Novel case of combination antibiotic therapy for treatment of a complicated polymicrobial urinary tract infection with one organism harboring a metallo-ß-lactamase (MBL) in a pregnant patient.

Carbapenem resistance due to metallo-beta-lactamases (MBLs) is a global phenomenon and an important challenge for antibiotic therapy (Boyd et al., 2020 [1]). While previous reports have demonstrated both in vitro and in vivo synergy using the combination of ceftazidime-avibactam and aztreonam against Stenotrophomonas maltophilia, an MBL-harboring organism, this treatment strategy has not been reported during pregnancy (Mojic et al., 2017 [2], [3], Mojica et al., 2016 [4], Alexander et al., 2020 [5]). We describe a 33-year-old pregnant female with polymicrobial, bilateral pyelonephritis caused by Stenotrophomonas maltophilia and other gram-negative bacteria. The organisms were eradicated with the combination of ceftazidime-avibactam and aztreonam followed by successful delivery with no observed adverse effects in either mother or child post-partum.

Temperature-controlled high-power short-duration ablation with 90 W for 4 s: outcome, safety, biophysical characteristics and cranial MRI findings in patients undergoing pulmonary vein isolation.

BACKGROUND: High-power short-duration (HPSD) radiofrequency ablation (RFA) is highly efficient and safe while reducing procedure and RF time in pulmonary vein isolation (PVI). The QDot™ catheter is a novel contact force ablation catheter that allows automated flow and power adjustments depending on the local tissue temperature to maintain a target temperature during 90 W/4 s lesions. We analysed intraprocedural data and periprocedural safety using the QDot-catheter in patients undergoing PVI for paroxysmal atrial fibrillation (PAF). METHODS: We included n = 48 patients undergoing PVI with the QDot-catheter with a temperature-controlled HPSD ablation mode with 90 W/4 s (TC-HPSD). If focal reconnection occurred besides repeat ablation, the ablation mode was changed to 50 W/15 s (QMode). N = 23 patients underwent cerebral MRI to detect silent cerebral lesions. RESULTS: Mean RF time was 8.1 ± 2.8 min, and procedure duration was 84.5 ± 30 min. The overall maximal measured catheter tip temperature was 52.0 °C ± 4.6 °C, mean overall applied current was 871 mA ± 44 mA and overall applied energy was 316 J ± 47 J. The mean local impedance drop was 12.1 ± 2.4 Ohms. During adenosine challenge, n = 14 (29%) patients showed dormant conduction. A total of n = 24 steam pops were detected in n = 18 patients (39.1%), while no pericardial tamponade occurred. No periprocedural thromboembolic complications occurred, while n = 4 patients (17.4%) showed silent cerebral lesion. CONCLUSIONS: TC-HPSD ablation with 90 W/4 s using the QDot-catheter led to a reduction of procedure and RF time, while no major complications occurred. Despite optimized temperature control and power adjustment, steam pops occurred in a rather high number of patients, while none of them leads to tamponade or to clinical or neurological deficits.

Edwardsiella tarda, a rare human pathogen isolated from a perihepatic abscess: Implications of transient versus long term colonization of the gastrointestinal tract.

Although gastroenteritis is the most commonly described manifestation of Edwardsiella tarda infection, the pathogenesis and transient or long-term colonization of the gastrointestinal tract of this organism in human disease is not clear. We describe a rare manifestation of E. tarda infection in a perihepatic abscess in the setting of a patient with perforated cholecystitis and its successful eradication following antibiotic treatment.

Novel double beta-lactam therapy for Granulicatella adiacens infective endocarditis.

Granulicatella adiacens, a nutritionally variant streptococci (NVS) is a well described organism associated with endocarditis. Previously communicated cases have documented the use of double beta-lactam therapy with ampicillin and ceftriaxone to treat patients with infective endocarditis due to Enterococcus faecalis and Streptocossus pneumoniae. We describe the first case of Granulicatella adiacens infective endocarditis in a patient successfully treated with the combination of intravenous ampicillin and ceftriaxone and document their synergistic activity.

[Comparison of sterile donor tomography in the eye bank and graft tomography after penetrating keratoplasty]. / Vergleich der sterilen Spendertomographie in der Hornhautbank mit der Tomographie des Transplantates nach perforierender Keratoplastik.

