Performance Comparison of GeneXpert MTB/RIF and ProbeTec ET Tests for Rapid Molecular Diagnosis of Extrapulmonary Tuberculosis in a Low TB/MDR-TB Incidence Country

ObjectiveThis study evaluated the performance of GeneXpert MTB/RIF (Xpert) and ProbeTec ET (PTec-ET) assays in diagnosing extrapulmonary tuberculosis (EPTB) in Kuwait.Materials and MethodsWe tested nonrespiratory clinical specimens (n = 3,995) collected from 3,995 patients suspected to have EPTB. These included cavitary fluids (n = 2,054), fine-needle aspirate (FNA)/pus/tissue biopsy (n = 1,461), urine (n = 302), cerebrospinal fluid (CSF, n = 118), and others (n = 60). All specimens were processed for acid-fast bacilli (AFB), culture in mycobacteria growth indicator tube 960 system, and nucleic acid detection by Xpert and PTec-ET according to manufacturer''s instructions.ResultsOf 3,995 specimens, 95 were AFB-positive, 403 were culture-positive, and an additional 86 samples had histopathology suggestive of TB. Using culture as reference, the sensitivity and specificity values were 88.33 and 97.3% for Xpert and 72.95 and 97.80% for PTec-ET, respectively. Although performance of both tests was comparable in AFB-positive samples, Xpert detected significantly more cases in culture-positive samples. Among culture-negative samples, Xpert detected 18 more cases including 16 with histopathological evidence of TB. Lowest positivity was detected for both tests in cavitary fluids. Xpert performed better than PTec-ET in culture-positive FNA/pus/tissue biopsy and CSF samples.ConclusionsAlthough performance of both tests was suboptimal for AFB-negative/culture-positive samples, Xpert performed better than PTec-ET and also detected more cases of AFB-negative/culture-negative/histopathology-positive samples. PTec-ET was positive in 3, while Xpert was positive in all 6 culture-positive CSF specimens for rapid diagnosis of TB meningitis. Xpert was thus superior to PTec-ET or smear microscopy in rapid diagnosis of EPTB.     

Multiple antitumor effects of picropodophyllin in colon carcinoma cell lines: clinical implications

Although colorectal cancer can be successfully treated by conventional strategies such as chemo/radiotherapy and surgery, a substantial number of cases, in particular those with liver metastases, remain incurable. Therefore, novel treatment approaches are warranted. The IGF-1R and its ligands, mainly IGF-1 and IGF-2, have been suggested to play pivotal roles in proliferation, survival and migration of adenocarcinoma cells of the colon/rectum. Therefore, interference with IGF-1R-mediated signaling may represent a therapeutic option for this malignancy. In this study, semi-quantitative RT-PCR analyses of 48 paired, colorectal cancer patient samples showed significant overexpression of tumor IGF-1R and IGF-2 mRNA. There was also an overexpression of MMP-7, which was significantly correlated with histopathological parameters. Based on these findings, the effect of the IGF-1R-inhibitory cyclolignan picropodophyllin (PPP) was assessed in the four colon carcinoma cell lines HT-29, HCT-116, DLD-1 and CaCO-2. PPP strongly and dose-dependently inhibited proliferation and migration in all cell lines. However, when exposed to 0.5 μM PPP, only HT-29 showed a net decrease of viable cells as compared with the cell number at the beginning of the experiment, a finding that coincided with decreased expression/phosphorylation of IGF-1R, AKT and ERK. This cell line also exhibited PPP-induced downregulation of MMP-7 and MMP-9. Similar to the DLD-1 and HCT-116 cell lines, HT-29 also showed substantial cell detachment in response to PPP. Although a net reduction of cells by PPP seems to require a synchronized downregulation of IGF-1R, AKT and ERK1/2, part of the antitumor effect may be explained by other, possibly IGF-1R-unrelated mechanism(s). Such a multitude of inhibitory effects of PPP in colon cancer cells together with its low toxicity in vivo makes it a promising drug candidate in the treatment of this disease.     

IgE, Reed-Sternberg Cells, and Eosinophilia in Hodgkin's Disease

Tissues containing Hodgkin's disease tumors of the nodular sclerosis and mixed cellularity subtypes are frequently infiltrated by numerous degranulating eosinophils that release granule proteins such as eosinophil peroxidase and major basic protein. Until recently, the causes of the eosinophil infiltration and degranulation in Hodgkin's disease tumors were unknown. Analysis of Hodgkin's disease tissues by a sensitive and specific immunoperoxidase technique has now demonstrated the extensive presence of IgE in the Reed-Sternberg cells and adjacent cells of Hodgkin's disease tumors. Because eosinophils express a cell-surface receptor (CD23) for IgE and degranulate in the presence of IgE deposits, the extensive eosinophilia that is frequently present in Hodgkin's disease tumors is, at least in part, attributable to the IgE deposits within the tumor. In this review, we discuss the possible mechanisms and biological significance of IgE-related eosinophilia in Hodgkin's disease.     

Rare case of norethisterone‐induced hepatitis: A case report

We report a case of probable norethisterone‐related liver injury, manifesting as a significant rise in liver transaminases in a 62‐year‐old woman. Upon discontinuation of norethisterone, liver transaminases decreased to normal level within two weeks. Knowledge of rare adverse effects of drugs such as norethisterone is necessary for rapid identification and management, especially in patients with risk factors such as non‐alcoholic liver disease and obesity.     

