Prevalence and correlates of cryptococcal antigen positivity among AIDS patients--United States, 1986-2012.

Cryptococcal meningitis (CM) is one of the leading opportunistic infections associated with human immunodeficiency virus (HIV) infection. The worldwide burden of CM among persons living with HIV/acquired immunodeficiency syndrome (AIDS) was estimated in 2009 to be 957,900 cases, with approximately 624,700 deaths annually. The high burden of CM globally comes despite the fact that cryptococcal antigen (CrAg) is detectable weeks before the onset of symptoms, allowing screening for cryptococcal infection and early treatment to prevent CM and CM-related mortality (2). However, few studies have been conducted in the United States to assess the prevalence of cryptococcal infection. To quantify the prevalence of undiagnosed cryptococcal infection in HIV-infected persons in the United States during 1986-2012, stored sera from 1,872 participants in the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study with CD4 T-cell counts <100 cells/µL were screened for CrAg, using the CrAg Lateral Flow Assay (LFA) (Immy, Inc.). This report describes the results of that analysis, which indicated the overall prevalence of CrAg positivity in this population to be 2.9% (95% confidence interval [CI] = 2.2%-3.7%)

Intravenous Cetirizine Versus Intravenous Diphenhydramine for the Treatment of Acute Urticaria: A Phase III Randomized Controlled Noninferiority Trial

STUDY OBJECTIVE: Acute urticaria is a frequent presentation in emergency departments (EDs), urgent care centers, and other clinical arenas. Treatment options are limited if diphenhydramine is the only intravenous antihistamine offered because of its short duration of action and well-known adverse effects. We evaluate cetirizine injection, the first second-generation injectable antihistamine, for acute urticaria in this multicenter, randomized, noninferiority, phase 3 clinical trial. METHODS: Adult patients presenting to EDs and urgent care centers with acute urticaria requiring an intravenous antihistamine were randomized to either intravenous cetirizine 10 mg or intravenous diphenhydramine 50 mg. The primary endpoint was the 2-hour pruritus score change from baseline, with time spent in treatment center and rate of return to treatment centers as key secondary endpoints. Frequency of sedation and anticholinergic adverse effects were also recorded. RESULTS: Among 262 enrolled patients, the 2-hour pruritus score change from baseline for intravenous cetirizine was statistically noninferior to that for intravenous diphenhydramine (-1.6 versus -1.5; 95% confidence interval -0.1 to 0.3), and in favor of cetirizine. Treatment differences also favored cetirizine for mean time spent in treatment center (1.7 versus 2.1 hours; P=.005), return to treatment center (5.5% versus 14.1%; P=.02), lower change from baseline sedation score at 2 hours (0.1 versus 0.5; P=.03), and adverse event rate (3.9% versus 13.3%). CONCLUSION: Intravenous cetirizine is an effective alternative to intravenous diphenhydramine for treating acute urticaria, with benefits of less sedation, fewer adverse events, shorter time spent in treatment center, and lower rates of revisit to treatment center

Lack of macrolide resistance in Mycoplasma genitalium infections in a cohort of pregnant women in South Africa

No abstract available.http://sti.bmj.comhj2022Medical Microbiolog

The Role and Limitations of 18-Fluoro-2-deoxy-d-glucose Positron Emission Tomography (FDG-PET) Scan and Computerized Tomography (CT) in Restaging Patients with Hepatic Colorectal Metastases Following Neoadjuvant Chemotherapy: Comparison with Operative and Pathological Findings