BACKGROUND: Since 2018 we routinely use sterile donor tomography in the eye bank to avoid refractive surprises after keratoplasty. The purpose of this study was to compare donor tomography parameters measured with anterior segment optical coherence tomography (AS-OCT) with tomography parameters of the graft after penetrating keratoplasty (PKP). METHODS: This study enrolled 193 eye bank donor corneal tissues used for PKP (graft diameter 8.2 ± 0.7 mm). Preoperative measurements were taken using the AS-OCT Casia 2 (Tomey, Nagoya, Japan). The measurements were repeated postoperatively after 5 ± 4 months with all sutures in place and after 22 ± 4 months after removal of all sutures. Preoperative and postoperative values were compared using a Wilcoxon signed-rank test. RESULTS: Postoperatively, with all sutures in place (or without sutures), the dioptric power (P) at the anterior surface (a) of the cornea remained unchanged (-0.2 D, p = 0.78) (2.7 D bigger, p < 0.01) in the steep meridian (S) (PaS) and 4.5 D (2.8 D, p < 0.01) smaller in the flat meridian (F) (PaF) in comparison with the donor tomography values. The astigmatism (a) was 4.3 D (5.4 D, p < 0.01) bigger. At the posterior surface (p) the PpS was 0.9 D (0.9 D, p < 0.01) and PpF 0.3 D (p < 0.01) (0.1 D, p = 0.42) smaller, while the astigmatism (p) was 0.7 D (0.9 D) bigger (p < 0.01). The central corneal thickness was 55.7 µm (p < 0.01) (27.5 µm, p = 0.01) smaller. The total power of the transplant after removal of all sutures did not change significantly in comparison with the eye bank measurements. CONCLUSION: Central corneal thickness, dioptric power (P) and astigmatism all changed postoperatively compared to donor tomography values, except P at the steep meridian of the anterior corneal surface with all sutures in place and P at the flat meridian of the posterior corneal surface after removal of all sutures; however, the total power of the transplant after removal of all sutures did not change significantly. This information may be of value for IOL power calculation in the classical triple procedure.

Urethroplasty performed with an autologous urothelium-vegetated collagen fleece to treat urethral stricture in the minipig model.

INTRODUCTION AND OBJECTIVE: Tissue-engineered materials in urethral reconstructive surgeries are a promising field for innovative therapy. Collagen matrices increase stability of cell-based implants and can promote viability and proliferation of urothelial cells. In this study, a collagen type I-based cell carrier (CCC) with stratified multi-layer autologous urothelium was used for urethroplasty after induction of urethral stricture in eight minipigs. MATERIALS AND METHODS: Minipigs underwent surgical procedures to induce urethral stricture by thermocoagulation. Simultaneously, bladder tissue was harvested. Urothelial cells were expanded, labeled with PKH26 and seeded onto CCC in high density. 3 weeks after strictures were induced and verified by urethrography, minipigs underwent urethroplasty using the seeded CCC. Two animals were euthanized after 1, 2, 4, and 24 weeks. Urethras were histologically examined for integration and survival of seeded CCC. In vivo phenotype of multi-layered urothelium matrix constructs was characterized via immunofluorescence staining with pancytokeratin, CK20, p63, E-cadherin and ZO-1. RESULTS: Seeded CCCs showed excellent stability and suturability after manipulation and application. Transplanted cells were detected using positive PKH26 fluorescence up to 6 months after labeling. Urothelium matrix implants integrated well into the host tissue without sign of inflammation. Animals showed no sign of rejection or stricture recurrence (urethrography) at any time during experimental period. Immunofluorescence analysis confirmed epithelial phenotype, junction formation and differentiation after 2 weeks. CONCLUSION: CCC can be suitable for urologic reconstructive surgeries and represents a promising option for clinical application. Longer follow-up results are required to exclude re-occurrence of stricture reformation.

[Structure of pain management facilities in Germany : Classification of medical and psychological pain treatment services-Consensus of the Joint Commission of the Professional Societies and Organizations for Quality in Pain Medicine]. / Struktur der schmerzmedizinischen Versorgung in Deutschland : Klassifikation schmerzmedizinischer Einrichtungen - Konsens der Gemeinsamen Kommission der Fachgesellschaften und Verbände für Qualität in der Schmerzmedizin.

On behalf of the Medical/Psychological Pain Associations, Pain Patients Alliance and the Professional Association of Pain Physicians and Psychologists, the Joint Commission of Professional Societies and Organizations for Quality in Pain Medicine, working in close collaboration with the respective presidents, has developed verifiable structural and process-related criteria for the classification of medical and psychological pain treatment facilities in Germany. Based on the established system of graded care in Germany and on existing qualifications, these criteria also argue for the introduction of a basic qualification in pain medicine. In addition to the first-ever comprehensive description of psychological pain facilities, the criteria presented can be used to classify five different levels of pain facilities, from basic pain management facilities, to specialized institutions, to the Centre for Interdisciplinary Pain Medicine. The recommendations offer binding and verifiable criteria for quality assurance in pain medicine and improved pain treatment.

