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High rate of in-stent restenosis after coronary intervention in carriers of the mutant mannose-binding lectin allele
No full textAbstract
Background
In-stent restenosis occurs in 10\u201330% of patients following bare metal stent (BMS) implantation and has various risk factors. Mannose-binding lectin (MBL) is known to have effect on the progression of atherosclerosis. Single nucleotide polymorphisms (SNP) of the MBL2 gene intron 1 (codon 52, 54, 57) are known to modulate the bioavailability of the MBL protein. Our aim was to identify the association of these polymorphisms of the MBL gene in the occurrence of in-stent restenosis after coronary artery bare metal stent implantation.
Methods
In a non-randomized prospective study venous blood samples were collected after recoronarography from 225 patients with prior BMS implantation. Patients were assigned to diffuse restenosis group and control group based on the result of the coronarography. MBL genotypes were determined using quantitative real-time PCR. Proportion of different genotypes was compared and adjusted with traditional risk factors using multivariate logistic regression.
Results
Average follow-up time was 1.0 (+\u2009\u2212\u20091.4) year in the diffuse restenosis group ( N \u2009=\u2009117) and 2.7 (+\u2009\u2212\u20092.5) years in the control group ( N \u2009=\u2009108). The age, gender distribution and risk status was not different between study groups. Proportion of the MBL variant genotype was 26.8% (29 vs. 79 normal homozygous) in the control group and 39.3% (46 vs. 71 normal homozygous) in the restenosis group ( p \u2009=\u20090.04). In multivariate analysis the mutant allele was an independent risk factor (OR\u2009=\u20091.96, p \u2009=\u20090.03) of in-stent restenosis.
Conclusions
MBL polymorphisms are associated with higher incidence of development of coronary in-stent restenosis. The attenuated protein function in the mutant allelic genotype may represent the underlying mechanism
Nasal carriage of methicillin resistant Staphylococcus aureus among health care workers at Al Shifa hospital in Gaza Strip
No full textAbstract
Background
Nasal carriage of Staphylococcus aureus among hospital personnel is a common cause of hospital acquired infections. Emergence of drug resistant strains especially methicillin resistant S. aureus (MRSA) is a serious problem in hospital environment. Therefore, the aim of this study was to determine the nasal carriage rate of S. aureus and MRSA among Health Care Workers (HCWs) at Al Shifa Hospital, the major hospital in Gaza Strip.
Methods
A cross sectional study was conducted on 200 HCWs. Nasal swabs were collected during February \u2014 April 2015, and cultured on blood and mannitol salt agar. The isolates were identified as S. aureus based on morphology, coagulase test, DNase test and mannitol salt agar fermentation. Disk diffusion antibiotic susceptibility tests were performed according to the guidelines of the Clinical and Laboratory Standards Institute. MRSA were confirmed by detection of the mecA gene by PCR.
Results
Out of the 200 healthcare workers, 62 (31%) carried S. aureus, of which 51 (82.3%) were MRSA. Therefore, 25.5% of all HCWs were identified as MRSA carriers. MRSA carriage rate was highest among nurses (30.4%) whereas the carriage rate among doctors was (16%). The majority of MRSA carriers were workers of internal medicine department and surgical wards (41.3 and 35% respectively). Out of the 51 MRSA isolates identified by oxacillin disc resistance, 40 were confirmed by PCR targeting the mecA gene. Penicillin showed the highest rate of resistance among MRSA and MSSA isolates (100%).
Conclusions
The high rate of nasal MRSA carriage among healthcare workers found in this study is alarming and highlights the need for adjusted infection control measures to prevent MRSA transmission from HCWs to the vulnerable patient
High prevalence and low cure rate of tuberculosis among patients with HIV in Xinjiang, China
No full textAbstract
Background
Tuberculosis and HIV co-epidemics are problems in many parts of the world. Xinjiang is a high tuberculosis and HIV prevalence area in China. We aimed to investigate the prevalence and cure rate of tuberculosis among HIV positive patients in Xinjiang.
Methods
In a retrospective study between 2006 and 2011, clinical and laboratory data on 333 patients with HIV and tuberculosis were compared to 2668 patients with HIV only. There were 31 HIV positive patients with no data on tuberculosis.