BACKGROUND: Recent data confirmed the importance of 18-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in the selection of patients with colorectal hepatic metastases for surgery. Neoadjuvant chemotherapy before hepatic resection in selected cases may improve outcome. The influence of chemotherapy on the sensitivity of FDG-PET and CT in detecting liver metastases is not known. METHODS: Patients were assigned to either neoadjuvant treatment or immediate hepatic resection according to resectability, risk of recurrence, extrahepatic disease, and patient preference. Two-thirds of them underwent FDG-PET/CT before chemotherapy; all underwent preoperative contrast-enhanced CT and FDG-PET/CT. Those without extensive extrahepatic disease underwent open exploration and resection of all the metastases according to original imaging findings. Operative and pathological findings were compared to imaging results. RESULTS: Twenty-seven patients (33 lesions) underwent immediate hepatic resection (group 1), and 48 patients (122 lesions) received preoperative neoadjuvant chemotherapy (group 2). Sensitivity of FDG-PET and CT in detecting colorectal (CR) metastases was significantly higher in group 1 than in group 2 (FDG-PET: 93.3 vs 49%, P < 0.0001; CT: 87.5 vs 65.3, P = 0.038). CT had a higher sensitivity than FDG-PET in detecting CR metastases following neoadjuvant therapy (65.3 vs 49%, P < 0.0001). Sensitivity of FDG-PET, but not of CT, was lower in group 2 patients whose chemotherapy included bevacizumab compared to patients who did not receive bevacizumab (39 vs 59%, P = 0.068). CONCLUSIONS: FDG-PET/CT sensitivity is lowered by neoadjuvant chemotherapy. CT is more sensitive than FDG-PET in detecting CR metastases following neoadjuvant therapy. Surgical decision-making requires information from multiple imaging modalities and pretreatment findings. Baseline FDG-PET and CT before neoadjuvant therapy are mandatory

Corneal Transduction by Intra-Stromal Injection of AAV Vectors In Vivo in the Mouse and Ex Vivo in Human Explants

The cornea is a transparent, avascular tissue that acts as the major refractive surface of the eye. Corneal transparency, assured by the inner stroma, is vital for this role. Disruption in stromal transparency can occur in some inherited or acquired diseases. As a consequence, light entering the eye is blocked or distorted, leading to decreased visual acuity. Possible treatment for restoring transparency could be via viral-based gene therapy. The stroma is particularly amenable to this strategy due to its immunoprivileged nature and low turnover rate. We assayed the potential of AAV vectors to transduce keratocytes following intra-stromal injection in vivo in the mouse cornea and ex vivo in human explants. In murine and human corneas, we transduced the entire stroma using a single injection, preferentially targeted keratocytes and achieved long-term gene transfer (up to 17 months in vivo in mice). Of the serotypes tested, AAV2/8 was the most promising for gene transfer in both mouse and man. Furthermore, transgene expression could be transiently increased following aggression to the cornea

Molecular Diagnosis of Primary Mediastinal B Cell Lymphoma Identifies a Clinically Favorable Subgroup of Diffuse Large B Cell Lymphoma Related to Hodgkin Lymphoma

Using current diagnostic criteria, primary mediastinal B cell lymphoma (PMBL) cannot be distinguished from other types of diffuse large B cell lymphoma (DLBCL) reliably. We used gene expression profiling to develop a more precise molecular diagnosis of PMBL. PMBL patients were considerably younger than other DLBCL patients, and their lymphomas frequently involved other thoracic structures but not extrathoracic sites typical of other DLBCLs. PMBL patients had a relatively favorable clinical outcome, with a 5-yr survival rate of 64% compared with 46% for other DLBCL patients. Gene expression profiling strongly supported a relationship between PMBL and Hodgkin lymphoma: over one third of the genes that were more highly expressed in PMBL than in other DLBCLs were also characteristically expressed in Hodgkin lymphoma cells. PDL2, which encodes a regulator of T cell activation, was the gene that best discriminated PMBL from other DLBCLs and was also highly expressed in Hodgkin lymphoma cells. The genomic loci for PDL2 and several neighboring genes were amplified in over half of the PMBLs and in Hodgkin lymphoma cell lines. The molecular diagnosis of PMBL should significantly aid in the development of therapies tailored to this clinically and pathogenetically distinctive subgroup of DLBCL

Unique cellular interactions between pancreatic cancer cells and the omentum.