Racial difference in circulating sex hormone-binding globulin levels in prepubertal boys

Racial differences in disease risk (eg, osteoporosis, metabolic cardiovascular syndrome, and prostate cancer) may arise partly on a hormonal basis. While reports of racial differences in gonadal steroid hormone levels in middle-aged men have produced conflicting results, there is evidence that high sex hormone-binding globulin (SHBG) and estradiol levels are more common among young adult African American men than white men. To determine whether this difference relates to pituitary-testicular functioning or to other factors, we conducted a cross-sectional study of 47 healthy prepubertal African American and white boys aged 5 to 9 years at the time of their annual school physical examination. Height, weight, blood pressure, waist and hip circumference, and Tanner staging were determined, and a fasting blood sample was obtained. The African Americans studied were slightly older than the whites (mean +/- SD, 82.4 +/- 15.0 vs 70.5 +/- 10.3 months, P = .003). African Americans were also slightly taller and heavier and had a lower waist-to-hip ratio, but these differences could be explained by the difference in age. Mean SHBG levels were 25% higher (P = .15) in African Americans than in whites (197 +/- 104 vs 157 +/- 79 nmol/L), and when adjusted for age, values were 46 nmol/L higher among African Americans. The fifth quintile for SHBG (values > 245 nmol/L) included 1 (4.2%) of 24 whites and 8 (35%) of 23 African Americans studied (P = .003). There was no significant correlation between age, body mass index, waist circumference, or fasting insulin and SHBG. Total testosterone, the free androgen index, and dehydroepiandrosterone increased with age in both groups, but after adjusting for age, no racial differences were found. Estradiol, estrone, and inhibin B levels, as well as systolic and diastolic blood pressures, were also comparable in both groups. We conclude that high levels of SHBG are more common among African American than in white boys and hypothesize that this difference and its effect on the ratio between bound and free steroid hormones may contribute to racial differences in disease risk in adult men.     

Invasive <Emphasis Type="Italic">Candida auris</Emphasis> infections in Kuwait hospitals: epidemiology,antifungal treatment and outcome

Purpose

Candida auris is a recently recognized yeast pathogen, which has attracted worldwide attention due to its multidrug-resistant nature and associated high mortality rates. Its persistence in hospital environment and propensity of nosocomial transmission underscores the need of continuous monitoring to prevent outbreaks. Since the first case of C. auris candidemia in May, 2014, we have identified 17 additional invasive cases, which are described here.

Methods

Identity of 17 isolates originating from proven or possible cases of invasive C. auris infection and identified as Candida haemulonii by Vitek 2 yeast identification system was confirmed by PCR-sequencing of rDNA. Information about risk factors, treatment and outcomes were retrospectively retrieved from case files. Antifungal susceptibility testing was performed by Etest.

Results

Thirteen cases of candidemia and 4 cases of other invasive infections were detected in 6 hospitals across Kuwait. Major risk factors included adult patients with cancer, diabetes, gastrointestinal/liver diseases and extended (>?25 days) hospital stay. All isolates were resistant to fluconazole. Additionally, 5 and 4 isolates were also resistant to voriconazole and amphotericin B, respectively. Despite antifungal treatment, 9 of 15 patients died. Most patients (n?=?12) were hospitalized in 2 hospitals that are in close proximity, whereas 5 other patients were from 3 hospitals that are situated?>?10 km apart.

Conclusions

Occurrence of successive cases of invasive C. auris infections with resulting mortality in nine patients suggests persistence of this multidrug-resistant yeast in major hospitals in Kuwait. Early detection by continuous surveillance and enforcement of infection control measures are recommended.

     

Association between vitamin B12 level and anti-parietal cells and anti-intrinsic factor antibodies among adult Jordanian patients with Helicobacter pylori infection

ObjectiveEvaluate the association of Helicobacter pylori infection with anti-parietal cell antibodies (APCA) and anti-intrinsic factor antibodies (AIFA) and their impact on vitamin B12 serum level.Patients and methodsOne hundred patients (M/F: 43/57; age 46.5 ± 17.5 years) who underwent upper gastrointestinal endoscopy at King Abdullah University Hospital, Irbid, Jordan were enrolled in the study. The patients were grouped as H. pylori-infected (n = 81) or H. pylori negative (n = 19) by histopathological examination. Fasting serum vitamin B12 levels, anti-parietal cell antibodies and anti-intrinsic factor antibodies for patients and controls were determined.ResultsAnti-parietal cell antibodies and anti-intrinsic factor antibodies were positive in 9.9% and 18.5% of H. pylori-positive patients respectively. None of the H. pylori negative subjects had anti-parietal cell antibodies or anti-intrinsic factor antibodies. Serum vitamin B12 level was lower in the H. pylori-infected patients (275 ± 70.4 pg/mL) than in controls (322.9 ± 60.7 pg/mL; p < 0.05). H. pylori was positive in 94% of the low-vitamin B12 group compared with 64.6% of the normal-vitamin B12 group (p < 0.5).ConclusionPatients with H. pylori infection are more likely to have anti-parietal cell antibodies and anti-intrinsic factor antibodies. There was an association between H. pylori infection and lower vitamin B12 levels. H. pylori infection might be a significant factor in the pathogenesis of autoimmune gastritis.