and tendon thickness. For color Doppler activity, mean differences were the following: glucocorticoid versus PRP: -2.6 (95% CI, -3.1 to -2.2); and glucocorticoid versus saline: -2.0 (95% CI, -2.5 to -1.6). For tendon thickness, mean differences were the following: glucocorticoid versus PRP: -0.5 (95% CI, -0.8 to -0.2); and glucocorticoid versus saline: -0.8 (95% CI, -1.2 to -0.5). CONCLUSION: Neither injection of PRP nor glucocorticoid was superior to saline with regard to pain reduction in LE at the primary end point at 3 months. However, injection of glucocorticoid had a short-term pain-reducing effect at 1 month in contrast to the other therapies. Injection of glucocorticoid in LE reduces both color Doppler activity and tendon thickness compared with PRP and saline.

Comparative effectiveness of injection therapies in lateral epicondylitis: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Injection therapy with glucocorticoids has been used since the 1950s as a treatment strategy for lateral epicondylitis (tennis elbow). Lately, several novel injection therapies have become available. PURPOSE: To assess the comparative effectiveness and safety of injection therapies in patients with lateral epicondylitis. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Randomized controlled trials comparing different injection therapies for lateral epicondylitis were included provided they contained data for change in pain intensity (primary outcome). Trials were assessed using the Cochrane risk of bias tool. Network (random effects) meta-analysis was applied to combine direct and indirect evidence within and across trial data using the final end point reported in the trials, and results for the arm-based network analyses are reported as standardized mean differences (SMDs). RESULTS: Seventeen trials (1381 participants; 3 [18%] at low risk of bias) assessing injection with 8 different treatments-glucocorticoid (10 trials), botulinum toxin (4 trials), autologous blood (3 trials), platelet-rich plasma (2 trials), and polidocanol, glycosaminoglycan, prolotherapy, and hyaluronic acid (1 trial each)-were included. Pooled results (SMD [95% confidence interval]) showed that beyond 8 weeks, glucocorticoid injection was no more effective than placebo (-0.04 [-0.45 to 0.35]), but only 1 trial (which did not include a placebo arm) was at low risk of bias. Although botulinum toxin showed marginal benefit (-0.50 [-0.91 to -0.08]), it caused temporary paresis of finger extension, and all trials were at high risk of bias. Both autologous blood (-1.43 [-2.15 to -0.71]) and platelet-rich plasma (-1.13 [-1.77 to -0.49]) were also statistically superior to placebo, but only 1 trial was at low risk of bias. Prolotherapy (-2.71 [-4.60 to -0.82]) and hyaluronic acid (-5.58 [-6.35 to -4.82]) were both more efficacious than placebo, whereas polidocanol (0.39 [-0.42 to 1.20]) and glycosaminoglycan (-0.32 [-1.02 to 0.38]) showed no effect compared with placebo. The criteria for low risk of bias were only met by the prolotherapy and polidocanol trials. CONCLUSION: This systematic review and network meta-analysis of randomized controlled trials found a paucity of evidence from unbiased trials on which to base treatment recommendations regarding injection therapies for lateral epicondylitis.

A pilot study of nuclear instability in archived renal and upper urinary tract tumours with putative ochratoxin aetiology.

DNA ploidy measurement has been applied uniquely to wax-embedded tissue of primary renal cell and metastatic tumours of a key experimental researcher on porcine ochratoxicosis, a control, and four transitional cell carcinomas from cases of Balkan endemic nephropathy. Primary renal tumour was diploid, and hyperdiploid metastasis was within the lower ploidy range for typical renal cell carcinoma. Three Balkan primary tumours showed extensive aneuploidy indicating marked nuclear instability, similar to model rat renal carcinoma caused by ochratoxin A. In contrast, much less nuclear instability in the putative occupational ochratoxicosis case fitted poorly with the ochratoxin A model.