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  • Ottosen posted an update 1 year, 1 month ago

    The complement system has been recently proposed to play an important role in the pathogenesis of ANCA-associated vasculitis (AAV). This study evaluated the value of serum and kidney deposited C3 in predicting renal outcomes in AAV.

    This was a retrospective study of 47 patients with AAV, who were categorized according to their serum C3 levels as hypo- or normo-complementemic and to those with positive or negative kidney biopsy immunofluorescence (IF) for C3. Baseline characteristics as well as progression to end-stage renal disease (ESRD) between the 2 groups were compared.

    In total, 23% (11/47) were hypo-complementemic; these patients were older (74 vs. 65 years,

     = 0.013), had higher creatinine levels (4.9 vs. 2.2 mg/dL,

     = 0.006), were more often hemodialysis dependent (64% vs. 19%,

     = 0.009) and progressed more often to ESRD (55% vs. 11%,

     = 0.01) compared to normo-complementemic patients (

     = 36). On multivariate analysis, serum creatinine at diagnosis (HR = 16.8, 95%CI 1.354-208.62,

     = 0.028) and low serum C3 (HR = 2.492; 95% CI 1.537-11.567;

     = 0.044) were independent predictors for ESRD. Among 25 patients with an available kidney biopsy, 56% had C3 deposition by IF and displayed more often a mixed histological pattern (72% vs. 27%,

     = 0.033), low serum C3 levels (42% vs. 18%,

     < 0.001) and serious infections during follow-up (57% vs. 18%,

     = 0.047) compared to those with negative (

     = 11) IF staining.

    Almost one of four patients with AAV has low C3 levels at diagnosis which is associated with more severe renal disease and worse renal outcomes (ESRD). This should be taken into account in therapeutic and monitoring strategies.

    Almost one of four patients with AAV has low C3 levels at diagnosis which is associated with more severe renal disease and worse renal outcomes (ESRD). This should be taken into account in therapeutic and monitoring strategies.The objective of this study was to extract low frequency respiratory “artifacts” from a standard arterial blood pressure (ABP) waveform to simultaneously derive reliable breathing rates (BR). Arterial blood pressure derived BR values were characterized against respiratory rates simultaneously obtained from the Respiratory Inductive Plethysmography (RIP) system (EMKA). Reference compounds were introduced to evaluate responsiveness of the derived measures to respiratory depressants and stimulants. Male beagle dogs (n = 3) were instrumented with minimally invasive telemetry devices for measurements of ABP and heart rate. The RIP system was utilized simultaneously to collect respiratory rate, tidal volume, and minute volume of each animal following pharmacological challenges. Early results revealed the derived BR’s from ABP waveforms did not correlate well with those measured from the RIP system. Post study X-ray visualization revealed suboptimal catheter positioning, causing poor concordance of BR tallied from the ABP waveforms. Follow-up evaluations were conducted using additional animals instrumented with the ABP catheter tip placement advanced proximal to the thoracic diaphragm. Preliminary data from this subset of animals significantly improved the correlation of BR derived from ABP and respiratory rates recorded by the RIP. This proof of concept investigation was intended to evaluate an algorithm designed to extract additional data from routine cardiac waveforms. We clearly demonstrated that with optimal blood pressure catheter placement and acquisition algorithm, a reliable breathing rate can also be extracted from safety studies without the need for additional studies/animals to capture those respiratory end points.About a fifth of individuals with colorectal cancer (CRC) present with disease metastasis at the time of diagnosis. While the role of the tumor microenvironment (TME) in governing CRC progression is undeniable, the role of the TME in either establishing or suppressing the formation of distant metastases of CRC is less well established. Despite advances in immunotherapy, many individuals with metastatic CRC do not respond to standard-of-care therapy. Therefore, understanding the role of the TME in establishing distant metastases is essential for developing new immunological agents. Here, we summarize our current understanding of the TME of CRC metastases, describe differences between the TME of primary tumors and their distant metastases, and discuss advances in the design and combinations of immunotherapeutic agents.

    A case of gonococcal keratoconjunctivitis rapidly diagnosed by a vaginal swab PCR Xpert® CT/NG assay.

    Case report.

    A 26-year-old woman presented to our emergency department with severe perilimbal stromal melting in both eyes and profuse purulent discharge for one day. Upon emergent ocular consultation, gonococcal keratoconjunctivitis was suspected. A vaginal swab was sent for rapid PCR Xpert® CT/NG assay which reported positive

    (NG) and

    (CT) DNA detection within 90 min. Due to the rapid diagnosis, adequate medical intervention with ceftriaxone injection was administered. Gonococcal keratitis with stromal melting was stabilized within 5 days of presentation. The patient was discharged with complete epithelial healing by the 8th day. However, 10 weeks after discharge, inadvertent rubbing of the left eye resulted in corneal perforation with iris prolapse. Lamellar keratoplasty with corneal patch graft was performed with amniotic membrane grafting. Xpert® CT/NG assay was performed again with conjunctival swab for recurring mild eye discharge. Both NG and CT were negative. The patient thus stabilized with no further complications.

    Rapid stromal melting can occur with un-diagnosed or delayed diagnosis of gonorrhea with ocular involvement. Speedy and accurate diagnosis by the highly sensitive and specific Xpert® CT/NG assay can provide early definite diagnosis for prompt treatment in prevention of gonococcal infection induced corneal perforations.

    Rapid stromal melting can occur with un-diagnosed or delayed diagnosis of gonorrhea with ocular involvement. Ulonivirine solubility dmso Speedy and accurate diagnosis by the highly sensitive and specific Xpert® CT/NG assay can provide early definite diagnosis for prompt treatment in prevention of gonococcal infection induced corneal perforations.

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