Lowest reported dose area product of 2.4 Gy∗cm2 for ultra-low-dose endovascular aortic aneurysm repair of a standard infrarenal aortic aneurysm.

This is a report of successful treatment of an abdominal aortic aneurysm via standard endovascular aortic repair with an ultra-low dose (ULD) of 2.4 Gy∗cm2 using the latest imaging software in a hybrid operating room. To the best of our knowledge, no case has yet been reported achieving a successful outcome with such ULD values to date. The key factors to achieving an ULD regarding the dose area product comprise the right technology, procedural standardization, and team education and training. This case highlights the potential for reducing the radiation dose routinely for patients and staff alike, especially for operating room staff with daily radiation exposure.

A dynamic time-to-event model for prediction of acute graft-versus-host disease in patients after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Acute graft-versus-host disease (aGvHD) is a major cause of death for patients following allogeneic hematopoietic stem cell transplantation (HSCT). Effective management of moderate to severe aGvHD remains challenging despite recent advances in HSCT, emphasizing the importance of prophylaxis and risk factor identification. METHODS: In this study, we analyzed data from 1479 adults who underwent HSCT between 2005 and 2017 to investigate the effects of aGvHD prophylaxis and time-dependent risk factors on the development of grades II-IV aGvHD within 100 days post-HSCT. RESULTS: Using a dynamic longitudinal time-to-event model, we observed a non-monotonic baseline hazard overtime with a low hazard during the first few days and a maximum hazard at day 17, described by Bateman function with a mean transit time of approximately 11 days. Multivariable analysis revealed significant time-dependent effects of white blood cell counts and cyclosporine A exposure as well as static effects of female donors for male recipients, patients with matched related donors, conditioning regimen consisting of fludarabine plus total body irradiation, and patient age in recipients of grafts from related donors on the risk to develop grades II-IV aGvHD. Additionally, we found that higher cumulative hazard on day 7 after allo-HSCT are associated with an increased incidence of grades II-IV aGvHD within 100 days indicating that an individual assessment of the cumulative hazard on day 7 could potentially serve as valuable predictor for later grades II-IV aGvHD development. Using the final model, stochastic simulations were performed to explore covariate effects on the cumulative incidence over time and to estimate risk ratios. CONCLUSION: Overall, the presented model showed good descriptive and predictive performance and provides valuable insights into the interplay of multiple static and time-dependent risk factors for the prediction of aGvHD.

Soil and human health: Understanding agricultural and socio-environmental risk and resilience in the age of climate change.

Prolonged monocropping of commodity crops, such as peanuts (Arachis hypogea L.) in West Africa, typically strips nutrients from soils and may exacerbate vulnerability to insects and diseases. In this paper, we focus on aflatoxins, toxic chemicals produced by certain molds growing on moist crops, as one risk of growing importance for its negative impacts on human health, crop yields, and agricultural livelihoods and ecosystems. We link the increased prevalence of this deadly fungus to the long history of peanut monoculture, exacerbated by market liberalization and China's increased investment and export demand for peanuts, climate change, food insecurity, as well as disregard for and displacement of traditional agricultural knowledge. We use a political ecology approach to place the public health threat from aflatoxin in the context of both historical pressures for cash-crop production of peanuts and contemporary soil degradation, food insecurity, climate change precarity and changes within social and economic systems of agriculture in Senegal.

Challenges and Pitfalls for Implementing Digital Health Solutions in Clinical Studies in Europe.

The increasing number of digital solutions developed for use in clinical health care settings is accompanied by new challenges to develop and conduct clinical studies that include eHealth technologies. Clinical study implementation plans often disregard or underestimate the necessity of additional administrative and logistic tasks required at clinical sites as well as ethical aspects to test digital solutions. Experiences made in the run-up of an observational clinical feasibility study at three international clinical sites in the framework of the MyPal project (https://mypal-project.eu/) result in recommendations to avoid delays and barriers in the planning of such prospective studies in clinical and also palliative care for increased efficiency.

