Biomechanical strength of triceps tendon repairs: systematic review and meta-regression analysis of human cadaveric studies.

PURPOSE: It is unclear which triceps tendon repair constructs and techniques produce the strongest biomechanical performance while minimizing the risk of gap formation and repair failure. We aimed to determine associations of construct and technique variables with the biomechanical strength of triceps tendon repairs. PubMed, Embase, Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov were systematically searched for peer-reviewed studies on biomechanical strength of triceps tendon repairs in human cadavers. 6 articles met the search criteria. Meta-regression was performed on the pooled dataset (123 specimens). Outcomes of interest included gap formation, failure mode, and ultimate failure load. Covariates were fixation type; number of implants; and number of sutures. Stratification by covariates was performed. We found no association between fixation type and ultimate failure load; however, suture anchor fixation was associated with less gap formation compared with transosseous direct repair (ß = - 1.1; 95% confidence interval [CI]:- 2.2, - 0.04). A greater number of implants was associated with smaller gap formation (ß = - 0.77; 95% CI: - 1.3, - 0.28) while a greater number of sutures was associated with higher ultimate failure load ( ß= 3; 95% CI: 21, 125). In human cadaveric models, the number of sutures used in triceps tendon repairs may be more important than the fixation type or number of implants for overall strength. If using a transosseous direct repair approach to repair triceps tendon tears, surgeons may choose to use more sutures in their repair in order to balance the risk of larger gap formation when compared to indirect repair techniques. LEVEL OF EVIDENCE: Level III.

Seasonal dynamics of ammonia-oxidizing bacteria but not archaea influence soil nitrogen cycling in a semi-arid agricultural soil.

Nitrification, a key pathway of nitrogen (N) loss from agricultural soils, is performed by ammonia-oxidizing bacteria (AOB) and archaea (AOA). We examined the seasonal dynamics (2 years) of ammonia oxidizer gene abundances across a gradient of soil carbon (C) and N in a semi-arid soil after 8 years of tillage and crop residue treatments. AOB was more dominant than AOA in the surface soil, as AOA were undetected in 96% of samples. Seasonal variation in AOB abundance was related to substrate availability; AOB gene copy numbers increased at the end of the growing season (during summer fallow) following higher concentrations in dissolved organic matter soil water. This suggests increased co-location between AOB and substrate resources in pores still filled with water as the soils dried. AOB was however not statistically related to soil ammonium concentrations, soil water content, rainfall or temperature. Organic matter inputs enhanced AOB abundance independent of seasonal variation. AOB abundance was greatest in autumn and immediately preceding the start of the growing season, and coincided with elevated soil nitrate concentrations. The growth of the AOB population is likely to contribute to increased risk of N loss through leaching and/or denitrification at the start of the crop growing season following summer fallow.

Role of Tim4 in the regulation of ABCA1+ adipose tissue macrophages and post-prandial cholesterol levels.

Dyslipidemia is a main driver of cardiovascular diseases. The ability of macrophages to scavenge excess lipids implicate them as mediators in this process and understanding the mechanisms underlying macrophage lipid metabolism is key to the development of new treatments. Here, we investigated how adipose tissue macrophages regulate post-prandial cholesterol transport. Single-cell RNA sequencing and protected bone marrow chimeras demonstrated that ingestion of lipids led to specific transcriptional activation of a population of resident macrophages expressing Lyve1, Tim4, and ABCA1. Blocking the phosphatidylserine receptor Tim4 inhibited lysosomal activation and the release of post-prandial high density lipoprotein cholesterol following a high fat meal. Both effects were recapitulated by chloroquine, an inhibitor of lysosomal function. Moreover, clodronate-mediated cell-depletion implicated Tim4+ resident adipose tissue macrophages in this process. Thus, these data indicate that Tim4 is a key regulator of post-prandial cholesterol transport and adipose tissue macrophage function and may represent a novel pathway to treat dyslipidemia.

Surface color spectrophotometry in a murine model of steatosis: an accurate technique with potential applicability in liver procurement.

