The effects of drug-drug interaction on linezolid pharmacokinetics: A systematic review.

OBJECTIVES: Linezolid is a commonly used antibiotic in the clinical treatment of gram-positive bacterial infections. The impacts of drug interactions on the pharmacokinetics of linezolid are often overlooked. This manuscript aims to review the medications that affect the pharmacokinetics of linezolid. METHODS: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we queried the PubMed, Embase, and Cochrane Library for publications from database establishment to November 3, 2023, using the search terms: "Linezolid" and "interaction," or "interact," or "drug-drug interaction," or "co-treatment," or "cotreatment," or "combined," or "combination." RESULTS: A total of 24 articles were included. Among the reported medication interactions, rifampicin, levothyroxine, venlafaxine, and phenobarbital could reduce the concentration of linezolid; clarithromycin, digoxin, cyclosporine, proton pump inhibitors, and amiodarone could increase the concentration of linezolid, while aztreonam, phenylpropanolamine, dextromethorphan, antioxidant vitamins, and magnesium-containing antacids had no significant effects on linezolid pharmacokinetics. The ratio of mean (ROM) of linezolid AUC in co-treatment with rifampicin to monotherapy was 0.67 (95%CI 0.58-0.77) and 0.63 (95%CI 0.43-0.91), respectively, in 2 studies, and co-treatment with 500 mg clarithromycin to monotherapy was 1.81 (95%CI 1.49-2.13). CONCLUSIONS: This systematic review found that numerous drugs have an impact on the pharmacokinetics of linezolid, and the purported main mechanism may be that linezolid is the substrate of P-glycoprotein. In clinical practice, it is prudent to pay attention to the changes in linezolid pharmacokinetics caused by interactions. Conducting therapeutic drug monitoring (TDM) is beneficial to improve efficacy and reduce adverse reactions of linezolid.

Small intestinal CaSR-dependent and CaSR-independent protein sensing regulates feeding and glucose tolerance in rats.

Proteins activate small intestinal calcium sensing receptor (CaSR) and/or peptide transporter 1 (PepT1) to increase hormone secretion1-8, but the effect of small intestinal protein sensing and the mechanistic potential of CaSR and/or PepT1 in feeding and glucose regulation remain inconclusive. Here we show that, in male rats, CaSR in the upper small intestine is required for casein infusion to increase glucose tolerance and GLP1 and GIP secretion, which was also dependent on PepT1 (ref. 9). PepT1, but not CaSR, is required for casein infusion to lower feeding. Upper small intestine casein sensing fails to regulate feeding, but not glucose tolerance, in high-fat-fed rats with decreased PepT1 but increased CaSR expression. In the ileum, a CaSR-dependent but PepT1-independent pathway is required for casein infusion to lower feeding and increase glucose tolerance in chow-fed rats, in parallel with increased PYY and GLP1 release, respectively. High fat decreases ileal CaSR expression and disrupts casein sensing on feeding but not on glucose control, suggesting an ileal CaSR-independent, glucose-regulatory pathway. In summary, we discover small intestinal CaSR- and PepT1-dependent and -independent protein sensing mechanisms that regulate gut hormone release, feeding and glucose tolerance. Our findings highlight the potential of targeting small intestinal CaSR and/or PepT1 to regulate feeding and glucose tolerance.

One-Step Automatic Radiosynthesis and Evaluation of [18F]TM-30089 as GPR44 Radiotracer.

Recently, a G-protein coupled receptor 44 (GPR44) was discovered to play a significant role in the process of inflammation-related diseases, including cancer and diabetes. However, the precise role of GPR44 has yet to be fully elucidated. Currently, there is a strong and urgent need for the development of GPR44 radiotracers as a non-invasive methodology to explore the exact mechanism of GPR44 on inflammation-related diseases and monitor the progress of therapy. TM-30089 is a potent GPR44 antagonist that exhibits a high specificity and selectivity for GPR44. Its structure contains a fluorine nuclide, which could potentially be replaced with 18F. In the present study, we successfully took a highly effective synthesis strategy that pretreated the unprotected carboxylic acid group of the precursor and developed a feasible one-step automatic radiosynthesis strategy for [18F]TM-30089 with a high radiochemical purity and a good radiochemical yield. We further evaluated this radiotracer using mice models implanted with 1.1 B4 cell lines (GPR44-enriched cell lines) and human islets (high GPR44 expression), respectively. The results revealed the persistent and specific uptake of [18F]TM-30089 in GPR44 region, indicating that [18F]TM-30089 is a promising candidate for targeting GPR44. Further evaluation is ongoing.