Ultrasound Evaluation for Incomplete Carpal Tunnel Release.

Background: Ultrasound can provide evaluation of the anatomy of the carpal tunnel in a convenient, noninvasive office setting. This study is intended to determine the accuracy and diagnostic performance of ultrasound, used by surgeons, for the evaluation of completeness of carpal tunnel release (CTR). Methods: Ten cadaver arms underwent randomized sectioning of 0%, 25%, 50%, 75%, or 100% of the transverse carpal ligament. Following a brief training session, a blinded observer used ultrasound to evaluate the percentage of the transverse carpal ligament release. The release amount was then confirmed with an open exposure of the transverse carpal ligament. Results: Cronbach α and Pearson correlation coefficients were 0.92 and 0.87, demonstrating excellent reliability and validity of the technique. Diagnostic performance including sensitivity, specificity, positive predictive value, and negative predictive value was 100%, 75%, 86%, and 100%, respectively, for the diagnosis of incomplete release of the transverse carpal ligament by a novice sonographer orthopedic surgeon. Conclusions: The ultrasound is a highly accurate tool for the diagnosis of incomplete transverse carpal ligament release and requires a minimal amount of training to use for this purpose. It provides a rapid means of diagnosing incomplete release of the transverse carpal ligament following CTR.

Benchmarking Wilms' tumor in multisequence MRI data: why does current clinical practice fail? Which popular segmentation algorithms perform well?

Wilms' tumor is one of the most frequent malignant solid tumors in childhood. Accurate segmentation of tumor tissue is a key step during therapy and treatment planning. Since it is difficult to obtain a comprehensive set of tumor data of children, there is no benchmark so far allowing evaluation of the quality of human or computer-based segmentations. The contributions in our paper are threefold: (i) we present the first heterogeneous Wilms' tumor benchmark data set. It contains multisequence MRI data sets before and after chemotherapy, along with ground truth annotation, approximated based on the consensus of five human experts. (ii) We analyze human expert annotations and interrater variability, finding that the current clinical practice of determining tumor volume is inaccurate and that manual annotations after chemotherapy may differ substantially. (iii) We evaluate six computer-based segmentation methods, ranging from classical approaches to recent deep-learning techniques. We show that the best ones offer a quality comparable to human expert annotations.

Novel drug targets in cell wall biosynthesis exploited by gene disruption in Pseudomonas aeruginosa.

For clinicians, Pseudomonas aeruginosa is a nightmare pathogen that is one of the top three causes of opportunistic human infections. Therapy of P. aeruginosa infections is complicated due to its natural high intrinsic resistance to antibiotics. Active efflux and decreased uptake of drugs due to cell wall/membrane permeability appear to be important issues in the acquired antibiotic tolerance mechanisms. Bacterial cell wall biosynthesis enzymes have been shown to be essential for pathogenicity of Gram-negative bacteria. However, the role of these targets in virulence has not been identified in P. aeruginosa. Here, we report knockout (k.o) mutants of six cell wall biosynthesis targets (murA, PA4450; murD, PA4414; murF, PA4416; ppiB, PA1793; rmlA, PA5163; waaA, PA4988) in P. aeruginosa PAO1, and characterized these in order to find out whether these genes and their products contribute to pathogenicity and virulence of P. aeruginosa. Except waaA k.o, deletion of cell wall biosynthesis targets significantly reduced growth rate in minimal medium compared to the parent strain. The k.o mutants showed exciting changes in cell morphology and colonial architectures. Remarkably, ΔmurF cells became grossly enlarged. Moreover, the mutants were also attenuated in vivo in a mouse infection model except ΔmurF and ΔwaaA and proved to be more sensitive to macrophage-mediated killing than the wild-type strain. Interestingly, the deletion of the murA gene resulted in loss of virulence activity in mice, and the virulence was restored in a plant model by unknown mechanism. This study demonstrates that cell wall targets contribute significantly to intracellular survival, in vivo growth, and pathogenesis of P. aeruginosa. In conclusion, these findings establish a link between cell wall targets and virulence of P. aeruginosa and thus may lead to development of novel drugs for the treatment of P. aeruginosa infection.