Steatosis is the most important prognostic histologic feature in the setting of liver procurement. The currently utilized diagnostic methods, including gross evaluation and frozen section examination, have important shortcomings. Novel techniques that offer advantages over the current tools could be of significant practical utility. The aim of this study is to evaluate the accuracy of surface color spectrophotometry in the quantitative assessment of steatosis in a murine model of fatty liver. C57BL/6 mice were divided into a control group receiving normal chow (n = 19), and two steatosis groups receiving high-fat diets for up to 20 weeks-mild steatosis (n = 10) and moderate-to-severe steatosis (n = 19). Mouse liver surfaces were scanned with a hand-held spectrophotometer (CM-600D; Konica-Minolta, Osaka, Japan). Spectral reflectance data and color space values (L*a*b*, XYZ, L*c*h*, RBG, and CMYK) were correlated with histopathologic steatosis evaluation by visual estimate, digital image analysis (DIA), as well as biochemical tissue triglyceride measurement. Spectral reflectance and most color space values were very strongly correlated with histologic assessment of total steatosis, with the best predictor being % reflectance at 700 nm (r = 0.91 [0.88-0.94] for visual assessment, r = 0.92 [0.88-0.95] for DIA of H&E slides, r = 0.92 [0.87-0.95] for DIA of oil-red-O stains, and r = 0.78 [0.63-0.87] for biochemical tissue triglyceride measurement, p < 0.0001 for all). Several spectrophotometric parameters were also independently predictive of large droplet steatosis. In conclusion, hepatic steatosis can accurately be assessed using a portable, commercially available hand-held spectrophotometer device. If similarly accurate in human livers, this technique could be utilized as a point-of-care tool for the quantitation of steatosis, which may be especially valuable in assessing livers during deceased donor organ procurement.

Recruited macrophages that colonize the post-inflammatory peritoneal niche convert into functionally divergent resident cells.

Inflammation generally leads to recruitment of monocyte-derived macrophages. What regulates the fate of these cells and to what extent they can assume the identity and function of resident macrophages is unclear. Here, we show that macrophages elicited into the peritoneal cavity during mild inflammation persist long-term but are retained in an immature transitory state of differentiation due to the presence of enduring resident macrophages. By contrast, severe inflammation results in ablation of resident macrophages and a protracted phase wherein the cavity is incapable of sustaining a resident phenotype, yet ultimately elicited cells acquire a mature resident identity. These macrophages also have transcriptionally and functionally divergent features that result from inflammation-driven alterations to the peritoneal cavity micro-environment and, to a lesser extent, effects of origin and time-of-residency. Hence, rather than being predetermined, the fate of inflammation-elicited peritoneal macrophages seems to be regulated by the environment.

What is the suboccipital nerve? Tracking this confusing historical nomenclature.

Since its initial description in the 2nd century, the suboccipital nerve has maintained a number of varying terminologies. Many of these terms were created in the 18th and 19th centuries to describe the first set of cervical spinal nerves that exited the spinal cord between the cranium and the atlas. Though the many terminologies have been reduced to mainly the suboccipital nerve, there are still two prevalent definitions used for this nerve. Herein, we discuss the history of the first spinal nerve and its branches with special attention to varying terminologies over time. Recent literature has described the suboccipital nerve as the entire nerve or as simply the dorsal ramus of the C1 spinal nerve. This interchangeability may lead to confusion about the specific part of the nerve being discussed. Following a review of the literature, we recommend the term C1 spinal nerve be applied to the entire nerve, whereas, suboccipital nerve be reserved solely for the posterior branch of the C1 spinal nerve.

Rate of replenishment and microenvironment contribute to the sexually dimorphic phenotype and function of peritoneal macrophages.