Primary prevention implantable cardioverter defibrillator in cardiac resynchronization therapy recipients with advanced chronic kidney disease.

Introduction: The implantable cardioverter defibrillator (ICD) is effective for the prevention of sudden cardiac death (SCD) in patients with heart failure and a reduced ejection fraction (HFrEF). The benefit of the ICD in patients with advanced CKD, remains elusive. Moreover, the benefit of the ICD in patients with advanced chronic kidney disease (CKD) and HFrEF who are cardiac resynchronization therapy (CRT) recipients may be attenuated. Hypothesis: We hypothesized that patients with CKD who are CRT recipients may derive less benefit from the ICD due to the competing risk of dying prior to experiencing an arrhythmia. Methods: The study population included 1,015 patients receiving CRT with defibrillator (CRT-D) device for primary prevention of SCD who were enrolled in either (Multicenter Automated Defibrillator Implantation Trial) MADIT-CRT trial or the Ranolazine in High-Risk Patients with Implanted Cardioverter Defibrillator (RAID) trial. The cohort was divided into two groups based on the stage of CKD: those with Stage 1 to 3a KD, labeled as (S1-S3a)KD. The second group included patients with Stage 3b to stage 5 kidney disease, labeled as (S3b-S5)KD. The primary endpoint was any ventricular tachycardia (VT) or ventricular fibrillation (VF) (Any VT/VF). Results: The cumulative incidence of Any VT/VF was 23.5% in patients with (S1-S3a)KD and 12.6% in those with (S3b-S5)KD (p < 0.001) The incidence of Death without Any VT/VF was 6.6% in patients with (S1-S3a)KD and 21.6% in patients with (S3b-S5)KD (p < 0.001). A Fine and Gray multivariate competing risk regression model showed that Patients with (S3b-S5)KD had a 43% less risk of experiencing Any VT/VF when compared to those with (S1-S3a)KD (HR = 0.56, 95% CI [0.33-0.94] p = 0.03. After two years of follow up, there was almost a 5-fold increased risk of Death without Any VT/VF among patients with (S3b-S5)KD when compared to those with (S1-S3a)KD [HR = 4.63, 95% CI (2.46-8.72), p for interaction with time = 0.012]. Conclusion: Due to their lower incidence of arrhythmias and higher risk of dying prior to experiencing an arrhythmia, the benefit of the ICD may be attenuated in CRT recipients with advanced CKD. Future prospective trials should evaluate whether CRT without a defibrillator may be more appropriate for these patients.

Indole-Based and Cyclopentenylindole-Based Analogues Containing Fluorine Group as Potential 18F-Labeled Positron Emission Tomography (PET) G-Protein Coupled Receptor 44 (GPR44) Tracers.

Recently, growing evidence of the relationship between G-protein coupled receptor 44 (GPR44) and the inflammation-cancer system has garnered tremendous interest, while the exact role of GPR44 has not been fully elucidated. Currently, there is a strong and urgent need for the development of non-invasive in vivo GPR44 positron emission tomography (PET) radiotracers that can be used to aid the exploration of the relationship between inflammation and tumor biologic behavior. Accordingly, the choosing and radiolabeling of existing GPR44 antagonists containing a fluorine group could serve as a viable method to accelerate PET tracers development for in vivo imaging to this purpose. The present study aims to evaluate published (2000-present) indole-based and cyclopentenyl-indole-based analogues of the GPR44 antagonist to guide the development of fluorine-18 labeled PET tracers that can accurately detect inflammatory processes. The selected analogues contained a crucial fluorine nuclide and were characterized for various properties including binding affinity, selectivity, and pharmacokinetic and metabolic profile. Overall, 26 compounds with favorable to strong binding properties were identified. This review highlights the potential of GPR44 analogues for the development of PET tracers to study inflammation and cancer development and ultimately guide the development of targeted clinical therapies.