Cmr is a redox-responsive regulator of DosR that contributes to M. tuberculosis virulence.

Mycobacterium tuberculosis (MTb) is the causative agent of pulmonary tuberculosis (TB). MTb colonizes the human lung, often entering a non-replicating state before progressing to life-threatening active infections. Transcriptional reprogramming is essential for TB pathogenesis. In vitro, Cmr (a member of the CRP/FNR super-family of transcription regulators) bound at a single DNA site to act as a dual regulator of cmr transcription and an activator of the divergent rv1676 gene. Transcriptional profiling and DNA-binding assays suggested that Cmr directly represses dosR expression. The DosR regulon is thought to be involved in establishing latent tuberculosis infections in response to hypoxia and nitric oxide. Accordingly, DNA-binding by Cmr was severely impaired by nitrosation. A cmr mutant was better able to survive a nitrosative stress challenge but was attenuated in a mouse aerosol infection model. The complemented mutant exhibited a ∼2-fold increase in cmr expression, which led to increased sensitivity to nitrosative stress. This, and the inability to restore wild-type behaviour in the infection model, suggests that precise regulation of the cmr locus, which is associated with Region of Difference 150 in hypervirulent Beijing strains of Mtb, is important for TB pathogenesis.

Mallet Fractures of the Thumb Compared With Mallet Fractures of the Fingers.

BACKGROUND: The purpose of this study was to look for differences in mechanism, radiographic findings, and treatment between mallet fractures of the thumb and mallet fractures of the index through small fingers. METHODS: This retrospective study included 24 mallet fractures of the thumb and 392 mallet fractures of other digits. We compared demographics, injury factors (side, dominant hand, time between injury and first visit, and injury mechanism), subluxation, fragment size, treatment, and time from injury to final evaluation between the 2 groups. RESULTS: Mallet fractures of the thumb presented for treatment sooner after injury (2.9 vs 13 days on average), had less fragment displacement (27% vs 33%), and less articular involvement (39% vs 46% on average). None of the mallet fractures of the thumb had radiographic evidence of subluxation, whereas 25% of mallet fractures of other fingers had initial or later subluxation. CONCLUSIONS: Mallet fractures of the thumb are not likely to subluxate.

Structure and Function of the PiuA and PirA Siderophore-Drug Receptors from Pseudomonas aeruginosa and Acinetobacter baumannii.

The outer membrane of Gram-negative bacteria presents an efficient barrier to the permeation of antimicrobial molecules. One strategy pursued to circumvent this obstacle is to hijack transport systems for essential nutrients, such as iron. BAL30072 and MC-1 are two monobactams conjugated to a dihydroxypyridone siderophore that are active against Pseudomonas aeruginosa and Acinetobacter baumannii Here, we investigated the mechanism of action of these molecules in A. baumannii We identified two novel TonB-dependent receptors, termed Ab-PiuA and Ab-PirA, that are required for the antimicrobial activity of both agents. Deletion of either piuA or pirA in A. baumannii resulted in 4- to 8-fold-decreased susceptibility, while their overexpression in the heterologous host P. aeruginosa increased susceptibility to the two siderophore-drug conjugates by 4- to 32-fold. The crystal structures of PiuA and PirA from A. baumannii and their orthologues from P. aeruginosa were determined. The structures revealed similar architectures; however, structural differences between PirA and PiuA point to potential differences between their cognate siderophore ligands. Spontaneous mutants, selected upon exposure to BAL30072, harbored frameshift mutations in either the ExbD3 or the TonB3 protein of A. baumannii, forming the cytoplasmic-membrane complex providing the energy for the siderophore translocation process. The results of this study provide insight for the rational design of novel siderophore-drug conjugates against problematic Gram-negative pathogens.

