HIV transcription is induced in dying cells

Using HeLa cells stably transfected with an HIV-LTR-CAT construct, we demonstrated a peak in CAT induction that occurs in viable (but not necessarily cell-division-competent) cells 24 h following exposure to some cell-killing agents. {gamma} rays were the only cell-killing agent which did not induce HIV transcription; this can be attributed to the fact that {gamma}-ray-induced apoptotic death requires functional p53, which is not present in HeLa cells. For all other agents, HIV-LTR induction was dose-dependent and correlated with the amount of cell killing that occurred in the culture. Doses which caused over 99% cell killing induced HIV-LTR transcription maximally, demonstrating that cells that will go on to die by 14 days are the cells expressing HIV-LTR-CAT

A retrospective analysis of normal saline and lactated ringers as resuscitation fluid in sepsis

BackgroundThe Surviving Sepsis Campaign suggested preferential resuscitation with balanced crystalloids, such as Lactated Ringer’s (LR), although the level of recommendation was weak, and the quality of evidence was low. Past studies reported an association of unbalanced solutions, such as normal saline (NS), with increased AKI risks, metabolic acidosis, and prolonged ICU stay, although some of the findings are conflicting. We have compared the outcomes with the preferential use of normal saline vs. ringer’s lactate in a cohort of sepsis patients.MethodWe performed a retrospective cohort analysis of patients visiting the ED of 19 different Mayo Clinic sites between August 2018 to November 2020 with sepsis and receiving at least 30 mL/kg fluid in the first 6 h. Patients were divided into two cohorts based on the type of resuscitation fluid (LR vs. NS) and propensity-matching was done based on clinical characteristics as well as fluid amount (with 5 ml/kg). Single variable logistic regression (categorical outcomes) and Cox proportional hazards regression models were used to compare the primary and secondary outcomes between the 2 groups.ResultsOut of 2022 patients meeting our inclusion criteria; 1,428 (70.6%) received NS, and 594 (29.4%) received LR as the predominant fluid (>30 mL/kg). Patients receiving predominantly NS were more likely to be male and older in age. The LR cohort had a higher BMI, lactate level and incidence of septic shock. Propensity-matched analysis did not show a difference in 30-day and in-hospital mortality rate, mechanical ventilation, oxygen therapy, or CRRT requirement. We did observe longer hospital LOS in the LR group (median 5 vs. 4 days, p = 0.047 and higher requirement for ICU post-admission (OR: 0.70; 95% CI: 0.51–0.96; p = 0.026) in the NS group. However, these did not remain statistically significant after adjustment for multiple testing.ConclusionIn our matched cohort, we did not show any statistically significant difference in mortality rates, hospital LOS, ICU admission after diagnosis, mechanical ventilation, oxygen therapy and RRT between sepsis patients receiving lactated ringers and normal saline as predominant resuscitation fluid. Further large-scale prospective studies are needed to solidify the current guidelines on the use of balanced crystalloids

Miliary tuberculosis presenting as a choroidal mass and a tuberculosis screening review

Anti-tumor necrosis factor alpha (anti-TNF) therapy is a standard of care in the management of many inflammatory conditions. However, anti-TNF pharmaceuticals increases the risk of reactivating tuberculosis making screening for latent tuberculosis infection (LTBI) a requirement prior to initiating therapy. Case: A middle-aged male from China with a past medical history of LTBI and Crohn's disease, previously on infliximab, presented to the United States for a second opinion on his abdominal pain. He also reported new onset visual changes. Ophthalmology evaluation revealed a 4 cm choroid mass of his left eye and a CT scan of the abdomen showed diffuse lymphadenopathy and lesions in his liver, spleen, and lung. He was admitted for treatment of miliary tuberculosis. Discussion: Immunocompromised patients are a unique population that brings challenges to LTBI testing. Conclusion: Clinicians should know the most up to date screening tools for LTBI and diagnostic workup for active tuberculosis infection. Keywords: Miliary tuberculosis, Choroidal mass, IGR

Serologic screening and infectious diseases consultation in renal transplant candidates for measles, mumps, rubella and varicella

Background. Renal transplant recipients are at increased risk for developing complications of vaccine-preventable diseases. They benefit from a comprehensive pre-transplant evaluation when they might safely receive live vaccines. The primary aim of our study was to investigate the number of renal transplant recipients who were evaluated for serologic status against measles, mumps, rubella (MMR), and varicella. Secondarily, we investigated if pre-transplant Infectious Diseases consultation (IDC) improved vaccination rates

Nontuberculous mycobacterial infections of the lower extremities: A 15-year experience