Macrophages reside in the body cavities where they maintain serosal homeostasis and provide immune surveillance. Peritoneal macrophages are implicated in the etiology of pathologies including peritonitis, endometriosis, and metastatic cancer; thus, understanding the factors that govern their behavior is vital. Using a combination of fate mapping techniques, we have investigated the impact of sex and age on murine peritoneal macrophage differentiation, turnover, and function. We demonstrate that the sexually dimorphic replenishment of peritoneal macrophages from the bone marrow, which is high in males and very low in females, is driven by changes in the local microenvironment that arise upon sexual maturation. Population and single-cell RNA sequencing revealed marked dimorphisms in gene expression between male and female peritoneal macrophages that was, in part, explained by differences in composition of these populations. By estimating the time of residency of different subsets within the cavity and assessing development of dimorphisms with age and in monocytopenic Ccr2 -/- mice, we demonstrate that key sex-dependent features of peritoneal macrophages are a function of the differential rate of replenishment from the bone marrow, whereas others are reliant on local microenvironment signals. We demonstrate that the dimorphic turnover of peritoneal macrophages contributes to differences in the ability to protect against pneumococcal peritonitis between the sexes. These data highlight the importance of considering both sex and age in susceptibility to inflammatory and infectious diseases.

Epidemiologic trends in Clostridioides difficile isolate ribotypes in United States from 2011 to 2016.

BACKGROUND: Geographic and temporal trends in the distribution of PCR ribotypes for Clostridioides difficile associated diarrheal isolates obtained in the United States (US) are changing. As part of a US national surveillance program of C. difficile susceptibility to fidaxomicin, we quantified the distribution of PCR ribotypes of stool isolates collected from 2011 to 2016. METHODS: C. difficile isolates or C. difficile toxin + stools from patients with C. difficile infection (CDI) were submitted for testing to Tufts Medical Center from 6 geographically distinct medical centers. Following isolation and confirmation as C. difficile, approximately 35% of the isolates were randomly sampled, stratified by center, for PCR ribotyping by capillary gel electrophoresis. Toxin gene profiling was performed on all isolates. RESULTS: 939 isolates from a total of 2814 (33.4%) isolated over the 6 years were analyzed. Seventy unique ribotypes were observed, including 19 ribotypes observed 10 or more times. Sixteen ribotypes were not previously observed in our data base. Ribotype 027 declined by more than 60% over the 6 years of the survey from 35.3% to 13.1% (p < 0.001). Ribotype 106 was the most common in 2016, followed by 027 and 014-020. There were strong correlations between 027 and binary toxin with the 18 base pair deletion of tcdC and ribotype 078-126 had 100% concordance with the previously described tcdC 39 base pair deletion. CONCLUSIONS: The frequency of ribotypes in the US has changed with a marked decline in 027. Each of the geographical areas had variations which differed from each other, but collectively, these results suggest that the changing epidemiology of C. difficile in the US is consistent with what is being seen in Europe. Continued surveillance and monitoring of changes in ribotype distributions of C. difficile are warranted.

Blood-Modified Carbapenem Inactivation Method: a Phenotypic Method for Detecting Carbapenemase-Producing Enterobacteriaceae Directly from Positive Blood Culture Broths.

A variant of the modified carbapenem inactivation method (mCIM) was developed to detect carbapenemase activity directly from positive blood culture broths. The method, termed "Blood-mCIM," was evaluated using Bactec blood culture bottles (Becton, Dickinson and Company, Franklin Lakes, NJ) inoculated with 27 different carbapenemase-producing Enterobacteriaceae (CPE) isolates and 34 different non-CPE isolates. The assay was positive for all blood culture broths inoculated with CPE isolates and negative for all blood culture broths inoculated with non-CPE isolates, corresponding to a diagnostic sensitivity and specificity of 100%, respectively. This assay is inexpensive using "off the shelf" reagents, does not require centrifugation or mechanical lysis, and can be readily implemented in any clinical microbiology laboratory. The Blood-mCIM should facilitate expedient administration of antimicrobial therapy targeted toward CPE bloodstream infections and assist infection control and public health surveillance.

U.S.-Based National Surveillance for Fidaxomicin Susceptibility of Clostridioides difficile-Associated Diarrheal Isolates from 2013 to 2016.