Mechanisms of intrinsic resistance and acquired susceptibility of Pseudomonas aeruginosa isolated from cystic fibrosis patients to temocillin, a revived antibiotic.

The ß-lactam antibiotic temocillin (6-α-methoxy-ticarcillin) shows stability to most extended spectrum ß-lactamases, but is considered inactive against Pseudomonas aeruginosa. Mutations in the MexAB-OprM efflux system, naturally occurring in cystic fibrosis (CF) isolates, have been previously shown to reverse this intrinsic resistance. In the present study, we measured temocillin activity in a large collection (n = 333) of P. aeruginosa CF isolates. 29% of the isolates had MICs ≤ 16 mg/L (proposed clinical breakpoint for temocillin). Mutations were observed in mexA or mexB in isolates for which temocillin MIC was ≤512 mg/L (nucleotide insertions or deletions, premature termination, tandem repeat, nonstop, and missense mutations). A correlation was observed between temocillin MICs and efflux rate of N-phenyl-1-naphthylamine (MexAB-OprM fluorescent substrate) and extracellular exopolysaccharide abundance (contributing to a mucoid phenotype). OpdK or OpdF anion-specific porins expression decreased temocillin MIC by ~1 two-fold dilution only. Contrarily to the common assumption that temocillin is inactive on P. aeruginosa, we show here clinically-exploitable MICs on a non-negligible proportion of CF isolates, explained by a wide diversity of mutations in mexA and/or mexB. In a broader context, this work contributes to increase our understanding of MexAB-OprM functionality and help delineating how antibiotics interact with MexA and MexB.

The relationship between therapist-rated function and patient-reported outcome measures.

STUDY DESIGN: Prospective cohort study. INTRODUCTION: Some third-party payers require hand therapists to rate patient's functional disability based on patient self-rating using patient-reported outcome measures (PROMs), objective measurements of impairment, and observation of functional tasks-hand therapist-rated function (HTRF). PURPOSE OF THE STUDY: To test the correlation between HTRF and PROMs (upper limb functional index [ULFI] and Patient-Reported Outcomes Measurement Information System upper extremity [PROMIS UE]) and its association with psychological factors. METHODS: In 2014, 100 new patients with upper extremity illness presenting to hand therapists were asked to participate in an observational cross-sectional study. Demographic-, condition-related, and psychological factors were obtained in addition to PROMs and HTRF. RESULTS: HTRF correlated moderately with PROMIS UE (r = -0.49, P < .001) and ULFI (r = -0.56, P < .001). Correlation between PROMIS UE and ULFI was strong (r = 0.78, P < .001). Psychological factors explained most of the variations in both HTRF and PROMs. CONCLUSIONS: Hand therapists' ratings of patient function correlate less strongly with PROMs than PROMs correlate with one other. The discrepancy between HTRF and PROMs may offer an opportunity to address stress, distress, or ineffective coping strategies that can interfere with recovery-an opportunity for therapists and patients to collaborate and develop goals and for future research to develop effective and feasible strategies for hand therapists. LEVEL OF EVIDENCE: Level II, diagnostic study.

The Association of Complementary Health Approaches With Mood and Coping Strategies Among Orthopedic Patients.

