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BackgroundClostridioides difficile Infection (CDI) is a healthcare-associated diarrheal disease prevalent worldwide. A common diagnostic algorithm relies on a two-step protocol that employs stool enzyme immunoassays (EIAs) to detect the pathogen, and its toxins, respectively. Active CDI is deemed less likely when the Toxin EIA result is negative, even if the pathogen-specific EIA is positive for C. difficile. We recently reported, however, that low-toxin-producing C. difficile strains recovered from Toxin-negative (‘discrepant’) clinical stool specimens can be fully pathogenic, and cause lethality in a rodent CDI model. To document frequency of discrepant CDI specimens, and evaluate C. difficile strain diversity, we performed longitudinal surveillance at a Southern Arizona tertiary-care hospital.MethodsDiarrheic stool specimens from patients with clinical suspicion of CDI were obtained over an eight-year period (2015–2022) from all inpatient and outpatient Units of a > 600-bed Medical Center in Southern Arizona. Clinical laboratory EIA testing identified C. difficile-containing specimens, and classified them as Toxin-positive or Toxin-negative. C. difficile isolates recovered from the stool specimens were DNA fingerprinted using an international phylogenetic lineage assignment system (“ribotyping”). For select isolates, toxin abundance in stationary phase supernatants of pure cultures was quantified via EIA.ResultsOf 8,910 diarrheic specimens that underwent diagnostic testing, 1733 (19.4%) harbored C. difficile. Our major findings were that: (1) C. difficile prevalence and phylogenetic diversity was stable over the 8-year period; (2) toxigenic C. difficile was recovered from 69% of clinically Tox-neg (‘discrepant’) specimens; (3) the six most prevalent USA ribotypes were recovered in significant proportions (>60%) from Tox-neg specimens; and (4) toxin–producing C. difficile recovered from discrepant specimens produced less toxin than strains of the same ribotype isolated from non-discrepant specimens.ConclusionOur study highlights the dominance of Toxin EIA-negative CDI specimens in a clinical setting and the high frequency of known virulent ribotypes in these specimens. Therefore, a careful reevaluation of the clinical relevance of diagnostically-discrepant specimens particularly in the context of missed CDI diagnoses and C. difficile persistence, is warranted.

Introduction: Intraoperative frozen section (FS) is an important tool in the management of neoplastic and non-neoplastic central nervous system (CNS) lesions. Although the final pathological diagnosis is based on the findings in paraffin tissue sessions, interpreting FS of CNS lesion is to assist the neurosurgeon in making the accurate judgment regarding the nature of the lesion and tissue adequacy. This study was to evaluate the agreement between FS and paraffin sections (PS) results; and to highlight the possible causes of error in discrepancy between FS and PS. Materials & Methods: This is a retrospective study of 85 cases of FS. H&E stained sections of both FS and PS of all these cases were reviewed with their histopathological reports. FS and PS results were compared. Possible causes of errors were reviewed and recorded. Results: Out of 85 cases; 76 cases (89.4%) showed no discrepancy, 2 cases (2.4%) minor discrepancy and 7 cases (8.2%) discrepancy. Sensitivity and specificity of FS were 90.1% and 85.7% respectively. Positive predictive value was 97.0% and negative predictive value was 63.1%. The false positive rate was 14.2% and false negative rate was 36.8%. The overall accuracy of FS was 89.4%. Conclusion: Our results showed high accuracy and specificity of FS. Therefore, FS is still useful, an effective tool for neurosurgeon although there are some challenges for histopathologists in reporting FS. The commonest discrepancy was seen between reactive gliosis and low-grade glioma. Over-diagnosis or under-diagnosis of FS can be reduced by closed cooperation among pathologist, neurosurgeon and radiologist. [ABSTRACT FROM AUTHOR]

Background: Clostridioides difficile Infection (CDI) is a healthcare-associated diarrheal disease prevalent worldwide. A common diagnostic algorithm relies on a two-step protocol that employs stool enzyme immunoassays (EIAs) to detect the pathogen, and its toxins, respectively. Active CDI is deemed less likely when the Toxin EIA result is negative, even if the pathogen-specific EIA is positive for C. difficile. We recently reported, however, that low-toxin-producing C. difficile strains recovered from Toxin-negative ('discrepant') clinical stool specimens can be fully pathogenic, and cause lethality in a rodent CDI model. To document frequency of discrepant CDI specimens, and evaluate C. difficile strain diversity, we performed longitudinal surveillance at a Southern Arizona tertiary-care hospital., Methods: Diarrheic stool specimens from patients with clinical suspicion of CDI were obtained over an eight-year period (2015-2022) from all inpatient and outpatient Units of a > 600-bed Medical Center in Southern Arizona. Clinical laboratory EIA testing identified C. difficile -containing specimens, and classified them as Toxin-positive or Toxin-negative. C. difficile isolates recovered from the stool specimens were DNA fingerprinted using an international phylogenetic lineage assignment system ("ribotyping"). For select isolates, toxin abundance in stationary phase supernatants of pure cultures was quantified via EIA., Results: Of 8,910 diarrheic specimens that underwent diagnostic testing, 1733 (19.4%) harbored C. difficile . Our major findings were that: (1) C. difficile prevalence and phylogenetic diversity was stable over the 8-year period; (2) toxigenic C. difficile was recovered from 69% of clinically Tox-neg ('discrepant') specimens; (3) the six most prevalent USA ribotypes were recovered in significant proportions (>60%) from Tox-neg specimens; and (4) toxin-producing C. difficile recovered from discrepant specimens produced less toxin than strains of the same ribotype isolated from non-discrepant specimens., Conclusion: Our study highlights the dominance of Toxin EIA-negative CDI specimens in a clinical setting and the high frequency of known virulent ribotypes in these specimens. Therefore, a careful reevaluation of the clinical relevance of diagnostically-discrepant specimens particularly in the context of missed CDI diagnoses and C. difficile persistence, is warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Anwar, Clark, Lindsey, Claus-Walker, Mansoor, Nguyen, Billy, Lainhart, Shehab, Viswanathan and Vedantam.)