In 2011, we initiated a sentinel surveillance network to assess changes in Clostridioides (formerly Clostridium) difficile antimicrobial susceptibility to fidaxomicin from 6 geographically dispersed medical centers in the United States. This report summarizes data from 2013 to 2016. C. difficile isolates or toxin-positive stools from patients were referred to a central laboratory. Antimicrobial susceptibility was determined by agar dilution. CLSI, EUCAST, or FDA breakpoints were used, where applicable. Toxin gene profiles were characterized by multiplex PCR on each isolate. A random sample of approximately 40% of isolates, stratified by institution and year, was typed by restriction endonuclease analysis (REA). Among 1,889 isolates from 2013 to 2016, the fidaxomicin MIC90 was 0.5 µg/ml; all isolates were inhibited at ≤1 µg/ml. There were decreases in metronidazole and vancomycin MICs over time. Clindamycin resistance remained unchanged (27.3%). An increase in imipenem resistance was observed. By 2015 to 2016, moxifloxacin resistance decreased in all centers. The proportion of BI isolates decreased from 25.5% in 2011 to 2012 to 12.8% in 2015 to 2016 (P < 0.001). The BI REA group correlated with moxifloxacin resistance (BI 84% resistant versus non-BI 12.5% resistant). Fidaxomicin MICs have not changed among C. difficile isolates of U.S. origin over 5 years post licensure. There has been an overall decrease in MICs for vancomycin, metronidazole, moxifloxacin, and rifampin and an increase in isolates resistant to imipenem. Moxifloxacin resistance remained high among the BI REA group, but the proportion of BI isolates has decreased. Continued geographic variations in REA groups and antimicrobial resistance persist.

EDTA-Modified Carbapenem Inactivation Method: a Phenotypic Method for Detecting Metallo-ß-Lactamase-Producing Enterobacteriaceae.

The increase in the prevalence and impact of infections caused by carbapenemase-producing Enterobacteriaceae is a global health concern. Therefore, rapid and accurate methods to detect these organisms in any clinical microbiology laboratory, including those in resource-limited settings, are essential to prevent and contain their spread. It is also important to differentiate between serine- and metal-dependent carbapenemases elaborated by carbapenemase-producing isolates for epidemiologic, infection control and prevention, and therapeutic purposes. Here, we describe the development and evaluation of the EDTA-modified carbapenem inactivation method (eCIM), an assay for discriminating between serine- and metal-dependent (i.e., metallo-ß-lactamases [MBLs]) carbapenemases when used in conjunction with the modified carbapenem inactivation method (mCIM). The eCIM had an overall sensitivity and specificity of 100% and was adopted by the Clinical and Laboratory Standards Institute as a method to use in combination with the mCIM to identify MBL-producing Enterobacteriaceae.

Dual ß-Lactam Combinations Highly Active against Mycobacterium abscessus Complex In Vitro.

As a consequence of a growing population of immunocompromised individuals, including transplant recipients and cystic fibrosis patients, there has been a dramatic increase in chronic infections caused by Mycobacterium abscessus complex (MABC) strains that are usually recalcitrant to effective antibiotic therapy. The recent rise of macrolide resistance in MABC has further complicated this clinical dilemma, dramatizing the need for novel agents. The repurposing of current antibiotics is one rapid path from discovery to patient care. In this study, we have discovered that dual ß-lactams, and specifically the combination of ceftazidime with either ceftaroline or imipenem, are synergistic and have clinically relevant activities, with MIC50s of 0.25 (ceftaroline with 100 µg/ml ceftazidime) and 0.5 µg/ml (imipenem with 100 µg/ml ceftazidime) against clinical MABC isolates. Similar synergy was observed in time-kill studies against the M. abscessus ATCC 19977 strain using clinically achievable concentrations of either imipenem (4 µg/ml) or ceftaroline (2 µg/ml), as the addition of ceftazidime at concentrations of ≥50 µg/ml showed a persistent bactericidal effect over 5 days. Treatment of THP-1 human macrophages infected with three different M. abscessus clinical isolates supported the in vitro findings, as the combination of 100 µg/ml ceftazidime and 0.125 µg/ml ceftaroline or 100 µg/ml ceftazidime and 0.25 µg/ml imipenem dramatically reduced the CFU counts to near baseline levels of infection. This study's finding that there is synergy between certain ß-lactam combinations against M. abscessus infection provides optimism toward identifying an optimum dual ß-lactam treatment regimen.IMPORTANCE The emergence of chronic MABC infections among immunocompromised populations and their inherent and acquired resistance to effective antibiotic therapy have created clinical challenges in advancing patients for transplant surgery and treating those with disease. There is an urgent need for new treatment regimens, and the repurposing of existing antibiotics provides a rapid strategy to advance a laboratory finding to patient care. Our recent discoveries that dual ß-lactams, specifically the combination of ceftazidime with ceftaroline or ceftazidime with imipenem, have significant in vitro MIC values and kill curve activities and are effective against infected THP-1 human macrophages provide optimism for a dual ß-lactam treatment strategy against MABC infections. The unexpected synergistic activities reported in this study create a new path of discovery to repurpose the large family of ß-lactam drugs.