Background: Variation in pain intensity and magnitude of disability among patients with musculoskeletal illness is largely accounted for by variations in symptoms of depression, catastrophic thinking, and heightened illness concern. It is possible that patients with greater stress, distress, and less effective coping strategies might be more likely to seek the use of Complementary Health Approaches (CHA). This study addressed the primary null hypothesis that there are no demographic, illness-related, or psychological factors associated with CHA use among patients with upper extremity illness. Methods: A cohort of 170 patients completed a web-based Complementary and Alternative Medicine (CAM) questionnaire the Patient Reported Outcomes Measurement Information System (PROMIS) Depression and Pain Interference questionnaires. We evaluated differences between patients who sought CAM treatment regarding the PROMIS Pain Interference and PROMIS Depression scores. Ninety-four patients (56%) use or plan to use CAM treatment. A CAM provider was consulted by 61 patients (37%): most commonly a massage therapist (30/61), chiropractor (26/61), or acupuncturist (14/61). Results: In bivariate analysis patients who sought CAM reported greater average PROMIS Pain Interference than those who did not. In multivariable logistic regression, CAM use was associated with a higher Pain Interference Score and the specific surgeon. Conclusion: In conclusion, CHA use is prevalent amongst orthopaedic patients and associated with less effective coping strategies. Orthopaedic surgeons might consider asking patients about CHA use and determining whether those patients are interested in cognitive behavioral therapy.

Swarming motility is modulated by expression of the putative xenosiderophore transporter SppR-SppABCD in Pseudomonas aeruginosa PA14.

In the present study, we characterised the putative peptide ABC transporter SppABCD, which is co-transcribed with the TonB-dependent receptor SppR in Pseudomonas aeruginosa PA14. However, our data show that this transporter complex is not involved in the uptake of peptides. The fact that the TonB-dependent receptor SppR is regulated by an iron starvation ECF sigma factor suggested that this transporter is probably involved in the uptake of xenosiderophores. Therefore, we screened culture supernatants of 23 siderophore-producing bacteria for their ability to induce the expression of the SppR-regulating ECF sigma factor. However, none of them had an effect on the expression of this ECF sigma factor. Since the spp operon is not expressed under standard laboratory conditions, we overexpressed it from plasmids in PA14, which led to an impairment of its swarming motility on semisolid agar. Since we excluded the possibility that the uptake of a culture medium component was responsible for the observed phenotype, we hypothesize that the Spp transport system is involved in the uptake of a compound from the periplasmic space or a compound secreted by P. aeruginosa. Furthermore, we found that rhamnolipid synthesis was decreased while biofilm and exopolysaccharide synthesis was slightly increased upon overexpression of the spp operon. Moreover, we observed an impact of spp overexpression on regulation of genes involved in siderophore and phenazine biosynthesis.

Factors Associated With Reoperation After Fixation of Displaced Olecranon Fractures.

BACKGROUND: Surgery for fixation of olecranon fractures is associated with reoperation, mostly for implant removal. A study of a large cohort of patients treated by many different surgeons allows us to determine if specific techniques or implants are associated with a higher rate of reoperation. QUESTIONS/PURPOSES: After open reduction and internal fixation of isolated olecranon fractures, what factors are associated with (1) reoperation and (2) implant removal? METHODS: Three hundred ninety-two adult patients who had operative treatment of a displaced olecranon fracture not associated with other fractures, dislocation, or subluxation at two area hospitals between January 2002 and May 2014 were analyzed to determine factors associated with reoperation. One hundred thirty-eight (35%) patients had plate and screw fixation and 254 (65%) tension band wiring. Nearly 100% of patients with displaced olecranon fractures are currently treated operatively at our hospitals. All patients were followed for at least four months. Two hundred three of the 392 (52%) patients were followed for one year or more. Ninety-nine patients (25%) had a second operation, 92 (93%) at least in part for implant removal (12 for wire migration [3% of all fractures, 12% of reoperations]). We considered patient-related, fracture-related, and implant-related endpoints as possible factors associated with reoperation. With a total sample size of 99 reoperations, an α of 0.05, and an effect size of 0.3, we had 87% power. RESULTS: Reoperation was less common in men (36 [36%], women: 63 [64%]; adjusted odds ratio, 0.32; 95% confidence interval, 0.18-0.56; p < 0.001) and older patients (adjusted odds ratio, 0.75; 95% confidence interval, 0.65-0.87; p < 0.001). Similarly, request for implant removal was less in men (33 [36%], women: 59 [64%], adjusted odds ratio, 0.31; 95% confidence interval, 0.18-0.56; p < 0.001) and older patients (adjusted odds ratio, 0.75; 95% confidence interval, 0.65-0.87; p < 0.001). CONCLUSIONS: Patients who have operative fixation of a fracture of the olecranon can be counseled that most patients keep their implants, that only 3% experience implant migration, and that technical factors such as the type or configuration of an implant seem less important than personal factors in determining who requests a second surgery for implant removal. LEVEL OF EVIDENCE: Level III, prognostic study.