Important factors determining the nanoscale tracking precision of dynamic microtubule ends.

Tracking dynamic microtubule ends in fluorescence microscopy movies provides insight into the statistical properties of microtubule dynamics and is vital for further analysis that requires knowledge of the trajectories of the microtubule ends. Here we analyse the performance of a previously developed automated microtubule end tracking routine; this has been optimized for comparatively low signal-to-noise image sequences that are characteristic of microscopy movies of dynamic microtubules growing in vitro. Sequences of simulated microtubule images were generated assuming a variety of different experimental conditions. The simulated movies were then tracked and the tracking errors were characterized. We found that the growth characteristics of the microtubules within realistic ranges had a negligible effect on the tracking precision. The fluorophore labelling density, the pixel size of the images, and the exposure times were found to be important parameters limiting the tracking precision which could be explained using concepts of single molecule localization microscopy. The signal-to-noise ratio was found to be a good single predictor of the tracking precision: typical experimental signal-to-noise ratios lead to tracking precisions in the range of tens of nanometres, making the tracking program described here a useful tool for dynamic microtubule end tracking with close to molecular precision.

Communication: A reduced scaling J-engine based reformulation of SOS-MP2 using graphics processing units.

We present a low-prefactor, cubically scaling scaled-opposite-spin second-order Møller-Plesset perturbation theory (SOS-MP2) method which is highly suitable for massively parallel architectures like graphics processing units (GPU). The scaling is reduced from O(N5) to O(N³) by a reformulation of the MP2-expression in the atomic orbital basis via Laplace transformation and the resolution-of-the-identity (RI) approximation of the integrals in combination with efficient sparse algebra for the 3-center integral transformation. In contrast to previous works that employ GPUs for post Hartree-Fock calculations, we do not simply employ GPU-based linear algebra libraries to accelerate the conventional algorithm. Instead, our reformulation allows to replace the rate-determining contraction step with a modified J-engine algorithm, that has been proven to be highly efficient on GPUs. Thus, our SOS-MP2 scheme enables us to treat large molecular systems in an accurate and efficient manner on a single GPU-server.

Transmission of photo-catalytic function in a self-replicating chemical system: in situ amphiphile production over two protocell generations.

Glass microsphere supported protocells were built to investigate the transmission of catalytic function during replication. The chemical system's replication was driven through in situ amphiphile production that resulted in the formation of free bilayers, the system's second "generation". It was demonstrated that both generations, once separated, still exhibited the ability to convert amphiphile precursors. This result shows that transmission of function in chemical systems is possible during self-replication.

Use of outpatient parenteral antimicrobial therapy for transrectal ultrasound-guided prostate biopsy prophylaxis in the setting of community-associated multidrug-resistant Escherichia coli rectal colonization.

OBJECTIVE: To study the use of ertapenem delivered in an outpatient parenteral antimicrobial therapy (OPAT) hospital-based unit setting for targeted transrectal ultrasound-guided prostate biopsy (TRUSPBx) prophylaxis in the setting of multidrug-resistant (MDR) Escherichia coli rectal colonization. E coli is the pathogen most commonly associated with post-TRUSPBx complications, and there is increasing prevalence of community-associated MDR E coli. METHODS: Prospective data analysis of all patients admitted to the OPAT unit for administration of intravenous antibiotics for prophylaxis for TRUSPBx over 18-month period was performed. Patients had identification of MDR E coli in rectal swab cultures and/or intolerance to available oral agents. Microbiologic data and tolerability of administered antibiotics and outcome after TRUSPBx were tabulated. RESULTS: Nine patients (median age 74 years) were referred because of antibiotic-resistant E coli from rectal swabs (all fluoroquinolone resistant, 7 MDR). All patients received ertapenem 1 g intravenously 1 day before TRUSPBx and the day of the procedure before TRUSPBx. None of the patients experienced infectious complications immediately after TRUSPBx or several weeks or months later, and no patient was lost to urologic follow-up. CONCLUSION: Increasing worldwide reports of prostatitis, urinary tract infections, and septicemia after TRUSPBx because of MDR E coli suggest rectal screening before procedure may be useful in decreasing complications. Targeted prophylaxis in these instances is necessary. Although carbapenems are used for treatment, they are not routinely used for prophylaxis. We report successful use of ertapenem delivered in a hospital-based OPAT unit for TRUSPBx prophylaxis.

