Prognostic value of HPV-mRNA in sentinel lymph nodes of cervical cancer patients with pN0-status

Up to 15% of patients with cervical cancer and pN0-status develop recurrent-disease. This may be due to occult metastatic spread of tumor cells. We evaluated the use of human-papillomavirus-(HPV)-mRNA as a molecular marker for disseminated tumor cells to predict the risk of recurrence. For this prospective, multi-center prognostic study, 189 patients free of lymphnode metastases by conventional histopathology could be analyzed. All patients underwent complete lymphadenectomy. Of each sentinel node (SLN) a biopsy was taken for the detection of HPV-E6-E7-mRNA. Median follow-up time after surgery was 8.1 years. HPV-mRNA could be detected in SLN of 52 patients (27.5%). Recurrence was observed in 22 patients. Recurrence-free-survival was significantly longer for patients with HPV-negative SLN (log rank p = 0.002). By Cox regression analysis the hazard ratio (95%CI) for disease-recurrence was 3.8 (1.5 – 9.3, p = 0.004) for HPV-mRNA-positive compared to HPV-mRNA-negative patients. After adjustment for tumor size as the most influential covariate the HR was still 2.8 (1.1 – 7.0, p = 0.030). In patients with cervical cancer and tumor-free lymph nodes by conventional histopathology HPV-mRNA-positive SLN were of prognostic value independent of tumor size. Particularly, patients with tumors larger than 20mm diameter could possibly benefit from further risk stratification using HPV-mRNA as a molecular marker.     

Reduced rate of copy number aberrations in mucinous colorectal carcinoma

Background

Mucinous carcinoma (MC) is found in 10%–15% of colorectal cancer (CRC) patients. It differs from the common adenocarcinoma (AC) in histopathological appearance and clinical behavior.

Methods

Genome-wide DNA copy number and survival data from MC and AC primary CRC samples from patients from two phase III trials (CAIRO and CAIRO2) was compared. Chromosomal copy number data from The Cancer Genome Atlas (TCGA) was used for validation. Altogether, 470 ACs were compared to 57 MCs.

Results

MC showed a reduced amount of copy number aberrations (CNAs) compared with AC for the CAIRO/CAIRO2 cohort, with a median amount of CNAs that was 1.5-fold lower (P = 0.002). Data from TCGA also showed a reduced amount of CNAs for MC. MC samples in both cohorts displayed less gain at chromosome 20q and less loss of chromosome 18p. A high rate of chromosomal instability was a strong negative prognostic marker for survival in MC patients from the CAIRO cohorts (hazard ratio 15.60, 95% CI 3.24–75.05).

Conclusions

Results from this study indicate that the distinct MC phenotype is accompanied by a different genetic basis when compared with AC and show a strong association between the rate of chromosomal instability and survival in MC patients.     

Susceptibilities of Campylobacter jejuni isolates from Germany to ciprofloxacin,moxifloxacin, erythromycin,clindamycin, and tetracycline

To elucidate Campylobacter jejuni resistance to antibiotics in Germany, MICs of ciprofloxacin, moxifloxacin, erythromycin, clindamycin, and tetracycline were determined (using agar dilution) for 144 clinical isolates. The data indicate a considerable ciprofloxacin resistance (45.1%) without a clonal relationship of the strains and a greater in vitro activity of moxifloxacin, erythromycin, and clindamycin.     

Modelling the Spatial and Temporal Dynamics of Paralytic Shellfish Toxins (PST) at Different Scales: Implications for Research and Management

Harmful algal blooms, in particular recurrent blooms of the dinoflagellate Alexandrium catenella, associated with paralytic shellfish poisoning (PSP), frequently limit commercial shellfish harvests, resulting in serious socio-economic consequences. Although the PSP-inducing species that threaten the most vulnerable commercial species of shellfish are very patchy and spatially heterogeneous in their distribution, the spatial and temporal scales of their effects have largely been ignored in monitoring programs and by researchers. In this study, we examined the spatial and temporal dynamics of PSP toxicity in the clam (Ameghinomya antiqua) in two fishing grounds in southern Chile (Ovalada Island and Low Bay). During the summer of 2009, both were affected by an intense toxic bloom of A. catenella (up to 1.1 × 10⁶ cells L⁻¹). Generalized linear models were used to assess the potential influence of different environmental variables on the field detoxification rates of PSP toxins over a period of 12 months. This was achieved using a four parameter exponential decay model to fit and compare field detoxification rates per sampling site. The results show differences in the spatial variability and temporal dynamics of PSP toxicity, given that greater toxicities (+10-fold) and faster detoxification (20% faster) are observed at the Ovalada Island site, the less oceanic zone, and where higher amounts of clam are annually produced. Our observations support the relevance of considering different spatial and temporal scales to obtain more accurate assessments of PSP accumulation and detoxification dynamics and to improve the efficacy of fisheries management after toxic events.     

Folic acid functionalization for targeting self-assembled paclitaxel-based nanoparticles

Hetero-nanoparticles self-assembled from a conjugate bearing folic acid as the targeting agent, and another bearing paclitaxel as the active agent are reported. Hetero-nanoparticles containing varying percentages of folic acid conjugates are characterised, and their biological activity is determined.

Self-assembled hetero-nanoparticles are obtained by mixing paclitaxel and folic acid conjugates.     

Isoniazid preventive therapy-related adverse events among Malawian adults on antiretroviral therapy: A cohort study

Adverse events may be a cause of observed poor completion of isoniazid preventive therapy (IPT) among people living with HIV in high tuberculosis burden areas. Data on IPT-related adverse events (AE) from sub-Saharan Africa are scarce. We report IPT-related AEs, associated clinical characteristics, and IPT discontinuations in adults who were stable on antiretroviral therapy (ART) when they initiated IPT. Cohort study nested within a randomized, controlled, clinical trial of cotrimoxazole and chloroquine prophylaxis in Malawians aged ≥ 18 years and virologically suppressed on ART. Eight hundred sixty-nine patients were followed for a median of 6 months after IPT initiation. IPT relatedness of AEs was determined retrospectively with the World Health Organization case-causality tool. Frailty survival regression modeling identified factors associated with time to first probably IPT-related AE. The overall IPT-related AE incidence rate was 1.1/person year of observation. IPT relatedness was mostly uncertain and few AEs were severe. Most common were liver and hematological toxicities. Higher age increased risk of a probably IPT-related AE (aHR = 1.02; 95% CI 1.00–1.06; P = .06) and higher weight reduced this risk (aHR = 0.98; 95% CI 0.96–1.00; P = .03). Of 869 patients, 114 (13%) discontinued IPT and 94/114 (82%) discontinuations occurred at the time of a possibly or probably IPT-related AE. We observed a high incidence of mostly mild IPT-related AEs among individuals who were stable on ART. More than 1 in 8 persons discontinued IPT. These findings inform strategies to improve implementation of IPT in adults on ART, including close monitoring of groups at higher risk of IPT-related AEs.     

Hemotropic Mycoplasma spp. in Aquatic Mammals,Amazon Basin,Brazil

Hemotropic Mycoplasma spp. (hemoplasmas) are uncultivable bacteria that infect mammals, including humans. We detected a potentially novel hemoplasma species in blood samples from wild river dolphins in the Amazon River Basin, Brazil. Further investigation could determine pathogenicity and zoonotic potential of the detected hemoplasma.