What Factors are Associated With a Surgical Site Infection After Operative Treatment of an Elbow Fracture?

BACKGROUND: Surgical site infections are one of the more common major complications of elbow fracture surgery and can contribute to other adverse outcomes, prolonged hospital stays, and increased healthcare costs. QUESTIONS/PURPOSES: We asked: (1) What are the factors associated with a surgical site infection after elbow fracture surgery? (2) When taking the subset of closed elbow fractures only, what are the factors associated with a surgical site infection? (3) What are the common organisms isolated from an elbow infection after open treatment? METHODS: One thousand three hundred twenty adult patients underwent surgery for an elbow fracture between January 2002 and July 2014 and were included in our study. Forty-eight of 1320 patients (4%) had a surgical site infection develop. Thirty-four of 1113 patients with a closed fracture (3%) had a surgical site infection develop. RESULTS: For all elbow fractures, use of plate and screw fixation (adjusted odds ratio [OR]= 2.2; 95% CI, 1.0-4.5; p = 0.041) and use of external fixation before surgery (adjusted OR = 4.7; 95% CI, 1.1-21; p = 0.035) were associated with higher infection rates. When subset analysis was performed for closed fractures, only smoking (adjusted OR = 2.2; 95% CI, 1.1-4.5; p = 0.023) was associated with higher infection rates. Staphylococcus aureus was the most common bacteria cultured (59%). CONCLUSIONS: The only modifiable risk factor for a surgical site infection after open reduction and internal fixation was cigarette smoking. Plate fixation and temporary external fixation are likely surrogates for more complex injuries, therefore no recommendations should be inferred from this association. Surgeons should counsel patients who smoke. LEVEL OF EVIDENCE: Level IV, prognostic study.

Operative Versus Nonoperative Management of Nonfunctioning Pancreatic Neuroendocrine Tumors.

INTRODUCTION: Surgical resection is the only curative treatment for pancreatic neuroendocrine tumors (PNETs), but pancreatic operations carry a significant morbidity. We investigated whether the resection of small, asymptomatic nonfunctioning PNETs is beneficial. Clinicopathologic factors were retrospectively reviewed for all PNET cases from 1998 to 2014. METHODS: Kaplan-Meier survival and multivariable regression analyses were performed. A total of 249 patients had nonfunctioning PNETs with adequate follow-up, of whom 193 were resected and 56 were observed. Median age was 56 years, and 48 % of the patients were female. RESULTS: Overall, the resected patients had a significantly longer survival (OS) (p = 0.001). However, for the patients with PNETs ≤2.5 cm in size and without metastasis at presentation, tumor size significantly modified the effect of resection on overall survival (p < 0.05). The protective effect of resection increased as tumor size increased. An operation became a significant predictor of overall survival for tumors >1.5 cm (p = 0.050 or less for larger tumors) but was not significant for tumors <1.5 cm (p = 0.317 or more for smaller tumors), controlling for age-adjusted Charlson comorbidity index. CONCLUSION: Resection of nonfunctioning PNETs over 1.5 cm is independently and significantly associated with a longer survival. However, the benefit of resection for tumors under 1.5 cm is unclear.

The Identification of Prognostic Factors and Survival Statistics of Conventional Central Chondrosarcoma.