To Evaluate the Efficacy of Diagnostic Periocular Punch Biopsy: Using a 4-mm Dermatology Punch.

PURPOSE: The dermatological punch biopsy is a minimally invasive procedure that provides conclusive diagnosis when managing periocular lesions. It aids with establishing histological diagnosis and subtype thereby facilitating management planning and eliminates the risk of unnecessary tissue sacrifice. The present literature provides limited evidence evaluating the value of punch biopsy in diagnosing periocular lesions. METHODS: A retrospective case note analysis of 400 consecutive 4-mm periocular punch biopsies performed between 2005 and 2016, from 353 patients was undertaken at a single institution. Three hundred fifty-nine lesions had an initial definite clinical diagnosis of malignancy (group A) and the remaining 41 lesions had an uncertain clinical diagnosis with enough suspicion to merit a biopsy (group B). RESULTS: In group A, 75.5% (n = 271) of the biopsies verified the clinical diagnosis of malignancy and 24.5% (n = 88) were benign. In group B, 70.7% (n = 29) of the lesions were benign and 29.3% (n = 12) were malignant and were subsequently treated as group A. Only 4, group A biopsies, which underwent formal excision, did not initially diagnose a malignancy (punch biopsy was repeated) providing a sensitivity of 98.6% and a specificity of 100%. One hundred seventeen were found to be benign avoiding unnecessary tissue sacrifice in 29.25% of cases. CONCLUSION: Our study provides the largest sample size in the literature that evaluates a 4-mm diagnostic periocular punch biopsy in managing eyelid lesions. In 29.5% of punch biopsies, unnecessary tissue sacrifice was avoided as they were histologically benign. The authors found that punch biopsies for lesions <7 mm carry a risk of inadvertent excision of lesion.

Liver Fibrosis Assessment Using Radiomics of Ultrasound Homodyned-K imaging Based on the Artificial Neural Network Estimator.

The homodyned-K distribution is an important ultrasound backscatter envelope statistics model of physical meaning, and the parametric imaging of the model parameters has been explored for quantitative ultrasound tissue characterization. In this paper, we proposed a new method for liver fibrosis characterization by using radiomics of ultrasound backscatter homodyned-K imaging based on an improved artificial neural network (iANN) estimator. The iANN estimator was used to estimate the ultrasound homodyned-K distribution parameters k and α from the backscattered radiofrequency (RF) signals of clinical liver fibrosis (n = 237), collected with a 3-MHz convex array transducer. The RF data were divided into two groups: Group I corresponded to liver fibrosis with no hepatic steatosis (n = 94), and Group II corresponded to liver fibrosis with mild to severe hepatic steatosis (n = 143). The estimated homodyned-K parameter values were then used to construct k and α parametric images using the sliding window technique. Radiomics features of k and α parametric images were extracted, and feature selection was conducted. Logistic regression classification models based on the selected radiomics features were built for staging liver fibrosis. Experimental results showed that the proposed method is overall superior to the radiomics method of uncompressed envelope images when assessing liver fibrosis. Regardless of hepatic steatosis, the proposed method achieved the best performance in staging liver fibrosis ≥F1, ≥F4, and the area under the receiver operating characteristic curve was 0.88, 0.85 (Group I), and 0.85, 0.86 (Group II), respectively. Radiomics has improved the ability of ultrasound backscatter statistical parametric imaging to assess liver fibrosis, and is expected to become a new quantitative ultrasound method for liver fibrosis characterization.

Passively scanned, single-fiber optical coherence tomography probes for gastrointestinal devices.