Insertion of an intrathecal catheter following a recognised accidental dural puncture reduces the need for an epidural blood patch in parturients: an Australian retrospective study.

BACKGROUND: There is no clear consensus about how best to prevent post-dural puncture headache (PDPH) following an accidental dural puncture in parturients. Our primary objective was to investigate whether the insertion of an intrathecal catheter following accidental dural puncture reduces the incidence of PDPH and therapeutic epidural blood patch. METHODS: Anaesthetic records from January 2009 to December 2015 were reviewed retrospectively and parturients who had an accidental dural puncture and/or PDPH were identified. Data from those with a recognised dural puncture in whom an intrathecal catheter was inserted at the time of accidental dural puncture (ITC group) were compared to those without an intrathecal catheter (non-ITC group), as were outcomes of patients with an intrathecal catheter for ≥24 hours compared to <24 hours. RESULTS: Of 94 recognised accidental dural punctures, 66 were in the ITC group (37 for ≥24 h) and 28 in the non-ITC group. In the ITC group, 22 (33.3%) required an epidural blood patch in comparison to 19 (67.9%) in the non-ITC group (P <0.01, 95% CI 12.5 to 52.0). In the ITC group, 62 (93.9%) developed PDPH in comparison to 28 (100%) in the non-ITC group (P=0.186, 95% CI -6.55 to 14.57). Intrathecal catheter insertion for ≥24 h obviated the need for an epidural blood patch in 28 (75.7%) parturients, compared to 13 (59.1%) if <24 h (P=0.184, 95% CI -7.08 to 39.72). CONCLUSION: Inserting an intrathecal catheter after a recognised accidental dural puncture significantly reduced the need for an epidural blood patch.

Efficacy of Minocycline in Naturally Occurring Nonacute Ehrlichia canis Infection in Dogs.

BACKGROUND: Minocycline has been used in the treatment of Ehrlichia canis infection in dogs as an alternative to doxycycline, the recommended treatment. However, efficacy of this alternative therapy is unknown. OBJECTIVE: To assess the efficacy of minocycline in the treatment of natural occurring E. canis infection in dogs. ANIMALS: Ten privately owned dogs of mixed breed positive for E. canis by blood PCR. METHODS: Prospective, randomized clinical study. Dogs positive for E. canis by PCR were housed in a kennel environment and randomly allocated to receive doxycycline 10 mg/kg bodyweight PO once daily ("gold standard" control group) or minocycline (extralabel) 10 mg/kg bodyweight PO twice daily (treatment test group) for 28 days. Blood, analyzed by PCR to determine the presence or absence of E. canisDNA, was collected weekly during treatment starting on the first day of treatment and including through day 35, 7 days after the last treatment. RESULTS: In both groups, one dog tested negative after 7 days of treatment. For the doxycycline group, the latest time to a negative PCR test was after 3 weeks of treatment. For the minocycline group, the latest time was on day 28 of treatment. All dogs tested negative 7 days after the end of treatment. CONCLUSION AND CLINICAL IMPORTANCE: Minocycline can be an effective alternative to doxycycline for clearing E. canis from the blood in nonacute infections.

