Successful use of extracorporeal membrane oxygenation in a human immunodeficiency virus infected patient with severe acute respiratory distress syndrome

Introduction

We report a case of an adult patient with human immunodeficiency virus (HIV), acute respiratory distress syndrome (ARDS) and ventilator associated pneumonia (VAP) caused by multidrug resistant (MDR) bacteria that was successfully managed with veno-venous extracorporeal membrane oxygenation (ECMO).

Case report

A 25 year old male with no significant past medical history had been admitted to a local hospital due to dyspnea and fever. His pulmonary function subsequently failed necessitating mechanical ventilation (MV) and introduction of ECMO support. The patient was transported for 300 km by road on ECMO to a tertiary medical center. The diagnosis of ARDS, HIV infection and MDR bacterial and fungal VAP was made. Patient was successfully treated with antiretroviral therapy (ART), anti-infective agents and 58 days of veno-venous ECMO support, with complete resolution of the respiratory symptoms.

Conclusion

HIV infected patients with ARDS and MDR bacterial VAP whose HIV replication is controlled by ART could be successfully managed with ECMO.

     

Influence of wrap length on the effectiveness of Nissen and Toupet fundoplications: 5-year results of prospective, randomized study

Background

Long-term results in antireflux surgery may depend on fundoplication type and wrap length. We compared the outcome of two different wrap lengths among the patients undergoing partial or total fundoplications. This study is the next part of a prospective 5-year follow-up assessment.

Methods

A total of 153 patients were randomized to Nissen or Toupet 1.5- or 3-cm wrap laparoscopic fundoplication. The primary endpoint—treatment failure rate was defined as a recurrent GERD or persistent dysphagia. Intensity of heartburn, dysphagia, gas-bloating, presence of esophagitis were assessed as a secondary outcome at 1-year and 5-year follow-up.

Results

At 5-year follow-up, data were collected from 129 (85 %) patients. At 1-year follow-up, 17 (11 %) treatment failures were detected. At the end of the fifth year, the numbers reached 23 (15 %). The failures were more common in the 1.5-cm Toupet (25 %) and the 3-cm Nissen group (18.2 %). The significant difference in failure rates was found between 1.5-cm and 3-cm Toupet groups (P < 0.05). Dysphagia remained low during the follow-up in all of the groups. The prevalence of higher scores of heartburn after 5 years was detected in Nissen 1.5-cm group (20.8 %). The lowest scores were observed in Toupet 3-cm group. Bloating symptoms were more prevalent among Nissen and Toupet 3-cm group patients at 5-year follow-up. At the end of the fifth year, the prevalence of esophagitis was lower in Nissen 1.5-cm (19.3 %) and Toupet 3-cm (13.3 %) groups. The highest prevalence of esophagitis—32.4 %—was found in Toupet 1.5-cm group.

Conclusions

Nissen and Toupet fundoplication achieved sufficient control of reflux with success rate of 85 % at 5-year follow-up. There were no significant differences in the postoperative dysphagia, esophagitis, and bloating rates. However, the distribution of treatment failures leads us to conclude that 1.5-cm wrap length is insufficient in cases of posterior partial fundoplication.     

Expression of CDKN1C in the bone marrow of patients with myelodysplastic syndrome and secondary acute myeloid leukemia is associated with poor survival after conventional chemotherapy

We tested the hypothesis that proliferative activity of hematopoietic stem cells has impact on survival in newly diagnosed patients with myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (AML). RNA expression profiles of CD34⁺ cells were analyzed in 125 MDS patients and compared to healthy controls. Prognostic impact on overall survival (OS) of mRNA proliferation signatures established for solid tumor cells was analyzed retrospectively. For validation on the protein level, immunofluorescence and immunohistochemistry analyses in bone marrow (BM) biopsies were performed, and an independent cohort of 223 MDS and secondary AML patients was investigated. Lower proliferative activity correlated with the expression of cyclin‐dependent kinase inhibitor 1C (CDKN1C) and with shorter OS (p < 0.001). In multivariable analysis, higher CDKN1C expression was associated with worse OS (p = 0.02). On the BM level, a total of 84 (38%) patients showed CDKN1C protein expression before start of treatment. Patient, disease and treatment characteristics did not differ between CDKN1C‐positive and ‐negative patients. Positive CDKN1C BM status was associated with shorter OS in multivariable analysis (HR 1.54, p = 0.04). There was an interaction between CDKN1C BM status and subsequent treatment with negative impact on OS being most pronounced in patients receiving conventional cytotoxic chemotherapy (n = 83, 2‐year OS 30% versus 58%, p = 0.002). In conclusion, low‐proliferative phenotype and CDKN1C expression were associated with shorter OS. CDKN1C protein expression in the BM of newly diagnosed, treatment‐naïve MDS and secondary AML patients was identified as a prognostic factor for poor survival in patients treated with antiproliferative chemotherapy.     