Results
The prevalence of tuberculosis co-infection among the HIV positive patients was 11% (95% CI 10\u201312%), significantly higher than the national figure in China of 2%. In most cases HIV was diagnosed late, with advanced immunodeficiency. The use of isoniazid preventive therapy was only 57.9% in patients without tuberculosis who fulfilled the criteria for receiving this prevention. The cure rate one year after diagnosis was 69.2%, which was lower than the officially reported 91.4% in all tuberculosis cases in Xinjiang in 2011. The hazard of not surviving over the five years was significantly higher in patients with HIV\u2009+\u2009tuberculosis compared to HIV only after adjusting for sex and Intravenous drug use with HR\u2009=\u20091.84 (95% CI 1.43-2.35; p \u2009<\u20090.0001).
Conclusions
The prevalence of tuberculosis among HIV positive patients in Xinjiang was higher than in China taken as a whole, and HIV was diagnosed late, with underuse of isoniazid preventive therapy. The low cure rate and reduced survival can be due to late diagnosis of HIV and no testing for antibiotic resistance, together with insufficient control of adherence to the treatment regimens for tuberculosis and HIV
A novel NHS mutation causes Nance-Horan Syndrome in a Chinese family
No full textAbstract
Background
Nance-Horan Syndrome (NHS) (OMIM: 302350) is a rare X-linked developmental disorder characterized by bilateral congenital cataracts, with occasional dental anomalies, characteristic dysmorphic features, brachymetacarpia and mental retardation. Carrier females exhibit similar manifestations that are less severe than in affected males.
Methods
Here, we report a four-generation Chinese family with multiple affected individuals presenting Nance-Horan Syndrome. Whole-exome sequencing combined with RT-PCR and Sanger sequencing was used to search for a genetic cause underlying the disease phenotype.
Results
Whole-exome sequencing identified in all affected individuals of the family a novel donor splicing site mutation (NM_198270: c.1045\u2009+\u20092T\u2009>\u2009A) in intron 4 of the gene NHS , which maps to chromosome Xp22.13. The identified mutation results in an RNA processing defect causing a 416-nucleotide addition to exon 4 of the mRNA transcript, likely producing a truncated NHS protein.
Conclusions
The donor splicing site mutation NM_198270: c.1045\u2009+\u20092T\u2009>\u2009A of the NHS gene is the causative mutation in this Nance-Horan Syndrome family. This research broadens the spectrum of NHS gene mutations, contributing to our understanding of the molecular genetics of NHS
Combining adverse pregnancy and perinatal outcomes for women exposed to antiepileptic drugs during pregnancy, using a latent trait model
No full textAbstract
Background
Application of latent variable models in medical research are becoming increasingly popular. A latent trait model is developed to combine rare birth defect outcomes in an index of infant morbidity.
Methods
This study employed four statewide, retrospective 10-year data sources (1999 to 2009). The study cohort consisted of all female Florida Medicaid enrollees who delivered a live singleton infant during study period. Drug exposure was defined as any exposure to Antiepileptic drugs (AEDs) during pregnancy. Mothers with no AED exposure served as the AED unexposed group for comparison. Four adverse outcomes, birth defect (BD), abnormal condition of new born (ACNB), low birth weight (LBW), and pregnancy and obstetrical complication (PCOC), were examined and combined using a latent trait model to generate an overall severity index. Unidimentionality, local independence, internal homogeneity, and construct validity were evaluated for the combined outcome.
Results
The study cohort consisted of 3183 mother-infant pairs in total AED group, 226 in the valproate only subgroup, and 43,956 in the AED unexposed group. Compared to AED unexposed group, the rate of BD was higher in both the total AED group (12.8% vs. 10.5%, P \u2009<\u2009.0001), and the valproate only subgroup (19.6% vs. 10.5%, P \u2009<\u2009.0001). The combined outcome was significantly correlated with the length of hospital stay during delivery in both the total AED group (Rho\u2009=\u20090.24, P \u2009<\u2009.0001) and the valproate only subgroup (Rho\u2009=\u20090.16, P \u2009=\u2009.01). The mean score for the combined outcome in the total AED group was significantly higher (2.04\u2009\ub1\u20090.02 vs. 1.88\u2009\ub1\u20090.01, P \u2009<\u2009.0001) than AED unexposed group, whereas the valproate only subgroup was not.