Pancreatic cancer is a common cause of cancer-related mortality. Omental spread is frequent and usually represents an ominous event, leading to patient death. Omental metastasis has been studied in ovarian cancer, but data on its role in pancreatic cancer are relatively scarce and the molecular biology of this process has yet to be explored. We prepared tissue explants from human omental fat, and used conditioned medium from the explants for various in vitro and in vivo experiments designed to evaluate pancreatic cancer development, growth, and survival. Mass spectrometry identified the fat secretome, and mRNA array identified specific fat-induced molecular alternations in tumor cells. Omental fat increased pancreatic cancer cellular growth, migration, invasion, and chemoresistance. We identified diverse potential molecules secreted by the omentum, which are associated with various pro-tumorigenic biological processes. Our mRNA array identified specific omental-induced molecular alternations that are associated with cancer progression and metastasis. Omental fat increased the expression of transcription factors, mRNA of extracellular matrix proteins, and adhesion molecules. In support with our in vitro data, in vivo experiments demonstrated an increased pancreatic cancer tumor growth rate of PANC-1 cells co-cultured for 24 hours with human omental fat conditioned medium. Our results provide novel data on the role of omental tissue in omental metastases of pancreatic cancer. They imply that omental fat secreted factors induce cellular reprogramming of pancreatic cancer cells, resulting in increased tumor aggressiveness. Understanding the mechanisms of omental metastases may enable us to discover new potential targets for therapy

Novel lateral flow assay for point-of-care detection of Neisseria gonorrhoeae infection in syndromic management settings: a cross-sectional performance evaluation.

BACKGROUND A rapid and affordable point-of-care test is a priority for Neisseria gonorrhoeae control. WHO and Foundation for Innovative New Diagnostics (FIND) have a target product profile for a non-molecular N gonorrhoeae rapid point-of-care test that requires a clinical sensitivity of greater than 80% and a specificity over 95% to be considered useful in syndromic management; test turnaround time should be 30 min or under, and the test should cost less than US$3. A novel lateral flow assay (LFA) was developed to achieve that profile. METHODS In this cross-sectional study we evaluated the performance of the novel N gonorrhoeae lateral flow assay (NG-LFA) at the primary health-care level in South Africa. Male patients with urethral discharge syndrome and female patients with vaginal discharge syndrome were recruited from five primary health-care facilities in the Buffalo City Metropolitan Municipality health district of South Africa. First-void urine specimens and nurse-collected vaginal swabs were tested in-facility with the NG-LFA and Xpert CT/NG PCR assay. N gonorrhoeae multi-antigen sequence typing (NG-MAST) was performed on all LFA positive specimens. FINDINGS Between March 7, and Sept 19, 2022, we enrolled 200 male patients with urethral discharge and 200 female patients with vaginal discharge. The median age of male patients was 24 years (IQR 21-31 years), and the median age of female patients was 25 years (IQR 21-32 years). In addition, 23 male patients and 12 female patients who presented at the facility with a partner notification slip were enrolled of whom one (4%) and five (42%) were symptomatic, respectively. NG-LFA and Xpert results were available for all participants. In urine specimens, NG-LFA sensitivity was 96·1% (Wilson 95% CI 91·2-98·3; 123 LFA-positive among 128 PCR-positive specimens) and 91·7% in vaginal swab specimens (78·2-97·1; 33 LFA-positive among 36 PCR-positive). The specificity was 97·2% in urine specimens (90·4-99·2; 70 LFA-negative among 72 PCR-negative) and 96·3% in vaginal specimens (92·2-98·3; 158 LFA-negative among 164 PCR-negative). In 156 LFA-positive specimens, NG-MAST showed 93 different sequence types. INTERPRETATION The novel NG-LFA had excellent clinical sensitivity and specificity in symptomatic male and female patients. The test met the optimal requirement for sensitivity and the minimal requirement for specificity specified in the target product profile. NG-LFA could provide an important tool to optimise clinical management and reduce excess antibiotic use in settings without direct access to laboratory testing. FUNDING Global Antimicrobial Resistance Innovation Fund (GAMRIF) via FIND and National Institutes of Health