Identification of high-affinity PB1-derived peptides with enhanced affinity to the PA protein of influenza A virus polymerase

The influenza A virus polymerase complex, consisting of the subunits PB1, PB2, and PA, represents a promising target for the development of new antiviral drugs. We have previously demonstrated the feasibility of targeting the protein-protein interaction domain between PA and PB1 using peptides derived from the extreme N terminus of PB1 (amino acids [aa] 1 to 15), comprising the PA-binding domain of PB1. To increase the binding affinity of these peptides, we performed a systematic structure-affinity relationship analysis. Alanine and aspartic acid scans revealed that almost all amino acids in the core binding region (aa 5 to 11) are indispensable for PA binding. Using a library of immobilized peptides representing all possible single amino acid substitutions, we were able to identify amino acid positions outside the core PA-binding region (aa 1, 3, 12, 14, and 15) that are variable and can be replaced by affinity-enhancing residues. Surface plasmon resonance binding studies revealed that combination of several affinity-enhancing mutations led to an additive effect. Thus, the feasibility to enhance the PA-binding affinity presents an intriguing possibility to increase antiviral activity of the PB1-derived peptide and one step forward in the development of an antiviral drug against influenza A viruses.     

Discovered on gastrointestinal stromal tumor 1 (DOG1) is expressed in pancreatic centroacinar cells and in solid-pseudopapillary neoplasms--novel evidence for a histogenetic relationship

Solid-pseudopapillary neoplasms of the pancreas are tumors of low malignant potential whose histogenesis has been discussed controversially. In the series of 15 solid-pseudopapillary neoplasms presented here, we demonstrate that discovered on gastrointestinal stromal tumor 1 is expressed significantly by these tumors (diffuse expression in 8 cases, focal expression in 4 cases, and scarce expression in 3 cases). Similar to the high expression of CD117, this finding parallels the immunohistochemical findings in gastrointestinal stromal tumors. Using double immunohistochemistry and immunofluorescence, we furthermore show that centroacinar cells express discovered on gastrointestinal stromal tumors 1. Thus, our findings suggest that, similarly to CD10 or vimentin, the expression of discovered on gastrointestinal stromal tumors 1 may serve as a novel marker for centroacinar cells and for solid-pseudopapillary neoplasms, which is suggestive of a centroacinar origin of these neoplasms.     

Differences in reporting somatic complaints in elderly by education level

Aim

To evaluate the association between somatic complaints and education level among elders in selected European countries.

Methods

Cross-sectional study among randomly selected community dwelling persons aged 60–84 years from seven cities in Europe: Ancona (Italy), Athens (Greece), Granada (Spain), Kaunas (Lithuania), Stuttgart (Germany), Porto (Portugal) and Stockholm (Sweden). Somatic complaints were measured with the 24-item version of the Giessen Complaint List (GBB-24). A regression analysis was done to investigate the association between education and somatic complaints. Results. The mean GBB-24 scale was 16.3±14.9. The most common complaints were pain in joints and limbs (29.6%), back-pain (24.1%), heaviness or tiredness in the legs (19.1%) and general tiredness (15.7%). Respondents with less than primary education reported higher levels of somatic symptoms compared to those with university degree. A regression analysis showed that higher education (OR=0.69) and being male (OR=0.48) were associated with a decreased risk for high levels of somatic complaints, and the opposite for older age (OR=1.03) and being single/divorced/window (OR=1.28).

Conclusions

The results indicate that less educated elders are more likely to expressed somatic complaints.     

KRAS,NRAS and BRAF mutations in colorectal cancer and melanoma

Cancers are the group of diseases, which arise because of the uncontrolled behavior of some of the genes in our cells. There are possibilities of gene amplifications, overexpressions, deletions and other anomalies which might lead to the development and spread of cancer. One of the most dangerous ways to the cancers is the mutations of the genes. The mutated genes can start unstoppable proliferation of cells, their uncontrolled motility, protection from apoptosis, the DNA mutation enhancement as well as other anomalies, leading to the cancer. This review focuses on the genes, which are frequently mutated in various cancers and are known to be important in the advance and progression of colorectal cancer and melanoma, namely KRAS, NRAS and BRAF.