BACKGROUND/OBJECTIVES: Optical coherence tomography (OCT) uses low coherence interferometry to obtain depth-resolved tissue reflectivity profiles (M-mode) and transverse beam scanning to create images of two-dimensional tissue morphology (B-mode). Endoscopic OCT imaging probes typically employ proximal or distal mechanical beam scanning mechanisms that increase cost, complexity, and size. Here, we demonstrate in the gastrointestinal (GI) tracts of unsedated human patients, that a passive, single-fiber probe can be used to guide device placement, conduct device-tissue physical contact sensing, and obtain two-dimensional OCT images via M-to-B-mode conversion. MATERIALS AND METHODS: We designed and developed ultrasmall, manually scannable, side- and forward-viewing single fiber-optic probes that can capture M-mode OCT data. Side-viewing M-mode OCT probes were incorporated into brush biopsy devices designed to harvest the microbiome and forward-viewing M-mode OCT probes were integrated into devices that measure intestinal potential difference (IPD). The M-mode OCT probe-coupled devices were utilized in the GI tract in six unsedated patients in vivo. M-mode data were converted into B-mode images using an M-to-B-mode conversion algorithm. The effectiveness of physical contact sensing by the M-mode OCT probes was assessed by comparing the variances of the IPD values when the probe was in physical contact with the tissue versus when it was not. The capacity of forward- and side-viewing M-mode OCT probes to produce high-quality B-mode images was compared by computing the percentages of the M-to-B-mode images that showed close contact between the probe and the luminal surface. Passively scanned M-to-B-mode images were qualitatively compared to B-mode images obtained by mechanical scanning OCT tethered capsule endomicroscopy (TCE) imaging devices. RESULTS: The incorporation of M-mode OCT probes in these nonendoscopic GI devices safely and effectively enabled M-mode OCT imaging, facilitating real-time device placement guidance and contact sensing in vivo. Results showed that M-mode OCT contact sensing improved the variance of IPD measurements threefold and side-viewing probes increased M-to-B-mode image visibility by 10%. Images of the esophagus, stomach, and duodenum generated by the passively scanned probes and M-to-B-mode conversion were qualitatively superior to B-mode images obtained by mechanically scanning OCT TCE devices. CONCLUSION: These results show that passive, single optical fiber OCT probes can be effectively utilized for nonendoscopic device placement guidance, device contact sensing, and two-dimensional morphologic imaging in the human GI tract in vivo. Due to their small size, lower cost, and reduced complexity, these M-mode OCT probes may provide an easier avenue for the incorporation of OCT functionality into endoscopic/nonendoscopic devices.

Tracking cryptic SARS-CoV-2 lineages detected in NYC wastewater.

Tracking SARS-CoV-2 genetic diversity is strongly indicated because diversifying selection may lead to the emergence of novel variants resistant to naturally acquired or vaccine-induced immunity. To monitor New York City (NYC) for the presence of novel variants, we deep sequence most of the receptor binding domain coding sequence of the S protein of SARS-CoV-2 isolated from the New York City wastewater. Here we report detecting increasing frequencies of novel cryptic SARS-CoV-2 lineages not recognized in GISAID's EpiCoV database. These lineages contain mutations that had been rarely observed in clinical samples, including Q493K, Q498Y, E484A, and T572N and share many mutations with the Omicron variant of concern. Some of these mutations expand the tropism of SARS-CoV-2 pseudoviruses by allowing infection of cells expressing the human, mouse, or rat ACE2 receptor. Finally, pseudoviruses containing the spike amino acid sequence of these lineages were resistant to different classes of receptor binding domain neutralizing monoclonal antibodies. We offer several hypotheses for the anomalous presence of these lineages, including the possibility that these lineages are derived from unsampled human COVID-19 infections or that they indicate the presence of a non-human animal reservoir.

Feasibility and Safety of Tethered Capsule Endomicroscopy in Patients With Barrett's Esophagus in a Multi-Center Study.