Cytokine and antioxidant gene profiles from peripheral blood mononuclear cells of Pelibuey lambs after Haemonchus contortus infection.

The expression profiles of cytokines and antioxidant genes were determined from an experimental infection with H. contortus in Pelibuey lambs. The infection was followed for 34 days (d) to determine the number of eggs per gram (epg) and the packed cell volume (PCV). Differential white cell counts and expression profile estimations of IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, FCεR1A, GPX and SOD1 were determined at 0 hour, 4 hours, 2 days and 14 days post-infection (PI) in infected and control groups. Comparison of the fold change between 0 and 4-hours, 4-hours and 2-days and 2- and 14-days periods was performed. Significant differences (P<.05) between epg (>2000) and PCV (>30%) were determined after 21 days and were also observed with regard to monocyte and lymphocyte cells after 2 and 7 days PI. At 0 hour and 14 days PI, the GPX and IL-2 genes showed a 0.37- and 0.49-fold decrease in expression, respectively. In contrast, upregulation was observed at 4 hours of IL-8 (2.58) and FCεR1A (2.71), at 2 days for IL-4 (2.14) and IL-8 (4.02) and at 14 days for IL-2 (0.41), IL-10 (2.35) and FCεR1A (2.28). The comparison between the intervals of infection showed high expression values against H. contortus infection in Pelibuey sheep after the 2nd period of PI involving a dichotomy T cells.

Tissue-specific differentiation of colonic macrophages requires TGFß receptor-mediated signaling.

Intestinal macrophages (mφ) form one of the largest populations of mφ in the body and are vital for the maintenance of gut homeostasis. They have several unique properties and are derived from local differentiation of classical Ly6Chi monocytes, but the factors driving this tissue-specific process are not understood. Here we have used global transcriptomic analysis to identify a unique homeostatic signature of mature colonic mφ that is acquired as they differentiate in the mucosa. By comparing the analogous monocyte differentiation process found in the dermis, we identify TGFß as an indispensable part of monocyte differentiation in the intestine and show that it enables mφ to adapt precisely to the requirements of their environment. Importantly, TGFßR signaling on mφ has a crucial role in regulating the accumulation of monocytes in the mucosa, via mechanisms that are distinct from those used by IL10.

Genetically Defined Oligodendroglioma Is Characterized by Indistinct Tumor Borders at MRI.

BACKGROUND AND PURPOSE: In 2016, the World Health Organization revised the brain tumor classification, making IDH mutation and 1p/19q codeletion the defining features of oligodendroglioma. To determine whether imaging characteristics previously associated with oligodendroglial tumors are still applicable, we evaluated the MR imaging features of genetically defined oligodendrogliomas. MATERIALS AND METHODS: One hundred forty-eight adult patients with untreated World Health Organization grade II and III infiltrating gliomas with histologic oligodendroglial morphology, known 1p/19q status, and at least 1 preoperative MR imaging were retrospectively identified. The association of 1p/19q codeletion with tumor imaging characteristics and ADC values was evaluated. RESULTS: Ninety of 148 (61%) patients had 1p/19q codeleted tumors, corresponding to genetically defined oligodendroglioma, and 58/148 (39%) did not show 1p/19q codeletion, corresponding to astrocytic tumors. Eighty-three of 90 (92%) genetically defined oligodendrogliomas had noncircumscribed borders, compared with 26/58 (45%) non-1p/19q codeleted tumors with at least partial histologic oligodendroglial morphology (P < .0001). Eighty-nine of 90 (99%) oligodendrogliomas were heterogeneous on T1- and/or T2-weighted imaging. In patients with available ADC values, a lower mean ADC value predicted 1p/19q codeletion (P = .0005). CONCLUSIONS: Imaging characteristics of World Health Organization 2016 genetically defined oligodendrogliomas differ from the previously considered characteristics of morphologically defined oligodendrogliomas. We found that genetically defined oligodendrogliomas were commonly poorly circumscribed and were almost always heterogeneous in signal intensity.