Rilpivirine versus efavirenz in HIV-1-infected subjects receiving emtricitabine/tenofovir DF: pooled 96-week data from ECHO and THRIVE Studies.

OBJECTIVES: Week 96 efficacy and safety of the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) was compared to efavirenz (EFV) in subset of 1,096 subjects who received emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in pooled data from 2 phase 3 studies. METHODS: ECHO and THRIVE are double-blind, double-dummy, randomized, active-controlled, non-inferiority phase 3 studies of RPV versus EFV plus 2 NRTIs in antiretroviral-naïve adult subjects. The primary and secondary endpoints were the proportion of subjects with HIV-1 RNA <50 copies/ mL using an intent-to-treat, time to loss of virologic response (ITT-TLOVR) analysis at weeks 48 and 96, respectively. Safety, tolerability, immunologic response, adherence level, and other measures were also evaluated. RESULTS: At week 48, noninferior efficacy of RPV+FTC/TDF over EFV+FTC/TDF was established, and at week 96 RPV+FTC/TDF remained noninferior (77% overall response rate in both groups). Through week 96, rates of virologic failure were higher in the RPV+FTC/ TDF group, with low and similar rates of virologic failure and resistance mutations occurring during the second year of follow-up. Treatment with RPV+FTC/TDF was associated with a lower rate of discontinuation due to adverse events and grade 2-4 adverse events including dizziness, abnormal dreams/nightmares, rash, and lipid abnormalities. CONCLUSIONS: The pooled ECHO and THRIVE studies demonstrated noninferiority of RPV+FTC/TDF in achieving virologic response with safety and tolerability advantages over EFV+FTC/TDF through 96 weeks. Higher rates of virologic failure in the RPV+FTC/TDF group were balanced with higher rates of discontinuations due to adverse events in the EFV+FTC/TDF group.

Lateral displacement induced disorder in L1(0)-FePt nanostructures by ion-implantation.

Ion implantation is a promising technique for fabricating high density bit patterned media (BPM) as it may eliminate the requirement of disk planarization. However, there has not been any notable study on the impact of implantation on BPM fabrication of FePt, particularly at nano-scale, where the lateral straggle of implanted ions may become comparable to the feature size. In this work, implantation of antimony ions in patterned and unpatterned L1(0)-FePt thin films has been investigated. Unpatterned films implanted with high fluence of antimony exhibited reduced out-of-plane coercivity and change of magnetic anisotropy from perpendicular direction to film-plane. Interestingly, for samples implanted through patterned masks, the perpendicular anisotropy in the unimplanted region was also lost. This noteworthy observation can be attributed to the displacement of Fe and Pt atoms from the implantation sites to the unimplanted areas, thereby causing a phase disorder transformation from L1(0) to A1 FePt.

Surface kinetics for cooperative fungal cellulase digestion of cellulose from quartz crystal microgravimetry.

The kinetic behavior of aqueous cellulase on insoluble cellulose is best quantified through surface-based assays on a well-defined cellulose substrate of known area. We use a quartz crystal microbalance (QCM) to measure the activity of binary mixtures of Trichoderma longibrachiatum cellobiohydrolase I (Cel7A) and endoglucanase I (Cel7B) on spin-coated cellulose films. By extending a previous surface kinetic model for cellulase activity, we obtain rate constants for competitive adsorption of Cel7A and Cel7B, their irreversible binding, their complexation with the cellulose surface, and their cooperative cellulolytic activity. The activity of the two cellulases is linked through the formation of cellulose chain ends by Cel7B that provide complexation sites from which Cel7A effects cellulose chain scission. Although the rate-limiting step in Cel7A activity is complexation, Cel7B activity is limited by adsorption to the cellulose surface. A 2:1 bulk mass ratio of aqueous Cel7A:Cel7B, corresponding to a 4:1 surface mass ratio, effects the greatest rate of cellulose degradation across a range of cellulase concentrations at 25 °C. We find that surface chain-end concentration is a major predictor of Cel7A activity. Disruption of the hydrogen-bonding structure of cellulose by Cel7B enhances the activity of Cel7A on the cellulose surface.

[Focal spontaneous colic perforation in term or near-term neonates: rare and potentially insidious]. / Perforation colique néonatale focale spontanée en dehors de la grande prématurité : rare et potentiellement insidieuse.