BACKGROUND & AIMS: Tethered capsule endomicroscopy (TCE) involves swallowing a small tethered pill that implements optical coherence tomography (OCT) imaging, procuring high resolution images of the whole esophagus. Here, we demonstrate and evaluate the feasibility and safety of TCE and a portable OCT imaging system in patients with Barrett's esophagus (BE) in a multi-center (5-site) clinical study. METHODS: Untreated patients with BE as per endoscopic biopsy diagnosis were eligible to participate in the study. TCE procedures were performed in unsedated patients by either doctors or nurses. After the capsule was swallowed, the device continuously obtained 10-µm-resolution cross-sectional images as it traversed the esophagus. Following imaging, the device was withdrawn through mouth, and disinfected for subsequent reuse. BE lengths were compared to endoscopy findings when available. OCT-TCE images were compared to volumetric laser endomicroscopy (VLE) images from a patient who had undergone VLE on the same day as TCE. RESULTS: 147 patients with BE were enrolled across all sites. 116 swallowed the capsule (79%), 95/114 (83.3%) men and 21/33 (63.6%) women (P = .01). High-quality OCT images were obtained in 104/111 swallowers (93.7%) who completed the procedure. The average imaging duration was 5.55 ± 1.92 minutes. The mean length of esophagus imaged per patient was 21.69 ± 5.90 cm. A blinded comparison of maximum extent of BE measured by OCT-TCE and EGD showed a strong correlation (r = 0.77-0.79). OCT-TCE images were of similar quality to those obtained by OCT-VLE. CONCLUSIONS: The capabilities of TCE to be used across multiple sites, be administered to unsedated patients by either physicians or nurses who are not expert in OCT-TCE, and to rapidly and safely evaluate the microscopic structure of the esophagus make it an emerging tool for screening and surveillance of BE patients. Clinical trial registry website and trial number: NCT02994693 and NCT03459339.

Protocol for safe, affordable, and reproducible isolation and quantitation of SARS-CoV-2 RNA from wastewater.

The following protocol describes our workflow for processing wastewater with the goal of detecting the genetic signal of SARS-CoV-2. The steps include pasteurization, virus concentration, RNA extraction, and quantification by RT-qPCR. We include auxiliary steps that provide new users with tools and strategies that will help troubleshoot key steps in the process. This protocol is one of the safest, cheapest, and most reproducible approaches for the detection of SARS-CoV-2 RNA in wastewater. Owing to a pasteurization step, it is safe for use in a BSL2 facility. In addition to making the protocol safe for the personnel involved, pasteurization had the added benefit of increasing the SARS-CoV-2 genetic signal. Furthermore, the RNA obtained using this protocol can be sequenced using both Sanger and Illumina sequencing technologies. The protocol was adopted by the New York City Department of Environmental Protection in August 2020 to monitor SARS-CoV-2 prevalence in wastewater in all five boroughs of the city. In the future, this protocol could be used to detect a variety of other clinically relevant viruses in wastewater and serve as a foundation of a wastewater surveillance strategy for monitoring community spread of known and emerging viral pathogens.

Parameter estimation of the homodyned K distribution based on an artificial neural network for ultrasound tissue characterization.

The homodyned K (HK) distribution allows a general description of ultrasound backscatter envelope statistics with specific physical meanings. In this study, we proposed a new artificial neural network (ANN) based parameter estimation method of the HK distribution. The proposed ANN estimator took advantages of ANNs in learning and function approximation and inherited the strengths of conventional estimators through extracting five feature parameters from backscatter envelope signals as the input of the ANN: the signal-to-noise ratio (SNR), skewness, kurtosis, as well as X- and U-statistics. Computer simulations and clinical data of hepatic steatosis were used for validations of the proposed ANN estimator. The ANN estimator was compared with the RSK (the level-curve method that uses SNR, skewness, and kurtosis based on the fractional moments of the envelope) and XU (the estimation method based on X- and U-statistics) estimators. Computer simulation results showed that the relative bias was best for the XU estimator, whilst the normalized standard deviation was overall best for the ANN estimator. The ANN estimator was almost one order of magnitude faster than the RSK and XU estimators. The ANN estimator also yielded comparable diagnostic performance to state-of-the-art HK estimators in the assessment of hepatic steatosis. The proposed ANN estimator has great potential in ultrasound tissue characterization based on the HK distribution.