Introduction. Chondrosarcomas are malignant bone tumors that are characterized by the production of chondroid tissue. Since radiation therapy and chemotherapy have limited effect on chondrosarcoma, treatment of most patients depends on surgical resection. We conducted this study to identify independent predictive factors and survival characteristics for conventional central chondrosarcoma and dedifferentiated central chondrosarcoma. Methods. A systematic literature review was performed in September 2014 using the Pubmed, Embase, and Cochrane databases. Subsequent to a beforehand-composed selection procedure we included 13 studies, comprising a total of 1114 patients. Results. The prognosis of central chondrosarcoma is generally good for the histologically low-grade tumors. Prognosis for the high-grade chondrosarcoma and the dedifferentiated chondrosarcoma is poor with lower survival rates. Poor prognostic factors in conventional chondrosarcoma for overall survival are high-grade tumors and axial/pelvic tumor location. In dedifferentiated chondrosarcoma the percentage of dedifferentiated component has significant influence on disease-free survival. Conclusion. Despite the fact that there are multiple prognostic factors identified, as shown in this study, there is a need for prospective and comparative studies. The resulting knowledge about prognostic factors and survival can give direction in the development of better therapies. This could eventually lead to an evidence-based foundation for treating chondrosarcoma patients.

Early Patient Satisfaction with Different Treatment Pathways for Trigger Finger and Thumb.

Little is known about factors related to patient satisfaction with treatment for trigger digits. This study tested the null hypothesis that there are no factors associated with treatment satisfaction 2 months after completion of treatment (absence of triggering) or 4 months after the last visit for patients with a trigger thumb or finger. Secondary null hypotheses were: 1) There are no factors associated with a change in patients' preferred treatment before and after consultation with a hand surgeon; and 2) Initial treatment provided is not different from final received treatment. In an observational study, 63 English-speaking adult patients were enrolled after being diagnosed with one or more new idiopathic trigger digits by one of two hand surgeons, but before the hand surgeon discussed treatment options. Patients were asked to fill out questionnaires at enrollment. Final evaluation was by phone. Satisfaction with treatment was not related to the initial treatment or other patient or disease factors. Twenty-three patients (37 %) had a different preference for treatment after talking with a hand surgeon. Involvement of the long and ring fingers were the only factors associated with staying with pre-visit treatment preferences. There was a significant difference in proportions of the various treatments provided at enrollment and final treatment recorded at the final phone evaluation, 14 patients (22 %) had a subsequent alternative form of treatment. Patients' preferences for trigger finger treatment often change after consulting with a hand surgeon and during treatment, but these choices do not affect treatment satisfaction.

Quantification of Fluoroquinolone Uptake through the Outer Membrane Channel OmpF of Escherichia coli.

Decreased drug accumulation is a common cause of antibiotic resistance in microorganisms. However, there are few reliable general techniques capable of quantifying drug uptake through bacterial membranes. We present a semiquantitative optofluidic assay for studying the uptake of autofluorescent drug molecules in single liposomes. We studied the effect of the Escherichia coli outer membrane channel OmpF on the accumulation of the fluoroquinolone antibiotic, norfloxacin, in proteoliposomes. Measurements were performed at pH 5 and pH 7, corresponding to two different charge states of norfloxacin that bacteria are likely to encounter in the human gastrointestinal tract. At both pH values, the porins significantly enhance drug permeation across the proteoliposome membranes. At pH 5, where norfloxacin permeability across pure phospholipid membranes is low, the porins increase drug permeability by 50-fold on average. We estimate a flux of about 10 norfloxacin molecules per second per OmpF trimer in the presence of a 1 mM concentration gradient of norfloxacin. We also performed single channel electrophysiology measurements and found that the application of transmembrane voltages causes an electric field driven uptake in addition to concentration driven diffusion. We use our results to propose a physical mechanism for the pH mediated change in bacterial susceptibility to fluoroquinolone antibiotics.