Two cases of neonatal focal spontaneous colic perforations are reported. The 1st infant, born at 36 3/7 weeks gestational age, presented on day 3 with crying, abdominal distension, and liquid stools. Clinical examination showed a slightly irritable hypothermic (35.7 °C) infant with a distended abdomen and few bowel sounds. Blood tests were normal apart from an elevated C-reactive protein level (59 mg/l). The abdomen x-ray was erroneously considered normal. The infant's condition remained stable for nearly 3 days. After reviewing the initial x-ray, pneumoperitoneum was suspected and confirmed by a cross-table lateral abdominal x-ray. The infant was started on antibiotics and operated. Macroscopically, the entire gut was normal apart from a focal sigmoid perforation, which was stitched. A transmural colic biopsy revealed focal vascular dilation but was negative for necrotising enterocolitis or Hirschsprung disease. The infant recovered quickly. She is now a healthy, normal 3-year-old. The 2nd infant, born at 38 5/7 weeks gestational age, presented between day 1 and 2 with clinical signs of infection associated with slowly progressive ileus. The chest and abdomen x-ray was mistakenly considered normal. Frank septicemia developed. After reviewing the initial x-ray, pneumoperitoneum was suspected and confirmed by a cross-table lateral abdominal x-ray. The infant was operated. Macroscopically, the small intestine was normal, the ascending and transverse colons were dilated, and the descending and sigmoid colons were narrow. Three cecal perforations were discovered and stitched. An ileostomy and multiple colic biopsies were also performed. The postoperative course was complicated by persistent septic ileus due to descending and sigmoid colon leaks, which led to colic resections with end-to-end anastomosis. Rectal aspiration biopsies were also performed. At 1 month of age, the infant was discharged from the hospital. The ileostomy was closed in two steps at 2 and 5 months of age. A normal sweat test excluded cystic fibrosis. All colic and rectal biopsies revealed nonspecific inflammatory signs and excluded necrotizing enterocolitis and Hirschsprung disease. Nonspecific irregular thinning of muscularis mucosae and muscularis propria were observed in the two resected colic segments. The boy is now a healthy 7-year-old. The incidence of neonatal focal spontaneous colic perforations at term or close to term is unknown but probably very rare. Our department is the neonatal referral center for approximately 14,000 annual births. In the last 10 years (2000-2009), out of 5115 neonatal admissions in our unit, only ten cases have presented a neonatal spontaneous intestinal perforation, seven of ten in very-low-birth-weight infants and three of ten in term or near-term neonates (one with Hirschsprung disease and the two cases reported herein). In the same period, 108 infants suffered from necrotizing enterocolitis, seven of 108 were term infants and 6 out of 7 had a congenital heart disease. The medical literature is poor on the subject of focal spontaneous colic perforations at term; no risk factor is described. The most specific clinical sign seems to be the abdominal distension. The presence of pneumoperitoneum on an abdominal x-ray is the most sensitive paraclinical sign. In case of an intestinal perforation, surgery must be performed quickly. The vital prognosis seems to be good. The objective of this study was to draw pediatricians' attention to focal spontaneous colic perforations in term or close to term newborns. In the cases reported, the diagnostic delays could have been prevented if the entity - with its radiological manifestation - had been well known.

Intramuscular interferon beta-1a in chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVE: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) shares immunologic features with multiple sclerosis (MS). Because IM interferon beta-1a (IM IFNbeta-1a) is an effective and safe treatment for MS, we conducted a dose-ranging efficacy study of IFNbeta-1a in patients with CIDP. METHODS: Adults with IV immunoglobulin (IVIg)-dependent CIDP (n = 67) were enrolled in this 32-week double-blind trial and randomized to IM IFNbeta-1a. Patients received 30 microg once weekly plus placebo (n = 12), IM IFNbeta-1a 60 microg once weekly plus placebo (n = 11), IM IFNbeta-1a 30 microg twice weekly (n = 11), IM IFNbeta-1a 60 microg twice weekly (n = 11), or placebo twice weekly (n = 22). Participants were maintained on IVIg through week 16, when IVIg was discontinued. Patients who worsened were restarted on IVIg. The primary outcome was total IVIg dose (g/kg) administered from week 16 to 32. RESULTS: There was no difference in total IVIg dose administered after week 16 for patients treated with IFNbeta-1a (1.20 g/kg) compared with placebo (1.34 g/kg; p = 0.75). However, exploratory analyses suggested IFNbeta-1a significantly reduced total dose of IVIg compared with placebo for participants who required either high-dose IVIg (>0.95 g/kg per month) or had greater weakness at baseline (Medical Research Council sum score <51). Adverse events included flu-like symptoms, headache, and fatigue in the IFNbeta-1a groups. CONCLUSIONS: Interferon beta-1a (IFNbeta-1a) therapy did not provide significant benefit over IV immunoglobulin (IVIg) therapy alone for patients with chronic inflammatory demyelinating polyradiculoneuropathy. However, IFNbeta-1a might be beneficial for patients with more severe disability or those needing high doses of IVIg. LEVEL OF EVIDENCE: This study was designed to provide Class I evidence for the safety and efficacy of IM IFNbeta-1a in the treatment of CIDP but has been subsequently classified as Class II due to a >20% patient dropout rate. Thus, this randomized, controlled clinical trial provides Class II evidence of no effect on primary and secondary endpoints of 4 dosage regimens of IM IFNbeta-1a added to IVIg in persons with CIDP.