Ultrasound Backscatter Envelope Statistics Parametric Imaging for Liver Fibrosis Characterization: A Review.

Early detection and diagnosis of liver fibrosis is of critical importance. Currently the gold standard for diagnosing liver fibrosis is biopsy. However, liver biopsy is invasive and associated with sampling errors and can lead to complications such as bleeding. Therefore, developing noninvasive imaging techniques for assessing liver fibrosis is of clinical value. Ultrasound has become the first-line tool for the management of chronic liver diseases. However, the commonly used B-mode ultrasound is qualitative and can cause interobserver or intraobserver difference. Ultrasound backscatter envelope statistics parametric imaging is an important group of quantitative ultrasound techniques that have been applied to characterizing different kinds of tissue. However, a state-of-the-art review of ultrasound backscatter envelope statistics parametric imaging for liver fibrosis characterization has not been conducted. In this paper, we focused on the development of ultrasound backscatter envelope statistics parametric imaging techniques for assessing liver fibrosis from 1998 to September 2019. We classified these techniques into six categories: constant false alarm rate, fiber structure extraction technique, acoustic structure quantification, quantile-quantile probability plot, the multi-Rayleigh model, and the Nakagami model. We presented the theoretical background and algorithms for liver fibrosis assessment by ultrasound backscatter envelope statistics parametric imaging. Then, the specific applications of ultrasound backscatter envelope statistics parametric imaging techniques to liver fibrosis evaluation were reviewed and analyzed. Finally, the pros and cons of each technique were discussed, and the future development was suggested.

An expanded multilocus sequence typing scheme for propionibacterium acnes: investigation of 'pathogenic', 'commensal' and antibiotic resistant strains.

The Gram-positive bacterium Propionibacterium acnes is a member of the normal human skin microbiota and is associated with various infections and clinical conditions. There is tentative evidence to suggest that certain lineages may be associated with disease and others with health. We recently described a multilocus sequence typing scheme (MLST) for P. acnes based on seven housekeeping genes (http://pubmlst.org/pacnes). We now describe an expanded eight gene version based on six housekeeping genes and two 'putative virulence' genes (eMLST) that provides improved high resolution typing (91eSTs from 285 isolates), and generates phylogenies congruent with those based on whole genome analysis. When compared with the nine gene MLST scheme developed at the University of Bath, UK, and utilised by researchers at Aarhus University, Denmark, the eMLST method offers greater resolution. Using the scheme, we examined 208 isolates from disparate clinical sources, and 77 isolates from healthy skin. Acne was predominately associated with type IA(1) clonal complexes CC1, CC3 and CC4; with eST1 and eST3 lineages being highly represented. In contrast, type IA(2) strains were recovered at a rate similar to type IB and II organisms. Ophthalmic infections were predominately associated with type IA(1) and IA(2) strains, while type IB and II were more frequently recovered from soft tissue and retrieved medical devices. Strains with rRNA mutations conferring resistance to antibiotics used in acne treatment were dominated by eST3, with some evidence for intercontinental spread. In contrast, despite its high association with acne, only a small number of resistant CC1 eSTs were identified. A number of eSTs were only recovered from healthy skin, particularly eSTs representing CC72 (type II) and CC77 (type III). Collectively our data lends support to the view that pathogenic versus truly commensal lineages of P. acnes may exist. This is likely to have important therapeutic and diagnostic implications.

The management of traumatic isolated inferior rectus rupture.

Traumatic inferior rectus rupture is a rare cause of diplopia following blunt trauma in the absence of blowout fracture. We report the case of a heavy goods vehicle driver, aged 42 years, with isolated rupture of the inferior rectus following blunt ocular trauma. The technique of repair, using a Hummelsheim-type procedure, is described. Good alignment was achieved at 1 month following surgery, with an excellent field of binocular vision. Other than vertical diplopia on extreme upgaze, the patient was asymptomatic and remained so 15 months following surgery. He was able to continue his job without any significant visual concerns. The surgical outcome was better than that described in previous reports of inferior rectus rupture. We feel that a Hummelsheim-type procedure is a useful option in the management of inferior rectus rupture.