Conclusions
Latent trait modeling can be an effective tool for combining adverse pregnancy and perinatal outcomes to assess prenatal exposure to AED, but evaluation of the selected components is essential to ensure the validity of the combined outcome
A matched-pair study comparing whole-brain irradiation alone to radiosurgery or fractionated stereotactic radiotherapy alone in patients irradiated for up to three brain metastases
No full textAbstract
Background
This matched-pair study was initiated to validate the results of a retrospective study of 186 patients published in 2007 that compared whole-brain irradiation (WBI) alone and radiosurgery (RS) alone for up to three brain metastases.
Methods
One-hundred-fifty-two patients receiving WBI alone for up to three brain metastases were matched with 152 patients treated with RS of fractionated stereotactic radiotherapy (FSRT) alone 1:1 for each of eight factors (age, gender, Eastern Oncology Cooperative Group (ECOG)-performance score, nature of tumor, brain metastases number, extra-cerebral spread, period from cancer detection to irradiation of brain metastases, and recursive partitioning analysis (RPA)-class. Groups were analyzed regarding intracerebral control (IC) and overall survival (OS).
Results
On univariate analysis of IC, type of irradiation did not significantly affect outcomes ( p \u2009=\u20090.84). On Cox regression, brain metastases number ( p \u2009<\u20090.001), nature of tumor ( p \u2009<\u20090.001) and period from cancer detection to irradiation of brain metastases ( p \u2009=\u20090.013) were significantly associated with IC. On univariate analysis of OS, type of irradiation showed no significant association with outcomes ( p \u2009=\u20090.63). On multivariate analyses, OS was significantly associated with ECOG performance score ( p \u2009=\u20090.011), nature of tumor ( p \u2009=\u20090.035), brain metastases number ( p \u2009=\u20090.048), extra-cerebral spread ( p \u2009=\u20090.002) and RPA-class ( p \u2009<\u20090.001).
Conclusion
In this matched-pair study, RS/FSRT alone was not superior to WBI alone regarding IC and OS. These results can be considered a revision of the findings from our retrospective previous study without matched-pair design, where RS alone resulted in significantly better IC than WBI alone on multivariate analysis
Case report: whole exome sequencing of primary cardiac angiosarcoma highlights potential for targeted therapies
No full textAbstract
Background
Primary cardiac angiosarcomas are rare, but they are the most aggressive type of primary cardiac neoplasms. When patients do present, it is with advanced pulmonary and/or cardiac symptoms. Therefore, many times the correct diagnosis is not made at the time of initial presentation. These patients have metastatic disease and the vast majority of these patients die within a few months after diagnosis. Currently the treatment choices are limited and there are no targeted therapies available.
Case presentation
A 56-year-old male presented with shortness of breath, night sweats, and productive cough for a month. Workup revealed pericardial effusion and multiple bilateral pulmonary nodules suspicious for metastatic disease. Transthoracic echocardiogram showed a large pericardial effusion and a large mass in the base of the right atrium. Results of biopsy of bilateral lung nodules established a diagnosis of primary cardiac angiosarcoma. Aggressive pulmonary disease caused rapid deterioration; the patient went on hospice and subsequently died. Whole exome sequencing of the patient\u2019s postmortem tumor revealed a novel KDR (G681R) mutation, and focal high-level amplification at chromosome 1q encompassing MDM4 , a negative regulator of TP53.
Conclusion
Mutations in KDR have been reported previously in angiosarcomas. Previous studies also demonstrated that KDR mutants with constitutive KDR activation could be inhibited with specific KDR inhibitors in vitro. Thus, patients harboring activating KDR mutations could be candidates for treatment with KDR-specific inhibitors
miR-663a regulates growth of colon cancer cells, after administration of antimicrobial peptides, by targeting CXCR4-p21 pathway
No full textAbstract
Background
Antimicrobial peptides (AMPs) play important roles in the innate immune system of all life forms and recently have been characterized as multifunctional peptides that have a variety of biological roles such as anticancer agents. However, detailed mechanism of antimicrobial peptides on cancer cells is still largely unknown.
Methods
miRNA array and real-time qPCR were performed to reveal the behavior of miRNA in colon cancer HCT116 cells during the growth suppression induced by the AMPs. Establishment of miR-663a over-expressing HCT116 cells was carried out for the evaluation of growth both in vitro and in vivo. To identify the molecular mechanisms, we used western blotting analysis.
