Composite structure of Streptococcus pneumoniae containing the erythromycin efflux resistance gene mefI and the chloramphenicol resistance gene catQ

In recent years mef genes, encoding efflux pumps responsible for M-type macrolide resistance, have been investigated extensively for streptococci. mef(I) is a recently described mef variant detected in particular isolates of Streptococcus pneumoniae instead of the more common mef(E) and mef(A). This study shows that mef(I) is located in a new composite genetic element, whose sequence was completely analyzed and the left and right junctions determined, demonstrating a unique genetic organization. The new composite structure (30,505 bp), designated the 5216IQ complex, consists of two halves: a left one (15,316 bp) formed by parts of the known transposons Tn5252 and Tn916, and a right one (15,115 bp) formed by a new fragment, designated the IQ element. While the defective Tn916 contained a silent tet(M) gene, the IQ element, ending with identical transposase genes on both sides and containing the mef(I) gene with an adjacent new msr(D) gene variant and a catQ chloramphenicol acetyltransferase gene, was completely different from the genetic elements carrying other mef genes in pneumococci. This is the first report demonstrating catQ in S. pneumoniae and showing its linkage with a mef gene. Analysis of the chromosomal region beyond the left junction revealed an organization more similar to that of S. pneumoniae strain TIGR4 than to that of strain R6. The 5216IQ complex was apparently nonmobile, with no detectable transfer of erythromycin resistance being obtained in repeated transformation and conjugation assays.     

Management of Subdural Hematomas: Part I. Medical Management of Subdural Hematomas

Purpose of review

Subdural hematomas (SDH) represent common neurosurgical problem associated with significant morbidity, mortality, and high recurrence rates. SDH incidence increases with age; numbers of patients affected by SDH continue to rise with our aging population and increasing number of people taking antiplatelet agents or anticoagulation. Medical and surgical SDH management remains a subject of investigation.

Recent findings

Initial management of patients with concern for altered mental status with or without trauma starts with Emergency Neurological Life Support (ENLS) guidelines, with a focus on maintaining ICP <?22 mmHg, CPP >?60 mmHg, MAP 80–110 mmHg, and PaO₂ >?60 mmHg, followed by rapid sequence intubation if necessary, and expedited acquisition of imaging to identify a space-occupying lesion. Patients are administered anti-seizure medications, and their antiplatelet medications or anticoagulation may be reversed if neurosurgical interventions are anticipated, or until hemorrhage is stabilized on imaging.

Summary

Medical SDH care focuses on (a) management of intracranial hypertension; (b) maintenance of adequate cerebral perfusion; (c) seizure prevention and treatment; (d) maintenance of normothermia, eucarbia, euglycemia, and euvolemia; and (e) early initiation of enteral feeding, mobilization, and physical therapy. Post-operatively, SDH patients require ICU level care and are co-managed by neurointensivists with expertise in treating increased intracranial pressure, seizures, and status epilepticus, as well as medical complications of critical illness. Here, we review various aspects of medical management with a brief overview of pertinent literature and clinical trials for patients diagnosed with SDH.

     

Review of the comparative effectiveness of radical prostatectomy,radiation therapy,or expectant management of localized prostate cancer in registry data

Summary

Evidence regarding the effectiveness of treatment for prostate cancer is primarily based on randomized controlled trials. Long-term outcomes are generally difficult to evaluate within experimental studies and may benefit from large pools of observational data. We conducted a systematic review of administrative and registry studies to evaluate the comparative effectiveness of treatment for clinically localized prostate cancer on overall and prostate-cancer specific mortality.

Does response to neo‐adjuvant chemotherapy impact breast reconstruction?

Neo‐adjuvant chemotherapy (NAC) is administered in breast cancer treatment for downstaging of disease. Here, we determined the impact of response to NAC on breast reconstruction uptake. A prospective NAC and mastectomy database with or without reconstruction were reviewed with IRB approval. Univariable analyses were conducted using Kruskal‐Wallis or Fisher's exact tests. Multivariable logistic regression was used to adjust for potential confounders. We identified 271 patients with unilateral breast cancer receiving NAC and either unilateral or bilateral mastectomy from 9/2013 to 5/2016. Seventy patients (25.8%) had a pCR to NAC. One hundred and seventy‐five patients (64.6%) had immediate reconstruction (IR), and 96 had no IR. On univariable analysis, younger age (P < .001), lower T‐stage at presentation (P < .001), bilateral versus unilateral mastectomy (P<.001) and HR‐negative tumor subtype (P = .006) were significantly associated with higher IR rates. On multivariable analysis, pCR (P = .792) and tumor subtype (P = 0.061) were not significantly associated with IR; T‐stage was significantly associated with IR (P < .001), such that patients with T4 tumors at presentation had lower odds of IR (OR 0.10, 95% CI 0.02‐0.50), even when accounting for response to NAC. One hundred and seventy‐three patients (63.8%) received adjuvant radiation therapy; this was associated with lower IR frequency (P = .048) but was not associated with reconstruction type (tissue expander versus autologous, P = 1.0) among 175 patients who had IR. In patients who have mastectomy after NAC, IR is influenced by age, T‐stage at presentation, and choice of bilateral mastectomy, but not by response to NAC. A subset of patients who are young, with earlier T‐stage and pCR, is more likely to proceed with bilateral mastectomy.     

Intestinal Protein Characterisation of SARS-CoV-2 Entry Molecules ACE2 and TMPRSS2 in Inflammatory Bowel Disease (IBD) and Fatal COVID-19 Infection

Inflammation - The coronavirus SARS-CoV-2 contributes to morbidity and mortality mainly as a result of immune-pathology in the lungs. Recent data has shown multi-system involvement with widespread...     

Clinical and Phenotypic Characterization of Common Variable Immunodeficiency Diagnosed in Younger and Older Adults

Journal of Clinical Immunology - Common variable immunodeficiency (CVID) is the most prevalent symptomatic immunodeficiency in adults. Little is known about the manifestations of CVID presenting in...     

Effects of antifungal interventions on the outcome of experimental infections with phenotypic switch variants of Cryptococcus neoformans

In cryptococcal infection, phenotypic switching from a smooth to a mucoid variant can occur in vivo, producing variants with enhanced virulence that are subsequently selected and affect the outcome of infection. Here, we demonstrate that antifungal treatment of the chronically infected host can promote this phenomenon. Amphotericin B treatment reduces fungal burden less effectively in mucoid variant-infected than in smooth variant-infected mice. Consequently, amphotericin B treatment resulted in a more pronounced prolongation of survival in smooth variant-infected than in mucoid variant-infected mice (20 versus 42 days; P < 0.05). Administration of anticapsular monoclonal antibody mediated better protection in smooth variant-infected than in mucoid variant-infected mice, although a protective effect was not consistently observed at all doses. Most interestingly, both antifungal drug therapy and administration of anticapsular monoclonal antibody promoted the selection of mucoid variants in smooth variant-infected mice, a phenomenon manifested by a statistically higher percentage of mucoid colonies in smooth variant-infected mice than in nontreated control mice. This finding suggests that both chemotherapeutic and immunological antifungal interventions may promote the selection of the more virulent mucoid variant, which could affect the outcome of infection in chronically infected hosts.