The research base establishing connections between children who identify as African American and increased disciplinary referrals due to defiance and/or insubordination has long been established. In August of 2014, the author was hired to serve as an assistant principal at a Title 1 urban public elementary school in the Midwestern USA. The author cataloged nearly 1000 referrals using an internal data management system while eliminating the consequence(s) of suspension and/or expulsion for the offense of 'defiance.' The study found that, despite this limitation, African American students were grossly overrepresented in both disciplinary referrals and exclusionary discipline. [ABSTRACT FROM AUTHOR]

In recent years, there has been greater awareness among hemostasis scientists and clinicians that factor VIII coagulant activity (FVIII:C) measured in certain patients with mild hemophilia A can show different results depending on the assay system. A subgroup of mild hemophilia families have a method-related discrepancy in FVIII:C results, whereby the one-stage clotting assay (FVIII:C-1) is significantly higher than the two-stage clotting assay (FVIII:C-2) or the chromogenic assay (FVIII:C-chr). To identify such patients, the routine laboratory can use automated procedures for the FVIII:C-chr to replace the complex, manual FVIII:C-2 method. Laboratories must employ appropriate quality management to ensure accurate and precise results, especially in the abnormal range. This discrepant phenotype of hemophilia A is seen in up to 40% of mild hemophilia A cases and represents a clinically significant bleeding disorder. A small proportion of these cases have FVIII:C-1 within the normal range and risk a missed diagnosis if the FVIII:C-chr is unavailable. Other patients may be mismanaged if FVIII:C-1 gives an overestimate of FVIII:C and their bleeding risk is consequently underestimated. Affected family members in the discrepant group of patients have a limited range of FVIII (F8) gene missense mutations, causing alterations of the structure of the A1, A2, or A3 domains of FVIII. Therefore, both FVIII:C-chr and F8 gene mutation analysis are recommended to confirm the diagnosis of mild hemophilia A and assist with decisions about the patient's phenotype. [ABSTRACT FROM AUTHOR]

This study reports the outcome of the first evaluation of the APAS® Independence for automated reading and preliminary interpretation of urine cultures in the routine clinical microbiology laboratory. In a 2-stage evaluation involving 3000 urine samples, two objectives were assessed; 1) the sensitivity and specificity of the APAS® Independence compared to microbiologists using colony enumeration as the primary determinant, and 2) the variability between microbiologists in enumerating bacterial cultures using traditional culture reading techniques, performed independently to APAS® Independence interpretation. Routine urine samples received into the laboratory were processed and culture plates were interpreted by standard methodology and with the APAS® Independence. Results were compared using typical discrepant result resolution and with a composite reference standard, which provided an alternative assessment of performance. The significant growth sensitivity of the APAS® Independence was determined to be 0.919 with a 95% confidence interval of (0.879, 0.948), and the growth specificity was 0.877 with a 95% confidence interval of (0.827, 0.916). Variability between microbiologists was demonstrated with microbiologist bi-plate enumerations in agreement with the consensus 88.6% of the time. The APAS® Independence appears to offer microbiology laboratories a mechanism to standardise the processing and assessment of urine cultures whilst augmenting the skills of specialist microbiology staff. • Laboratory evaluation of APAS Independence for automated reading of urine cultures. • Artificial intelligence increases efficiencies and standardises culture assessment. • Human assessment of urine cultures is variable. • Composite reference standard as an alternative to discrepant result resolution. [ABSTRACT FROM AUTHOR]

Any newly diagnosed patient should be referred to a multidisciplinary team experienced in the treatment of pituitary adenomas. The therapeutic management of acromegaly always requires a personalized strategy. Normal age-matched IGF-I values are the treatment goal. Transsphenoidal surgery by an expert neurosurgeon is the primary treatment modality for most patients, especially if there are neurological complications. In patients with poor clinical conditions or who refuse surgery, primary medical treatment should be offered, firstly with somatostatin analogs (SSAs). In patients who do not reach hormonal targets with first-generation depot SSAs, a second pharmacological option with pasireotide LAR or pegvisomant (alone or combined with SSA) should be offered. Irradiation could be proposed to patients with surgical remnants who would like to be free from long-term medical therapies or those with persistent disease activity or tumor growth despite surgery or medical therapy. Since the therapeutic tools available enable therapeutic targets to be achieved in most cases, the challenge is to focus more on the quality of life., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Acromegaly is a rare disease. Improvements in lifespan in these patients have recently been reported due to transsphenoidal surgery (TSS), advances in medical therapy, and strict criteria for defining disease remission. This document reports the opinions of a group of Italian experts who have gathered together their prolonged clinical experience in the diagnostic and therapeutic challenges of acromegaly patients. Both GH and IGF-I (only IGF-I in those treated with Pegvisomant) are needed in the diagnosis and follow-up. Comorbidities (cardio-cerebrovascular disease, sleep apnea, metabolic derangement, neoplasms, and bone/joint disease) should be specifically addressed. Any newly diagnosed patient should be referred to a multidisciplinary team experienced in the treatment of pituitary adenomas., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)