Results
miR-663a is upregulated by administration of the human cathelicidin AMP, LL-37, and its analogue peptide, FF/CAP18, in the colon cancer cell line HCT116. Over-expression of miR-663a caused anti-proliferative effects both in vitro and in vivo. We also provide evidence supporting the view that these effects are attributed to suppression of the expression of the chemokine receptor CXCR4, resulting in the abrogation of phosphorylation of Akt and cell cycle arrest in G2/M via p21 activation.
Conclusions
This study contributes to the understanding of the AMPs\u2019 mediated anti-cancer mechanisms in colon cancer cells and highlights the possibility of using AMPs and miRNAs towards developing future strategies for cancer therapy
Prognostic relevance of lactate dehydrogenase in advanced pancreatic ductal adenocarcinoma patients
No full textAbstract
Background
The prognostic role of pretreatment serum lactate dehydronegase (LDH) has been well established in many malignant tumors, albeit it remains under-discussed in pancreatic cancer. In the present study, we aimed to assess the association between baseline LDH levels and overall survival (OS) in advanced pancreatic ductal adenocarcinoma (PDAC) patients who did and did not receive subsequent chemotherapy.
Methods
In total, 135 retrospectively determined patients with locally advanced or metastatic PDAC, who were diagnosed between 2012 and 2013, were analyzed. Baseline LDH levels were detected within 20\ua0days after histopathological confirmation of the diagnosis. Multivariate Cox proportional hazards regression model was applied to estimate the adjusted hazards ratio (HR) for LDH levels and OS of PDAC. We used restricted cubic spline (RCS) to further investigate dose-effect relationship in the association.
Results
Having adjusted for possible confounders, we found that in advanced PDAC patients who went through subsequent chemotherapy, an elevated pretreatment LDH level (\u2265250 U/L) had an adjusted HR of 2.47 (95% CI\u2009=\u20091.28\u20134.77) for death, but patients, who did not receive chemotherapy, had no significant HR (adjusted HR\u2009=\u20091.57; 95% CI\u2009=\u20090.83\u20132.96). RCS fitting results revealed a steep increase in HR for PDAC patients received chemotherapy with a baseline LDH\u2009>\u2009500 U/L.
Conclusions
Pretreatment LDH levels had noticeable prognostic value in PDAC patients who received subsequent chemotherapy. Tackling elevated LDH levels before the initiation of chemotherapy might be a promising measure for improving OS of patients after treatment for their advanced PDAC. Studies with a large sample size and a prospective design are warranted to substantiate our findings
Healthcare-seeking behaviour of primary caregivers for acute otitis media in children aged 6\ua0months to <30\ua0months in Panama: results of a cross-sectional survey
No full textAbstract
Background
Acute otitis media (AOM) is the most common bacterial childhood infection. However, caregivers with children having mild episodes often do not seek healthcare services, which may lead to an under-appreciation of the disease experienced by the community. The objectives of this survey were to estimate the proportion of primary caregivers who went to a healthcare facility when they suspected that their child aged 6 to <30\ua0months was having an AOM episode during the past 6\ua0months and to assess what factors influenced their decision.
Methods
This observational, cross-sectional survey of primary caregivers (\u226518\ua0years), with at least one child aged 6 to <30\ua0months was performed in 19 healthcare facilities in Panama (March to May 2013). A 28-item paper questionnaire was administered to assess demographic data, AOM symptoms, as well as potential healthcare-seeking behaviour and factors influencing this behaviour. Potential confounding effects were individually assessed using Chi-squared or Cochran-Mantel-Haenszel tests, and all together in logistic regression models.
Results
The total number of eligible participants was 1330 (mean age 28.5\u2009\ub1\u20098.0\ua0years). Of these, 245 participants had at least one child whom they suspected had an AOM episode during the past 6\ua0months. Of the 245 participants, 213 (86.9%) sought healthcare at a facility. Several factors were associated with healthcare usage: perceived severity of illness ( p \u2009=\u20090.001), occupational status of the caregiver ( p \u2009=\u20090.002), household income ( p \u2009=\u20090.016) and length of time since the last suspected AOM episode ( p \u2009=\u20090.032).
Conclusions
When confronted with a child with obvious symptoms of AOM, the majority of caregivers reported seeking healthcare. This behaviour appeared to be associated with factors related to the severity of the illness, the length of time since the last episode, as well as with the income and occupational status of the caregivers themselves. As many episodes of AOM present with non-specific respiratory symptoms, our results apply only to caregivers who were confronted with children with an obvious symptom