Safety of high-dose intravenous daptomycin treatment: three-year cumulative experience in a clinical program.

BACKGROUND: There are limited safety data for high-dose and long-term daptomycin treatment (16mg/kg administered for >or=14 days). We present our experience in 61 patients. METHODS: We performed a retrospective chart review for all patients treated with daptomycin at New York Hospital Queens (Flushing) from 1 January 2004 through 30 April 2007; patients were identified through a computerized hospital pharmacy database. RESULTS: Sixty-one patients (29 male and 32 female patients; mean age, 66.6 years) received a mean dose of 8 mg/kg of daptomycin for a median of 25 days (range, 14-82 days). Twelve patients (with bone and skin and softtissue infections) did not have an identified microbiologic isolate. Gram-positive infections included bloodstream infection with or without infective endocarditis (n = 32), skin and soft-tissue infection (n = 14), bone and joint infection (n = 9), and intra-abdominal infection (n = 5), and unidentified infection (n = 1). Prosthetic devices were removed from 11 of 20 patients. Grade 1 adverse events occurred in 22 patients and did not lead to daptomycin discontinuation. Fifty-eight patients underwent creatine phosphokinase (CPK) analysis (34 patients had paired CPK analyses at the beginning of and during therapy, and 13 patients had random CPK analysis performed during treatment). Three patients had constitutional and/or musculoskeletal symptoms accompanying CPK levels 110 times upper limit of normal (grade 3). All occurred after 24 days of treatment and improved after daptomycin treatment was discontinued. Two of 3 patients were morbidly obese (body mass index grade III). CONCLUSIONS: Daptomycin treatment was well tolerated at a mean dose of 8 mg/kg for a median duration of 25 days. The incidence of symptomatic CPK level elevation was within the range reported with lower doses of daptomycin and/or for shorter treatment durations.

Effect of statins on clinical and molecular responses to intramuscular interferon beta-1a.

BACKGROUND: Findings from a small clinical study suggested that statins may counteract the therapeutic effects of interferon beta (IFNbeta) in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: We conducted a post hoc analysis of data from the Safety and Efficacy of Natalizumab in Combination With IFNbeta-1a in Patients With Relapsing-Remitting Multiple Sclerosis (SENTINEL) study to determine the effects of statins on efficacy of IFNbeta. SENTINEL was a prospective trial of patients with RRMS treated with natalizumab (Tysabri, Biogen Idec, Inc., Cambridge, MA) plus IM IFNbeta-1a (Avonex, Biogen Idec, Inc.) 30 microg compared with placebo plus IM IFNbeta-1a 30 microg. Clinical and MRI outcomes in patients treated with IM IFNbeta-1a only (no-statins group, n = 542) were compared with those of patients taking IM IFNbeta-1a and statins at doses used to treat hyperlipidemia (statins group, n = 40). RESULTS: No significant differences were observed between treatment groups in adjusted annualized relapse rate (p = 0.937), disability progression (p = 0.438), number of gadolinium-enhancing lesions (p = 0.604), or number of new or enlarging T2-hyperintense lesions (p = 0.802) at 2 years. More patients in the statins group reported fatigue, extremity pain, muscle aches, and increases in hepatic transaminases compared with patients in the no-statins group. Statin treatment had no ex vivo or in vitro effect on induction of IFN-stimulated genes. CONCLUSIONS: Statin therapy does not appear to affect clinical effects of IM interferon beta-1a in patients with relapsing-remitting multiple sclerosis or the primary molecular response to interferon beta treatment.