Objectives: Nontuberculous mycobacterial infection (NTMI), which is increasing in prevalence, is challenging to diagnose and manage despite the availability of capable laboratories because of subtle and nonspecific clinical findings and nonstandardized treatment guidelines. We aimed to present our experience with lower-extremity NTMI and to compare clinical characteristics and treatment outcomes between immunocompetent and immunocompromised patients. Methods: To determine clinical presentations and outcomes, we reviewed electronic health records of all patients with lower-extremity NTMI treated and followed up at our institution from January 2002 through December 2017. Results: Twenty-four patients were included in this study. Mean (SD) age was 58 (19) years. Eighteen patients (75%) were men; 13 (54%) were immunocompetent; and 9 (37%) had bone and joint involvement. No significant differences existed between immunocompetent and immunocompromised patients, except immunocompetent patients had significantly more infections at the hip, thigh, and toe. Bone and joint infection required significantly longer treatment time than skin and soft-tissue infection. Conclusions: Regardless of immune status, patients with lower-extremity NTMI had similar characteristics, treatments, and outcomes. However, immunosuppression can be a major risk factor in the development of disseminated NTMI and associated complications. Acid-fast bacilli culture is strongly recommended for evaluation of delayed or nonhealing lesions. Aggressive medical and surgical management can be associated with good clinical outcomes. Keywords: Bone and joint, Immunosuppression, Lower extremity, Nontuberculous mycobacterial infection, Skin and soft tissu

Value of Broad Range 16S Ribosomal RNA Gene PCR / Sequencing (Br-PCR) of CSF in the Diagnosis of Bacterial Meningitis

Bacterial meningitis is a life-threatening condition that requires quick and definitive diagnosis. Bacterial cultures from cerebrospinal fluid (CSF) return with a negative result as treatment with antimicrobials are sometimes started before sampling of CSF can be obtained which makes isolating the causative bacteria challenging. The value of Broad Range 16S Ribosomal RNA Gene Polymerase Chain Reaction / Sequencing of CSF (Br-PCR) can address this problem by amplifying and identifying any bacterial DNA present in a clinical sample.A 65-year-old female presented with rapid onset of high fevers, headache, chills and right hip pain. She had blood cultures drawn, unremarkable CSF analysis in the emergency department, and was discharged home. Ten hours later, she developed vomiting and altered mental status, returned to hospital and started on antimicrobials for gram negative bacteremia and emergently intubated with repeat lumbar puncture showed evidence of bacterial meningitis with pleocytosis and elevated opening pressures. Empiric antimicrobial therapy was started. All subsequent CSF microbiological stains, cultures, and molecular analyses were negative. The blood cultures grew Haemophilus influenzae and H. influenzae meningitis was presumed to be the cause. Therefore, Br-PCR on CSF was sent which detected Haemophilus species DNA. She received a 3-week course of ceftriaxone. After rehabilitation, she returned home without any significant neurological deficits. No relapse of meningitis at 4 months was noted.The application for Br-PCR in the setting of suspected bacterial meningitis with negative stains and cultures could improve a diagnostic algorithm for bacterial meningitis

MRSA Spinal Epidural Abscess as a Neurosurgical and Infectious Disease Emergency with Unresolved Antimicrobial Solution

Spinal epidural abscess caused by MRSA, a life-threatening organism resistant to methicillin and other antibiotics, is a rare but important infectious pathology due to its potential damage to the spinal cord. We present the case of a 74-year-old man who hematogenously seeded his entire epidural spinal canal from C1 to sacrum with MRSA bacteria and remained infected even after maximal treatment with vancomycin and daptomycin. Ceftaroline, a new 5th generation antibiotic with recently described clearance of widespread MRSA infection in epidural complex spine infections, was added to vancomycin as dual therapy for his MRSA infection. A 74-year-old diabetic man with prior right total knee arthroplasty and MRSA infection presented with persistent bacteremia and sepsis. He was transferred to our academic center after diagnosis of entire spine epidural abscesses from C1 to sacral levels with midthoracic MRI T2 hyperintensities of the vertebral bodies and disc concerning for osteomyelitis and discitis. Despite surgery and IV vancomycin with MIC of 1, suggesting extreme susceptibility, the patient’s blood cultures remained persistently bacteremic at day 5 of treatment. After 48 hours of dual antibiotic therapy with vancomycin and ceftaroline, his blood cultures came back showing no growth. The patient’s outcome was unfavorable due to the advanced nature of his infection and multiple comorbidities, but his negative blood cultures after the addition of ceftaroline to his regime require further investigation into this dual therapy. Randomized controlled trials of 5th generation or combinatorial antibiotics should be considered for this disease

HIV transcription is induced with some forms of cell killing

Using HeLa cells stably transfected with an HIV-LTR-CAT construct`, we demonstrated a peak in CAT induction that occurs in viable (but not necessarily cell-division-competent) cells 24 h following exposure to some cell-killing agents. {Gamma} rays were the only cell-killing agent which did not induce HIV transcription; this can be attributed to the fact that {gamma}-ray-induced apoptotic death requires function p53, which is missing in HeLa cells. For all other agents, HIV-LTR induction was dose-dependent and correlated with the amount of cell killing that occurred in the culture