A novel multilocus sequence typing scheme for the opportunistic pathogen Propionibacterium acnes and characterization of type I cell surface-associated antigens.

We have developed a novel multilocus sequence typing (MLST) scheme and database (http://pubmlst.org/pacnes/) for Propionibacterium acnes based on the analysis of seven core housekeeping genes. The scheme, which was validated against previously described antibody, single locus and random amplification of polymorphic DNA typing methods, displayed excellent resolution and differentiated 123 isolates into 37 sequence types (STs). An overall clonal population structure was detected with six eBURST groups representing the major clades I, II and III, along with two singletons. Two highly successful and global clonal lineages, ST6 (type IA) and ST10 (type IB(1)), representing 64 % of this current MLST isolate collection were identified. The ST6 clone and closely related single locus variants, which comprise a large clonal complex CC6, dominated isolates from patients with acne, and were also significantly associated with ophthalmic infections. Our data therefore support an association between acne and P. acnes strains from the type IA cluster and highlight the role of a widely disseminated clonal genotype in this condition. Characterization of type I cell surface-associated antigens that are not detected in ST10 or strains of type II and III identified two dermatan-sulphate-binding proteins with putative phase/antigenic variation signatures. We propose that the expression of these proteins by type IA organisms contributes to their role in the pathophysiology of acne and helps explain the recurrent nature of the disease. The MLST scheme and database described in this study should provide a valuable platform for future epidemiological and evolutionary studies of P. acnes.

Acute deterioration of a Chiari I malformation: an uncommon neurosurgical emergency.

OBJECTIVES: Report and discuss acute neurological deterioration of Chiari I malformation (CMI), surgical treatment and timing, clinical outcome and literature review. CASE REPORT: We report a recent case of a 15-year-old girl admitted for an acute neurological deterioration caused by an undiagnosed hindbrain herniation that required an urgent foramen magnum decompression and external ventricular drainage insertion. Moreover, we report and discuss the literature. To the authors' knowledge, this is only the third paediatric patient identified in this setting to be treated for an acute neurological deterioration due to a previous asymptomatic hindbrain herniation. The patient made an uncomplicated recovery and was discharged home on the seventh postoperative day and has remained well at review. DISCUSSION: Acute deterioration of CMI in completely asymptomatic patients in absence of concomitant pathological findings is rarely reported in the literature, and exceptional in children. CONCLUSIONS: CMI is typically treated electively, but as this case illustrates, it can present with rapidly deteriorating neurological signs. Symptoms usually respond well to surgical intervention with rapid improvement.

Postcataract endophthalmitis: incidence and microbial isolates in a United Kingdom region from 1996 through 2004.

PURPOSE: To investigate the incidence of endophthalmitis after cataract surgery, analyze the microbiologic spectrum of infecting organisms, and assess the diagnostic utility of an anterior chamber paracentesis and vitreous biopsy. SETTING: United Kingdom tertiary referral center used by 13 operating suites. METHODS: A retrospective noncomparative consecutive series comprised 105 postcataract endophthalmitis cases. RESULTS: The annual mean incidence of endophthalmitis over the study period was 0.099% (101/101 920) [corrected] and there was no significant increase in the incidence during the study. The culture-positive rate was 58.1% (61/105). Gram-positive microbes were isolated in 93.4% of cases (57/61), with coagulase-negative staphylococci accounting for 62.3% (38/61). Anterior chamber taps yielded positive cultures in 25.7% of cases, and vitreous biopsy was positive in 53.4%. CONCLUSIONS: The incidence of endophthalmitis in this region of the United Kingdom remained stable, with gram-positive microbes accounting for 93.4% of the isolates. A combination of anterior chamber tap and vitreous biopsy should be performed in suspected cases of endophthalmitis.